Lynch I et al., 2026·Integrated Environmental Assessment and Management
The pervasive use of lip cosmetics results in chronic, low-dose exposure to complex mixtures of chemicals via multiple routes, yet current cosmetic safety regulations treat lip products as conventional topical applications to skin. While the EU safety assessment framework acknowledges ingestion as an exposure route for lip products, standardised lip-specific testing models do not currently exist. The US requires no mandatory pre-market safety review for cosmetic ingredients and systemic exposure consideration is confined to voluntary industry assessment (except for colour additives). In both jurisdictions, exposure estimates are based on usage data from 2005 that do not reflect current real-world usage patterns of lip cosmetics, including frequent reapplication, product layering, and marketing based on food characteristics. The unique physiology of the lips, which represent a transitional tissue between external skin and oral mucosa provides an additional exposure route: the vermilion and labial mucosa are characterized by a markedly thinner and incompletely keratinised epithelium, reduced lipid barrier components, high vascularisation, and constant moisture-collectively conferring substantially higher permeability than facial skin. Evidence from pharmacology demonstrates that oral mucosal tissues are deliberately exploited for rapid systemic drug delivery. By comparing how the oral mucosal exposure route is evaluated across cosmetic, food, and pharmaceutical regulatory regimes, this review identifies a critical regulatory gap: chemicals applied to the lips are assessed under frameworks designed for low-permeability skin, despite a biological reality more consistent with mucosal exposure. This mismatch undermines the accuracy of current risk assessments and may lead to systematic underestimation of internal dose for certain lip cosmetic ingredients including microplastics. Addressing this gap will require lip-specific exposure models, physiologically relevant in vitro systems, and updated regulatory guidance to ensure that cosmetic safety assessment accurately reflects the unique exposure profile of lip products.
Velmahos AH et al., 2026·Journal of Restorative Reproductive Medicine·
Open Access
To evaluate the extent to which a history of infertility is associated with adherence to specific diets among reproductive-aged females. Cross-sectional analysis Between 2017–2023, 7,227 North American female pregnancy planners aged 21-45 years enrolled in PRESTO (Pregnancy Study Online), a preconception cohort study. Participants completed self-administered baseline questionnaires during preconception. Exposure: Infertility history, defined as: 1) self-reported 12-month clinical infertility, 2) history of visiting a clinician for an infertility work-up, and/or 3) clinician-identified cause of infertility (e.g., ovulatory or tubal). Adherence to specific diets, including vegetarian, vegan, Mediterranean, Paleo, Weight Watchers®, ketogenic, dairy free, gluten free, Atkins®, South Beach®, Zone®, raw foods, or other at baseline. Multivariable log-binomial regression models estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs), adjusted for age, income, and body mass index (BMI). The percentage of participants with a history of infertility was 26% based on the 12-month clinical infertility definition, 30% based on visiting a physician for infertility evaluation, and 26% based on an infertility diagnosis following a physician visit. Overall adherence to any particular diet was low (4.6% vegetarian, 2.8% ketogenic, 1.7% Weight Watchers®, 1.4% Mediterranean, 1.3% vegan, 0.8% Paleo, and all other diets: <0.8%); 86.6% reported not adhering to any particular diet. A history of 12-month clinical infertility was associated with lower adherence to vegetarian (PR=0.78; 95% CI: 0.60-1.03), Paleo (PR=0.43; 95% CI: 0.19-0.98), and Weight Watchers® (PR=0.55; 95% CI: 0.34-0.91) diets. An infertility history involving a medical work-up was associated with a higher prevalence of adherence to a ketogenic diet (PR=1.56; 95% CI: 1.17-2.09). Participants whose infertility was attributed to ovulatory or tubal causes were nearly two times more likely to adhere to a ketogenic diet (PR=2.01; 95% CI: 1.38-2.94; PR=2.22; 95% CI: 1.09-4.49, respectively). The cross-sectional design cannot establish temporality or causality. Data on dietary patterns and infertility history were self-reported, which can introduce misclassification. Generalizability may be limited because participants were pregnancy planners not using fertility treatments; participants were also more likely to be non-Hispanic White and of higher socioeconomic status than the general population. The ketogenic diet was more prevalent among females with an infertility history, while vegetarian, Paleo, and Weight Watchers® diets were less prevalent. These associations mirror the results of studies evaluating the reverse relationship, suggesting that some patients with infertility seek information for behavioral modifications via evidence-based medicine.
Environmental Exposures · Personal Care and Household Products
Dominguez-Liste A et al., 2025·Environmental Research
The contemporary textile industry utilizes a vast array of chemical substances spanning multiple functional and structural classes. Recent data suggest that over 8000 xenobiotic compounds may be employed throughout various stages of textile manufacturing. This widespread chemical usage raises significant public health concerns, particularly because the routine act of wearing clothing implies exposure on a daily basis. Of particular concern is the vulnerability associated with early-life exposure, especially during perinatal and childhood developmental periods. Accordingly, textiles intended for infant use warrant thorough investigation as a potential source of chemical exposure. The present study aimed to implement a non-targeted screening and suspect screening (NTS-SS) methodology to analyze 43 infant garments, with the goal of identifying xenobiotic substances with known or suspected hazardous properties. The selected clothing items were subjected to four distinct treatment conditions to evaluate the leaching behavior of detected compounds and thus their potential bioavailability. Thus, 303 chemicals have been identified, belonging to different classes: pesticides/biocides, adjuvant for biocides, surfactants, food additives/flavorings, fragrances, preservatives, UV filters/anticorrosion agents, intermediates chemical for production, flame retardants, plasticizers/rubber accelerators, pharmaceuticals, and natural products. To the best of our knowledge, this is the first investigation to explore the potential infant exposure to textile-related xenobiotics using an NTS-SS approach. The findings contribute important evidence regarding the plausible health risks posed by chemical constituents present in fabrics designed for infant use.
Bisphenol A (BPA) is an endocrine disruptor, and exposure to low doses in utero has been associated with the development of metabolic diseases. Previous studies have suggested that bone marrow (BM) may be particularly susceptible to BPA exposure.
Here, we investigate how developmental exposure to low levels of BPA affects the BM transcriptome and the blood metabolic profile in Fischer 344 rats later in life. We compare these effects to those observed in human metabolic syndrome (MetS) using a population-based cohort.
The results show an unexpectedly extensive sex-biased effect on the BM transcriptome from a BPA dose approximately eight times lower than the recent temporary European Food Safety Authority (EFSA) human tolerable daily intake (TDI) and a higher dose considered safe in 2015. BPA exposure induces sex-specific changes in gene expression, progressing toward a hypometabolic cancer-like state in females and a hypermetabolic autoimmunity-like state in males, with a blood metabolic profile that significantly overlaps with human MetS in a cross-sectional study.
We conclude that developmental low-dose BPA exposure might induce metabolic syndrome specifically in males, possibly by affecting T cell activity in a sex-specific manner. Our study provides biologically plausible and convincing evidence for significant effects from low-dose BPA exposure, supporting the substantial lowering of the human BPA TDI by EFSA based on its critical effects on T cells.
Russo LM et al., 2025·Ecotoxicol Environ Saf·
Open Access
Prior studies have observed impacts of air pollution on semen quality, but timing of exposure during developmental windows of spermatogenesis and impacts of low-to-moderate air pollution is less well understood. We examined the relation between air pollution and semen quality in the Folic Acid and Zinc Supplementation Trial (2013-2018), which enrolled male partners of couples seeking infertility treatment in the Salt Lake City, Utah region (n = 2015). Semen quality parameters were assessed at baseline, 2-, 4-, and 6-months follow-up. Measures of daily air pollutants at each participant's residence were abstracted from Community Multiscale Air Quality models (fine particulate matter: PM2.5, sulfur dioxide, nitrogen dioxide, and ozone: O3), linked to participants' residential addresses, and averaged across the 74-day spermatogenesis window prior to the sample collection date for each study visit, and across four developmental windows of spermatogenesis (mitosis, meiosis I-II, spermiogenesis, and spermiation). Generalized linear mixed models considered four repeated semen sample measures per participant and adjusted for co-pollutants, age, season, and income. In multi-pollutant models, O3 during early-to-mid spermatogenesis (meiosis I+II and spermiogenesis) was related to lower percent normal morphology (% difference -6.73, 95 % CI -9.82, -3.54 and % difference -3.83, 95 % CI -7.51, 0.00, respectively). Additionally, PM2.5 and O3 during late spermatogenesis (spermiation) were associated with lower count and concentration, and PM2.5 with lower progressive motility. These findings suggest that exposure to low-to-moderate levels of air pollution may negatively impact semen quality and indicate that exposure to O3 during meiosis and spermiogenesis may particularly affect normal sperm morphological development.
Understanding and mitigating health risks from poor indoor air quality, particularly fine particulate matter (PM2.5), is critical, yet conventional monitoring methods are costly and require skilled operators. Low-cost sensors (LCS) offer an accessible alternative; however, their accuracy under varying environmental conditions remains uncertain. This study evaluates how humidity, temperature, deployment duration, and concentration levels affect the calibration accuracy of low-cost PM2.5 monitors. Nineteen Plantower PMS 3003 sensors deployed in 11 Salt Lake County homes participating in the Green & Healthy Homes Initiative were calibrated before and after residential deployment using a TSI DustTrak aerosol monitor. Linear and Lasso regression analyses were performed to evaluate the influence of environmental factors on calibration parameters. Significant variability was observed in environmental conditions. Higher humidity (p = 0.0197) and longer deployment durations (p = 0.0178) significantly altered calibration slopes, while mean PM2.5 exposure (p = 0.0040) was strongly associated with intercept adjustments. These findings emphasize the need to account for environmental factors in calibration models to improve LCS accuracy and reliability. Environmental conditions significantly impact the performance of low-cost PM2.5 sensors. Modeling these impacts can streamline the calibration process, making it more efficient and cost-effective. Future research should focus on refining calibration models and exploring additional environmental factors to optimize LCS performance.
Prada D et al., 2025·Environmental health : a global access science source
Acetaminophen is the most commonly used over-the-counter pain and fever medication taken during pregnancy, with > 50% of pregnant women using acetaminophen worldwide. Numerous well-designed studies have indicated that pregnant mothers exposed to acetaminophen have children diagnosed with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), at higher rates than children of pregnant mothers who were not exposed to acetaminophen. We applied the Navigation Guide methodology to the scientific literature to comprehensively and objectively examine the association between prenatal acetaminophen exposure and NDDs and related symptomology in offspring. We conducted a systematic PubMed search through February 25, 2025, using predefined inclusion criteria and rated studies based on risk of bias and strength of evidence. Due to substantial heterogeneity, we opted for a qualitative synthesis, consistent with the Navigation Guide's focus on environmental health evidence. We identified 46 studies for inclusion in our analysis. Of these, 27 studies reported positive associations (significant links to NDDs), 9 showed null associations (no significant link), and 4 indicated negative associations (protective effects). Higher-quality studies were more likely to show positive associations. Overall, the majority of the studies reported positive associations of prenatal acetaminophen use with ADHD, ASD, or NDDs in offspring, with risk-of-bias and strength-of-evidence ratings informing the overall synthesis. Our analyses using the Navigation Guide thus support evidence consistent with an association between acetaminophen exposure during pregnancy and increased incidence of NDDs. Appropriate and immediate steps should be taken to advise pregnant women to limit acetaminophen consumption to protect their offspring's neurodevelopment.
Environmental Exposures · Plastics and Microplastics
Plastic pollution is a pervasive and growing global problem1-4. Chemicals in plastics are often not sufficiently considered in the overall strategy to prevent and mitigate the impacts of plastics on human health, the environment and circular economy5-7. Here we present an inventory of 16,325 known plastic chemicals with a focus on their properties, presence in plastic and hazards. We find that diverse chemical structures serve a small set of functions, including 5,776 additives, 3,498 processing aids, 1,975 starting substances and 1,788 non-intentionally added substances. Using a hazard-based approach, we identify more than 4,200 chemicals of concern, which are persistent, bioaccumulative, mobile or toxic. We also determine 15 priority groups of chemicals, for which more than 40% of their members are of concern. Finally, we examine data gaps regarding the basic properties, hazards, uses and exposure potential of plastic chemicals. Our work maps the chemical landscape of plastics and contributes to setting the baseline for a transition towards safer and more sustainable materials and products. We propose that removing known chemicals of concern, disclosing the chemical composition and simplifying the formulation of plastics can provide pathways towards this goal.
Environmental Exposures · Plastics and Microplastics
Microplastics (MPs) are becoming one of the most serious environmental threats worldwide. They have been shown to induce male reproductive toxicity in animal studies. However, evidence of their adverse effects on male reproductive health in human is still lacking. In this study, we evaluated the presence of MPs in human semen and explored their associations with semen quality. A total of 45 semen samples from men attending a fertility center were collected. MPs in the semen samples were analyzed by laser direct infrared (LD-IR) spectroscopy. MPs were found in 34 out of 45 semen samples, with an average abundance of 17.0 (42.0) particles/g. The size of MPs ranged from 20.3 μm to 189.7 μm and the majority (57.8%) were smaller than 50 μm. A total of 15 distinct MPs polymers were identified, and polyethylene (PET) accounted for 35.9% of the total amount of MPs, followed by butadiene rubber (BR, 26.4%) and chlorinated polyethylene (CPE, 12.2%). Analysis of the association of MP exposure with semen quality showed that participants exposed to PET MPs experienced a reduction in sperm progressive motility (20.6% ± 12.8% vs. 34.9% ± 15.9%, p = 0.056). However, no significant association was found between MP exposure and sperm concentration or total sperm count. Our findings confirmed the presence of MPs in human semen and suggested that MP exposure might have adverse impacts on male reproductive health. However, further large-scale studies are needed to confirm these findings.
Redondo‐Delgado P et al., 2025·Acta Obstet Gynecol Scand·
Open Access
Physical activity is known to improve physical and psychological outcomes in pregnant women. While aerobic exercise is typically emphasized in physical activity guidelines for pregnant women, emerging research suggests that strength training may offer unique benefits beyond those provided by aerobic exercise alone. This systematic review aimed to systematically explore the effects and characteristics of strength training interventions on the health‐related quality of life of pregnant women, with the goal of informing more comprehensive and specific exercise guidelines. Material and A systematic literature search was conducted across PubMed, Web of Science, and EBSCO Host databases without time restrictions, following PRISMA guidelines (Prospero Id: CRD42024511477). Nine randomized controlled trials met the inclusion criteria, involving a total of 1581 participants. The studies reviewed demonstrated that strength training during pregnancy can mitigate excessive weight gain, alleviate low back and sciatic pain, enhance mood, and improve various aspects of health‐related quality of life. These aspects include physical activity levels, muscular strength, flexibility, sleep quality, energy expenditure, and psychological well‐being. Despite these promising findings, this review highlights the need for standardized methodologies and detailed reporting in future research. Incorporating strength training into general exercise recommendations for pregnant women has the potential to optimize maternal health outcomes such as muscle strength, weight gain, physical activity levels, low back pain, pelvic pain, fatigue, anxiety, energy levels, vitality, sleep duration, and health status.
Wang S et al., 2025·Journal of Hazardous Materials
Currently, there is limited information regarding the presence of chemicals in female underwear and the potential risks involved. This study investigated the levels of ten bisphenols in brassieres and briefs made in China, revealing total concentrations ranging from 13.9 to 52,967 ng/g. Bisphenol S (BPS), bisphenol F (BPF), and bisphenol A (BPA) made up a median of 53.2 %, 24.4 %, and 22.2 % of the total concentrations, respectively. The concentrations of bisphenols were significantly higher in darker samples compared to most other colors. When compared to previous reports on other textiles, this study found similar levels of BPA but higher concentrations of BPF and BPS. Furthermore, the median migration rates of BPF (39.1 %) and BPS (25.2 %) in artificial sweat were significantly greater than that of BPA (6.58 %), leading to higher exposure levels for BPF and BPS. The estimated non-carcinogenic risks associated with the three primary bisphenols in the underwear were deemed acceptable. However, the estimated exposure to BPS and BPF from this source represented about 2.53-12.0 % and 11.8-38.2 % of total human exposure, respectively, suggesting that the contamination of these chemicals in underwear is a concern that should not be overlooked.
Rovira J et al., 2025·Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering·
Global textile production, driven by consumer demand, raises significant concerns about exposure to chemicals in clothing and related products. This review synthesizes evidence (2019-2025) on hazardous substances in textiles, including dyes, plasticizers, per- and polyfluoroalkyl substances (PFAS), and metals, and identifies and categorizes their associated human health risks. Emerging evidence highlights microfibers as critical vectors for chemical exposure via inhalation and dermal routes, necessitating updated risk assessments. Focusing on dermal absorption as the primary exposure route, risks to vulnerable populations (e.g., infants, pregnant women) and gaps in regulatory frameworks are highlighted. The current analysis reveals that chronic exposure to chemical mixtures in textiles remains poorly understood, with current safety assessments often neglecting synergistic effects. Key findings include elevated risks from phthalates in infant clothing, PFAS in water-repellent fabrics, and carcinogenic aromatic amines (AAs) from azo dyes. We underscore the urgency of harmonized global regulations, advanced biomonitoring, and sustainable alternatives (e.g., enzymatic dyes, biodegradable finishes). Public awareness initiatives and stricter enforcement of certifications like OEKO-TEX(®) or GOTS are critical to mitigating risks. Interdisciplinary collaboration among textile technologists, toxicologists, and public health experts is essential to develop safer textile alternatives and integrate health-centric approaches into sustainability agendas, safeguarding consumers, workers, and ecosystems.
Marroquin JM et al., 2025·Environ Health Perspect·
Open Access
Perand polyfluoroalkyl substances (PFAS) exposure is widespread and has been linked with gynecologic disease. To our knowledge, no study has measured PFAS in endometrial tissue. Eutopic endometrial tissue specimens (n=434) were collected from Investigating Mixtures of Pollutants and Endometriosis in Tissue (IMPLANT) study participants undergoing laparoscopy or laparotomy for any indication (2007-2009). Nine PFAS were measured by high-performance liquid chromatography-tandem mass spectrometry [perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorododecanoic acid (PFDoDA), perfluoroheptanoic acid (PFHpA), perfluorooctanesulfonamide (PFOSA), and perfluoroundecanoic acid (PFUnDA)]. Surgeons diagnosed endometriosis by gold-standard visualization and evaluated the endometriosis staging as moderate and severe (stages 3 and 4) compared to minimal and mild (stages 1 and 2) using American Society of Reproductive Medicine (ASRM) classification. We used modified Poisson regression models adjusted for age (continuous), race (white, all other race/ethnicities), smoking status (serum cotinine >10 ng/mL), study site (Utah, California), and body mass index (continuous) to obtain relative risks (RR) of endometriosis diagnosis and 95% confidence intervals (CIs) for each PFAS. PFAS mixtures were evaluated using Bayesian kernel machine regression. Participants were, on average, 33±7 years old, and 75% of participants were non-Hispanic white. Of the 181 participants with an incident endometriosis diagnosis, 73% had ASRM stage 1 or 2, while 27% had stage 3 or 4. Median [interquartile range (IQR)] eutopic endometrium tissue levels, in nanograms per gram, were 6.58 (6.44) for PFOS, 1.93 (1.71) for PFOA, 0.65 (0.75) for PFHxS, 0.58 (0.52) for PFNA, and 0.12 (0.18) for PFOSA. PFAS in the endometrial tissue was not associated with endometriosis. However, select PFAS in the eutopic tissue were associated with a risk of more advanced (stage 3 or 4 vs. 1 or 2) endometriosis [PFOSA RR=1.25 (95% CI: 1.10, 1.43), PFHxS RR=1.37 (95% CI: 1.12, 1.68), PFOS RR=1.36 (95% CI: 1.02, 1.81)]. PFAS were widely detected in eutopic endometrial tissue. There was no evidence that PFAS in endometrial tissue were associated with a higher risk of endometriosis diagnosis. However, PFOS, PFOSA, and PFHxS in the endometrial tissue were associated with risk of more severe stage of endometriosis. https://doi.org/10.1289/EHP15852.
Palmore M et al., 2025·Environ Epigenet·
Open Access
Prenatal exposure to air pollution is an important risk factor for child health outcomes, including asthma. Identification of DNA methylation changes associated with air pollutant exposure can provide new intervention targets to improve children's health. The aim of this study is to test the association between prenatal air pollutant exposure and DNA methylation in developmental and asthma-/allergy-relevant biospecimens (placenta, buccal, cord blood, nasal mucosa, and lavage). A subset of 2294 biospecimens collected from 1906 child participants enrolled in the Environmental Influences on Child Health Outcomes program with prenatal air pollutant and high-quality Illumina Asthma&Allergy DNA methylation array measures (n = 37 197 probes) were included. Prenatal ozone, nitrogen dioxide, and fine particulate matter were derived using residential history during pregnancy and spatiotemporal models. For each pollutant, biospecimen type, and prenatal exposure window, we estimated the effects of air pollution on gene DNA methylation levels. We compared results across pollutants, biospecimen types, and trimesters and tested for critical months of exposure using distributed lag models. DNA methylation levels at 154 out of 4746 tested genes were associated with air pollution; over 95% were exposure window, pollutant, and biospecimen-type specific. The fewest gene associations were detected in trimester 2, relative to other exposure windows. A variety of trends in methylation patterns were observed in response to lagged monthly pollution levels. Child DNA methylation changes at specific respiratoryand immune-relevant genes are associated with prenatal air pollutant exposures. Future studies should examine the relationship between these pollution-sensitive genes and child health.
Nutrition and Metabolic Health · Body Weight and Composition
Identifying atypical body mass index (BMI) trajectories in children and understanding associated, modifiable early-life factors may help prevent childhood obesity. To characterize multiphase BMI trajectories in children and identify associated modifiable early-life factors.Design, Setting, and ParticipantsThis cohort study included longitudinal data obtained from January 1997 to June 2024, from the Environmental influences on Child Health Outcomes (ECHO) cohort, which included children aged 1 to 9 years with 4 or more weight and height assessments. Analyses were conducted from January to June 2024. Exposure: sPrenatal exposure to substances and stress (smoking, alcohol, depression, anxiety), maternal characteristics (prepregnancy BMI, gestational weight gain), child characteristics (preterm birth, birth weight, breastfeeding), and demographic covariates.Main Outcomes and MeasuresBMI (calculated as weight in kilograms divided by length in meters squared for children aged 1 and 2 years and as weight in kilograms divided by height in meters squared for children older than 2 years) obtained using medical records, staff measurements, caregiver reports, or remote study measures. The analysis was conducted using a multiphase latent growth mixture model. This study included 9483 children (4925 boys [51.9%]). Two distinct 2-phase BMI patterns were identified: typical and atypical. The typical group (n = 8477 [89.4%]) showed linear decreases in BMI (b2, −0.23 [95% CI, −0.24 to −0.22]), with the lowest BMI at age 6 years (95% CI, 5.94-6.11), followed by linear increases from 6 to 9 years (slope difference [b4 − b2], 0.81 [95% CI, 0.76-0.86]; mean BMI at 9 years: 17.33). The atypical group (n = 1006 [10.6%]) showed a stable BMI from ages 1 to 3.5 years (b6, 0.06 [95% CI, −0.04 to 0.15]), followed by rapid linear increases from ages 3.5 to 9 years (slope difference [b8 − b6], 1.44 [95% CI, 1.34-1.55]). At age 9 years, this group reached a mean BMI (26.2) that exceeded the 99th percentile. Prenatal smoking, high prepregnancy BMI, high gestational weight gain, and high birth weight were key risk factors for the atypical trajectory. Conclusions and RelevanceIn this cohort study of children in the ECHO cohort, analyses identified children on the path to obesity as early as age 3.5 years. Modifiable factors could be targeted for early prevention and intervention programs aimed at reducing childhood obesity.
Are dietary patterns associated with age at menarche after accounting for BMI-for-age (BMIz) and height? We observed associations between both the Alternative Healthy Eating Index (AHEI) and the Empirical Dietary Inflammatory Pattern (EDIP) and age at menarche. Dietary patterns have been sparsely examined in relation to age at menarche and no studies have examined the association between the AHEI, a healthier diet, and EDIP, a pro-inflammatory diet, and menarche. STUDY DESIGN, SIZE, The Growing Up Today Study (GUTS) is a prospective cohort of children ages 9-14 years at study enrollment. GUTS enrolled in two waves with enrollment beginning in 1996 (GUTS1) and 2004 (GUTS2). For this analysis, GUTS1 and GUTS2 participants were followed through 2001 and 2008, respectively. PARTICIPANTS/MATERIALS, SETTING, We included 7530 participants who completed food frequency questionnaire(s) (FFQ) prior to menarche who then self-reported age at menarche during study follow-up. Cox proportional hazard models were used to calculate multivariable hazard ratios (HRs) and 95% CIs for the associations between two dietary patterns, the AHEI and EDIP, and age at menarche, with and without adjustment for time-varying BMIz and height. MAIN Six thousand nine hundred ninety-two participants (93%) reported menarche during the study period. On average, participants completed the baseline FFQ 1.75 years prior to menarche. Participants in the highest quintile of AHEI diet score (indicating a healthier diet) were 8% less likely to attain menarche within the next month compared to those in the lowest quintile (95% CI = 0.85-0.99; Ptrend = 0.03). This association remained after adjustment for BMIz and height (corresponding HR = 0.93; 95% CI = 0.86-1.00; Ptrend = 0.04). Participants in the highest quintile of the EDIP score (i.e. most inflammatory diet), were 15% more likely to attain menarche in the next month relative to those in the lowest quintile (95% CI = 1.06-1.25; Ptrend = 0.0004), and the association remained following adjustment for BMIz and height (corresponding HR = 1.15; 95% CI = 1.06-1.25; Ptrend = 0.0004). LIMITATIONS, Self-reported questionnaires are subject to some error; however, given our prospective study design it is likely this error is non-differential with respect to the outcome. Our findings of an association between both the AHEI and EDIP and age at menarche indicate that diet quality may play a role in age at menarche independent of BMI or height. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Breast Cancer Research Foundation. The GUTS is supported by the National Institutes of Health U01 HL145386. C.P.D. was supported by National Institutes of Health T32 CA094880. The authors have no conflicts of interest to disclose. N/A.
Sahal A et al., 2025·Food Chemistry: X·
Open Access
Urtica dioica is widely distributed across temperate regions of the world and is highly beneficial and packed with nutritional value including a rich profile of phytochemicals, amino acids, and essential minerals. Due to abundance of these attributes, the nutritional, antioxidant, and antimicrobial properties of Urtica dioica were assessed systematically. Additionally, proximate, functional, antinutrient, mineral, polyphenolic compounds, FRAP, and DPPH assays were also examined. The findings revealed that Urtica dioica contains high Mg, Ca, Fe, and Zn. The examined values of DPPH and FRAP showed high antioxidant potential of Urtica dioica. UHPLC and GC-MS analysis confirmed Urtica dioica as an excellent source of phenolic and bioactive compounds. In view of these experimental findings, Urtica dioica can be incorporated into edible coatings and functional foods. Its excellent antimicrobial properties against Gram +ve and Gram -ve bacteria underscore its viability as an excellent source of functional ingredients in edible coatings.
Environmental Exposures · Solvents and Industrial Chemicals
Textile products contain various chemicals, making safety evaluation complex. We conducted an exploratory investigation of aryl hydrocarbon receptor (AhR) agonists in textile products using effect-directed analysis (EDA), which combines biological assays and chemical analysis. A cell-based assay was employed to detect the activation of the AhR, using a cell line that expresses the AhR-responsive luciferase gene. Testing the extracts of 10 commercially available textile products revealed high AhR agonistic activities in two of them. To identify the specific AhR agonist in one product, the sample was fractionated using chemical techniques. The active fractions were further separated using liquid chromatography. Confirmation of the active component was achieved through Orbitrap-liquid chromatography/mass spectrometry (MS), which matched the retention time and tandem MS spectrum with the standard for Disperse Violet 93:1. It has also been confirmed that Disperse Violet 93:1 activates the AhR in a dose-dependent manner. Additionally, the AhR agonistic properties of other disperse dyes were examined, leading to the discovery of Disperse Blue 291 and Disperse Blue 373 as AhR agonists. These disperse dyes had not been previously recognized as AhR agonists. Textile products have received little attention as potential sources of exposure to AhR agonists. Activation of the AhR has both positive and negative effects on human health. Therefore, conducting detailed exposure assessments and toxicity evaluations is crucial to comprehensively assess the health risks associated with these substances. The identification of disperse dyes that activate the AhR suggests that it is now possible to conduct these detailed assessments in the future.
Fang R et al., 2025·Aerosol Air Qual. Res.·
Open Access
Background Low-cost sensors (LCS) are widely used for air quality monitoring, but their accuracy depends on proper calibration. This study compares linear regression (LR) and machine learning (ML) techniques, particularly random forest (RF), to determine optimal calibration strategies. Objectives This study aims to compare the effectiveness of LR and RF models in calibrating the Plantower PMS 3003 sensor under different environmental conditions. It also explores ways to streamline calibration efforts while maintaining accuracy. Methods Sensor data were collected in a controlled laboratory setting, with measurements compared against a reference monitor. LR and RF models were developed to calibrate the sensor, and their performance was evaluated based on RMSE, R2, and bias. Additionally, the study examined whether using fewer sensors for training could still produce reliable calibration models. Results Both LR and RF models demonstrated strong calibration performance. LR models were effective for low to moderate PM2.5 concentrations and required fewer computational resources, making them suitable for large-scale monitoring with limited resources. RF models captured nonlinear relationships, showing superior accuracy at high PM concentrations and in conditions with high relative humidity. The findings suggest that LR models trained on smaller datasets can achieve practical accuracy, reducing the need for extensive individual sensor calibration. Conclusions The selection of a calibration model should be guided by study-specific requirements, including environmental conditions and resource availability. LR models are recommended for large-scale studies with constrained resources, while RF models may offer advantages in high-exposure environments due to their ability to model complex interactions. This study is the first to explore reducing sensor calibration efforts while maintaining accuracy, highlighting the potential for optimized strategies in resource-limited settings. Future research should validate these findings in real-world deployments to further refine calibration models for LCS applications. Graphical Abstract
Nutrition and Metabolic Health · Body Weight and Composition
Brito J et al., 2025·Journal of applied physiology (Bethesda, Md. : 1985)·
Open Access
Understanding changes to gut microbiota composition in response to hormonal birth control (HBC) may provide insight into the microbial mechanisms underlying the metabolic effects of HBC, for example, altered short-chain fatty acid (SCFA) production. Athletes' unique physiological demands may interact with these microbial mechanisms in distinct ways; however, there is limited research on HBC and gut microbiota diversity and composition across different menstrual cycle phases in physically active females. A pilot cohort of physically active females using HBC (oral contraceptives, hormone-based intrauterine devices, or arm implants) and a control group not using HBC (n = 12 per group; 22 ± 2 yr, 24 ± 4 kg/m2 vs. 22 ± 4 yr, 23 ± 4 kg/m2; Ps ≥ 0.496) provided fecal samples alongside self-reported menstrual phase and circulating sex hormones. α-diversity (microbial richness and evenness) was assessed using the Shannon index whereas β-diversity (microbial composition differences) was analyzed using PERMANOVA based on Bray-Curtis dissimilarity. Circulating estrogen and luteinizing hormone increased from early (days 1-5) to mid-cycle (days 12-17) in both groups (time effect Ps ≤ 0.01), with greater changes in Control (Ps ≤ 0.046) than HBC (Ps ≥ 0.231). Although no menstrual phase effect was observed on either diversity measure (Ps ≥ 0.473), β-diversity differed between Control and HBC groups (P = 0.015), reflecting distinct gut microbiota profiles irrespective of menstrual phase. Seven taxa linked to SCFA production were less abundant in the HBC group (unadjusted Ps ≤ 0.046), though significance was lost after adjusting for multiple comparisons. These findings suggest that in physically active females, hormonal contraception influences gut microbial composition, which may have downstream effects on metabolism and performance.NEW & NOTEWORTHY This study is the first to investigate interactions between hormonal contraception and the gut microbiota in a cohort of physically active young females across the menstrual cycle. Our findings suggest that hormonal contraception may influence gut microbiota composition, potentially through a reduced relative abundance of short-chain fatty acid-producing taxa. Experimental studies are needed to confirm these associations and explore their potential implications for metabolism, health, and performance.
Ushida T et al., 2025·Hypertension research : official journal of the Japanese Society of Hypertension·
Open Access
Preeclampsia (PE) is a common pregnancy complication characterized by hypertension, proteinuria, and end-organ dysfunction. However, to date, no effective treatment has been established other than iatrogenic delivery, and the importance of prevention as an alternative approach to addressing PE has been emphasized. There is growing evidence on the effectiveness of pharmacological and non-pharmacological prophylaxis in preventing PE. In this review, we focused on dietary supplements as non-pharmacological prophylaxis for PE. Calcium is a well-documented supplement for the prevention of PE. Daily 500 mg calcium supplementation can roughly halve the risk of PE in settings where calcium intake is low, including in Japan. According to recent systematic reviews and network meta-analyses, current evidence on the efficacy of vitamin D supplementation is inconsistent. Although vitamin D is a candidate for the prevention of PE, future large-scale randomized control trials are necessary to draw definitive conclusions. We also reviewed other dietary supplements, including vitamins (vitamins A, B6, C, and E, folic acid, and multivitamins), minerals (magnesium, zinc, and iron), amino acids (l-arginine and l-carnitine), anti-oxidants (lycopene, resveratrol, and astaxanthin), and other agents (omega-3 fatty acids, coenzyme Q10, melatonin, and s-equol). In this study, we provide a comprehensive approach to help develop better preventive strategies and ultimately reduce the burden of PE.
Environmental Exposures · Personal Care and Household Products
ABSTRACTBackgroundChronic prurigo (CP) is a condition characterised by chronic pruritus and pruriginous lesions. While frequently associated with atopic dermatitis (AD), its link with allergic contact dermatitis (ACD) is less understood.ObjectivesTo describe the clinical features, diagnostic findings, and therapeutic outcomes of CP associated with ACD.Patients/Materials/MethodsThis case series included patients diagnosed with CP or prurigo nodularis, identified through medical records from a specialised ACD clinic. Inclusion criteria were positive patch tests identifying relevant allergens, complete medical histories, and resolution or improvement of CP lesions after allergen avoidance. Patch testing was performed using the Spanish Extended Baseline Series and additional allergen panels as needed, following International Contact Dermatitis Research Group guidelines.ResultsSix patients were identified: four cases of CP associated with fragrances and two with textile dyes. All patients improved significantly with allergen avoidance; two required dupilumab. Histological findings and clinical responses suggested a Th2‐driven immune response in fragrance‐induced ACD and a Th2/Th17 involvement in azo dye‐related cases.ConclusionsACD caused by textile dyes and fragrances may manifest as papular dermatitis with features consistent with CP. Patch testing should be considered for idiopathic CP or cases associated with AD. Further studies are needed to clarify the immune mechanisms underlying this association.
Abstract Per- and polyfluoroalkyl substances (PFAS), previously known as perfluorinated compounds (PFC), are a group of synthetic chemicals widely used over the past decades. Their extensive application, combined with their environmental persistence, has contributed to their ubiquitous presence in the environment and the associated toxicological risks. Regarding humans, blood serum testing remains the primary method for biomonitoring PFAS exposure, while breast milk has also been used due to the transfer of these substances from mothers to infants during lactation. This paper aims to review the scientific literature (using PubMed and Scopus databases) on PFAS concentrations in the breast milk of non-occupationally exposed women. Where available, the estimated daily intake of these compounds by breastfeeding infants is also examined. The reviewed studies are categorized by continent and country/region, revealing a significant lack of data for many countries, including both developed and developing nations. The findings indicate substantial variability in PFAS concentrations, influenced by factors such as geographic location, sampling year, and the specific PFAS analyzed. Among the identified compounds, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are most commonly detected, along with perfluorohexanesulfonic acid (PFHxS) and perfluorononanoic acid (PFNA), being the only PFAS with regulated maximum levels in certain foodstuffs. Most studies were conducted before the implementation of the current (updated) tolerable weekly intake (TWI) values for these substances. Consequently, the majority reported a low health risk for breastfeeding infants, even in high-intake scenarios. Nevertheless, biomonitoring studies are urgently needed in countries with limited or no data, and new investigations should assess whether current estimated intakes exceed the updated TWI. Special focus should be given to rural and industrial areas where exposure levels remain poorly understood.
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in consumer and industrial products due to their unique physicochemical properties. However, their persistence and bioaccumulative potential pose significant environmental and human health risks. This review focuses on the use of non-invasive matrices—urine, hair, and nails—for the human biomonitoring of PFAS, highlighting key findings from scientific studies. While urine offers a non-invasive and practical option, its limited sensitivity for long-chain PFAS requires further analytical advances. Hair and nails have demonstrated potential for use in biomonitoring, with higher detection frequencies and concentrations for certain PFAS compared to urine. The variability in PFAS levels across studies reflects differences in population characteristics, exposure sources, and geographic regions. This review emphasizes the need for standardized analytical methods, expanded population studies, and the use of complementary matrices to enhance the accuracy and reliability of PFAS exposure assessment.
Per- and polyfluoroalkyl substances (PFASs) have been widely used in the production of consumer products globally due to the excellent water and oil resistance and anti-fouling properties. The multiple toxic effects of some PFASs also pose a threat to human health and ecosystem, and the frequent use of certain consumer products increased the risk of human exposure to PFASs. More data on the occurrence, concentration, and migration of PFASs in consumer products is urgently needed to address the possible risks posed by exposure to consumer products. This paper reviews the PFAS concentrations found, the migration characteristics known, and the exposure risks of PFASs arising from several types of consumer products over the last five years. The types of consumer products considered here include food contact materials, textiles, and disposable personal hygiene products. The influence of different factors on the migration process of PFASs from these products are summarized and discussed. Additionally, the main approaches and models of exposure assessment are evaluated and summarized. Current challenges and future research prospects in this field are discussed with a view to providing guidance for the future assessment and regulation of PFASs in consumer products.
Nutrition and Metabolic Health · Body Weight and Composition
Winstanley YE et al., 2025·Nature Communications·
Open Access
Abstract
The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis. Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization. Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length.
Processed foods, accounting for most consumable food categories today, contain considerable amounts of food additives. Food additives are substances added to food products to improve taste, consistency, appearance, or shelf life. Various food additives, such as phthalates, bisphenol A, tartrazine, erythrosine, artificial sweeteners, and parabens, have been identified as potential sources of endocrine-disrupting chemicals (EDCs) in processed foods. EDCs are substances that frequently interfere with the regular functioning of the endocrine system, creating an unusual environment in the biological system, which leads to adverse health effects such as the disruption of hormone synthesis, receptor binding, and signal transduction pathways, as well as energy metabolic homeostatic disorders which potentially increasing the risk of obesity, type-2 diabetes, cardiometabolic diseases and may also trigger allergic reactions. Consequently, they can also impact mammary gland development, and reproductive function, further leading to developmental abnormalities. This review aims to insights into the various food additives that act as potential endocrine-disrupting chemicals (EDCs) and to describe their applications in the food industry, as well as the failure of hormonal homeostatic mechanisms, which eventually result in hazardous health effects. It also outlines strategies to reduce the use of food additives and suggests alternative additives with minimal or no endocrine-disrupting properties, highlighting their importance for maintaining human health.
Environmental Exposures · Plastics and Microplastics
Microplastics are environmental pollutants detected in various human organs and tissues. These particles originate from multiple sources including the degradation of larger plastic items and the intentional inclusion in consumer goods. Potential risks for human health resulting from microplastics exposure have also been reported. However, the distribution in the male reproductive system and its effect remains largely unknown. This study aims to investigate the presence of multiple microplastics in human semen and urine and their association with sperm quality in a multi-site study across China. We conducted a cross-sectional study involving 113 male participants from three regions in China. Semen and urine samples were collected and analysed using Raman microscopy to detect eight types of microplastics: polystyrene (PS), polypropylene (PP), polycarbonate (PC), polyethylene (PE), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS). Semen quality parameters, including total sperm count, concentration, motility, and morphology, were assessed. Statistical analyses, including single and multi-variable models, were used to evaluate the relationship between microplastic exposure and semen quality, with a focus on PTFE, after adjusting confounding factors of age, body mass index (BMI), smoking, alcohol drinking, and sites. Microplastics were detected in all semen and urine samples, with participants typically exposed to 3-5 different types. The detection rates of PS, PP and PE were the highest. Notably, PTFE exposure was significantly associated with decreased semen quality. Participants exposed to PTFE showed reductions in total sperm count [188.90 ± 163.71 vs. 207.67 ± 132.36 million, p = 0.091], sperm concentration [52.13 ± 47.47 vs. 58.32 ± 37.26 million/mL, p = 0.041], and progressive motility [40.29% ± 19.06 vs. 34.11% ± 17.02, p = 0.083]. The multi-linear regression analysis indicated that each additional type of microplastic exposure was associated with a significant decrease in total sperm number [β = -15.4 (95% CI: -25.6, -5.2)], sperm concentration [β = -7.2 (95% CI: -12.4, -2.0)], and progressive motility [β = -8.3 (95% CI: -13.5, -3.1)]. Latent category analysis further refined these groups by types of microplastic exposure, highlighting specific types more strongly associated with decreased semen quality (OR = 3.5, 95% CI: 1.8, 6.9, p < 0.001). The nomogram can be used to assess the risk of sperm damage by combining the type of microplastic exposure in urine with age and BMI. Our findings highlight the potential reproductive health risks posed by microplastic contamination, particularly PTFE, a non-stick pan coating material, and raise concerns about the potential of urine testing as an indicator of male reproductive microplastic exposure. Future research is warranted to further elucidate the mechanisms underlying the adverse effects of microplastics on male fertility and cross-generational effects. This study was funded by the Clinical Research Project of Shanghai Municipal Commission of Health and Family planning (20224Y0085), Open Fund Project of Guangdong Academy of Medical Sciences (YKY-KF202202), CAMS Innovation Fund for Medical Sciences (2019-I2M-5-064), Shanghai Clinical Research Center for Gynecological Diseases (22MC1940200), Shanghai Urogenital System Diseases Research Centre (2022ZZ01012), Key Discipline Construction Project (2023-2025) of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (GWVI-11.1-35, GWVI-11.2-YQ29) and Shanghai Frontiers Science Research Base of Reproduction and Development.
Folic acid (FA), which in its chemical form is pteroylglutamic acid, is the fully oxidised, water-soluble, monoglutamic form of vitamin B9. This compound is part of the folate group but with higher bioavailability, and it is found in vitamin supplements and fortified foods and drugs. Folate metabolism is complex and associated with various metabolic pathways, all of which confer protection on the cell and allow its survival. We conducted a non-systematic search of articles published in English and Spanish including controlled trials, cohort studies, systematic re-views, and meta-analyses were included, as well as key studies in animal models related to pharmacokinetic studies. Search terms encompassed: "folic acid", "folates", "5-metyltetrahydrofolate", "5-MTHF", "neural tube defects", "supplementation", "fortification", AND "homocysteine" A crucial role demonstrated for FA is to help prevent neural tube defects (NTDs). However, more studies are definitely still needed to establish 5-MTHF as a safe and effective therapeutic approach comparable with FA. Moreover, there is a lack of clinical studies that evaluate the efficacy of 5-MTHF supplementation in the prevention of NTDs. The present evidence-based narrative review discusses differences between FA and 5-MTHF in terms of structure, metabolism, bioavailability, clinical efficacy, and safety. Despite the potential value of 5-MTHF as an alternative to FA, clinical studies would be urgently needed to support the efficacy, dosage, timing, and/or safety of its use as a supplement.
Environmental Exposures · Solvents and Industrial Chemicals
The objective of the present study was to investigate some commonly detected halogenated textile pollutants for their bioavailability and hazardous properties. Release into artificial sweat and skin absorption in vitro were examined as well as mutagenic effects by Ames test, and skin-sensitizing properties from a peptide reactivity assay combined with a cell test. All investigated compounds were shown to migrate from the textile into sweat and be absorbed by the skin, although to a different extent. The experimental values for migration were found to be up to 390 times higher compared to literature values. Two of the studied compounds, 2,5-dinitrochlorobenzene and 3,5-dinitrobromobenzene, both exhibited mutagenic effects in the Ames test, while both 2,5-dinitrochlorobenzene and 2,6-dichlorobenzene-1,4-diamine were classified as skin sensitizers. The allergenic reactivity of the latter was found to be due to an oxidized transformation product. Risks for the induction of skin allergy and other non-carcinogenic effects from dermal exposure to the individual compounds were found low, even when considering clothing with the highest reported levels. However, the complex mixtures of chemicals often present in garments may still constitute a health risk, especially when considering the many hours of daily exposure. It is important to further study the toxicity of other frequently occurring chemicals as well as the synergistic effects of chemicals that co-occur in clothing.
Aldegunde-Louzao N et al., 2024·Environmental Toxicology and Pharmacology·
Open Access
Phthalate esters (PAEs) are widely used as plasticizers to enhance the flexibility and durability of different consumer products, including clothing. However, concerns have been raised about the potential adverse health effects associated with the presence of phthalates in textiles, such as endocrine disruption, reproductive toxicity and potential carcinogenicity. Based on examination of more than 120 published articles, this paper presents a comprehensive review of studies concerning the phthalate content in clothing and other textile products, with special emphasis on those conducted in the last decade (2014-2023). The types and role of PAEs as plasticizers, the relevant legislation in different countries (emphasizing the importance of monitoring PAE levels in clothing to protect consumer health) and the analytical methods used for PAE determination are critically evaluated. The review also discusses the models used to evaluate exposure to PAEs and the associated health risks. Finally, the study limitations and challenges related to determining the phthalate contents of textile products are considered.
Ramamurthy K et al., 2024·Environmental Science and Pollution Research
The textile industry, with its extensive use of dyes and chemicals, stands out as a significant source of water pollution. Exposure to certain textile dyes, such as azo dyes and their breakdown products like aromatic amines, has been associated with health concerns like skin sensitization, allergic reactions, and even cancer in humans. Annually, the worldwide production of synthetic dyes approximates 7 × 107 tons, of which the textile industry accounts for over 10,000 tons. Inefficient dyeing procedures result in the discharge of 15-50% of azo dyes, which do not adequately bind to fibers, into wastewater. This review delves into the genotoxic impact of azo dyes, prevalent in the textile industry, on aquatic ecosystems and human health. Examining different families of textile dye which contain azo group in their structure such as Sudan I and Sudan III Sudan IV, Basic Red 51, Basic Violet 14, Disperse Yellow 7, Congo Red, Acid Red 26, and Acid Blue 113 reveals their carcinogenic potential, which may affect both industrial workers and aquatic life. Genotoxic and carcinogenic characteristics, chromosomal abnormalities, induced physiological and neurobehavioral changes, and disruptions to spermatogenesis are evident, underscoring the harmful effects of these dyes. The review calls for comprehensive investigations into the toxic profile of azo dyes, providing essential insights to safeguard the aquatic ecosystem and human well-being. The importance of effective effluent treatment systems is underscored to mitigate adverse impacts on agricultural lands, water resources, and the environment, particularly in regions heavily reliant on wastewater irrigation for food production.
The determination of hexavalent chromium in textiles and clothes is challenging since during extraction, the original oxidation state should not be altered. Since, as a matter of fact, current analytical methods are focused only on total chromium determination, the purpose of this research is to develop a reliable analytical method for the determination of Cr(VI) in textiles and tissues of daily use for a reliable application of risk analysis models, which are usually based on total Cr data. After optimization, a 0.0025 M Na3PO4 extraction solution was selected for the extraction of Cr(VI) from textiles. This solution minimizes possible interconversion redox reactions and interference, and provides good extraction recoveries (88.4 ± 2.5% - 105.5 ± 0.6 %, according to Cr(VI) concentration) and quantitation limits (0.017 mg/kg), fully complying the current limits set for Cr(VI) in textiles in contact with skin, and for leachable Cr(VI). The developed method was validated investigating intra-day repeatability (n = 10) and inter-day repeatability (n = 30) which were below 12%, and matrix effect which was below 6% confirming the precision of the method and the negligibility of a matrix interference during the whole analysis. The method, which was proved to be suited also for bioaccessibility studies in saliva and sweat, was applied to the analysis of tank top, coloured paper napkin, polyamide tights, panties, highlighting Cr(VI) content in the panties only at very low concentration (0.028 mg/kg). As verified by ECHA and US EPA approaches, this amount does not pose a non-carcinogenic risk for human health. As regards carcinogenic risk, considering both adult and child exposure, the dermal contact with the panties poses an acceptable risk (R ≤ 10-6).
Dutta S et al., 2024·Journal of Environmental Management
Textile dyes are the burgeoning environmental contaminants across the world. They might be directly disposed of from textile industries into the aquatic bodies, which act as the direct source for the entire ecosystem, ultimately impacting the human beings. Hence, it is essential to dissect the potential adverse outcomes of textile dye exposure on aquatic plants, aquatic fauna, terrestrial entities, and humans. Analysis of appropriate literature has revealed that textile dye effluents could affect the aquatic biota by disrupting their growth and reproduction. Various aquatic organisms are targeted by textile dye effluents. In such organisms, these chemicals affect their development, behavior, and induce oxidative stress. General populations of humans are exposed to textile dyes via the food chain and drinking contaminated water. In humans, textile dyes are biotransformed into electrophilic intermediates and aromatic amines by the enzymes of the cytochrome family. Textile dyes and their biotransformed products form the DNA and protein adducts at sub-cellular moiety. Moreover, these compounds catalyze the production of free radicals and oxidative stress, and trigger the apoptotic cascades to produce lesions in multiple organs. In addition, textile dyes modulate epigenetic factors like DNA methyltransferase and histone deacetylase to promote carcinogenesis. Several bioremediation approaches involving algae, fungi, bacteria, biomembrane filtration techniques, etc., have been tested and some other hybrid systems are currently under investigation to treat textile dye effluents. However, many such approaches are at the trial stage and require further research to develop more efficient, cost-effective, and easy-to-handle techniques.
Zhu H et al., 2024·Science of The Total Environment
The endocrine disruptor phthalates (PAEs) are widely used as important chemical additives in a variety of areas around the globe. PAEs are toxic to reproduction and development and may adversely affect the health of adolescents. Risk assessments of exposure to PAEs from different sources are more reflective of actual exposure than single-source assessments. We used personal exposure parameters to estimate the dose of PAEs to 107 university students from six media (including dormitory dust, dormitory air, clothing, food, disposable food containers, and personal care products (PCPs)) and three exposure routes (including ingestion, inhalation, and dermal absorption). Individual factors and lifestyles may affect PAE exposure to varying degrees. Based on a positive matrix factorization (PMF) model, the results indicated that the main sources of PAEs in dust were indoor building materials and plastics, while PCPs and adhesives were the major sources of airborne PAEs. The relative contribution of each source to PAE exposure showed that food and air were the primary sources of dimethyl phthalate (DMP) and dibutyl phthalate (DBP). Air source contributed the most to diethyl phthalate (DEP) exposure, followed by PCPs. Food was the most significant source of diisobutyl phthalate (DiBP), benzyl butyl phthalate (BBP), and bis(2-ethylhexyl) phthalate (DEHP) exposure. Additionally, the exposure of DEHP to dust was not negligible. The ingestion pathway was the most dominant among the three exposure pathways, followed by dermal absorption. The non-carcinogenic risk of PAEs from the six sources was within acceptable limits. DEHP exhibits a low carcinogenic risk. We suggest university students maintain good hygienic and living habits to minimize exposure to PAEs.
Impaired vitamin D status is highly prevalent among women with UFs. The objective of this first-ever systematic review and meta-analysis was to summarize the effect of vitamin D supplementation on the size of uterine fibroids (UFs). We performed a comprehensive literature search for published randomized controlled trials (RCTs) in Medline, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to September 2022. Five trials including 511 participants (256 cases and 255 controls) were included. Pooling results from five trials, which compared size of UFs between experimental and placebo groups, revealed that vitamin D supplementation could significantly decrease the size of UFs (standardized mean difference [SMD]: -0.48, 95% confidence interval [CI]: -0.66, -0.31) and cause improvement in serum level of vitamin D compared to placebo group (SMD: 3.1, 95% CI: 0.66, 5.55). A significant effect was observed in the subset of trials administering vitamin D supplementation for >8 wk (SMD: -0.62, 95% CI: -0.88, -0.37). In conclusion, vitamin D supplementation significantly increases serum levels of vitamin D and reduces the size of UFs. However, larger, well-designed RCTs are still needed to determine the effect of vitamin D on other parameters of UFs.
Per- and polyfluoroalkyl substances (PFAS) is persistent endocrine disrupting chemicals. Previous evidence suggests that exposure to PFAS is associated with reproductive hormone levels, but the results of relevant studies are inconsistent. The objective of our study is to determine the association between exposure to PFAS and reproductive hormone levels in gender-specific general population. Based on scientific search strategies, we systematically searched PubMed, Web of Science, Embase, Medline, and Scopus to obtain the eligible studies published before January 21, 2023. The quality of the included articles was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias tool. We combined the β coefficient and 95% confidence intervals (CI) using Stata.17 with random-effect model or fixed-effect model. We also performed subgroup analysis, sensitivity analysis, and Begger's and Egger's tests. Eleven studies involving 7714 participants were included. Meta-analysis showed that PFHxS exposure was positively associated with estradiol (E2) levels in female [β = 0.030, 95% CI: (0.013, 0.046), P = 0.000]. A negative association was found between PFOA [β = -0.012, 95% CI: (-0.023, -0.002), P = 0.017] and PFOS [β = -0.011; 95% CI: (-0.021, -0.000), P = 0.042] exposure with male testosterone (TT) levels. In the subgroup analysis, there were stronger associations in children than in adults. And the high heterogeneity was mainly due to the cross-sectional studies. Publication bias was not found in most of the analyses. Our study showed that PFAS exposure was significantly associated with reproductive hormone levels. Further related studies are needed to identify the association and potential mechanism in the future.
Textile production involves using various chemicals that may remain in clothing and pose health risks. Alkylphenol ethoxylates are non-ionic surfactants which may be involved in various textile printing and dyeing auxiliaries due to their excellent emulsification, wetting and decontamination abilities. This study aimed to determine the dermal exposure doses and health risks of alkylphenol ethoxylates in 10 unwashed textile samples for infants, toddlers and pregnant women. The concentrations of alkylphenol ethoxylates and alkylphenols (APs) were determined by liquid chromatography–mass spectrometry (LC-MS/MS). The total concentrations of alkylphenol ethoxylates (nonylphenol ethoxylates and octylphenol ethoxylates) in 10 textile samples were 113.21–1431.18 mg/kg, among which nonylphenol ethoxylates with ethoxy groups of 2–10 were the dominant chemicals. The highest dermal exposure dose was found in the toddler group, which was 1.27 and 4.14 times higher than those in the infant and pregnant women groups. When the maximum concentration was used for risk assessment based on tolerable daily intake, the hazard indices ( HI) for toddlers and infants were estimated to be 10.62 and 8.37, which may pose a higher risk to human health. Our assessment was specifically focused on new garments before washing. The garments containing alkylphenol ethoxylates can be washed to significantly reduce the exposure risk. The results of our study offer important information on human exposure to alkylphenol ethoxylates in textiles and clothing and provide a scientific basis for planning risk management measures for alkylphenol ethoxylates.
Jurikova M et al., 2024·Environ Sci Pollut Res Int·
Open Access
AbstractGiven the increasing concern about chemical exposure from textiles, our study examines the risks of dermal exposure to bisphenol A (BPA), bisphenol S (BPS), bisphenol B (BPB) and bisphenol F (BPF) from conventional and recycled textiles for adults, aiming to obtain new data, assess exposure, and evaluate the impact of washing on bisphenol levels. A total of 57 textile samples (33 from recycled and 24 from conventional material) were subjected to ultrasound-assisted extraction (UAE) followed by ultra-high performance liquid chromatography with tandem mass spectrometry analysis (UHPLC-MS/MS). The BPA and BPS concentrations varied widely (BPA: < 0.050 to 625 ng/g, 0.277–2,474 ng/g). The median BPA content in recycled textiles (13.5 ng/g) was almost twice as high as that of 7.66 ng/g in conventional textiles. BPS showed a median of 1.85 ng/g in recycled textiles and 3.42 ng/g in conventional textiles, indicating a shift from BPA to BPS in manufacturing practices. Simulated laundry experiments showed an overall reduction in bisphenols concentrations after washing. The study also assessed potential health implications via dermal exposure to dry and sweat-wet textiles compared to a tolerable daily intake (TDI) of 0.2 ng/kg bw/day for BPA set by the European Food Safety Authority (EFSA). Exposure from dry textiles remained below this threshold, while exposure from wet textiles often exceeded it, indicating an increased risk under conditions that simulate sweating or humidity. By finding the widespread presence of bisphenols in textiles, our study emphasises the importance of being aware of the potential risks associated with recycling materials as well as the benefits.
Koivisto AJ et al., 2024·Open Res Eur·
Open Access
Background Silver (Ag) nanoparticles (NPs) are used increasingly in consumer and healthcare fabrics due to their antimicrobial properties. Abrasive leaching experiments have shown that AgNPs can be released during textile wear and cause a dermal exposure. Derived-no-effect-limit value for AgNPs ranges from 0.01 to 0.0375 mg/kg-body-weight, and thus, low exposures levels can cause relevant risk. Methods In this study AgNP release from textiles by artificial sweat immersion and mechanical stress was investigated. A mass balance model was used to calculate dermal Ag exposure and potential intake via percutaneous absorption and inadvertent (peri-)oral intake during wear of face mask, suit with a full body exposure and gloves. Mass flow analysis was performed for up to 8-h wear time and by using Ag penetration rate constants reported for fresh-, cryopreserved- and glycerolized skin grafts. Results Dermal intake risk characterization ratio (RCR) during 8-h wear time for glycerolized skin was up to 0.02 for face mask and 0.9 for full body wear in a worst-case condition. Wearing gloves for 1-h followed by single unintentional fingertip mouthing (contact area 11.5 cm 2 ) resulted in an RCR of 0.0002. RCR varied depending on the type of textile-product, exposure wear duration and skin type. Conclusions This study provides a comprehensive assessment of AgNPs release from textiles and their potential impact on human dermal exposure and was essential for understanding the safety implications for different exposure scenarios and mitigating potential risks.
Duchette C et al., 2024·International journal of women's health
Research demonstrates resistance training is not only safe but also beneficial for pregnant women. However, exercise recommendations for pregnant women still minimize the importance of resistance exercise and provide minimal guidance. With a large increase in strength-focused sports among women, it is critical to re-evaluate the risk/benefit ratio of these exercises and ensure the latest recommendations reflect the latest clinical research. The purpose of this review is to highlight the safety and benefits of resistance training for both maternal and fetal health, particularly focusing on recent work. Relevant research involving resistance training during pregnancy was accessed and analyzed via a quasi-systematic search. Results demonstrate that appropriate prenatal resistance training can help alleviate some of the common symptoms of pregnancy, such as fatigue, back pain, and poor mental health. Resistance exercise can assist with glucose control in gestational diabetes mellitus, as well as decrease the risk of infant macrosomia and childhood metabolic dysfunction associated with uncontrolled gestational diabetes. Resistance training can also increase the likelihood of a vaginal delivery, which is beneficial for both mother and baby. Concerning fetal health, resistance training increases uterine blood flow, decreases the risk of neonatal macrosomia, and improves cognitive function and metabolic health in childhood. As with all forms of exercise, pregnant women should avoid resistance exercises that involve the supine position for extended bouts of time, trauma (or risk of trauma) to the abdomen, ballistic movements, movements that rely heavily on balance, and conditions that prohibit appropriate temperature control. With these considerations in mind, resistance training's benefits far surpass the lack of risk to the fetus. Resistance training is a safe and effective way to improve and maintain physical fitness during pregnancy and represents no risk to fetal health and development. Thus, healthcare providers should recommend resistance training for pregnant women.
Environmental Exposures · Plastics and Microplastics
Montano L et al., 2023·The Science of the total environment·
Open Access
The presence of microplastics (MPs) in human fluids and organs is a great concern, since, as highlighted by recent studies on animal models, they could cause alterations of several physiological functions, including reproduction. In this study, semen samples collected from men living in a polluted area of the Campania Region (Southern Italy), were analyzed to assess the presence of MPs. N. 16 pigmented microplastic fragments (ranging from 2 to 6 μm in size) with spheric or irregular shapes were found in six out of ten samples. All the detected MPs were characterized in terms of morphology (size, colour, and shape) and chemical composition by Raman Microspectroscopy. Chemical composition showed the presence of polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), polyvinylchloride (PVC), polycarbonate (PC), polyoxymethylene (POM) and acrylic, suggesting ingestion and/or inhalation as a route of exposure to environmental MPs. In this work, we propose for the first time a mechanism by which MPs pass into the semen most likely through the epididymis and seminal vesicles, which are the most susceptible to inflammation.
The maternal status of multiple micronutrients during pregnancy and postpartum and their potential associations with maternal health outcomes are largely undescribed. This study aimed to examine associations between maternal iron and vitamin D status, individually and in combination, on depression symptoms in pregnant individuals. The Alberta Pregnancy Outcomes and Nutrition cohort study included pregnant participants and their children from Calgary and Edmonton, Canada. Iron biomarkers (serum ferritin [SF], soluble transferrin receptor, and hepcidin) were measured via immunoassays and vitamin D [25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25-hydoxyvitamin D3 (3-epi-25(OH)D3)] metabolites were quantifed using liquid chromatography with tandem mass spectroscopy. Four categories of maternal iron and vitamin D status during the second trimester were conceptualized using concentrations of SF and total 25-hydoxyvitamin D [25(OH)D], respectively. Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 mo postpartum (n = 1822) were obtained. Concentrations of maternal 25(OH)D3, 3-epi-25(OH)D3, and the ratio of both metabolites were significantly higher during the second trimester compared with their status at 3 mo postpartum. Higher second trimester maternal concentrations of SF (β: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (β: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (β: -0.01; 95% CI: -0.02, -0.004) predicted lower maternal EPDS scores during the third trimester. Pregnant individuals with a low iron (SF <15 μg/L) and replete vitamin D (25(OH)D ≥75 nmol/L) (β: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 μg/L) and vitamin D (25(OH)D <75 nmol/L) (β: 2.2; 95% CI: 0.3, 4.2) status during midpregnancy had higher third trimester EPDS scores compared with those that were replete in both micronutrients. A higher midpregnancy maternal iron and vitamin D status, independently or in combination, predicted fewer maternal depression symptoms in the third trimester. Concentrations of maternal 25(OH)D3 and 3-epi-25(OH)D3 may be lower in the postpartum period compared with midpregnancy.
Underwear is a potential source of women's exposure to heavy metals owing to its direct contact with the skin, especially the skin of the vagina and vulva, which has a strong absorptive capacity. However, information regarding the prevalence of metals in female underwear, and its potential hazards, remains scarce. In the present study, we examined the concentrations and potential release of Cr, Co, Ni, Cu, As, Cd, Sb, and Pb in brassieres and briefs manufactured in China. We detected higher levels of Pb and moderate levels of other metals, relative to the metal levels reported for other textiles in the literature. Cu, As, Ni and Cd, had higher migration rates (MRs) from the underwear, with medians of 100%, 100%, 30.1%, and 20.7%, respectively. The median MRs of the other metals were in the range 1.07%-15.7%. On the whole, the total and extractable concentrations of these metals differed by item and fabric type. The pollution of raw materials and the use of chemical additives containing metals commonly contributed to the metals in the underwear. On the basis of the exposure estimation, the non-carcinogenic risks posed by the underwear metals were acceptable, but the carcinogenic risks from the metals in 5.18% of brassiere samples exceeded the acceptable level.
Qin XD et al., 2023·Environmental health perspectives
Estrogens play a critical role in parturition, and poly- and perfluoroalkyl substances (PFAS), which have estrogenic effects, have been associated with preterm birth. However, the impact of estrogens on the association between PFAS and preterm birth is unknown. The objective of this study is to investigate if estrogens modified the association between PFAS and preterm birth, using a nested case-control study design. A total of 371 preterm births and 508 controls were selected from a birth cohort study in China between 2016 and 2018. Perfluorobutanoic acid (PFBA), perfluorohexanesulfonic acid (PFHxS) and its branched isomer, perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and its branched isomer, and perfluorononanoic acid (PFNA) were quantified in maternal serum (mean gestational age of 32 wk). Estradiol and estriol were quantified in cord serum. Preterm birth was defined as live delivery at <37 gestational weeks. Causal mediation analysis was used to estimate the mediation and interaction effects of estrogen on the association between PFAS and preterm birth. Latent profile analysis was used to identify important estrogen profiles. Multiple linear regression was used to estimate associations between PFAS and preterm birth and interactions between PFAS and estrogens on preterm birth. Overall, higher odds ratios (ORs) of preterm birth were associated with each 1 ln-unit PFAS increase: PFBA [1.20, 95% confidence interval (CI): 1.14, 1.26], PFNA (1.30, 95% CI: 1.21, 1.39), PFOA (1.98, 95% CI: 1.54, 2.55), and PFOS (1.91, 95% CI: 1.76, 2.07) and its branched isomer (1.91, 95% CI: 1.90, 1.92). We detected statistically significant interactions between cord estradiol and PFAS on preterm birth, while no mediation effects of cord estrogen were observed. The ORs of PFOS (4.29, 95% CI: 1.31, 8.25), its branched isomer (6.71, 95% CI: 1.06, 11.91), and preterm birth were greater for participants with high cord estrogen levels than for participants with low cord estrogen levels. Our findings suggest that estrogen modified the association between maternal PFAS exposure and preterm birth. Further studies on maternal PFAS exposure and preterm birth, taking interaction effects of cord estrogens into account, are warranted. https://doi.org/10.1289/EHP11377.
Lahimer M et al., 2023·Front Public Health·
Open Access
The deleterious effects of chemical or non-chemical endocrine disruptors (EDs) on male fertility potential is well documented but still not fully elucidated. For example, the detection of industrial chemicals' metabolites in seminal plasma and follicular fluid can affect efficiency of the gametogenesis, the maturation and competency of gametes and has guided scientists to hypothesize that endocrine disrupting chemicals (EDCs) may disrupt hormonal homoeostasis by leading to a wide range of hormonal control impairments. The effects of EDCs exposure on reproductive health are highly dependent on factors including the type of EDCs, the duration of exposure, individual susceptibility, and the presence of other co-factors. Research and scientists continue to study these complex interactions. The aim of this review is to summarize the literature to better understand the potential reproductive health risks of EDCs in France.
Environmental Exposures · Solvents and Industrial Chemicals
Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p-aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential.
Identifying how specific nutrients can impact fertility, pregnancy, and neonatal outcomes will yield important insights into the biological mechanisms linking diet and reproductive health. Our study investigates how dietary vitamin C intake affects various fertility parameters and pregnancy and neonatal outcomes in the guinea pig, a natural model of vitamin C dependency. Dunkin Hartley guinea pigs were fed an optimal (900 mg/kg feed) or low (100 mg/kg feed) vitamin C diet ad libitum for at least three weeks prior to mating and throughout pregnancy. We found that animals receiving the low vitamin C diet had an increased number of unsuccessful matings, a higher incidence of foetal reabsorption, and, among pregnancies resulting in delivery at term, produced fewer offspring. Neonates from mothers on the low vitamin C diet had significantly decreased plasma vitamin C concentrations at birth and exhibited mild growth impairments in a sex-dependent manner. We conclude that a diet low of vitamin C induces a state of subfertility, reduces overall fecundity, and adversely impacts both pregnancy outcomes and growth in the offspring. Our study provides an essential foundation for future investigations to determine whether these findings translate to humans. If so, they could have important clinical implications for assisted reproductive technologies and nutritional recommendations for couples trying to conceive, pregnant women, and breastfeeding mothers.
In recent years, the interest in determining the chemical composition of textile products has increased among the scientific community and regulatory agencies, driven by toxicological issues and environmental concerns. Chemical elements are naturally present in clothing as natural fibers or intentionally added during manufacture. Some of them show physical-chemical properties that allow their absorption through the skin. In addition, chronic situations increase the dermal exposure capacity. Because of age-specific behavioral characteristics and underdeveloped physiological function, children may be especially sensitive to exposure to trace elements. This study aimed to analyze the levels of twenty trace elements in 120 clothing items commercialized in Spain. Textile products for pregnant women and children <36 months old were included. The potential health implication of this dermal exposure in early life was also evaluated. Aluminum, zinc, and titanium showed the highest concentrations, with median levels of 27.6, 5.6, and 4.2 mg/kg, respectively. Since chromium is employed as a metal complex dye in synthetic fibers, high levels of this element were found in black polyester. Dermal exposure to titanium, which is a ubiquitous element in clothes made of synthetic fibers, was associated with a hazard quotient (HQ) higher than the threshold value (HQ > 1), with values of 1.13 for pregnant women and 1.22 for newborns. On the other hand, HQ values of other elements and cancer risks were lower than the recommended values. Assessing early-life exposure to toxic elements can help to identify potential sources and to prevent or reduce human exposure, mainly in vulnerable groups.
Vitamin D deficiency and its potential impact on testosterone levels have been subjects of scientific interest. This systematic review aims to evaluate the association between vitamin D deficiency and testosterone levels in adult males and examine the effects of vitamin D supplementation on testosterone. A comprehensive literature search was conducted in accordance with the PRISMA guidelines across PubMed, Google Scholar, and ScienceDirect. The inclusion criteria involved studies published in English between 2013 and 2023, which investigated the correlation between vitamin D and testosterone levels in adult males. The process of data extraction and synthesis encompassed various aspects, including study characteristics, participant demographics, measurement methods, and outcomes pertaining to the association. The initial search resulted in a pool of 354,235 articles. Through the application of relevant filters and the review of titles and abstracts, 48 articles were chosen for further assessment. Out of these, eight studies fulfilled the inclusion criteria and were ultimately incorporated into the final review. The included studies consisted of four cross-sectional studies, three randomized controlled trials (RCTs), and one analysis utilizing Mendelian randomization. The results showed heterogeneity among the studies, as some reported a positive correlation between vitamin D levels and testosterone, while others did not find a significant association. The effects of vitamin D supplementation on testosterone levels were inconclusive, with limited evidence of significant changes in total testosterone. However, potential influences on sex hormone-binding globulin and free testosterone levels were observed. To establish more definitive evidence regarding the impact of vitamin D on testosterone levels, there is a need for further well-designed, long-term RCTs that encompass diverse populations.
Sleep deprivation is known to be a risk factor for premenstrual syndrome and primary dysmenorrhea in adults. However, it has rarely been investigated in adolescents. The aim of this study was to investigate whether sleep pattern, duration, and quality independently affect premenstrual syndrome and primary dysmenorrhea in adolescent girls. An additional purpose was to investigate the sleep status in Korean adolescent girls during the COVID-19 pandemic. A cross-sectional survey study was conducted in 519 high school girls aged 15 to 18 years in Gyeonggido, South Korea, in 2021 during the COVID-19 lockdown. Menstrual pain intensity and menstrual symptoms were assessed using the visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS), respectively. Premenstrual syndrome was assessed by the premenstrual symptoms screening tool (PSST). Sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI). The known risk factors of dysmenorrhea, including menstrual and lifestyle characteristics and stress, were assessed as covariates. During the pandemic, approximately 68% of girls slept 7 h or less, while about 60% reported poor sleep quality. Additionally, 64% of participants had a bedtime later after 1AM, and 34% woke up later after 8AM. Late bedtime significantly affected VAS (P = 0.05), CMSS severity and frequency (both P < 0.01), and PSST symptom (P < 0.01). Waking up late affected CMSS severity (P < 0.05), PSST symptom (P = 0.05), and PSST function (P < 0.05). However, the significance of these effects disappeared after controlling for covariates. Sleeping less than 5 h affected CMSS frequency (P < 0.05) and PSST symptoms (P < 0.001). After controlling for covariates, the significance of the effect on PSST symptom remained (P < 0.05). General sleep quality and PSQI components, including subjective sleep quality, sleep latency, sleep disturbance, use of sleeping medication, and daytime dysfunction, significantly affected CMSS frequency and severity and PSST symptom after controlling for covariates (P < 0.05, P < 0.01, or P < 0.001). The multiple regression analysis revealed that among sleep characteristics, sleep quality was the most important risk factor of premenstrual syndrome and dysmenorrhea. Our study result heightens the importance of healthy sleep hygiene, especially sleep quality in the management of premenstrual syndrome and dysmenorrhea in adolescent girls.
Zhang W et al., 2023·Journal of Environmental Sciences
The production of face towels is growing at an annual rate of about 4% in China, reaching 1.13 million tons by 2021. Phthalates (PAEs) are widely used in textiles, and face towels, as an important household textile, may expose people to PAEs via the skin, further leading to health risks. We collected new face towels and analyzed the distribution characterization of PAEs in them. The changes of PAEs were explored in a face towel use experiment and a simulated laundry experiment. Based on the use of face towels by 24 volunteers, we calculated the estimated daily intake (EDI) and comprehensively assessed the hazard quotient (HQ), hazard index (HI), and dermal cancer risk (DCR) of PAEs exposure in the population. PAEs were present in new face towels at total concentrations of <MDL-2388 ng/g, with a median of 173.2 ng/g, which was a lower contamination level compared with other textiles. PAE contents in used face towels were significantly higher than in new face towels. The concentrations of PAEs in coral velvet were significantly higher than those in cotton. Water washing removed some PAEs, while detergent washing increased the PAE content on face towels. Gender, weight, use time, and material were the main factors affecting EDI. The HQ and HI were less than 1, which proved PAEs had no significant non-carcinogenic health risks. Among the five target PAEs studied, DEHP was the only carcinogenic PAE and may cause potential health risks after long-term exposure. Therefore, we should pay more attention to DEHP.
Environmental Exposures · Solvents and Industrial Chemicals
Souza MCO et al., 2023·Journal of Environmental Management
The staggering amount of chemicals in clothes and their harmful effects on human health and the environment have attracted the attention of regulatory agencies and the scientific community worldwide. Azo dyes are synthetic dyestuffs with widespread use in textile industries, currently classified as emerging pollutants of great health concern to consumers. These compounds may release one or more aromatic amines (AAs) after reductive cleavage of their azo bounds. Twenty-two AAs have already been regulated due to their carcinogenic effects. However, since information on their potential toxicity is not currently available, several AAs have not been still regulated by the European Union. Considering this gap, the present study aimed to assess the levels of forty non-regulated AAs in 240 clothing items from Spain and Brazil. The potential impact on the health of vulnerable population groups after dermal exposure to those garments was also evaluated. In Brazil, at least one AA was detected in the clothes, while in samples obtained in Spain, only two of them showed values below the limit of detection for AAs. In 75 clothes, at least one of the measured AAs was higher than the hazardous threshold (30 mg/kg), which can mean risks to human health since these compounds are suspected to be mutagenic. Aniline, the most common AA, showed a high detection rate (82%) in clothes, with significantly higher concentrations in items commercialized in Brazil (0.35 vs. 0.17 mg/kg; p = 0.032). Moreover, o-aminobenzenesulfonic and p-phenylenediamine, suspected mutagenic, were found at relevant concentrations in several clothes, mainly made of synthetic fibers. In this study, the hazard index associated with exposure to AAs through clothing was low (0.006-0.13) for all the population groups of both countries in the medium-bound scenario. However, its value was close to 1 for Brazilian pregnant women (0.998) when the maximum concentration value was considered under an upper-bound scenario. The risk of exposure to non-regulated AAs may be underestimated since only dermal exposure was considered for risk assessment. Moreover, the co-occurrence of other carcinogenic and non-carcinogenic substances present in skin-contact clothes should mean an additional source of potential risk.
Neural tube defects are among the most common congenital malformations in the US, with an estimated 3000 pregnancies affected each year. Many of these neural tube defects are caused by low folate levels in the body. The US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update on the benefits and harms of folic acid supplementation. Population: Persons who are planning to or could become pregnant.Evidence AssessmentThe USPSTF concludes that, for persons who are planning to or could become pregnant, there is high certainty that folic acid supplementation has a substantial net benefit to prevent neural tube defects in their offspring.RecommendationThe USPSTF recommends that all persons planning to or who could become pregnant take a daily supplement containing 0.4 to 0.8 mg (400 to 800 μg) of folic acid. (A recommendation)
Environmental Exposures · Plastics and Microplastics
Zhao Q et al., 2023·The Science of the total environment
The health risk of microplastics (MPs) is a growing global concern. Evidence of reproductive health damage caused by the accumulation of MPs in males is still lacking. In the present study, 6 testis and 30 semen samples were collected, and MPs were detected using both pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and laser direct infrared spectroscopy (LD-IR). The results showed that MPs were detected in both testis and semen, with an average abundance of 0.23 ± 0.45 particles/mL in semen and 11.60 ± 15.52 particles/g in testis. Microplastics in the testis were composed of polystyrene (PS) with 67.7 %, while polyethylene (PE) and polyvinyl chloride (PVC) were the predominant polymers in semen. Compared to fragments, fiber, and film detected in semen, the fragment was the main shape the in testis. The sizes of these microplastics ranged from 21.76 μm to 286.71 μm, and most (67 % and 80.6 %) were 20-100 μm in semen and testis. In summary, this study revealed for the first time that MPs pollute the human male reproductive system and that various MP characteristics appear in different regions, which provides critical information and basic data for the risk assessment of MPs to human health.
Herrero M et al., 2023·Science of The Total Environment
Textile manufacturing consists of a multiple-step process in which a wide range of chemicals is used, some of them remaining in the final product. Bisphenols (BPs) are non-intentionally added compounds in textiles, whose prolonged skin contact may mean a significant source of daily human exposure, especially in vulnerable groups of the population. The present study aimed to determine the levels of bisphenol A (BPA) and some BP analogs (BPB, BPF, and BPS) in 120 new clothes commercialized in Spain for pregnant women, newborns, and toddlers. In addition, exposure assessment and risk characterization were also carried out. Traces of BPA were found in all the samples, with a median concentration of 7.43 ng/g. The highest values were detected in textile samples made of polyester. Regarding natural fibers, higher concentrations of BPs were observed in garments made of conventional cotton than in those made of organic cotton, with a significant difference for BPS (1.24 vs. 0.76 ng/g, p < 0.05). Although toddlers have a larger skin-area-to-body-weight ratio, pregnant women showed higher exposure to BPs than children. Anyhow, the non-carcinogenic risks associated with BPA exposure were below the unity, even under the upper-bound scenario. However, risks could be underestimated because other exposure routes were not considered in this study. The use of BPA has been restricted in some food-related products; therefore, BPA should also be regulated in the textile industry.
Environmental Exposures · Solvents and Industrial Chemicals
Keshava C et al., 2023·Environment International·
Open Access
Azo dyes are used in textiles and leather clothing. Human exposure can occur from wearing textiles containing azo dyes. Since the body's enzymes and microbiome can cleave azo dyes, potentially resulting in mutagenic or carcinogenic metabolites, there is also an indirect health concern on the parent compounds. While several hazardous azo dyes are banned, many more are still in use that have not been evaluated systematically for potential health concerns. This systematic evidence map (SEM) aims to compile and categorize the available toxicological evidence on the potential human health risks of a set of 30 market-relevant azo dyes. Peer-reviewed and gray literature was searched and over 20,000 studies were identified. These were filtered using Sciome Workbench for Interactive computer-Facilitated Text-mining (SWIFT) Review software with evidence stream tags (human, animal, in vitro) yielding 12,800 unique records. SWIFT Active (a machine-learning software) further facilitated title/abstract screening. DistillerSR software was used for additional title/abstract, full-text screening, and data extraction.Results187 studies were identified that met populations, exposures, comparators, and outcomes (PECO) criteria. From this pool, 54 human, 78 animal, and 61 genotoxicity studies were extracted into a literature inventory. Toxicological evidence was abundant for three azo dyes (also used as food additives) and sparse for five of the remaining 27 compounds. Complementary search in ECHA's REACH database for summaries of unpublished study reports revealed evidence for all 30 dyes. The question arose of how this information can be fed into an SEM process. Proper identification of prioritized dyes from various databases (including U.S. EPA's CompTox Chemicals Dashboard) turned out to be a challenge. Evidence compiled by this SEM project can be evaluated for subsequent use in problem formulation efforts to inform potential regulatory needs and prepare for a more efficient and targeted evaluation in the future for human health assessments.
Environmental Exposures · Plastics and Microplastics
The exposure to plastic derivatives during human life is deleterious. Infants conceived using ART (IVF or ICSI) have twice as many risks of major birth defects compared to naturally conceived infants. Could plastic ware used during ART trigger defects in the fetal development? Three groups of blastocysts were transferred to pseudopregnant mice. One was obtained after IVF and embryo development in plastic ware, the second in glass ware. The third, was obtained in vivo by natural mating. On day 16.5 of pregnancy, females were sacrificed and fetal organs collected for gene expression analysis. Fetal sex was determined by RT-PCR. RNA was extracted from a pool of five placental or brain samples coming from at least two litters from the same group and analyzed by hybridisation onto the mouse Affymetrix 430.2.0 GeneChips, confirmed by RT-qPCR for 22 genes. This study highlights a major impact of plastic ware on placental gene expression (1121 significantly deregulated genes), while glassware was much closer to in vivo offspring (only 200 significantly deregulated genes). Gene Ontology indicated that the modified placental genes were mostly involved in stress, inflammation and detoxification. A sex specific analysis revealed in addition a more drastic effect on female than male placentas. In the brains, whatever the comparison, less than 50 genes were found deregulated. Embryos incubated in plastic ware resulted in pregnancy with massive alterations of placental gene expression profile in concerted biological functions. There were no obvious effects on the brains. Besides other effects, this suggests that plastic ware in ART could be a cause of the increased level of pregnancy disorders observed recurrently in ART pregnancies. This study was funded by two grants from the Agence de la Biomedecine in 2017 and 2019.
The evidence on the association between diet and miscarriage risk is scant and conflicting. To summarize the evidence on the association between periconceptual diet and miscarriage risk in healthy women of reproductive age. Data Sources: Electronic databases were searched from inception to August 2022 without restriction of regions, publication types, or languages. Experimental or observational studies were considered for inclusion. The population was healthy women of reproductive age. Exposure was periconception diet. Study quality was assessed using the modified Newcastle-Ottawa Scale. Summary effect sizes (odds ratio [OR] with 95% confidence interval [CI]) were calculated for each food category. Outcomes: Miscarriage rate (as defined by primary studies). We included 20 studies (11 cohort and 9 case-control), of which 6 presented data suitable for meta-analysis (2 cohort and 4 case-control, n = 13,183 women). Our primary analyses suggest a reduction in miscarriage odds with high intake of the following food groups: fruit (OR, 0.39; 95% CI, 0.33-0.46), vegetables (OR, 0.59; 95% CI, 0.46-0.76), fruit and vegetables (OR, 0.63; 95% CI, 0.50-0.81), seafood (OR, 0.81; 95% CI, 0.71-0.92), dairy products (OR, 0.63; 95% CI, 0.54-0.73), eggs (OR, 0.81; 95% CI, 0.72-0.90), and cereal (grains) (OR, 0.67; 95% CI, 0.52-0.87). The evidence was uncertain for meat, red meat, white meat, fat and oil, and sugar substitutes. We did not find evidence of an association between adherence to predefined dietary patterns and miscarriage risk. However, a whole diet containing healthy foods as perceived by the trialists, or with a high Dietary Antioxidant Index score (OR, 0.43; 95% CI, 0.20-0.91) may be associated with a reduction in miscarriage risk. In contrast, a diet rich in processed food was demonstrated to be associated with increased miscarriage risk (OR, 1.97; 95% CI, 1.36-3.34). A diet abundant in fruit, vegetables, seafood, dairy, eggs, and grain may be associated with lower miscarriage odds. Further interventional studies are required to accurately assess the effectiveness of periconception dietary modifications on miscarriage risk. PROSPERO Registration: CRD42020218133.
Environmental Exposures · Solvents and Industrial Chemicals
Azo dyes used in textile products contain aromatic amines (AAs), which may be released into the environment after skin bacteria cleavage the azo bond. In Europe, 22 carcinogenic AAs are regulated. Unfortunately, no information is available in many non-European countries, including Brazil. This study aimed to determine the concentrations of 20 regulated AAs in clothes marketed in Brazil and Spain. Generally, higher levels of regulated AAs were found in samples sold in Brazil than in Spain, which is linked to the lack of regulation. Sixteen AAs showed concentrations above 5 mg/kg in samples commercialized in Brazil, while 11 exceeded that threshold in Spain. Regulated AAs with levels above 5 mg/kg were more found in synthetic clothes of pink color. Concentrations in clothing were also used to evaluate the dermal exposure to AAs in 3 vulnerable population groups. The highest exposure corresponded to 2,4-diaminoanisole for toddlers in Brazil and 4,4-oxydianiline for newborns in Spain. Non-cancer risks associated with exposure to 4,4-benzidine by Brazilian toddlers was 14.5 (above the threshold). On the other hand, 3,3-dichlorobenzidine was associated with potential cancer risks for newborns and toddlers in Brazil. Given this topic's importance, we recommend conducting continuous studies to determine the co-occurrence of carcinogenic substances.
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder, affecting 13% of reproductive-aged women. While lifestyle management is the first-line treatment for improving complications, women experience challenges with implementation. This cross-sectional study aims to identify the types and sources of dietary and physical activity (PA) interventions implemented by women with PCOS and understand how they use self-management strategies to support lifestyle change. An online questionnaire was disseminated via a consumer-based PCOS website (May 2015-2016). Women (n = 1167) were aged 18-45 years and primarily born within the United States (70%). A quarter or less of women (diet 25%, PA 14%) sought lifestyle advice from health professionals (medical clinicians or dietitians) compared to over half (diet 59%, PA 67%) using alternative sources, namely from online platforms. While only 33% and 16% of women reported following formal dietary or PA guidelines, respectively, 57% had implemented a 'special diet' to manage their condition, many of which were inconsistent with evidence-based practice in PCOS. Participants also displayed a low level of engagement with important self-management behaviors, including goal setting and positive self-talk. These findings suggest that online information may promote inaccurate and ineffective lifestyle advice and emphasize the need to increase engagement with qualified health professionals.
Environmental Exposures · Radiation and Electromagnetic Exposure
Giménez MC et al., 2023·Biology (Basel)·
Open Access
Modern urban human activities are largely restricted to the indoors, deprived of direct sunlight containing visible and near-infrared (NIR) wavelengths at high irradiance levels. Therapeutic exposure to doses of red and NIR, known as photobiomodulation (PBM), has been effective for a broad range of conditions. In a double-blind, randomized, placebo-controlled study, we aimed to assess the effects of a PBM home set-up on various aspects of well-being, health, sleep, and circadian rhythms in healthy human subjects with mild sleep complaints. The effects of three NIR light (850 nm) doses (1, 4, or 6.5 J·cm(-2)) were examined against the placebo. Exposure was presented five days per week between 9:30 am and 12:30 pm for four consecutive weeks. The study was conducted in both summer and winter to include seasonal variation. The results showed PBM treatment only at 6.5 J·cm(-2) to have consistent positive benefits on well-being and health, specifically improving mood, reducing drowsiness, reducing IFN-γ, and resting heart rate. This was only observed in winter. No significant effects on sleep or circadian rhythms were noted. This study provides further evidence that adequate exposure to NIR, especially during low sunlight conditions, such as in the winter, can be beneficial for human health and wellness.
Shen L et al., 2023·The Science of the total environment
Endometriosis affects up to 10 % of women of reproductive age and can lead to infertility. Research investigating whether combined exposure to arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) is related to an increased risk of endometriosis, especially using different biological samples to validate the association, is very limited. This investigation aimed to evaluate the associations between the concentrations of As, Cd, Pb and Hg in blood and follicular fluid and the risk of endometriosis. A total of 609 endometriosis cases and controls seen at the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between April 2020 and December 2021 were included in our study. Blood (217 cases and 234 controls) and follicular fluid (182 cases and 203 controls) samples were collected from these subjects. The concentrations of Cd, Hg, As and Pb in the blood and follicular fluid were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were used to assess the associations between Cd, Hg, As or Pb levels and the risk of endometriosis; Bayesian kernel machine regression (BKMR) was used to evaluate the combined effect of metals on the risk of endometriosis. We found significant associations between blood concentrations of As (highest vs. lowest tertile: aOR = 5.53, 95 % CI: 2.97, 10.30), Cd (second vs. lowest tertile: aOR = 1.96, 95 % CI: 1.07, 3.58; highest vs. lowest tertile: aOR = 3.21, 95 % CI: 1.79, 5.77), Pb (highest vs. lowest tertile: aOR = 2.73, 95 % CI: 1.56, 4.78) and Hg (high-level group vs. low-level group: aOR = 13.10, 95 % CI: 6.74, 25.44; second vs. lowest tertile: aOR = 15.27, 95 % CI: 4.96, 46.97; highest vs. lowest tertile: aOR = 35.66, 95 % CI: 11.99, 106.08) and increased risk of endometriosis adjusting for confounders. Follicular fluid As (highest vs. lowest tertile: aOR = 2.42, 95 % CI: 1.35, 4.33), Hg (highest vs. lowest tertile: aOR = 1.86, 95 % CI: 1.05, 3.29), Cd (second vs. lowest tertile: aOR = 2.45, 95 % CI: 1.29, 4.65; highest vs. lowest tertile: aOR = 3.12, 95 % CI: 1.67, 5.83), and Pb (second vs. lowest tertile: aOR = 1.97, 95 % CI: 1.11, 3.52) concentrations were positively associated with endometriosis risk. The BKMR analyses showed linear associations between the metal mixtures and the risk of endometriosis. Both in blood and in follicular fluid, As exhibited the highest contribution. The data from this study suggest that toxic metals, individually and as a mixture, play a role in the risk of endometriosis, thus providing a novel idea for endometriosis prevention.
Patterns of vitamin D intake are relatively unexplored among women living with HIV, despite its importance for women's health. We compared vitamin D dietary and supplement intakes in women with HIV and population-based national controls and investigated barriers to intake. In this case-control study, women with HIV in the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) cohort were matched with Canadian Multicentre Osteoporosis Study (CaMos) controls. Participants were queried for vitamin D in dairy consumption, supplementation/dosage, and sociodemographic variables. We assessed barriers to supplementation and factors associated with dietary intake by regression modelling. Ninety-five women living with HIV were age-matched to 284 controls. Women with HIV had lower income and bone mineral density and were more likely to smoke, take multiple medications and be non-white. Vitamin D dietary intake was lower in women living with HIV versus controls [0.76 vs. 1.79 μg/day; adjusted odds ratio (aOR) for greater than or equal to median intake 0.29 (0.12-0.61), p = 0.002], but any supplementation was higher [62.2% vs. 44.7%; aOR = 3.44 (95% CI: 1.16-11.00), p = 0.03]. Total vitamin D intake was similar between groups. Smoking was associated with no supplementation; non-white ethnicity and low income were related to lower dietary intake. Women living with HIV showed lower dietary vitamin D intake but higher supplementation rates, suggesting that care providers are promoting supplementation. Women living with HIV who smoke, have low incomes and are non-white may particularly benefit from targeted efforts to improve vitamin D intake.
Environmental Exposures · Solvents and Industrial Chemicals
Carlsson J et al., 2023·Anal Bioanal Chem·
Open Access
AbstractThe global production of textiles utilizes numerous large-volume chemicals that may remain to some extent in the finished garments. Arylamines, quinolines, and halogenated nitrobenzene compounds are possible mutagens, carcinogens and/or skin sensitizers. For prevention, control of clothing and other textiles must be improved, especially those imported from countries without regulations of textile chemicals. An automated analytical methodology with on-line extraction, separation, and detection would largely simplify screening surveys of hazardous chemicals in textiles. Automated thermal desorption-gas chromatography/mass spectrometry (ATD-GC/MS) was developed and evaluated as a solvent-free, direct chemical analysis for screening of textiles. It requires a minimum of sample handling with a total run time of 38 min including sample desorption, chromatographic separation, and mass spectrometric detection. For most of the studied compounds, method quantification limit (MQL) was below 5 µg/g for 5 mg of textile sample, which is sufficiently low for screening and control of quinoline and arylamines regulated by EU. Several chemicals were detected and quantified when the ATD-GC/MS method was applied in a limited pilot screening of synthetic fiber garments. A number of arylamines were detected, where some of the halogenated dinitroanilines were found in concentrations up to 300 µg/g. This is ten times higher than the concentration limit for similar arylamines listed by the EU REACH regulation. Other chemicals detected in the investigated textiles were several quinolines, benzothiazole, naphthalene, and 3,5-dinitrobromobenzene. Based on the present results, we suggest ATD-GC/MS as a screening method for the control of harmful chemicals in clothing garments and other textiles. Graphical abstract
Wang C et al., 2023·Environmental Pollution·
Open Access
The coronavirus pandemic (COVID-19) has posed a huge global health threat since December 2019. Wearing face masks is known as an effective measure for controlling the wide spread of COVID-19 and its variants. But on the other hand, face masks could be a potential source of organophosphate esters (OPEs) and phthalic acid esters (PAEs) as they are extensively added in masks. However, knowledge associated with the occurrence as well as inhalation risks of OPEs and PAEs in masks is limited. In this study, OPEs and PAEs were determined in different types of mask samples collected from the local market. OPEs and PAEs were detected in mask samples ranging from 36.7 to 855 ng/g, and from 251 to 3830 ng/g, respectively. Relatively lower OPEs and PAEs concentrations were observed in disposable mask for toddlers. Simulated inhalation experiment indicated that the mass loss of OPEs and PAEs was 136 and 3910 ng/mask in disposable masks, 71.9 and 763 ng/mask in disposable mask for toddlers, 924 and 1020 ng/mask in N95 mask after 12 h, respectively. Significantly negative correlations were exhibited between the decrement of OPEs in masks and the increment of OPEs in corresponding polyurethane foams (PUFs) during the course, elucidating OPEs released from masks could be well captured by PUFs. With regard to the variation over time, predominant OPE and PAE analogues showed semblable release and absorption tendency in mask and corresponding PUF. Inhalation exposure risk of OPEs and PAEs was estimated based on the increment of pollutants in PUF. The estimated daily intakes (EDIs), hazard index (HI) and carcinogenic risk (CR) were also calculated and they were within the threshold levels. This study provides the evidence of OPEs and PAEs releasing from the face masks during wearing and unveiled a potential source of OPEs and PAEs exposure to humans.
Environmental Exposures · Plastics and Microplastics
The growing worldwide population is directly responsible for the increased production and consumption of textile products. One of the key reasons for the generation of microfibers is the use of textiles and garment materials, which is expected to increase. The textile industry is responsible for the invisible pollution that is created by textile microfibers, which have been detected in marine sediments and organisms. The present review paper demonstrates that the microfibers discharged from functionalized textiles exhibit non-biodegradable characteristics and that a considerable proportion of them possess toxic properties. This is primarily attributed to the impact of textiles’ material functionalization on their biodegradability. The potential for these microfibers, which are released from textiles that contain a variety of dyes, toxic chemicals, and nanomaterials, to pose a variety of health risks to both humans and other living organisms is discussed in this paper. In addition, this paper covers a wide variety of preventative and minimizing measures for reduction, which are discussed in terms of several phases ranging from sustainable production through the consumer, end of life, domestic washing, and wastewater treatment phases.
Environmental Exposures · Solvents and Industrial Chemicals
Martí M et al., 2023·Textile Research J·
Open Access
Many flame retardants (FRs) are brominated, and many of them are considered toxic, persistent and/or bio accumulative. A switch to non-halogenated alternatives for textile finishing is considered beneficial, but there is little knowledge about their environmental impact, their health risks during the production process and those in their final use. A conventional and an alternative FR (based on dialkyl phosphono carboxylic acid amine and ammonium sulfamate; urea and organophosphonate PO(OH)2-R-PO(OH)2, respectively) were applied to cotton fabrics that could be in touch with the skin in their final use. Burning and thermal behaviors and dermal toxicity when exposed to skin rubbing are evaluated. Fabrics treated show that both FR products act as FRs. The increase in the thermal stability of the tissue that causes an increase in the decomposition temperature is a relevant effect associated with the application of the conventional FR in the tissue, while the most important effect of the alternative FR lies in the increase of the residue at 600°C, associated with the generation of fewer volatiles, which has an impact on the intensity of combustion. The study of the dermal toxic potential of FR-treated cotton bed sheets showed that the two tested products do not penetrate into the skin when applied under the conditions used and were safe when in contact with the skin. Moreover, the alternative FR seems to be safer when in contact with the skin considering also its higher concentration in the textile.
Infertility has been confirmed as a significant medical and social problem. Heavy metal exposure refers to a risk factor for infertility, which is capable of damaging the reproductive system of males and females. However, heavy metal exposure and female infertility have rarely been investigated. The aim of this study was to analyze the association between heavy metal exposure and female infertility. A cross-sectional study using data from three cycles of the National Health and Nutrition Examination Survey (NHANES, 2013-2018) was performed. Female infertility was evaluated by positive responses to question rhq074 in the questionnaire. Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) levels in blood or urine were examined by inductively coupled plasma mass spectrometry. The correlation between heavy metal and female infertility was analyzed through weighted logistic regression. A total of 838 American women aged 20-44 years were covered in the study. Among all participants, 112 (13.37%) women were subjected to infertility. Urinary Cd and urinary As levels were significantly higher in infertile women than in control women (P < 0.05, P < 0.05). Urinary As showed a positive correlation with the prevalence of female infertility, and the risk of infertility rose with the increase of urinary As levels (P for trend = 0.045). Urinary Cd was associated with female infertility in some weighted logistic regression (Crude, Q2: OR = 3.99, 95% CI 1.82, 8.74, Q3: OR = 2.90, 95% CI 1.42, 5.92. Model 1, Q2: OR = 3.68, 95% CI 1.64, 8.27, Q3: OR = 2.33, 95% CI 1.13, 4.48. Model 2, Q2: OR = 4.11, 95% CI 1.63, 10.07, Q3: OR = 2.44, 95% CI 1.07, 5.53. Model 3, Q2: OR = 3.77, 95% CI 1.52, 9.35). Moreover, blood Pb (OR = 1.52, 95% CI 1.07, 2.16), urinary Pb (OR = 1.68, 95% CI 1.11, 2.55), and urinary As (OR = 1.02, 95% CI 1.00, 1.03) were positively correlated with the risk of infertility in women aged 35-44 years. The blood Pb (OR = 1.67, 95% CI 1.16, 2.40, 2.49) and urinary Pb (OR = 1.54, 95% CI 1.00, 2.38) in women with BMI ≥25 were positively correlated with the risk of infertility. Urinary As was significantly associated with female infertility, and the risk of infertility increased with higher urinary As levels. To some extent, urinary Cd was correlated with infertility. Blood/urine Pb was related to infertility in advanced age and overweight/obese women. The results of this study need to be further validated in future prospective studies.
AbstractEnvironmental contamination brought on by the discharge of wastewater from textile industries is a growing concern on a global scale. Textile industries produce a huge quantity of effluents containing a myriad of chemicals, mostly dyes. The discharge of such effluents into the aquatic environment results in pollution that adversely affects aquatic organisms. Synthetic dyes are complex aromatic chemical structures with carcinogenic and mutagenic properties in addition to high biological oxygen demand (BOD) and chemical oxygen demand (COD). This complex aromatic structure resists degradation by conventional techniques. The bioremediation approach is the biological clean-up of toxic contaminants from industrial effluents. Biological treatment methods produce less or no sludge and are cost-effective, efficient, and eco-friendly. Microorganisms, mostly microalgae and bacteria, and, in some instances, fungi, yeast, and enzymes decolorize textile dye compounds into simple, non-toxic chemical compounds. Following a thorough review of the literature, we are persuaded that microalgae and bacteria might be one of the potential decolorizing agents substituting for most other biological organisms in wastewater treatment. This article presents extensive literature information on textile dyes, their classification, the toxicity of dyes, and the bioremediation of toxic textile industry effluent utilizing microalgae and bacteria. Additionally, it combines data on factors influencing textile dye bioremediation, and a few suggestions for future research are proposed.
Premenstrual syndrome (PMS) is one of the most common disorders faced by women of reproductive age. More than 200 symptoms of varying severity associated with PMS have been identified. Because of the broad spectrum of action of PMS and its impact on quality of life, symptom relief is the main challenge of treating PMS and premenstrual dysphoric disorder (PMDD). The review aims to analyze and identify the potential impact of dietary and nutritional therapies on PMS and, respectively, for its better management. The study was conducted by accessing Internet databases such as PubMed, ScienceDirect, and Scopus and using relevant keywords such as PMS, symptoms, dietary patterns (DPs), macro and micronutrients, and supplements. The results showed that diet is an essential modulating factor in reducing and managing PMS symptoms. But research on the actual effect of foods and nutrients on PMS is sparse, sporadic, and studied with insufficient scientific rigor. No correlations were identified between the consumption of macronutrients and protein, fat, carbohydrates, and fiber, but the effectiveness of micronutrients, especially calcium, magnesium, vitamin D, B vitamins, and herbal supplements, was demonstrated. Researchers remain unanimous that the evidence is insufficient and limited to support their use as an effective treatment. Nevertheless, the results could contribute to providing quality information to help women and girls make evidence-based decisions regarding premenstrual health and the adoption of dietary and nutritional therapies.
Endometriosis is characterized by the presence of endometrial tissues outside the uterine lining, typically on the external surface of the uterus, the ovaries, fallopian tubes, abdominal wall, or intestines. The prevalence of endometriosis in North America, Australia, and Europe is \~1-5% in women of reproductive age. Treatment options for endometriosis are limited. While over-the-counter medications may be used to reduce acute pain, hormonal treatments are common and may interfere with fertility. In more severe cases, laparoscopic excision procedures and even hysterectomies are used to treat the pain associated with endometriosis. Nutritional interventions may be helpful in the prevention and treatment of endometriosis and associated pain. Reducing dietary fat and increasing dietary fiber have been shown to reduce circulating estrogen concentrations, suggesting a potential benefit for individuals with endometriosis, as it is an estrogen-dependent disease. Meat consumption is associated with greater risk of developing endometriosis. Anti-inflammatory properties of plant-based diets may benefit women with endometriosis. Additionally, seaweed holds estrogen-modulating properties that have benefitted postmenopausal women and offers potential to reduce estradiol concentrations in pre-menopausal women. Furthermore, consumption of vitamin D has been shown to reduce endometrial pain via increased antioxidant capacity and supplementation with vitamins C and E significantly reduced endometriosis symptoms, compared with placebo. More randomized clinical trials are needed to elucidate the role of diet in endometriosis.
Islam T et al., 2022·Environmental Science and Pollution Research
The rapid growth of population and industrialization have intensified the problem of water pollution globally. To meet the challenge of industrialization, the use of synthetic dyes in the textile industry, dyeing and printing industry, tannery and paint industry, paper and pulp industry, cosmetic and food industry, dye manufacturing industry, and pharmaceutical industry has increased exponentially. Among these industries, the textile industry is prominent for the water pollution due to the hefty consumption of water and discharge of coloring materials in the effluent. The discharge of this effluent into the aquatic reservoir affects its biochemical oxygen demand (BOD), chemical oxygen demand (COD), total dissolved solids (TDS), total suspended solids (TSS), and pH. The release of the effluents without any remedial treatment will generate a gigantic peril to the aquatic ecosystem and human health. The ecological-friendly treatment of the dye-containing wastewater to minimize the detrimental effect on human health and the environment is the need of the hour. The purpose of this review is to evaluate the catastrophic effects of textile dyes on human health and the environment. This review provides a comprehensive insight into the dyes and chemicals used in the textile industry, focusing on the typical treatment processes for their removal from industrial wastewaters, including chemical, biological, physical, and hybrid techniques.
The Mediterranean diet pattern is inversely associated with the leading causes of morbidity and mortality, including metabolic diseases and cardiovascular disease, but there are limited data on its association with adverse pregnancy outcomes (APOs) among US women. To evaluate whether concordance to a Mediterranean diet pattern around the time of conception is associated with lower risk of developing any APO and individual APOs. DESIGN, SETTING, This prospective, multicenter, cohort study, the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, enrolled 10 038 women between October 1, 2010, and September 30, 2013, with a final analytic sample of 7798 racially, ethnically, and geographically diverse women with singleton pregnancies who had complete diet data. Data analyses were completed between June 3, 2021, and April 7, 2022. An Alternate Mediterranean Diet (aMed) score (range, 0-9; low, 0-3; moderate, 4-5; and high, 6-9) was computed from data on habitual diet in the 3 months around conception, assessed using a semiquantitative food frequency questionnaire. Adverse pregnancy outcomes were prospectively ascertained and defined as developing 1 or more of the following: preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, delivery of a small-for-gestational-age infant, or stillbirth. Of 7798 participants (mean [SD] age, 27.4 [5.5] years), 754 (9.7%) were aged 35 years or older, 816 (10.5%) were non-Hispanic Black, 1294 (16.6%) were Hispanic, and 1522 (19.5%) had obesity at baseline. The mean (SD) aMed score was 4.3 (2.1), and the prevalence of high, moderate, and low concordance to a Mediterranean diet pattern around the time of conception was 30.6% (n=2388), 31.2% (n=2430), and 38.2% (n=2980), respectively. In multivariable models, a high vs low aMed score was associated with 21% lower odds of any APO (adjusted odds ratio [aOR], 0.79 [95% CI, 0.68-0.92]), 28% lower odds of preeclampsia or eclampsia (aOR, 0.72 [95% CI, 0.55-0.93]), and 37% lower odds of gestational diabetes (aOR, 0.63 [95% CI, 0.44-0.90]). There were no differences by race, ethnicity, and prepregnancy body mass index, but associations were stronger among women aged 35 years or older (aOR, 0.54 [95% CI, 0.34-0.84]; P = .02 for interaction). When aMed score quintiles were evaluated, similar associations were observed, with higher scores being inversely associated with the incidence of any APO. This cohort study suggests that greater adherence to a Mediterranean diet pattern is associated with lower risk of APOs, with evidence of a dose-response association. Intervention studies are needed to assess whether dietary modification around the time of conception can reduce risk of APOs and their downstream associations with future development of cardiovascular disease risk factors and overt disease.
Chen H et al., 2022·Ecotoxicology and Environmental Safety·
Open Access
Clothing may be a potential contributor to body metal burden in children. However, available information on heavy metals in children's clothing is extremely limited and the associated health risks remain poorly understood. This study investigated the concentrations of Pb, Cd, Co, Zn, Cr, As, Cu and Ni in new preschool children's clothing manufactured in four Asian regions. The children's clothing had higher levels of Ni and Cr but lower levels of Pb and Cd in comparison to the concentrations reported in other textile products. The concentrations of Cd were higher in the black clothing than those in the white and color samples. The non-cotton samples contained higher Co concentrations. The Pb concentrations in the samples manufactured in China were significantly higher than those in the other three regions. We estimated the dermal exposure doses for these metals and calculated the associated risks. The results indicated that the health risks from exposure to these metals in the children's clothing were acceptable. However, more research is required to investigate heavy metals and the associated risks in child clothing due to the increasing complexity of their materials and manufacturing processes.
Xia C et al., 2022·Environmental Science & Technology·
Open Access
We analyzed 72 children's textile products marketed as stain-resistant from US and Canadian stores, particularly school uniforms, to assess if clothing represents a significant route of exposure to per- and polyfluoroalkyl substances (PFAS). Products were first screened for total fluorine (total F) using particle-induced γ-ray emission (PIGE) spectroscopy (n = 72), followed by targeted analysis of 49 neutral and ionic PFAS (n = 57). PFAS were detected in all products from both markets, with the most abundant compound being 6:2 fluorotelomer alcohol (6:2 FTOH). Total targeted PFAS concentrations for all products collected from both countries ranged from 0.250 to 153 000 ng/g with a median of 117 ng/g (0.0281-38 100 μg/m2, median: 24.0 μg/m2). Total targeted PFAS levels in school uniforms were significantly higher than in other items such as bibs, hats, stroller covers, and swimsuits, but comparable to outdoor wear. Higher total targeted PFAS concentrations were found in school uniforms made of 100% cotton than synthetic blends. Perfluoroalkyl acids (PFAAs) precursors were abundant in school uniforms based on the results of hydrolysis and total oxidizable precursor assay. The estimated median potential children's exposure to PFAS via dermal exposure through school uniforms was 1.03 ng/kg bw/day. Substance flow analysis estimated that ∼3 tonnes/year (ranging from 0.05 to 33 tonnes/year) of PFAS are used in US children's uniforms, mostly of polymeric PFAS but with ∼0.1 tonne/year of mobile, nonpolymeric PFAS.
Infertility is a global health concern affecting 48 million couples and 186 million individuals worldwide. Infertility creates a significant economic and social burden for couples who wish to conceive and has been associated with suboptimal lifestyle factors, including poor diet and physical inactivity. Modifying preconception nutrition to better adhere with Food-Based Dietary Guidelines (FBDGs) is a non-invasive and potentially effective means for improving fertility outcomes. While several dietary patterns have been associated with fertility outcomes, the mechanistic links between diet and infertility remain unclear. A key mechanism outlined in the literature relates to the adverse effects of inflammation on fertility, potentially contributing to irregular menstrual cyclicity, implantation failure, and other negative reproductive sequelae. Therefore, dietary interventions which act to reduce inflammation may improve fertility outcomes. This review consistently shows that adherence to anti-inflammatory diets such as the Mediterranean diet (specifically, increased intake of monounsaturated and n-3 polyunsaturated fatty acids, flavonoids, and reduced intake of red and processed meat) improves fertility, assisted reproductive technology (ART) success, and sperm quality in men. Therefore, integration of anti-inflammatory dietary patterns as low-risk adjunctive fertility treatments may improve fertility partially or fully and reduce the need for prolonged or intensive pharmacological or surgical interventions.
To evaluate the effect of birth ball abdominal core training on fatigue, waist pain, and delivery outcomes in middle and late pregnancy. A prospective study of 209 primipara in total with 24–27 weeks of gestation were recruited and divided into the training group (109 cases) and the control group (100 cases). The control group received routine prenatal exercise. On the basis of routine prenatal exercise, pregnant women in the training group were given birth ball exercises based on abdominal core training. The difference in pregnancy fatigue, waist discomfort, and delivery outcomes between the two groups were compared. The waist pain and fatigue ratings of women were significantly lower and the vaginal delivery rate (74.3%) was significantly higher (62%) (P < 0.001) in the training group. There were no significant differences in the total stage of labor, postpartum hemorrhage, neonatal weight and 1‐min neonatal Apgar score between the two groups. The rate of episiotomy in the training group (14.7%) was significantly lower than that in the control group (25.0%) (P < 0.05). Birth ball exercises can relieve fatigue and waist pain in middle and late 2021 pregnancy, reduce the rate of episiotomy, and promote spontaneous vaginal delivery.
Environmental Exposures · Solvents and Industrial Chemicals
Sanchez Armengol E et al., 2022·International Immunopharmacology·
Open Access
Textile production forms one of the most polluting industries worldwide. However, other than damaging environmental effects, chemical waste products, such as formaldehyde or thiazolinone, are problematic for human health, as allergic potential is present in these compounds. Mostly, contact dermatitis occurs when human skin is exposed to textiles. Moreover, non-eczemous variants are mainly associated to textiles. In order to diagnose the possible allergy of the patient towards these compounds, in vivo and in vitro methods ca be performed, such as patch testing or cytokine detection assays, respectively. Newest research focuses on medical textiles such as garments or sutures to help in diagnosis, therapy and recovery of the patients. Sutures and dressings with antimicrobial properties, with the release of oxygen and growth factors offer greater properties. In this review, state of the art in the field as well as future perspectives will be discussed, which are based on the smart textiles that are going to become more important and probably widespread after the current limits exceeded.
Welch BM et al., 2022·JAMA pediatrics·
Open Access
Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. DESIGN, SETTING, Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.
For three decades, the US Public Health Service has recommended that all persons capable of becoming pregnant consume 400 μg/day of folic acid (FA) to prevent neural tube defects (NTDs). The neural tube forms by 28 days after conception. Fortification can be an effective NTD prevention strategy in populations with limited access to folic acid foods and/or supplements. This review describes the status of mandatory FA fortification among countries that fortify (n = 71) and the research describing the impact of those programs on NTD rates (up to 78% reduction), blood folate concentrations [red blood cell folate concentrations increased ∼1.47-fold (95% CI, 1.27, 1.70) following fortification], and other health outcomes. Across settings, high-quality studies such as those with randomized exposures (e.g., randomized controlled trials, Mendelian randomization studies) are needed to elucidate interactions of FA with vitamin B12 as well as expanded biomarker testing.
Nutrition and Metabolic Health · Eating Disorders and Underfueling
Dave SC et al., 2022·Current problems in pediatric and adolescent health care
Relative Energy Deficiency in Sport (RED-S) refers to a condition in which energy imbalance leads to impaired physiological function of multiple organ systems and expands on the diagnosis previously known as the Female Athlete Triad. Researchers attribute the medical complications of RED-S to low energy availability, in which energy availability is defined as dietary energy intake minus exercise energy expenditure divided by fat-free mass. This article reviews the history of this diagnosis, the changing terminology, and the reasons for the expansion. Accepted definitions of each part of the energy availability equation are considered and the difficulties that exist using these equations in practice or comparatively in the literature are assessed. The review analyzes the broad spectrum of health consequences of RED-S, especially as it relates to hypoestrogenemia and menstrual function, gives guidance to those caring for athletes on the identification and management of RED-S, and sheds lights on the important role of coaches, athletic trainers, and families in recognizing this diagnosis and in helping getting patients to care.
Herrero M et al., 2022·Environmental Pollution·
Open Access
Clothes may contain a large range of chemical additives and other toxic substances, which may eventually pose a significant risk to human health. Since they are associated with pigments, polychlorinated biphenyls (PCBs) may be especially relevant. On the other hand, infants are very sensitive to chemical exposure and they may wear some contact and colored textiles for a prolonged time. Consequently, a specific human health risk assessment is required. This preliminary study was aimed at analyzing the concentrations of PCBs in ten bodysuits purchased in on-line stores and local retailers. The concentrations of 12 dioxin-like and 8 non-dioxin-like PCB congeners were determined by gas chromatography coupled to high resolution mass spectrometry, with detection limits ranging between 0.01 and 0.13 pg/g. The dermal absorption to PCBs of children at different ages (6 months, 1 year and 3 years old) was estimated, and the non-cancer and cancer risks were evaluated. Total levels of PCBs ranged from 74.2 to 412 pg/g, with a mean TEQ concentration of 13.4 pg WHO-TEQ/kg. Bodysuits made of organic cotton presented a total mean PCB concentration substantially lower than clothes made of regular cotton (11.0 vs. 15.8 pg WHO-TEQ/kg). The dermal absorption to PCBs for infants was calculated in around 3·10-5 pg WHO-TEQ/kg·day, regardless the age. This value is > 10,000-fold lower than the dietary intake of PCBs, either through breastfeeding or food consumption. Furthermore, this exposure value would not pose any health risks for the infants wearing those bodysuits. Anyhow, as it is a very preliminary study, this should be confirmed by analyzing larger sets of textile samples. Further investigations should be also focused on the co-occurrence of PCBs and other toxic chemicals (i.e., formaldehyde, bisphenols and aromatic amines) in infant clothes.
Tamblyn JA et al., 2022·Fertility and sterility·
Open Access
To investigate whether a significant association between vitamin D status and the risk of miscarriage or recurrent miscarriage (RM) exists. Systematic review and meta-analysis. Not applicable. PATIENT(S): Women with miscarriage and RM. INTERVENTION(S): We searched the Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to May 2021. Randomized and observational studies investigating the association between maternal vitamin D status and miscarriage and/or vitamin D treatment and miscarriage were included. MAIN OUTCOME MEASURE(S): The primary outcome was miscarriage or RM, with vitamin D status used as the predictor of risk. Whether vitamin D treatment reduces the risk of miscarriage and RM was also assessed. RESULT(S): Of 902 studies identified, 10 (n = 7,663 women) were included: 4 randomized controlled trials (n = 666 women) and 6 observational studies (n = 6,997 women). Women diagnosed with vitamin D deficiency (<50 nmol/L) had an increased risk of miscarriage compared with women who were vitamin D replete (>75 nmol/L) (odds ratio, 1.94; 95% confidence interval, 1.25-3.02; 4 studies; n = 3,674; I2 = 18%). Combined analysis, including women who were vitamin D insufficient (50-75 nmol/L) and deficient (<50 nmol/L) compared with women who were replete (>75 nmol/L), found an association with miscarriage (odds ratio, 1.60; 95% confidence interval, 1.11-2.30; 6 studies; n = 6,338; I2 = 35%). Although 4 randomized controlled trials assessed the effect of vitamin D treatment on miscarriage, study heterogeneity, data quality, and reporting bias precluded direct comparison and meta-analysis. The overall study quality was "low" or "very low" using the Grading of Recommendations, Assessment, Development and Evaluations approach. CONCLUSION(S): Vitamin D deficiency and insufficiency are associated with miscarriage. Whether preconception treatment of vitamin D deficiency protects against pregnancy loss in women at risk of miscarriage remains unknown. CRD42021259899.
Marshall NE et al., 2022·American journal of obstetrics and gynecology
Most women in the United States do not meet the recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman should look like. The message should be "eat better, not more." This can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report "prudent" or "health-conscious" eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine reproductive disorders in women. Vitamin D deficiency is also quite common in this condition. The degree of vitamin D deficiency correlates with the severity of PCOS. Both male and female vitamin D levels play a role in fertility and affect the outcomes of in vitro fertilization (IVF). Moreover, fertility and IVF indicators are improved by vitamin D not only in healthy women but in those diagnosed with PCOS. Both vitamin D deficiency and PCOS increase pregnancy-related complications. Vitamin D supplementation and optimal vitamin D levels decrease both maternal and fetal risk for complications and adverse events. Furthermore, vitamin D supplementation may ameliorate or even prevent pregnancy-related reversible bone loss in mothers. This review emphasizes the roles of vitamin D deficiency and vitamin D supplementation and their correlation with PCOS regarding reproductive health.
van der Veen I et al., 2022·Environmental Science & Technology·
Open Access
To make outdoor clothing water- or dirt-repellent, durable water-repellent (DWR) coatings based on side-chain fluorinated polymers (SFPs) are used. During use of outdoor clothing, per- and polyfluoroalkyl substances (PFASs) can be emitted from the DWR to the environment. In this study, the effects of aging, washing, and tumble drying on the concentration of extractable PFASs in the DWR of perfluorohexane-based short-chain SFPs (FC-6 chemistry) and of perfluorooctane-based long-chain SFPs (FC-8 chemistry) were assessed. For this purpose, polyamide (PA) and polyester (PES) fabrics were coated with FC-6- and FC-8-based DWRs. Results show that aging of the coated fabrics causes an increase in concentration and formation of perfluoroalkyl acids (PFAAs). The effect of aging on the volatile PFASs depends on the type of fabric. Washing causes a decrease in PFAA concentrations, and in general, volatile PFASs are partly washed out of the textiles. However, washing can also increase the extractable concentration of volatile PFASs in the fabrics. This effect becomes stronger by a combination of aging and washing. Tumble drying does not affect the PFAS concentrations in textiles. In conclusion, aging and washing of fabrics coated with the DWR based on SFPs release PFASs to the environment.
Nutrition and Metabolic Health · Blood Sugar and Insulin
Olivera-Nappa Á et al., 2022·Front Nutr·
Open Access
A growing body of evidence indicates that dietary polyphenols could be used as an early intervention to treat glucose-insulin (G-I) dysregulation. However, studies report heterogeneous information, and the targets of the intervention remain largely elusive. In this work, we provide a general methodology to quantify the effects of any given polyphenol-rich food or formulae over glycemic regulation in a patient-wise manner using an Oral Glucose Tolerance Test (OGTT). We use a mathematical model to represent individual OGTT curves as the coordinated action of subsystems, each one described by a parameter with physiological interpretation. Using the parameter values calculated for a cohort of 1198 individuals, we propose a statistical model to calculate the risk of dysglycemia and the coordination among subsystems for each subject, thus providing a continuous and individual health assessment. This method allows identifying individuals at high risk of dysglycemia-which would have been missed with traditional binary diagnostic methods-enabling early nutritional intervention with a polyphenol-supplemented diet where it is most effective and desirable. Besides, the proposed methodology assesses the effectiveness of interventions over time when applied to the OGTT curves of a treated individual. We illustrate the use of this method in a case study to assess the dose-dependent effects of Delphinol® on reducing dysglycemia risk and improving the coordination between subsystems. Finally, this strategy enables, on the one hand, the use of low-cost, non-invasive methods in population-scale nutritional studies. On the other hand, it will help practitioners assess the effectiveness of an intervention based on individual vulnerabilities and adapt the treatment to manage dysglycemia and avoid its progression into disease.
Fan Y et al., 2022·Science of The Total Environment
Exploration of multiple sources of brominated (BFRs) and organophosphate flame retardants (OPFRs) for children promotes the understanding of exposure pathways and health risk. 10 BFRs and 9 OPFRs were measured in skin wipes from hands, forehead, and arms of 30 children, and surface wipe samples from sills, toys, desks and floors, and indoor air samples of kindergartens from Xinxiang, China. Higher ∑9OPFRs concentrations were observed in the forehead (1840 ng/m2), followed by hand (1420 ng/m2) and arm wipes (1130 ng/m2), and the ∑8BFRs concentrations in forehead, hand and arm wipes were 116, 315 and 165 ng/m2, respectively. The total concentration of OPFRs and BFRs in floor wipes (66.1 and 24.5 ng/m2) were lower than those in toy (205 and 535 ng/m2), sill (227 and 30.1 ng/m2) and desk (84.4 and 139 ng/m2) wipes. Concentrations of FRs in forehead wipes were significantly correlated with those in gaseous air (p < 0.05), moderate correlations were found between the hand wipes and surface wipes (p = 0.054). We estimated the daily average dosages (DADs) of children exposure to FRs via multiple pathways. Compared to DADs via inhalation and hand-to-mouth transfer, dermal exposure was determined to be the predominant exposure pathway to ∑9OPFRs and ∑8BFRs.
Male fertility has been declining globally over the past several decades, advancing from a personal issue to a public health problem. Beyond any doubt, a reduction in fertility (often characterized by low sperm count or motility) can severely threaten reproductive health and lifecourse framework in a long-term fashion. Aside from uncovering the currently unknown etiology of modern-day male infertility, the scientific and medical community faces a double burden: finding an efficient biomarker of impaired fertility and exploring any intervention that can act to enhance fertility. A plethora of nutritional compounds have been recognized as possible modulators of semen quality, and specific dietary patterns and nutrients appear to be accompanied by a lower risk of male infertility. Creatine, a conditionally essential nutrient, has caught attention as a male fertility-promoting candidate due to its role in sperm energy metabolism. This mini-review describes the creatine-related bioenergetics of spermatozoa, explores a connection between creatine levels and sperm quality in men, and critically examines available evidence for interventional studies with creatine to affect sperm viability.
While some studies have found an association between marijuana use and adverse neonatal outcomes, results have not been consistent across all trials. To assess available data on neonatal outcomes in marijuana-exposed pregnancies. PubMed, Medline, ClinicalTrials.gov, Cochrane, Scopus, and Web of Science were searched from each database's inception until August 16, 2021. All interventional and observational studies that included pregnant women who were exposed to marijuana compared with pregnant women who were not exposed to marijuana and that reported neonatal outcomes were included. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Data were extracted by 2 authors for all outcomes, which were pooled using a random-effects model as mean difference or risk ratio (RR) and 95% CI. Data were analyzed from August through September 2021. All outcomes were formulated prior to data collection. Outcomes included incidence of birth weight less than 2500 g, small for gestational age (defined as less than the fifth percentile fetal weight for gestational age), rate of preterm delivery (defined as before 37 weeks' gestation), gestational age at time of delivery, birth weight, incidence of neonatal intensive care unit (NICU) admission, Apgar score at 1 minute, Apgar score at 5 minutes, incidence of an Apgar score less than 7 at 5 minutes, fetal head circumference, and fetal length. Among 16 studies including 59 138 patients, there were significant increases in 7 adverse neonatal outcomes among women who were exposed to marijuana during pregnancy vs those who were not exposed during pregnancy. These included increased risk of birth weight less than 2500 g (RR, 2.06 [95% CI, 1.25 to 3.42]; P = .005), small for gestational age (RR, 1.61 [95% CI, 1.44 to 1.79]; P < .001), preterm delivery (RR, 1.28 [95% CI, 1.16 to 1.42]; P < .001), and NICU admission (RR, 1.38 [95% CI, 1.18 to 1.62]; P < .001), along with decreased mean birth weight (mean difference, -112.30 [95% CI, -167.19 to -57.41] g; P < .001), Apgar score at 1 minute (mean difference, -0.26 [95% CI, -0.43 to -0.09]; P = .002), and infant head circumference (mean difference, -0.34 [95% CI, -0.63 to -0.06] cm; P = .02). This study found that women exposed to marijuana in pregnancy were at a significantly increased risk of some adverse neonatal outcomes. These findings suggest that increasing awareness about these risks may be associated with improved outcomes.
Environmental Exposures · Solvents and Industrial Chemicals
Carlsson J et al., 2022·Anal Bioanal Chem·
Open Access
AbstractThe global manufacturing of clothing is usually composed of multistep processes, which include a large number of chemicals. However, there is generally no information regarding the chemical content remaining in the finished clothes. Clothes in close and prolonged skin contact may thus be a significant source of daily human exposure to hazardous compounds depending on their ability to migrate from the textiles and be absorbed by the skin. In the present study, twenty-four imported garments on the Swedish market were investigated with respect to their content of organic compounds, using a screening workflow. Reversed-phase liquid chromatography coupled to electrospray ionization/high-resolution mass spectrometry was used for both suspect and non-target screening. The most frequently detected compound was benzothiazole followed by quinoline. Nitroanilines with suspected mutagenic and possible skin sensitization properties, and quinoline, a carcinogenic compound, were among the compounds occurring at the highest concentrations. In some garments, the level of quinoline was estimated to be close to or higher than 50,000 ng/g, the limit set by the REACH regulation. Other detected compounds were acridine, benzotriazoles, benzothiazoles, phthalates, nitrophenols, and organophosphates. Several of the identified compounds have logPand molecular weight values enabling skin uptake. This pilot study indicates which chemicals and compound classes should be prioritized for future quantitative surveys and control of the chemical content in clothing as well as research on skin transfer, skin absorption, and systemic exposure. The results also show that the current control and prevention from chemicals in imported garments on the Swedish market is insufficient.Graphical abstract
Clothes contain a wide range of chemicals, some of them potentially hazardous. Recently, there has been a growing interest in eco-friendly clothing, including the use of organic cotton. However, the process of eco-friendly fabric production does not exclude the use of toxic substances, such as formaldehyde, a known human carcinogen. The present investigation was aimed at determining the presence of formaldehyde in eco-friendly and conventional clothing of pregnant women, babies, and toddlers from the Catalan (Spain) market. The potential effects of washing were also investigated by comparing the reduction of formaldehyde in unwashed and washed clothing. Formaldehyde was detected in 20% of samples, with a mean level of 8.96 mg/kg. Formaldehyde levels were surprisingly higher in eco-friendly than in regular garments (10.4 vs. 8.23 mg/kg). However, these differences were only significant (p < 0.05) for bras (11.6 vs. 7.46 mg/kg) and panties (27.1 vs. 6.38 mg/kg) of pregnant women. Dermal exposure and health risks were assessed for three vulnerable population groups: pregnant women, babies, and toddlers. In general, exposure was higher in babies (up to 1.11 × 10−3 mg/kg/day) than in other groups (2.58 × 10−4 and 4.50 × 10−3 mg/kg/day in pregnant women and toddlers, respectively). However, both non-carcinogenic and carcinogenic risks were below the safety limits (<1 and <10−5, respectively) according to national regulations. Notwithstanding, although formaldehyde levels were below the legal limits (<75 mg/kg) and health risks were within acceptable ranges, clothing may contain other toxic substances in addition to formaldehyde, thus increasing the risks. Finally, since no formaldehyde was detected in washed textile samples, a safe and simple practice for the consumers is to wash clothing before the first use.
Xie H et al., 2022·Journal of Hazardous Materials·
Open Access
Face masks are necessary for fighting against the coronavirus disease 2019 around the world. As the face mask is usually made from polymers and phthalates are widely-used additives into the polymers, the face mask could be a potential source of phthalate exposure to humans. However, limited knowledge is available on the occurrence and risks of the phthalates from the face mask. In this study, twelve phthalates were determined in 56 mask samples collected from different countries. The phthalates were detected in all the samples with total levels ranging from 115 ng/g to 37,700 ng/g. Estimated daily intakes (EDIs) of the phthalates from the masks ranged from 3.71 to 639 ng/kg-bw/day, and the EDIs of the phthalates from masks for toddlers were approximately 4-5 times higher than those for adults. Non-carcinogenic risks in relation to the phthalates in masks were found to be within safe levels, yet 89.3% of the mask samples exhibited potential carcinogenic effects to humans. The extent of the risks for wearing masks located at a moderate level comparing with other skin-contacted products. This study unveiled a potential source of phthalate exposure to human, and indicated necessity of managing types and levels of additives in the face masks.
AbstractBackgroundDisperse dyes (DDs) are the most prevalent causes of textile‐related allergic contact dermatitis and are used for colouring synthetic textile materials based on fibres such as polyester, acrylic, acetate and polyamide. Eight DDs are included in a textile dye mix (TDM) 6.6% petrolatum (pet.) in the European baseline patch test series.ObjectivesThe aim of this study was to patch test TDM 6.6% pet. positive individuals with the extracts of synthetic fibre clothes that do not contain any of the pure DDs present in the TDM 6.6% to study the reactivity pattern.MethodsSeventy‐three TDM‐positive former patients tested between 2012 and 2017 at the Department of Occupational and Environmental Dermatology in Malmö, Sweden were invited to join the study, 10 participated. Twenty‐four textile items (collected in nine countries in Europe, Asia and North America in 2012) were extracted in dichloromethane. The TDM 6.6% was patch tested simultaneously with the 24 textile item preparations in petrolatum made from the extracts. Prior to patch testing the participants filled the 7‐question questionnaire regarding possible symptoms from textile exposure.ResultsTen individuals, agreed to join the study. Eight of them reacted to TDM 6.6%. Nine participants reacted to 20 of 24 extracts. One reacted to 19 extracts, another to 14, 3 to 5 extracts, 1 to 4, 1 to 3 extracts and 2 to 2 extracts. One was negative to all tested preparations including TDM 6.6%. The participants mainly reacted to six textile extracts. All controls tested negatively to tested extracts. Four individuals of the 10 TDM‐allergic individuals previously had had problems after wearing clothes. Four out of the 10 participants had had atopic eczema in childhood. All women had dyed their hair with permanent hair dyes but none of the males.ConclusionTDM‐positive patients react to textile extracts made from synthetic garments, even if they do not contain any of the pure DDs present in TDM 6.6%. More studies are needed to pin‐point the culprit haptens in these extracts.
The objectives of this study were: (1) to identify subjects with hyperprolactinemia in a clinical sample of patients; (2) to compare the neurologic, psychiatric, and sleep conditions found in patients subgrouped by excessive daytime sleepiness (EDS) and hyperprolactinemia; and (3) to identify patients with hyperprolactinemia and EDS not supported by the presence of any other neurologic, psychiatric, or sleep disorder, or substance/medication use. A retrospective chart review of inpatients was carried out in order to identify all patients in whom the prolactin (PRL) serum levels were determined. A total of 130 subjects were retrieved: 55 had increased levels of PRL, while the remaining 75 participants had normal PRL levels. EDS was reported by 32 (58.2%) participants with increased PRL and 34 (45.3%) with normal PRL. Obstructive sleep apnea or other sleep or neurologic/psychiatric conditions could explain EDS in all participants with normal PRL. Among subjects with increased PRL, eight had no other neurologic/psychiatric or sleep disorder (or drug) potentially causing EDS; these participants, at polysomnography, had time in bed, sleep period time, and total sleep time longer than those with EDS associated to another condition. These findings can be considered as a preliminary indication of a role of hyperprolactinemia in EDS and represent a basis for future controlled studies able to test this hypothesis in a reliable, objective, and methodologically more appropriate way.
Skoracka K et al., 2021·Advances in nutrition (Bethesda, Md.)
Infertility is an increasing problem that affects couples attempting pregnancy. A growing body of evidence points to a link between diet and female fertility. In fact, data show that a diet high in trans fats, refined carbohydrates, and added sugars can negatively affect fertility. Conversely, a diet based on the Mediterranean dietary patterns, i.e., rich in dietary fiber, omega-3 (ɷ-3) fatty acids, plant-based protein, and vitamins and minerals, has a positive impact on female fertility. An unhealthy diet can disrupt microbiota composition, and it is worth investigating whether the composition of the gut microbiota correlates with the frequency of infertility. There is a lack of evidence to exclude gluten from the diet of every woman trying to become pregnant in the absence of celiac disease. Furthermore, there are no data concerning adverse effects of alcohol on female fertility, and caffeine consumption in the recommended amounts also does not seem to affect fertility. On the other hand, phytoestrogens presumably have a positive influence on female fertility. Nevertheless, there are many unanswered questions with regard to supplementation in order to enhance fertility. It has been established that women of childbearing age should supplement folic acid. Moreover, most people experience vitamin D and iodine deficiency; thus, it is vital to control their blood concentrations and consider supplementation if necessary. Therefore, since diet and lifestyle seem to be significant factors influencing fertility, it is valid to expand knowledge in this area.
Environmental Exposures · Radiation and Electromagnetic Exposure
Infrared light (760 nm-1 mm) constitutes approximately 40% of the solar radiation reaching the ground at sea level. Shortest wavelength near-infrared (NIR) photons (NIR or 760-1,400 nm) can penetrate the epidermis, dermis, and subcutaneous tissue with numerous biological effects. NIR used to have a bad reputation on the basis of past studies using high-intensity artificial light sources (above the solar IR-A irradiance threshold) at high doses leading to detrimental effects (i.e., upregulation of matrix metalloproteinase-1). However, when looking at the other side of the coin and what we can learn from the sun, NIR intensity matters. Hence, mimicking sunlight NIR intensity (30-35 mW/cm2) will rather trigger beneficial cutaneous effects. It is likely that intensity is more important than the fluence (dose) delivered. Moreover, the law of reciprocity (i.e., the biological effect is directly proportional to the total dose irrespective of intensity) does not always apply when considering tissue response in photobiology. In fact, the biphasic dose curve (Arndt-Schulz curve) of photobiomodulation establishes that if irradiance is lower than the physiological threshold value for a given target, it does not produce beneficial effects, even when -irradiation duration is extended. Also, photo-inhibitory deleterious effects may occur at higher irradiances. Remarkably, the beneficial "sweet spot" in between corresponds to the irradiance of the sun. NIR might even precondition the skin from an evolutionary standpoint as exposure to early morning NIR wavelengths in sunlight may prepare the skin for upcoming mid-day harmful UVR. Consequently, NIR light appears to be the solution, not the problem.
Thiamine or vitamin B1 is an essential, water-soluble vitamin required for mitochondrial energetics-the production of adenosine triphosphate (ATP). It is a critical and rate-limiting cofactor to multiple enzymes involved in this process, including those at the entry points and at critical junctures for the glucose, fatty acid, and amino acid pathways. It has a very short half-life, limited storage capacity, and is susceptible to degradation and depletion by a number of products that epitomize modern life, including environmental and pharmaceutical chemicals. The RDA for thiamine is 1.1-1.2 mg for adult females and males, respectively. With an average diet, even a poor one, it is not difficult to meet that daily requirement, and yet, measurable thiamine deficiency has been observed across multiple patient populations with incidence rates ranging from 20% to over 90% depending upon the study. This suggests that the RDA requirement may be insufficient to meet the demands of modern living. Inasmuch as thiamine deficiency syndromes pose great risk of chronic morbidity, and if left untreated, mortality, a more comprehensive understanding thiamine chemistry, relative to energy production, modern living, and disease, may prove useful.
Chang WH et al., 2021·Science of The Total Environment
Phthalate esters (PAEs) are one of the most widely used plasticizers in polymer products and humans are increasingly exposed to them. The constant exposure to PAEs-contained products has raised some concerns against human health. Thus, the impacts of PAEs and their metabolites on human health require a comprehensive study for a better understanding of the associated risks. Here, we attempt to review eight main health effects of PAE exposure according to the most up-to-date studies. We found that epidemiological studies demonstrated a consistent association between PAE exposure (especially DEHP and its metabolites) and a decrease in sperm quality in males and symptom development of ADHD in children. Overall, we found insufficient evidence and lack of consistency of the association between PAE exposure and cardiovascular diseases (hypertension, atherosclerosis, and CHD), thyroid diseases, respiratory diseases, diabetes, obesity, kidney diseases, intelligence performance in children, and other reproductive system-related diseases (anogenital distance, girl precocious puberty, and endometriosis). Future studies (longitudinal and follow-up investigations) need to thoroughly perform in large-scale populations to yield more consistent and powerful results and increase the precision of the association as well as enhance the overall understanding of potential human health risks of PAEs in long-term exposure.
In recent years, consumption of ultra-processed food around the world has been increasing. The nutritional profile of an ultra-processed diet is associated with the development of cellular alterations that lead to oxidative stress. The chronic prooxidative state leads to an environment that influences the proliferation, apoptosis, and signaling pathways of immune cells. Likewise, the decrease in the transcription factor NRF2, owing to exacerbated production of reactive oxygen species, leads to changes in immune function and response to infections. This review aims to analyze the connection between an ultra-processed diet, systemic oxidative stress, and immune tolerance, as a contribution to the scientific evidence on the impact of oxidative stress on health and the possible risk of infections-an important consideration in the association of eating pattern and the immune response.
This study investigated the effects of Tartrazine and Erythrosine (T+E) on the reproductive hormones and expression of some pro-inflammatory cytokines and testicular genes in testis of male Wistar rats. 25 male Wistar rats (150-180g) were divided into 5 groups (n=5). Group 1 received distilled water while groups 2, 3, 4 and 5 were treated with T+E (2.5mg/kg, 5mg/kg, 10mg/kg and 20mg/kg) for the period of 23 days. Toxicity studies of the combined dye were investigated by evaluating serum reproductive hormones [Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Testosterone], gene expression and profiling, and testes histology. male Wistar rats (150-180g) were divided into 5 groups (n=5). Group 1 received distilled water while groups 2, 3, 4 and 5 were treated with T+E (2.5mg/kg, 5mg/kg, 10mg/kg and 20mg/kg) for the period of 23 days. Toxicity studies of the combined dye were investigated by evaluating serum reproductive hormones [Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Testosterone], gene expression and profiling, and testes histology. This present study reveals that the dyes could impair testicular function as evident in the up-regulation of pro-inflammatory cytokines and down-regulation of TESK-1 gene expression and architecture of the testes leading to Orchitis.
Evaluation of vitamin D supplementation on ovarian reserve in women with diminished ovarian reserve and vitamin D deficiency. The study is a before-and-after intervention study that was performed on women with diminished ovarian reserve referred to Shahid Mofteh Clinic in Yasuj, Iran. Eligible women were prescribed vitamin D tablets at a dose of 50,000 units weekly for up to 3 months. Serum levels of vitamin D and AMH were evaluated at the end of 3 months. Significance level was also considered P ≤ 0.05. Our results have been showed there was a statistically significant difference in vitamin D levels of participants before [12.1(6.5)] and after [26(9.15)] the intervention (P < 0.001). Moreover, there was a statistically significant difference in serum AMH levels of participants before [0.50(0.44)] and after [0.79(0.15)] the intervention (P=0.02 ). In conclusion, the results of the current study support a possible favorable effect of vitamin D on increase AMH expression by acting on the AMH gene promoter. Therefore, it is possible that vitamin D increases AMH levels without changing the antral follicle count/ovarian reserve.
Phthalate exposure is associated with altered reproductive function, but little is known about associations of phthalate exposure with risk of hot flashes. To investigate associations of urinary phthalate metabolite levels with four hot flash outcomes in midlife women. A cross-sectional study of the first year of a prospective cohort of midlife women, the Midlife Women's Health Study (2006-2015), a convenience sample from an urban setting. 728 multi-racial/ethnic pre- and perimenopausal women aged 45-54 years. Women completed questionnaires about hot flash experience and provided 1-4 urine samples over four consecutive weeks that were pooled for analysis. Phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates: ƩPhthalates; ƩDEHP), exposure sources (plastics: ƩPlastic; personal care products: ƩPCP), and modes of action (anti-androgenic: ƩAA). Covariate-adjusted logistic regression models were used to assess associations of continuous natural log-transformed phthalate metabolite concentrations with hot flash outcomes. Analyses were conducted to explore whether associations differed by menopause status, body mass index (BMI), race/ethnicity, and depressive symptoms. Overall, 45% of women reported a history of hot flashes. Compared to women who never experienced hot flashes, every two-fold increase in ƩPlastic was associated with 18% (OR: 1.18; 95%CI: 0.98, 1.43) and 38% (OR: 1.38; 95%CI: 1.11, 1.70) higher odds of experiencing hot flashes in the past 30 days and experiencing daily/weekly hot flashes, respectively. Some associations of phthalates with certain hot flash outcomes differed by menopause status, BMI, race/ethnicity, and depressive symptoms. This study suggests that phthalates are associated with hot flash experience and may impact hot flash risk in women who are susceptible to experiencing hot flashes.
Smith SJ et al., 2021·Advances in nutrition (Bethesda, Md.)·
Open Access
Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk of morbidity and mortality. Currently, the primary treatment for AD is testosterone replacement therapy (TRT), which may exacerbate pre-existing medical conditions. Therefore, the use of alternative options, such as herbs, spices, plants, or their extracts, has been explored as a potential treatment option for AD. The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y). From the 4 databases searched, there were 13 herbs identified in 32 studies, published between 2001 and 2019. The main findings of this review indicate that 2 herbal extracts, fenugreek seed extracts and ashwagandha root and root/leaf extracts, have positive effects on testosterone concentrations in men. Also, some evidence exists for another herb and herbal extract, Asian red ginseng and forskohlii root extract. Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations. Moreover, 6 studies out of 32 were judged as having a low risk of bias. Current evidence is largely based on young, nonclinical populations, with 16 out of 32 studies using men <40 y of age. Conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Also, further research is required before definitive conclusions on efficacy and safety can be made. This systematic review was registered at PROSPERO as CRD42020173623.
Wang Y et al., 2021·Healthcare (Basel, Switzerland)
Phthalates are a series of widely used chemicals that demonstrate to be endocrine disruptors and are detrimental to human health. Phthalates can be found in most products that have contact with plastics during producing, packaging, or delivering. Despite the short half-lives in tissues, chronic exposure to phthalates will adversely influence the endocrine system and functioning of multiple organs, which has negative long-term impacts on the success of pregnancy, child growth and development, and reproductive systems in both young children and adolescents. Several countries have established restrictions and regulations on some types of phthalates; however, we think that more countries should establish constraints or substitute measures for phthalates to reduce health risks. This article aims to summarize the adverse impacts of phthalates on human health, analyze the toxicity mechanism, assess the risks, and finally provide feasible strategies to reduce exposure of the public to phthalates.
Jimenez MP et al., 2021·Int J Environ Res Public Health·
Open Access
There is extensive empirical literature on the association between exposure to nature and health. In this narrative review, we discuss the strength of evidence from recent (i.e., the last decade) experimental and observational studies on nature exposure and health, highlighting research on children and youth where possible. We found evidence for associations between nature exposure and improved cognitive function, brain activity, blood pressure, mental health, physical activity, and sleep. Results from experimental studies provide evidence of protective effects of exposure to natural environments on mental health outcomes and cognitive function. Cross-sectional observational studies provide evidence of positive associations between nature exposure and increased levels of physical activity and decreased risk of cardiovascular disease, and longitudinal observational studies are beginning to assess long-term effects of nature exposure on depression, anxiety, cognitive function, and chronic disease. Limitations of current knowledge include inconsistent measures of exposure to nature, the impacts of the type and quality of green space, and health effects of duration and frequency of exposure. Future directions include incorporation of more rigorous study designs, investigation of the underlying mechanisms of the association between green space and health, advancement of exposure assessment, and evaluation of sensitive periods in the early life-course.
Lucaccioni L et al., 2021·International Journal of Molecular Sciences·
Open Access
Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update the knowledge on the neuroendocrine consequences of neonatal and perinatal exposure to phthalates.
A maternal Western-style diet (WSD) is associated with poor reproductive outcomes, but whether this is from the diet itself or underlying metabolic dysfunction is unknown. Here, we performed a longitudinal study using regularly cycling female rhesus macaques (n = 10) that underwent 2 consecutive in vitro fertilization (IVF) cycles, one while consuming a low-fat diet and another 6-8 months after consuming a high-fat WSD. Metabolic data were collected from the females prior to each IVF cycle. Follicular fluid (FF) and oocytes were assessed for cytokine/steroid levels and IVF potential, respectively. Although transition to a WSD led to weight gain and increased body fat, no difference in insulin levels was observed. A significant decrease in IL-1RA concentration and the ratio of cortisol/cortisone was detected in FF after WSD intake. Despite an increased probability of isolating mature oocytes, a 44% reduction in blastocyst number was observed with WSD consumption, and time-lapse imaging revealed delayed mitotic timing and multipolar divisions. RNA sequencing of blastocysts demonstrated dysregulation of genes involved in RNA binding, protein channel activity, mitochondrial function and pluripotency versus cell differentiation after WSD consumption. Thus, short-term WSD consumption promotes a proinflammatory intrafollicular microenvironment that is associated with impaired preimplantation development in the absence of large-scale metabolic changes.
Mathews DM et al., 2021·Human reproduction (Oxford, England)
Iodine is a vital micronutrient and its importance in thyroid function is well established. However, abnormalities in iodine intake may also have other effects. In particular, iodine is taken up avidly by the ovary and endometrium. Iodine deficiency is associated with reduced fertility. The use of high iodine concentration contrast media has recently been shown to improve conception rates in couples with unexplained infertility (UI). We hypothesize that this improvement could be related to the iodine excess and mechanisms independent of its action on thyroid. In this article, the metabolism of iodine and its potential role in fertility will be discussed, including the impact of both iodine deficiency and excess states and the importance of iodine in normal fetal development. This will include insights from animal studies on the effect of iodine in the uterine and ovarian structural environment, hormonal milieu and immunological factors affecting implantation. We speculate that iodine may well have a role as a potential therapy for UI.
Environmental Exposures · Personal Care and Household Products
Rashid MM et al., 2021·Nanomaterials (Basel)·
Open Access
Nanotechnology has enabled tremendous breakthroughs in the development of materials and, nowadays, is well established in various economic fields. Among the various nanomaterials, TiO2 nanoparticles (NPs) occupy a special position, as they are distinguished by their high availability, high photocatalytic activity, and favorable price, which make them useful in the production of paints, plastics, paper, cosmetics, food, furniture, etc. In textiles, TiO2 NPs are widely used in chemical finishing processes to impart various protective functional properties to the fibers for the production of high-tech textile products with high added value. Such applications contribute to the overall consumption of TiO2 NPs, which gives rise to reasonable considerations about the impact of TiO2 NPs on human health and the environment, and debates regarding whether the extent of the benefits gained from the use of TiO2 NPs justifies the potential risks. In this study, different TiO2 NPs exposure modes are discussed, and their toxicity mechanisms—evaluated in various in vitro and in vivo studies—are briefly described, considering the molecular interactions with human health and the environment. In addition, in the conclusion of this study, the toxicity and biocompatibility of TiO2 NPs are discussed, along with relevant risk management strategies.
Nutrition and Metabolic Health · Eating Disorders and Underfueling
Areta JL et al., 2021·European journal of applied physiology
Energy availability (EA) is defined as the amount of dietary energy available to sustain physiological function after subtracting the energetic cost of exercise. Insufficient EA due to increased exercise, reduced energy intake, or a combination of both, is a potent disruptor of the endocrine milieu. As such, EA is conceived as a key etiological factor underlying a plethora of physiological dysregulations described in the female athlete triad, its male counterpart and the Relative Energy Deficiency in Sport models. Originally developed upon female-specific physiological responses, this concept has recently been extended to males, where experimental evidence is limited. The majority of data for all these models are from cross-sectional or observational studies where hypothesized chronic low energy availability (LEA) is linked to physiological maladaptation. However, the body of evidence determining causal effects of LEA on endocrine, and physiological function through prospective studies manipulating EA is comparatively small, with interventions typically lasting ≤ 5 days. Extending laboratory-based findings to the field requires recognition of the strengths and limitations of current knowledge. To aid this, this review will: (1) provide a brief historical overview of the origin of the concept in mammalian ecology through its evolution of algebraic calculations used in humans today, (2) Outline key differences from the 'energy balance' concept, (3) summarise and critically evaluate the effects of LEA on tissues/systems for which we now have evidence, namely: hormonal milieu, reproductive system endocrinology, bone metabolism and skeletal muscle; and finally (4) provide perspectives and suggestions for research upon identified knowledge gaps.
Rondanelli M et al., 2020·Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)·
Open Access
Boron is a trace element that plays an important role in numerous biological functions, including calcium metabolism, growth and maintenance of bone tissue. However, there are still no precise indications regarding a possible role of boron supplementation, and its amount of supplementation, to maintain bone health. So the aim of this narrative review was to consider the state of the art on the effectiveness of boron supplementation (alone or with other micronutrients) on growth and maintenance of bone in humans through control of calcium, vitamin D and sex steroid hormone metabolism in order to suggest a daily dosage of boron supplementation. This review included 11 eligible studies: 7 regarding the supplementation with boron alone and 4 regarding supplementation with boron and other nutrients. Despite the number of studies considered being low, the number of subjects studied is high (594) and the results are interesting. The studies considered in this narrative review have evaluated the positive effectiveness on bone, in humans, through control of calcium, vitamin D and sex steroid hormone metabolism, considering a dietary supplementation of 3 mg/day of boron (alone or with other nutrients); this supplementation is demonstrably useful to support bone health (in order to prevent and maintain adequate bone mineral density), also considering the daily dose of 3 mg is much lower than the Upper Level indicated by EFSA in the daily dose of 10 mg.
Bariani MV et al., 2020·Current opinion in endocrinology, diabetes, and obesity
Uterine leiomyoma (fibroids) is a gynecologic disorder impacting the majority of women in the United States. When symptomatic, these noncancerous tumors can cause severe morbidity including pelvic pain, menorrhagia, and infertility. Endocrine-disrupting chemicals (EDCs) may represent a modifiable risk factor. The aim of this review is to summarize recent human and experimental evidence on EDCs exposures and fibroids. Multiple EDCs are associated with fibroid outcomes and/or processes including phthalates, parabens, environmental phenols, alternate plasticizers, Diethylstilbestrol, organophosphate esters, and tributyltin. Epidemiologic studies suggest exposure to certain EDCs, such as di-(2-ethylhxyl)-phthalate (DEHP), are associated with increased fibroid risk and severity. Both human and experimental studies indicate that epigenetic processes may play an important role in linking EDCs to fibroid pathogenesis. In-vitro and in-vivo studies show that DEHP, bisphenol A, and diethylstilbestrol can impact biological pathways critical to fibroid pathogenesis. While research on EDCs and fibroids is still evolving, recent evidence suggests EDC exposures may contribute to fibroid risk and progression. Further research is needed to examine the impacts of EDC mixtures and to identify critical biological pathways and windows of exposure. These results could open the door to new prevention strategies for fibroids.
Nutrition and Metabolic Health · Blood Sugar and Insulin
This study aims to evaluate the effects of myo-inositol supplementation on gestational diabetes mellitus (GDM) rates and body water distribution in overweight non-obese women. 223 overweight non-obese women pregnant were randomly assigned to the treatment group (2 g of myo-inositol plus 200 µg of folic acid) or to the placebo one (200 µg of folic acid). The treatment lasted until three weeks after delivery. A tetrapolar impedance analyser was used to study body composition. The incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group. There was a significant increase in TBW, ECW and ICW values in the placebo group compared to the myo-inositol group. We have recorded a significant reduction in the overall incidence of pregnancy-induced hypertension in the myo-inositol group compared with the placebo group. Our results demonstrate the effectiveness of myo-inositol supplementation in preventing GDM in overweight non-obese pregnant women.
Per- and polyfluoroalkyl substances (PFASs) are used in specialty/functional textiles to impart oil, water, and stain repellency. Little is known, however, with regard to the occurrence of PFASs in textiles including infant clothing. In this study, 13 perfluoroalkyl acids (PFAAs), comprising four perfluoroalkyl sulfonic acids (PFSAs; C4-C10) and nine perfluoroalkyl carboxylic acids (PFCAs; C4-C12) were determined in 160 textile samples collected from the United States. Two extraction methods, one involving a simple solvent extraction (i.e., before oxidation) and the other with an oxidative treatment (i.e., after oxidation) of textile extracts, were used. The sum concentrations of 13 PFAAs (i.e., ∑PFAA) in textile extracts before oxidation ranged from 2 (2 (14.2 ng/g). ∑PFAA concentrations were the highest in flame retarded textiles (n = 23; mean: 13.3 μg/m2; 59.4 ng/g), followed by water repellent textiles (n = 56; 2.88 μg/m2; 12.9 ng/g) and infant clothes (n = 81; 0.521 μg/m2; 2.33 ng/g). C4-C10 PFCAs accounted for at least three-quarters of the ∑PFAA content in our textile samples. Textile extracts analyzed after oxidative treatment exhibited ∑PFAA concentrations 10-fold higher than those in extracts analyzed prior to oxidation, which suggested that PFAA precursors are used in textiles. Precursors that generated C4-C5 PFCAs, upon oxidation, were more prevalent than those that yielded PFOA. The calculated dermal exposure doses in infants of PFAAs present in clothes were at least 1-2 orders of magnitude below the reference doses proposed by the United States Environmental Protection Agency. This is the first time that the oxidative treatment was applied in the analysis of PFASs in textiles, and our results suggest the existence of PFCA precursors in textiles.
Nutrition and Metabolic Health · Eating Disorders and Underfueling
Skorseth P et al., 2020·Orthopaedic journal of sports medicine
Investigations of the female athlete triad (Triad) in high school athletes have found that 36% had low energy availability, 54% had menstrual abnormalities, and 16% had low bone mineral density (BMD). Limited data are available showing the prevalence of these risk factors in high school distance runners or regarding best practice on screening for the Triad in the adolescent population. To (1) evaluate the prevalence of Triad risk factors and iron supplementation in high school distance runners and (2) pilot a screening tool for Triad risk score. Descriptive epidemiology study. The study population included female high school athletes who participated in cross-country/track. Participants completed a survey including questions regarding dietary habits, menstrual history, and bone stress injury (BSI) history. They then underwent evaluation of 25-hydroxyvitamin D, free triiodothyronine (T3), and dual-energy x-ray absorptiometry scan to measure body fat and BMD through use of age-, sex-, and ethnicity-matched Z scores. Triad scores were calculated. Relationships were analyzed using Spearman correlation coefficient. There were 38 study participants (mean age, 16.9 years). Average body mass index was 19.8 kg/m2. Disordered eating or eating disorders were reported in 76.3% of runners; in addition, 23.7% reported delayed menarche, 45.9% had a history of amenorrhea or oligomenorrhea, 42.1% had low BMD (Z score < -1.0), and 15.8% reported prior BSI. Low free T3 was significantly associated with higher Triad risk scores (r S = -0.36; P = .028). More than 42% of athletes were supplementing iron. The prevalence of Triad risk factors in high school distance runners was high. Free T3 was inversely associated with Triad score, which may serve as an indicator of low energy availability. Nearly half of the athletes were using iron supplementation.
Nutrition and Metabolic Health · Body Weight and Composition
Hu Q et al., 2020·Utah Womens Health Rev·
Open Access
To investigate the association between pre-pregnancy body mass index (BMI) and subfertility within a population-based cohort, exploring Hispanic ethnicity as a potential effect modifier. We used cross-sectional study data from the Utah Pregnancy Risk Assessment Monitoring System from 2012-2015. Relationships between maternal pre-pregnancy BMI and subfertility were evaluated via Poisson regression models with robust error variance, accounting for the stratified survey sampling. Preconception BMI was analyzed continuously and categorically. Women's subfertility was defined via self-report in two ways: 1) time trying to achieve pregnancy; and 2) report of using fertility-related drugs/medical procedures. The median age was 27.0; 18.8% were obese, and 15.9% were Hispanic. Women with preconception obesity (BMI>30kg/m(2)), compared to normal weight women (18.4kg/ m(2)<BMI<25kg/m(2)) had a 1.85 (95% CI 1.43, 2.38) higher adjusted prevalence ratio (aPR) for having subfertility defined by time trying and a 1.73 (95% CI 1.20, 2.32) higher aPR for receiving fertility-enhancing drugs/medical procedures. Continuous models indicated a linear relationship between BMI and subfertility (aPR 1.04, 95% CI 1.03, 1.06 for time trying; and 1.06, 95% CI 1.03, 1.10 for receiving fertility-enhancing drugs/medical procedures). Obese women, but not underweight or overweight women, reported higher subfertility than normal-weight women. Findings among this cohort of at-risk new mothers, oversampled on low education and birth weight and comprised of higher than the national average of Hispanics, indicated a dose-response relationship between obesity and subfertility.
Our findings highlight the importance of population-oriented obesity prevention for at-risk women with intentions to conceive.
Nutrition and Metabolic Health · Blood Sugar and Insulin
Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable.
Environmental Exposures · Pesticides and Agricultural Chemicals
Numerous evidences have alerted on the toxic effects of the exposure to glyphosate on living organisms. Glyphosate is the herbicide most used in crops such as maize and soybean worldwide, which implies that several non-target species are at a high risk of exposure. Although the Environmental Protection Agency (EPA-USA) has reaffirmed that glyphosate is safe for users, there are controversial studies that question this statement. Some of the reported effects are due to exposure to high doses; however, recent evidences have shown that exposure to low doses could also alter the development of the female reproductive tract, with consequences on fertility. Different animal models of exposure to glyphosate or glyphosate-based herbicides (GBHs) have shown that the effects on the female reproductive tract may be related to the potential and/or mechanisms of actions of an endocrine-disrupting compound. Studies have also demonstrated that the exposure to GBHs alters the development and differentiation of ovarian follicles and uterus, affecting fertility when animals are exposed before puberty. In addition, exposure to GBHs during gestation could alter the development of the offspring (F1 and F2). The main mechanism described associated with the endocrine-disrupting effect of GBHs is the modulation of estrogen receptors and molecules involved in the estrogenic pathways. This review summarizes the endocrine-disrupting effects of exposure to glyphosate and GBHs at low or "environmentally relevant" doses in the female reproductive tissues. Data suggesting that, at low doses, GBHs may have adverse effects on the female reproductive tract fertility are discussed.
Qiu Y et al., 2020·Archives of gynecology and obstetrics
No consensus exists on the relationship between vitamin D status and endometriosis. The chief aim of our study was to evaluate the association between serum vitamin D levels and endometriosis. We searched for MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases for studies elucidated the circulating vitamin D levels in endometriosis. The standardized mean differences (SMDs) or odds ratios (ORs) with their 95% confidence interval (CIs) were calculated to evaluate the association between vitamin D levels and endometriosis. Nine studies were included in this meta-analysis. The pooled results indicated that women with endometriosis had lower vitamin D status than that in controls (SMD - 0.97 ng/mL, 95% CI - 1.80 to - 0.14; p = 0.02), and vitamin D status had a negative correlation with the severity of the disease (stage III-IV vs stage I-II: SMD - 1.33 ng/mL, 95% CI - 2.54 to - 0.12; p = 0.03). Although it was not statistically significantly different, hypovitaminosis D had a tendency to be associated with endometriosis (OR 2.77, 95% CI 0.85-6.08, p = 0.10). Heterogeneity was high among included studies. Subgroup analyses revealed that women with no hormone use had lower vitamin D status when compared with controls (SMD - 1.38 ng/mL, 95% CI - 2.59 to - 0.18; p = 0.02). For studies which sample size < 100, serum vitamin D levels were significantly lower in patients than that in controls (SMD - 0.65 ng/mL, 95% CI - 1.19 to - 0.11; p = 0.02). Women with endometriosis had lower vitamin D status when compared with controls, and a negative relationship between vitamin D levels and severity of endometriosis was observed. In addition, hypovitaminosis D was a potential risk factor for endometriosis.
Kwiatkowski CF et al., 2020·Environmental Science & Technology Letters·
Open Access
This commentary presents a scientific basis for managing as one chemical class the thousands of chemicals known as PFAS (per- and polyfluoroalkyl substances). The class includes perfluoroalkyl acids, perfluoroalkylether acids, and their precursors; fluoropolymers and perfluoropolyethers; and other PFAS. The basis for the class approach is presented in relation to their physicochemical, environmental, and toxicological properties. Specifically, the high persistence, accumulation potential, and/or hazards (known and potential) of PFAS studied to date warrant treating all PFAS as a single class. Examples are provided of how some PFAS are being regulated and how some businesses are avoiding all PFAS in their products and purchasing decisions. We conclude with options for how governments and industry can apply the class-based approach, emphasizing the importance of eliminating non-essential uses of PFAS, and further developing safer alternatives and methods to remove existing PFAS from the environment.
Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.
Waterfield G et al., 2020·Environmental health : a global access science source
Per- and polyfluoroalkyl substances (PFASs) have been detected in drinking water supplies around the world and are the subject of intense regulatory debate. While they have been associated with several illnesses, their effects on reproductive outcomes remains uncertain. We analyzed birth outcomes in the east Minneapolis-St. Paul metropolitan area from 2002 to 2011, where a portion of the population faced elevated exposure to PFASs due to long-term contamination of drinking water supplies from industrial waste disposal. Installation of a water filtration facility in the highly contaminated city of Oakdale, MN at the end of 2006 resulted in a sharp decrease in exposure to PFASs, creating a "natural experiment". Using a difference-in-differences approach, we compare the changes in birth outcomes before and after water filtration in Oakdale to the changes over the same period in neighboring communities where the treatment of municipal water remained constant. Average birth weight and average gestational age were statistically significantly lower in the highly exposed population than in the control area prior to filtration of municipal water supply. The highly exposed population faced increased odds of low birth weight (adjusted odds ratio 1.36, 95% CI 1.25-1.48) and pre-term birth (adjusted odds ratio 1.14, 95% CI 1.09-1.19) relative to the control before filtration, and these differences moderated after filtration. The general fertility rate was also significantly lower in the exposed population (incidence rate ratio 0.73, 95% CI 0.69-0.77) prior to filtration and appeared to be rebounding post-2006. Our findings provide evidence of a causal relationship between filtration of drinking water containing high levels of exposure to PFASs and improved reproductive outcomes.
Tang Z et al., 2020·Journal of Hazardous Materials
Phthalates could be introduced into clothing as chemical additives or impurities, becoming a potential source of human exposure. We measured the concentrations of 15 phthalates in new preschool children's clothing manufactured in seven Asian countries. Phthalates were prevalent in all samples, and total concentrations were 2.92-223 μg/g, indicating a moderate contamination level. Bis(2-ethylhexyl) phthalate, di(isobutyl) phthalate and di-n-butyl phthalate were the most abundant phthalates measured, representing a median of 48.5 %, 13.6 % and 13.4 % of the total concentrations, respectively. Total concentrations did not differ significantly by country of manufacture, while the concentrations of individual phthalates and their composition profiles varied widely. We also found differing phthalate levels by item type, fabric composition, and color. Under the assumed two exposure scenarios, the median of summed dermal exposure doses of six phthalate were 539 and 950 ng/kg of body weight per day, respectively. When children wore trousers, long-sleeved shirts, briefs and socks at the same time, the reproductive risks exceeded acceptable level, although the carcinogenic risk of DEHP was low. Our results suggested that new clothing is an important route of phthalate exposure to preschool children. More research is required to investigate the contaminations and associated with risks in child clothing.
Liew Z et al., 2020·Environmental health perspectives
Per- and polyfluoroalkyl substances (PFAS) are widespread persistent organic pollutants and endocrine disruptors. High doses of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure can cause pregnancy loss and infant deaths in animals, but the associations between PFAS exposures and risk of miscarriage in humans are not well studied. Using a case-control study nested within the Danish National Birth Cohort (DNBC, 1996-2002), we compared 220 pregnancies ending in miscarriage during weeks 12-22 of gestation, with 218 pregnancies resulting in live births. Levels of seven types of PFAS [PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctanesulfonic acid (PFOSA)] were measured in maternal plasma collected in early gestation (mean gestational week 8). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PFAS as a continuous variable or in quartiles, controlling for maternal age, parity, socio-occupational status, smoking and alcohol intake, gestational week of blood sampling, and maternal history of miscarriage. Stratification by parity and PFAS mixture analyses using weighted quantile sum (WQS) regression were also conducted. We observed a monotonic increase in odds for miscarriage associated with increasing PFOA and PFHpS levels. The ORs comparing the highest PFOA or PFHpS quartile to the lowest were 2.2 (95% CI: 1.2, 3.9) and 1.8 (95% CI: 1.0, 3.2). The ORs were also elevated for the second or third quartile of PFHxS or PFOS, but no consistent exposure-outcome pattern emerged. An interquartile range (IQR) increment in the WQS index of seven PFAS was associated with 64% higher odds for miscarriage (95% CI: 1.15, 2.34). The associations were stronger in parous women, while findings were inconsistent among nulliparous women. Maternal exposures to higher levels of PFOA, PFHpS, and PFAS mixtures were associated with the risk of miscarriage and particularly among parous women. Larger replication studies among nulliparous women are needed to allay concerns about confounding by reproductive history. https://doi.org/10.1289/EHP6202.
To estimate the association between physical activity and risk of subclinical and clinical pregnancy loss among women with a history of pregnancy loss.
Prospective cohort study as a secondary analysis of the Effects of Aspirin in Gestation and Reproduction randomized controlled trial of preconception-initiated low-dose aspirin among women with one or two prior pregnancy losses.
Four U.S. clinical centers, 2007-2011. PATIENT(S): Women with confirmed pregnancy (n = 785) as determined from hCG testing in longitudinally collected biospecimens. MAIN OUTCOME MEASURE(S): Subclinical loss of pregnancy detected only by hCG testing and clinically recognized loss. RESULT(S): Among 785 women (mean [SD] age, 28.7 [4.6] years) with an hCG-confirmed pregnancy, 188 (23.9%) experienced pregnancy loss. In multivariable models adjusted for confounders, compared with the first tertile of physical activity (median = 7.7 metabolic equivalent of task hours/week), there was a roughly twofold higher risk of subclinical loss in the second (risk ratio = 2.06; 95% confidence interval, 1.03-4.14) and third tertiles (risk ratio = 1.92; 95% confidence interval, 0.94-3.90), with median metabolic equivalent of task hours/week of 27.8 and 95.7, respectively. No relations were observed between physical activity and clinically recognized loss. CONCLUSION(S): Risk related to physical activity is different for pregnancy failure close to the time of implantation compared with that for later, clinical pregnancy loss. Higher physical activity levels were associated with an elevated risk of subclinical loss (i.e., pregnancies detected only by hCG, n = 55); however, no relationship was observed with clinically recognized loss. Further work is required to confirm these findings, assess generalizability to women without prior losses, and evaluate mechanisms. Ethical Approval: Each participating center's Institutional Review Board approved the study, and participants provided written informed consent. The trial was registered on ClinicalTrials.gov (NCT00467363), and a Data Safety and Monitoring Board provided oversight. : Estimar la asociación entre la actividad física y el riesgo de pèrdida gestacional subclínica y clínica entre mujeres con historia de pèrdida gestacional. DISEÑO:: Estudio prospectivo de cohortes como análisis secundario de un estudio aleatorizado de los efectos de aspirina en la gestación y la reproducción, utilizando bajas dosis de aspirina desde la preconcepción entre mujeres con una o dos pèrdidas gestacionales previas. : Cuatro clínicas en Estados Unidos, entre 2007–2011. : Mujeres con embarazo confirmado (n= 785) determinado por pruebas de hCG en muestras biológicas recogidas longitudinalmente. PRINCIPALES MEDIDAS DE RESULTADO(S):: Pérdida gestacional subclínica detectada sólo por la prueba de hCG y la reconocida clínicamente. : Entre 785 mujeres (media de edad [Deviación standard], 28,7 [4,6] años) con una gestación confirmada con hCG, 188 (23.9%) que tuvieron pérdida gestacional. En un modelo multivariante ajustado para factores de confusión comparado con el primer tercil de actividad física (media= 7,7 equivalentes metabólicos de trabajo horas/semana) hubo un riesgo bruto dos veces mayor de pérdida subclínica en el segundo (relación de riesgo= 2,06; Intervalo de confianza 95%, 1,03–4,14) y el tercer tercil (Relación de riesgo = 1,92 Intervalo de confianza 95%, 0,94–3,9) con una media metabólica equivalente de trabajo horas/semana de 27,8 y 95,7 respectivamente. No hubo relación entre actividad física y pérdidas gestacionales clínicas. : El riesgo asociado a actividad física es diferente para fallo gestacional próximo al momento de la implantación comparado con el más tardío de pérdida gestacional clínica. Niveles mayores de actividad física estuvieron asociados con un riesgo elevado de pérdida subclínica (por ejemplo, embarazos detectados solo por hCG, n=55); sin embargo, no se observó relación con pérdida clínicamente reconocida. Se necesitan más trabajos para confirmar estos hallazgos, evaluando de forma general mujeres sin pérdidas gestacionales previas, y evaluar sus mecanismos. APROBACIÓN ÉTICA:: El comité de revisión institucional de cada centro participante aprobó el estudio y los participantes dieron por escrito su consentimiento informado. El ensayo fue registrado en ClinicalTrial.gov (NCT00467363), y el comité de seguridad y monitorización de los datos dio su aprobación
Endometriosis is a chronic disease with no known cure. Persons affected by this disease often use complementary therapies such as dietary changes to reduce their symptoms, and so it is important to investigate whether and how these therapies affect endometriosis symptoms. The aim of this study was to explore how persons with endometriosis experienced their health after dietary changes. Semi-structured qualitative interviews were conducted with 12 persons with endometriosis who had made individual dietary changes aimed at decreasing their endometriosis symptoms. The interviews were recorded and transcribed verbatim, and analysed using thematic analysis. Region Västra Götaland and the estern part of Central Sweden, Sweden. Twelve persons with endometriosis aged 28 to 44 were recruited from two Swedish endometriosis support forums on the Internet. Participants experienced an increase in well-being and a decrease in symptoms following their dietary and lifestyle changes. They also felt that the dietary changes led to increased energy levels and a deeper understanding of how they could affect their health by listening to their body's reactions. The participants understood that they could influence their symptoms through lifestyle changes. Support from family and friends was important in implementing and sustaining the dietary changes. However, the participants stressed the lack of support from healthcare professionals. This study contributes to filling the knowledge gap about dietary strategies in endometriosis and lifestyle change as a method of alleviating suffering and increasing well-being. An important finding is that the participants experienced decreased symptoms and increased well-being after adopting an individually-adapted diet. Healthcare professionals should take their patients' knowledge and experience into consideration, and allow patients to participate in their own care. Further research is necessary to give evidenced-based dietary advices in endometriosis.
Nowadays, most of the swimsuits are mainly made of artificial fibres, which have interesting properties such as water repellence and fast drying. Swimsuits contain a wide range of additives, which can mean a hazard for the environment and/or human health. In this study, the concentrations of formaldehyde (free and water soluble), 24 aromatic amines, and 28 trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sr, Sn, Tl, Ti, V and Zn) were analysed in 39 swimsuits covering a wide range of materials, colours and brands. Dermal exposure and health risks were assessed for adults (men and women) aged > 18 years old, babies between 2 and < 3 years old, children (boys and girls) between 3 and < 6 years old and 6 and < 11 years old, and teenagers (boys and girls) between 11 and < 16 years old, wearing swimsuits for 4 h or 8 h. Formaldehyde and aromatic amines were below their respective detection limits in all samples (<16 and < 1.5 mg/kg, respectively). Regarding trace elements, Ti showed the highest mean levels (1844 mg/kg), being significantly higher in polyamide (3759 mg/kg) than in polyester (24.1 mg/kg) swimsuits. These high Ti levels were confirmed by environmental scanning electron microscope in a single sample made of polyamide. Increased concentrations of Cr were also observed, but only in polyamide black fabrics, with values ranging from 624 to 932 mg/kg. Non-cancer risks (hazard quotients) derived from the exposure to trace elements were in a safe zone for all analysed trace elements. Furthermore, the carcinogenic risks were evaluated for As, Cr and Pb, exhibiting values below the 10-5 threshold, with the exception of Cr in babies and children-girls. For Ti, health risks could not be calculated due to the lack of information on toxicological data. However, because Ti was the element with the highest concentrations in swimsuits, and taking into account the potential toxicity of TiO2 nanoparticles, further research is needed to assess the migration of this element from fibres to skin.
Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report. To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood. DESIGN, SETTING, This prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018. Three cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth. Physician-diagnosed ADHD, ASD, and other DDs as documented in the child's medical records. Of 996 participants (mean [SD] age, 9.8 [3.9] years; 548 [55.0%] male), the final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; OR for third tertile, 2.86; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14; 95% CI, 0.93-5.13; OR for third tertile, 3.62; 95% CI, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen buden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD. Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.
Female fecundity is finely regulated by hormonal signaling, representing a potential target for endocrine-disrupting chemicals. Among the chemicals of most concern are the perfluoroalkyl substances (PFAS), widely used in consumer goods, that are associated with adverse effects on reproductive health. In this context, the endometrium clearly represents an important fertility determining factor. The aim of this study was to investigate PFAS interference on hormonal endometrial regulation. This study was performed within a screening protocol to evaluate reproductive health in high schools. We studied a cohort of 146 exposed females aged 18-21 from the Veneto region in Italy, one of the four areas worldwide heavily polluted with PFAS, and 1080 non-exposed controls. In experiments on Ishikawa cells included UV-Vis spectroscopy, microarray analysis and qPCR. We report a significant dysregulation of the genetic cascade leading to embryo implantation and endometrial receptivity. The most differentially-expressed genes upon PFOA coincubation were ITGB8, KLF5, WNT11, SULT1E1, ALPPL2 and G0S2 (all p < 0.01). By qPCR, we confirmed an antagonistic effect of PFOA on all these genes, which was reversed at higher progesterone levels. Molecular interference of PFOA on progesterone was confirmed by an increase in the intensity of absorption spectra at 250 nm in a dose-dependent manner, but not in the presence of β-estradiol. Age at menarche (+164 days, p = 0.006) and the frequency of girls with irregular periods (29.5% vs 21.5%, p = 0.022) were significantly higher in the exposed group. Our results are indicative of endocrine-disrupting activity of PFAS on progesterone-mediated endometrial function.
In 2006-2008, 610 premenopausal, spontaneously menstruating women in the Metro Vancouver region participated in a Canadian Institutes of Health Research (CIHR)-funded singlecycle in which they collected first morning urine specimens for estrogen and progesterone metabolites1. Following that study, after analyses, we retrieved the remaining urine specimens from the analyzing laboratory (University of Washington). We sorted data so that samples from all those women who were anovulatory by the two combined urinary steroid evaluation methods2,3, plus from those who were ovulatory with the highest and the lowest urinary hormone values were shipped to Health Canada (HC) via Dr. Warren Foster’s laboratory at McMaster University. Those data on flame retardant contaminants in women’s urine have been published4, but the cycle-phase specific data are still in analysis (personal communication, S Kalyan, 2019). In 2017, HC basic scientists launched applications to HC to fund a similar study to assess flame retardant excretory changes in the same population/locale 10 years later. This application was funded in 2018 at Health Canada with Dr. JC Prior as a collaborator. Extensive negotiations by CeMCOR and HC scientists ensued about funding the process of obtaining these follow-up specimens. CeMCOR managed to obtain a HC agreement to fund the minimal cost of recruiting, training and obtaining two menstrual phase-specific urine specimens from 250 Metro Vancouver women. Because of the lack of a progesterone threshold for ovulation, we will collect one follicular and one luteal/premenstrual urine sample per woman. However, this time we will better characterize the ovulatory cycle using a validated quantitative basal temperature method5,6 that can assess luteal phase length as well as the presence/absence of evidence for ovulation. In addition we will collect serial salivary progesterone and estradiol values measured by the state-of-the-art sensitive and specific tandem mass spectrometry (LC-MS/MS) methods7 to use as the gold standard for an ovulatory cycle. There is increasing evidence that many variables differ across women’s two main menstrual cycle phases: follicular and luteal7-10. These real and potential differences in metabolism may alter the susceptibility of women to environment exposures, and also could change their urinary elimination. Those are the root reasons for doing this study.
Environmental Exposures · Solvents and Industrial Chemicals
Saleem H et al., 2020·Materials (Basel)·
Open Access
At present, nanotechnology is a priority in research in several nations due to its massive capability and financial impact. However, due to the uncertainties and abnormalities in shape, size, and chemical compositions, the existence of certain nanomaterials may lead to dangerous effects on the human health and environment. The present review includes the different advanced applications of nanomaterials in textiles industries, as well as their associated environmental and health risks. The four main textile industry fields using nanomaterials, nanofinishing, nanocoatings, nanofibers, and nanocomposites, are analyzed. Different functional textiles with nanomaterials are also briefly reviewed. Most textile materials are in direct and prolonged contact with our skin. Hence, the influence of carcinogenic and toxic substances that are available in textiles must be comprehensively examined. Proper recognition of the conceivable benefits and accidental hazards of nanomaterials to our surroundings is significant for pursuing its development in the forthcoming years. The conclusions of the current paper are anticipated to increase awareness on the possible influence of nanomaterial-containing textile wastes and the significance of better regulations in regards to the ultimate disposal of these wastes.
Environmental Exposures · Radiation and Electromagnetic Exposure
Chen PE et al., 2019·Evid Based Complement Alternat Med·
Open Access
Previous studies have reported the use of complementary therapies to reduce the risk of gout attacks. In this study, we assessed the effectiveness of cherries in reducing uric acid levels associated with gout. We searched for relevant studies on PubMed, Embase, and the Cochrane Library without restrictions on language from inception until August 15, 2019. The risk of bias was evaluated using the PRISMA statement and checklist, and the methodological quality was assessed using the Cochrane Collaboration tool. The six studies included in this systematic review reported decreases in the incidence and severity of gout following the ingestion of cherries. Gout patients regularly ingesting cherry extract/juice reported fewer gout flare ups than those patients who did not supplement their diets with cherry products. Overall, we observed a positive correlation between the consumption of tart cherry juice and a decrease in serum uric acid concentration. Current evidence supports an association between cherry intake and a reduced risk of gout attacks. Note however that we were unable to conduct effective meta-analysis due to a lack of relevant studies and a high degree of variation in the methodologies and metrics used in previous studies. Further comprehensive trials or long-term follow-up studies will be required to evaluate the efficacy of cherry intake in treating patients with gout or hyperuricemia.
Women who experience pregnancy loss are especially prone to high stress, though the effects of stress on reproductive outcomes in this vulnerable population are unknown. We assessed relationships between perceived stress and hormones, anovulation, and fecundability among women with prior loss. One thousand two hundred fourteen women with 1-2 prior losses were followed for ≤6 cycles while attempting pregnancy and completed end-of-cycle stress assessments. For cycles 1 and 2, women also collected daily urine and completed daily perceived stress assessments. We assessed anovulation via. an algorithm based on human chorionic gonadotropin (hCG), pregnanediol-3-glucuronide (PdG), luteinizing hormone (LH), and fertility monitor readings. Pregnancy was determined via. hCG. Adjusted weighted linear mixed models estimated the effect of prospective phase-varying (menses, follicular, periovulatory, and luteal) perceived stress quartiles on estrone-1-glucuronide (E1G), PdG, and LH concentrations. Marginal structural models accounted for time-varying confounding by hormones and lifestyle factors affected by prior stress. Poisson and Cox regression estimated risk ratios and fecundability odds ratios of cycle-varying stress quartiles on anovulation and fecundability. Models were adjusted for age, race, body mass index (BMI), parity, and time-varying caffeine, alcohol, smoking, intercourse, and pelvic pain. Women in the highest versus lowest stress quartile had lower E1G and PdG concentrations, a marginally higher risk of anovulation [1.28; 95% confidence interval (CI) = 1.00, 1.63], and lower fecundability (0.71; 95% CI = 0.55, 0.90). Preconception perceived stress appears to adversely affect sex steroid synthesis and time to pregnancy. Mechanisms likely include the effects of stress on ovulatory function, but additional mechanisms, potentially during implantation, may also exist.
Is pre-conception 25(OH)D associated with the per cycle probability of conception, i.e fecundability, in a prospective cohort study? There are suggestive associations of high 25(OH)D (at least 50 ng/ml) with increased fecundability and low 25(OH)D (<20 ng/ml) with reduced fecundability, but the estimates were imprecise. Vitamin D has been associated with reproductive function and fertility in animal studies, but few human studies exist. STUDY DESIGN, SIZE, This community-based prospective cohort study included 522 women attempting to become pregnant between 2010 and 2016. The women completed online daily and monthly diaries until a positive home pregnancy test was observed or 12 months had elapsed. PARTICIPANTS/MATERIALS, SETTING, The study included women from central North Carolina who were aged 30-44 with no history of infertility, with no more than 3 months of attempt time at recruitment. Women recorded vaginal bleeding so that the ongoing number of attempt cycles could be counted and used to quantify a woman's pregnancy attempt time. Blood collected at the study entry was analysed for 25(OH)D using liquid chromatography tandem mass spectrometry. Associations with fecundability were estimated with a log-binomial discrete time-to-event model. MAIN Among 522 women, 257 conceived during the study. The mean age was 33 years and the mean 25(OH)D was 36 ng/ml. There was an estimated 10% higher fecundability with each 10 ng/ml increase in 25(OH)D (fecundability ratio (FR) 1.10, 95% CI: 0.96, 1.25). The suggestive dose-response association with the continuous measure of 25(OH)D was driven by women in the lowest and the highest categories of 25(OH)D. Compared to women with 25(OH)D of 30-40 ng/ml, women below 20 ng/ml had an estimated 45% reduction in fecundability (FR (CI): 0.55 (0.23, 1.32)), and women with at least 50 ng/ml had an estimated 35% increase in fecundability (FR (CI): 1.35 (0.95, 1.91)). Across these three categories (25(OH)D of <20 ng/ml, 30-40 ng/ml and > 50 ng/ml), the probability of taking longer than 6 months to conceive was, respectively, 51% (17%, 74%), 28% (17%, 39%) and 15% (10%, 37%). LIMITATIONS, While the distribution of 25(OH)D was wide, the number of observed cycles with high 25(OH)D (N = 107) or low 25(OH)D (N = 56) was small. Our findings are consistent with prior reports of reduced fertility in women with 25(OH)D concentrations below the clinically defined deficiency level (20 ng/ml). Further studies are needed to evaluate the possible reproductive benefits of considerably higher 25(OH)D concentration (>50 ng/ml). STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under award numbers R00HD079659 and R01HD067683 and supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, under projects ES103086, ES049003 and ES044003. ClearBlue ovulation predictor kits were generously donated to AMZJ and AJW by Swiss Precision Diagnostics. Drs Wilcox and Jukic report non-financial support from Swiss Precision Diagnostics during the conduct of the study; Dr Jukic reports non-financial support from Theralogix, LLC, outside the submitted work. Otherwise there are no competing interests. N/A.
Nutrition and Metabolic Health · Blood Sugar and Insulin
D'Anna R et al., 2019·J Nutr Sci Vitaminol (Tokyo)·
Open Access
Gestational Diabetes Mellitus (GDM) is one of the most frequent complications of pregnancy and is characterized by a carbohydrate intolerance which is diagnosed with the oral glucose tolerance test. The prevalence of GDM in our population is about 12%, but risk factors like a previous GDM, ethnicity, a parent with diabetes mellitus type 2 and maternal overweight may increase its occurrence. Complications of GDM are a pre-term birth (before 37 wk gestation), macrosomia (birth weight ≥4 kg) and gestational hypertension. Actually, GDM is principally treated with diet and, if it is necessary, with insulin; but the challenge is the prevention of GDM. Among the measures used, changes in life-style (diet+exercise) failed to prevent GDM whereas metformin showed conflicting results. A promising supplement is myo-inositol (MI) which was given from first trimester until delivery to women at risk for GDM reporting a significant decrease in GDM occurrence by more than 60% comparing to the placebo group. Recently, a secondary analysis from 3 randomized controlled trials demonstrated that MI may also significantly reduce some of GDM complications such as pre-term birth and macrosomia with a favorable impact on mother and fetus well being.
Prior studies among women with impaired fecundity have consistently demonstrated a positive association between daily perceived stress and the ability to conceive. However, the effects of daily stress on time to pregnancy (TTP) among women with proven fertility is not known. One hundred and forty-three women ages 18-35, in a relationship of proven fertility, who desired to conceive were included in the analysis. Daily diaries recording perceived stress (scale 0-10) were completed for up to 7 menstrual cycles or until pregnancy. Cox proportional hazards regression models were used to estimate the association between time-varying perceived stress tertiles (high [>4.1-7.2], moderate [>2.7-4.1], and low [0.1-2.7]) and adjusted fecundability odds ratio (aFOR), 95% confidence intervals (CI), after taking into account age, parity, education, time-varying caffeine and alcohol intake, fertility awareness tracking, and cycle intent to conceive. Among the 111 participants who completed daily diaries, 90 (81.1%) conceived. Women reporting high or moderate stress, versus low stress, had no difference in probability of achieving pregnancy (aFOR: 1.11 [95% CI: 0.58, 2.14]; and aFOR: 1.37 [0.71, 2.67]), respectively. Additional adjustment for intercourse frequency during narrow fertile window, or narrowing exposure focus to pre-ovulatory or pre-implantation stress did not appreciably alter the estimates. Daily perceived stress was not adversely associated with TTP among women with proven fertility. While a growing body of evidence supports adverse effects of more severe stressful life events on female reproductive function, moderate psychological stress, commonly referred to as eustress, among relatively healthy women with proven fertility does not appear to adversely impact TTP.
In recent years, there has been a growing interest in nutraceuticals, which may be considered as an efficient, preventive, and therapeutic tool in facing different pathological conditions, including thyroid diseases. Although iodine remains the major nutrient required for the functioning of the thyroid gland, other dietary components play important roles in clinical thyroidology-these include selenium, l-carnitine, myo-inositol, melatonin, and resveratrol-some of which have antioxidant properties. The main concern regarding the appropriate and effective use of nutraceuticals in prevention and treatment is due to the lack of clinical data supporting their efficacy. Another limitation is the discrepancy between the concentration claimed by the label and the real concentration. This paper provides a detailed critical review on the health benefits, beyond basic nutrition, of some popular nutraceutical supplements, with a special focus on their effects on thyroid pathophysiology and aims to distinguish between the truths and myths surrounding the clinical use of such nutraceuticals.
Kołomańska-Bogucka D et al., 2019·Medicina (Kaunas, Lithuania)
During pregnancy and the postnatal period many changes occur in a woman's body, both in mental and physical spheres. The birth of a child and a new role-of a mother-can sometimes be associated with numerous negative emotions, uncertainty, fear, anxiety, disgust, depression, or sadness. In the puerperium period, the development of baby blues or postpartum depression may occur. Postpartum depression develops within one month of childbirth and may last up to one year. Depressive disorders that may develop in a young mother affect both her and the newborn's health. That is why it is so important to try to search for factors that could significantly reduce the likelihood of developing depression in this period. The study aims at assessing the relationship between physical activity during pregnancy and puerperium or in the postpartum and the development of postnatal depression. A review of the literature was carried out in the Medline-PubMed database. The search terms were "pregnancy" AND "physical activity AND postpartum depression". The study included only English-language publications published in the period 2000-2018. A total of 216 references were found. After establishing the inclusion and exclusion criteria based on the analysis of titles and abstracts, 173 articles were excluded from the review. A total of 43 publications were read in full. Finally, 16 articles were included in the review. It was shown that regular physical activity during pregnancy, pregnancy, and puerperium, or in the postnatal period itself as compared to inactivity, reduces the risk of developing depression in pregnant women and after the birth of a child. Physical activity can be an essential factor in the prevention of depressive disorders of women in the postnatal period.
Li HL et al., 2019·Science of The Total Environment
Clothing easily adsorbed the chemicals in the environment, and became a source of human exposure to chemicals. However, large contacted surface area and long exposure duration have elevated human exposure to chemicals from clothing, such as phthalates. Among them, cotton clothing, which infants prefer to wear, has been proven to adsorb phthalates more easily than other fabrics. While infants are developing, they are easily affected by phthalates. In this study, in order to study accumulation of phthalates in infant cotton clothing during the whole process from production to the first wearing, 24 infant cotton clothing samples were collected from shopping malls in Harbin, China. High detection rates and concentrations suggest that phthalates in the environment are widely adsorbed to infant cotton clothing, and traditional laundering for infant clothing cannot remove phthalates completely. The median concentration of the total phthalates was 4.15 μg/g. Di-(2-ethylhexyl) phthalate (DEHP) has become the dominant phthalate. For the estimated daily intakes (EDIs) for infants, dibutyl phthalate (DBP) had the highest contribution, followed by di-iso-butyl phthalate (DiBP) and DEHP. Dermal absorption has become the main route of infant exposure to phthalates, and ingestion contributed very little. The result of comparing with the EDIs via dermal absorption from house air and dust suggests that clothing plays an important role of dermal absorption exposure to phthalates. For risk assessment, the carcinogenic risk of BBP and DEHP indicates that the level of DEHP in infant cotton clothing might pose potential adverse effects to infant health.
Bisphenol A (BPA) is a non-persistent endocrine-disrupting chemical with nearly ubiquitous, involuntary exposure. Previous studies have shown that BPA causes reproductive dysfunction in animal models, but there are limited data regarding the effects of BPA exposure on time to pregnancy (TTP) in humans. To evaluate whether peri-conceptional BPA exposure of women and men is associated with couples' TTP. A total of 164 heterosexual couples (164 women; 163 men) who have available BPA information as well as time to pregnancy from the Home Observation of Peri-conceptional Exposures (HOPE) Study were included and were followed up to 12 months. Women collected first-morning urine samples starting at the beginning of the fertile window and continued until the onset of menses or 18 days after the estimated day of ovulation (EDO+18 days). The time to pregnancy (TTP) after the enrolment was self-reported and used for the analysis. Discrete-time Cox proportional hazards models were performed to generate fecundability odds ratio (FOR) between BPA and TTP after adjusting for education and age, accounting for right censoring and prior number of cycles trying to conceive. Among 164 couples, 125 couples became pregnant during the study. There was no association between TTP and peri-conceptional BPA exposure for both men (FOR 1.02, 95% CI 0.72, 1.47) and women (FOR 1.07, 95% CI 0.75, 1.53) after adjusting for education and age. No association was found between peri-conceptional BPA exposure and fecundability in this preconception cohort of relatively young, healthy pregnancy planners.
Mumtaz M et al., 2019·Frontiers of Environmental Science & Engineering
Organofluorinated surfactants are widely employed in textile finishing agents (TFAs) to achieve oil, water, and stain repellency. This has been regarded as an important emission source of per-and polyfluoroalkyl substances (PFASs) to the environment. China is the biggest manufacturer of clothes, and thus TFA production is also a relevant industrial activity. Nevertheless, to date, no survey has been conducted on PFAS contents in commercially available TFAs. In the present study, TFA products were investigated by the Kendrick mass defect method. The quantification results demonstrated a significant presence of perfluorooctane sulfonate (0.37 mg/L) in TFAs manufactured by electrochemical fluorination technology. The products obtained by short-chain PFAS-based telomerization were dominated by perfluorooctanoic acid (mean concentration: 0.29 mg/L), whose values exceeded the limits stated in the European Chemical Agency guidelines (0.025 mg/L). Moreover, the total oxidizable precursor assay indicated high levels of indirectly quantified precursors with long alkyl chains (C7-C9). Together, these results suggest that there is currently a certain of environmental and health risks in China that originates from the utilization of TFAs, and a better manufacturing processes are required to reduce such risks.
Metabolic syndrome (MetS) is highly correlated with obesity and cardiovascular risk, but the importance of dietary carbohydrate independent of weight loss in MetS treatment remains controversial. Here, we test the theory that dietary carbohydrate intolerance (i.e., the inability to process carbohydrate in a healthy manner) rather than obesity per se is a fundamental feature of MetS. Individuals who were obese with a diagnosis of MetS were fed three 4-week weight-maintenance diets that were low, moderate, and high in carbohydrate. Protein was constant and fat was exchanged isocalorically for carbohydrate across all diets. Despite maintaining body mass, low-carbohydrate (LC) intake enhanced fat oxidation and was more effective in reversing MetS, especially high triglycerides, low HDL-C, and the small LDL subclass phenotype. Carbohydrate restriction also improved abnormal fatty acid composition, an emerging MetS feature. Despite containing 2.5 times more saturated fat than the high-carbohydrate diet, an LC diet decreased plasma total saturated fat and palmitoleate and increased arachidonate. Consistent with the perspective that MetS is a pathologic state that manifests as dietary carbohydrate intolerance, these results show that compared with eucaloric high-carbohydrate intake, LC/high-fat diets benefit MetS independent of whole-body or fat mass. ClinicalTrials.gov Identifier: NCT02918422. Dairy Management Inc. and the Dutch Dairy Association.
Spending time in natural environments can benefit health and well-being, but exposure-response relationships are under-researched. We examined associations between recreational nature contact in the last seven days and self-reported health and well-being. Participants (n = 19,806) were drawn from the Monitor of Engagement with the Natural Environment Survey (2014/15-2015/16); weighted to be nationally representative. Weekly contact was categorised using 60 min blocks. Analyses controlled for residential greenspace and other neighbourhood and individual factors. Compared to no nature contact last week, the likelihood of reporting good health or high well-being became significantly greater with contact ≥120 mins (e.g. 120-179 mins: ORs [95%CIs]: Health = 1.59 [1.31-1.92]; Well-being = 1.23 [1.08-1.40]). Positive associations peaked between 200-300 mins per week with no further gain. The pattern was consistent across key groups including older adults and those with long-term health issues. It did not matter how 120 mins of contact a week was achieved (e.g. one long vs. several shorter visits/week). Prospective longitudinal and intervention studies are a critical next step in developing possible weekly nature exposure guidelines comparable to those for physical activity.
Freire C et al., 2019·Environment International·
Open Access
Little information is available on the content of bisphenol A (BPA) and other endocrine-disrupting chemicals (EDCs) such as parabens in infant textiles and clothes.Objectives1) To determine the concentrations of BPA and parabens in socks for infants and young children purchased in Spain, 2) to assess the (anti-)estrogenicity and (anti-)androgenicity of extracts from the socks, and 3) to estimate dermal exposure doses to these chemicals. Thirty-two pairs of socks for infants and young children (1-48 months) were purchased from 3 stores in Granada (Spain). Textile material was cut from the foot, toe, and leg of each sock (n = 96 samples) for chemical analysis. Hormone-like activities were determined in foot sections (n = 32 samples) by using the E-Screen assay for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity. BPA was present in 90.6% of samples at concentrations ranging from <0.70 to 3736 ng/g. BPA levels were around 25-fold higher in socks from store 1, which had a higher cotton content compared to stores 2 and 3. Ethyl-paraben was found in 100% of samples, followed by methyl-paraben (81.0%), and propyl-paraben (43.7%). No butyl-paraben was detected in any sample. Estrogenic activity was detected in 83.3% of socks from store 1 (range = 48.2-6051 pM E2eq/g) but in only three socks from stores 2 and 3. Anti-androgenic activity was detected in six of the 32 socks studied (range = 94.4-2989 μM Proceq/g), all from store 1. Estimated dermal exposure to BPA was higher from socks for children aged 36-48 months (median = 17.6 pg/kg/day), and dermal exposure to parabens was higher from socks for children aged 24-36 months (median = 0.60 pg/kg/day). This is the first report in Europe on the wide presence of BPA and parabens in socks marketed for infants and children. BPA appears to contribute to the hormone-like activity observed in sock extracts.
Purdue‐Smithe A et al., 2019·Current Developments in Nutrition·
Open Access
The association between caffeine and pregnancy loss remains controversial due to limitations of prior studies such as relying on self-reported intake only, exposure measurement after clinical confirmation of pregnancy, and potential time-varying confounding by nausea/vomiting and lifestyle factors, which may be affected by prior caffeine exposure. Thus, our aim was to evaluate associations of preconception and early pregnancy serum caffeine, paraxanthine, and theobromine, self-reported intake of caffeinated beverages, and risk of pregnancy loss among 1228 reproductive-age women attempting pregnancy in the EAGeR trial during 2007–2011. We estimated HRs and 95% CIs for any pregnancy loss, hCG loss (prior to ultrasound confirmation), and clinical loss (after ultrasound confirmation) according to caffeinated beverage intake and caffeine biomarkers measured at preconception and the 8(th) week of gestation using weighted adjusted Cox proportional hazards models. At preconception, 67%, 28%, and 9% of women reported any intake of caffeinated sodas, coffee, and tea, respectively. Preconception total caffeinated beverage intake of ≥3 vs. 0 cups/day was associated with 85% (95% CI: 1.18, 2.94) higher risk of any pregnancy loss, driven primarily by associations for hCG loss (HR: 2.88 (95% CI: 1.20, 6.91)). Caffeinated soda intake was associated with hCG loss (≥2 vs. 0.2 vs. ≤0.2 ng/mL) at preconception was strongly associated with hCG loss (HR: 4.51 (95% CI: 1.36, 14.91)). Serum caffeine, paraxanthine, and theobromine measured at the 8th week of gestation were not associated with risk of loss. Collectively, these data suggest that caffeine intake prior to pregnancy may increase risk of pregnancy loss, particularly in early gestation. Funding Sources: Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD.
Endocrine-disrupting chemicals are known to interfere with normal reproductive function and hormone signaling. Phthalates, bisphenol A, pesticides, and environmental contaminants such as polychlorinated biphenyls and dioxins are known endocrine-disrupting chemicals that have been shown to negatively affect both male and female reproduction. Exposure to these chemicals occurs on a daily basis owing to these compounds being found in plastics, personal care products, and pesticides. Recently, studies have shown that these chemicals may cause transgenerational effects on reproduction in both males and females. This is of concern because exposure to these chemicals prenatally or during adult life can negatively impact the reproductive health of future generations. This mini-review summarizes the endocrine-disrupting chemicals that humans are exposed to on a daily basis and what is known about the transgenerational effects that these chemicals may have on male and female reproduction.
The concentration of a number of trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Cr, Co, Cu, Fe, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sr, Sn, Tl, Ti, V and Zn) were determined in 42 commercialized denim garments (jeans and shirts), being dermal exposure subsequently assessed. Migration experiments with artificial acid and basic sweat were also conducted to determine the release of these elements, as well as indigo dye. In a similar way than for the total content, Mg (124 and 99.4 µg/g) and Mn (27.1 and 7.20 µg/g) showed the highest concentrations in both artificial sweat, acid and basic, respectively. Indigo dye migrated at levels ranged from 3.22 to 7.76 mg/g, being higher in dark than in light blue fabrics. The levels of trace elements and indigo were analysed according to materials of fabric, colour, brand, and eco-labelling. Using total content and migrations rates, dermal exposure to trace elements for adult men, women and teenagers were calculated under the two sweat extractions. Non-carcinogenic and carcinogenic risks due to dermal exposure to the elements here analysed in cloths were assessed. Both risks were in the limits of safe to according to international regulations. However, the maximum exposure to Sb reached a hazard quotient (HQ) of 0.3 in clothes partially made of polyester. Despite some authors have established that indigo is an agonist of the aril receptor, health risks due to exposure to indigo dye were not calculated due the lack of toxicological data.
Licina D et al., 2019·Environmental Science & Technology
A growing body of evidence identifies clothing as an important mediator of human exposure to chemicals and particles, which may have public health significance. This paper reviews and critically assesses the state of knowledge regarding how clothing, during wear, influences exposure to molecular chemicals, abiotic particles, and biotic particles, including microbes and allergens. The underlying processes that govern the acquisition, retention, and transmission of clothing-associated contaminants and the consequences of these for subsequent exposures are explored. Chemicals of concern have been identified in clothing, including byproducts of their manufacture and chemicals that adhere to clothing during use and care. Analogously, clothing acts as a reservoir for biotic and abiotic particles acquired from occupational and environmental sources. Evidence suggests that while clothing can be protective by acting as a physical or chemical barrier, clothing-mediated exposures can be substantial in certain circumstances and may have adverse health consequences. This complex process is influenced by the type and history of the clothing; the nature of the contaminant; and by wear, care, and storage practices. Future research efforts are warranted to better quantify, predict, and control clothing-related exposures.
Gou X et al., 2019·The Australian and New Zealand journal of psychiatry
Acetaminophen is a widely used medication for fever and pain management during pregnancy. However, recent studies have found a possible connection between maternal prenatal acetaminophen use and attention deficit/hyperactivity disorder in children. We aimed to explore the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. PubMed, Embase, Web of Science and Cochrane Library were searched from their initial publications through November 2018 for studies. We included all studies that examined the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring if the authors reported odds ratios, risk ratios, hazard ratios, regression coefficient, standard error and 95% confidence intervals. Two reviewers independently extracted data on the definition of exposure and outcome, exposed, non-exposed and total number of participants in the sample population, adjusted potential confounders and outcome parameters. Study quality was also assessed. Eight cohort studies with a total of 244,940 participants were included. Maternal exposure to acetaminophen during pregnancy increased the risk of attention deficit/hyperactivity disorder in offspring with a pooled adjusted risk ratio of 1.25 (95% confidence interval = [1.17, 1.34]). Children exposed prenatally to acetaminophen in the third trimester seemed to have the greatest risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.26; 95% confidence interval = [1.08, 1.47]). In addition, a longer duration of maternal acetaminophen use during pregnancy was correlated with a higher risk ratio. Children whose mothers used acetaminophen for 28 or more days during gestation had a higher risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.63; 95% confidence interval = [1.23, 2.16]). There is an association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. The timing and duration of acetaminophen use during pregnancy may have a major effect on the risk of attention deficit/hyperactivity disorder.
Cheah YK et al., 2019·Int J Pediatr Adolesc Med·
Open Access
The objective of the present study is to examine factors affecting time spent in physical activity among adolescents in Malaysia. A nationally representative data of adolescents that consists of 25399 respondents is used. The demographic (age, gender, education) and lifestyle (fruits and vegetables consumption, carbonated soft drink consumption, cigarette smoking, alcohol drinking, sex behaviour, participation in physical education class, obesity) determinants of physical activity are assessed using binomial regression. The results show that age is negatively associated with time spent in physical activity. However, being male and education levels are positively related to time spent in physical activity. Having unhealthy lifestyle and being obese are associated with low levels of physical activity. Physical education seems to promote participation in physical activity. In conclusion, demographic and lifestyle factors play an important role in determining levels of physical activity among adolescents. In order to reduce the prevalence of physically inactive adolescents, policy makers should focus primarily on late adolescents, females, adolescents who engage in unhealthy lifestyle and seldom attend physical education classes, as well as obese adolescents.
Environmental Exposures · Personal Care and Household Products
Svedman C et al., 2019·Current Treatment Options in Allergy·
Open Access
Purpose of the review: Textile dermatitis can sometimes be difficult to diagnose due to the fact that it is difficult to clinically suspect, and when allergic, patch test correctly and advice the patient as to what garments to avoid. Recent findings: The textile fibres as such are rarely the causative agent. Allergic contact dermatitis due to textiles is primarily caused by substances that are used to give the material certain qualities or performances. The textile dye mix, now in the baseline series, has proven to be a useful tool in diagnosing allergic contact dermatitis but additional patch testing with own material is advocated. Future research will hopefully facilitate the diagnostic procedure. This review is a short update on textile dermatitis, both irritant and allergic, the present recommendations regarding patch testing when suspecting contact allergy and the advice to give to those allergic that will hopefully help the clinician in daily work.
It is well known that a number of substances used in the textile industry can mean not only environmental, but also health problems. The scientific literature regarding potential adverse health effects of chemical substances in that industry is mainly related with human exposure during textile production. However, information about exposure of consumers is much more limited. Although most research on the health effects of chemicals in textiles concern allergic skin reactions, contact allergy is not the only potential human health problem. In this paper, we have reviewed the current scientific information regarding human exposure to chemicals through skin-contact clothes. The review has been focused mainly on those chemicals whose probabilities of being detected in clothes were rather higher. Thus, we have revised the presence of flame retardants, trace elements, aromatic amines, quinoline, bisphenols, benzothiazoles/benzotriazoles, phthalates, formaldehyde, and also metal nanoparticles. Human dermal exposure to potentially toxic chemicals through skin-contact textiles/clothes shows a non-negligible presence in some textiles, which might lead to potential systemic risks. Under specific circumstances of exposure, the presence of some chemicals might mean non-assumable cancer risks for the consumers.
Nutrition and Metabolic Health · Eating Disorders and Underfueling
Krug I et al., 2019·Neuropsychiatric disease and treatment
Emerging evidence suggests that disordered eating, particularly binge-eating symptomatology, is overrepresented within Polycystic Ovary Syndrome (PCOS) populations. This comorbidity presents a clinical dilemma as current treatment approaches for PCOS emphasize the importance of weight management, diet, exercise, and the potential for harm of such treatment approaches in PCOS patients with comorbid disordered eating. However, limited research has assessed the occurrence of binge eating and disordered eating in PCOS patients. Consequently, little is known about the prevalence of binge eating in PCOS, and the possible etiological processes to explain this comorbidity remain poorly understood. Given the paucity of research on this topic, the aims of this narrative review are fourfold: 1) to outline the main symptoms of PCOS and binge eating; 2) to provide an overview of the prevalence of binge eating in PCOS; 3) to outline possible etiological factors for the comorbidity between PCOS and binge eating; and 4) to provide an overview of management strategies of binge eating in PCOS.
Nutrition and Metabolic Health · Blood Sugar and Insulin
Celentano C et al., 2018·J Matern Fetal Neonatal Med·
To identify the effects of different dietary inositol stereoisomers on insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk for this disorder.Design: A preliminary, prospective, randomized, placebo controlled clinical trial. Nonobese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy. Supplementation with myo-inositol, d-chiro-inositol, combined myoand d-chiro-inositol or placebo.Main Development of GDM on a 75 grams oral glucose tolerance test at 24-28 weeks' gestation. Secondary outcome measures were increase in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia. The group of women allocated to receive myo-inositol alone had a lower incidence of abnormal oral glucose tolerance test (OGTT). Nine women in the control group (C), one of the myo-inositol (MI), five in d-chiro-inositol (DCI), three in the myo-inositol/D-chiro-inositol group (MI/DCI) required insulin (p = .134). Basal, 1-hour, and 2 hours glycemic controls were significantly lower in exposed groups (p < .001, .011, and .037, respectively). The relative risk reduction related to primary outcome was 0.083, 0.559, and 0.621 for MI, DCI, and MI/DCI groups. This study compared the different inositol stereoisomers in pregnancy to prevent GDM. Noninferiority analysis demonstrated the largest benefit in the myo-inositol group. The relevance of our findings is mainly related to the possibility of an effective approach in GDM. Our study confirmed the efficacy of inositol supplementation in pregnant women at risk for GDM.
Hemmert R et al., 2018·Paediatr Perinat Epidemiol·
Caffeine, alcohol, smoking and physical activity are known to alter sex steroid synthesis, which may affect hormone-dependent gynaecologic disease risk, such as endometriosis; however, few studies have assessed life style factors prior to endometriosis diagnosis. Four hundred and seventy three women, ages 18-44 years, underwent laparoscopy or laparotomy, regardless of clinical indication, at 14 clinic sites, 2007-2009. Women with prior surgically confirmed endometriosis were excluded. Life style factors were assessed prior to surgery. Adjusted risk ratios (RR) of endometriosis by caffeine, alcohol, smoking (serum cotinine), and physical activity were estimated, adjusting for age, marital status, education, race/ethnicity, age at menarche, gravidity, BMI, study site, and other life style factors. There were no associations between women with endometriosis and alcohol consumption (RR 0.9, 95% CI 0.7, 1.3), caffeine consumption (RR 1.1, 95% CI 0.8, 1.5), or smoking (serum cotinine <10 vs ≥10 ng/mL; RR 1.0, 95% CI 0.7, 1.6). Similar null findings were found between endometriosis and weekly occurrences of physical activity and total walking, moderate, and vigorous activity; a modest trend was found between total daily sitting time and increased endometriosis risk. This study, which is unique in its capture of life style exposures prior to incident endometriosis diagnosis, largely found no association between alcohol, caffeine, smoking, and physical activity and risk of endometriosis.
Although minerals are linked to several reproductive outcomes, it is unknown whether dietary minerals are associated with ovulatory function. We hypothesised that low intakes of minerals would be associated with an increased risk of anovulation. We investigated associations between dietary mineral intake and both reproductive hormones and anovulation in healthy women in the BioCycle Study, which prospectively followed up 259 regularly menstruating women aged 18-44 years who were not taking mineral supplements for two menstrual cycles. Intakes of ten selected minerals were assessed through 24-h dietary recalls at up to four times per cycle in each participant. Oestradiol, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex-hormone-binding globulin and testosterone were measured in serum up to eight times per cycle. We used weighted linear mixed models to evaluate associations between minerals and hormones and generalised linear models for risk of anovulation. Compared with Na intake ≥1500 mg, Na intake <1500 mg was associated with higher levels of FSH (21·3 %; 95 % CI 7·5, 36·9) and LH (36·8 %; 95 % CI 16·5, 60·5) and lower levels of progesterone (-36·9 %; 95 % CI -56·5, -8·5). Na intake <1500 mg (risk ratio (RR) 2·70; 95 % CI 1·00, 7·31) and Mn intake <1·8 mg (RR 2·00; 95 % CI 1·02, 3·94) were associated with an increased risk of anovulation, compared with higher intakes, respectively. Other measured dietary minerals were not associated with ovulatory function. As essential minerals are mostly obtained via diet, our results comparing insufficient levels with sufficient levels highlight the need for future research on dietary nutrients and their associations with ovulatory cycles.
Is physical activity (PA) associated with fecundability in women with a history of prior pregnancy loss? Higher fecundability was related to walking among overweight/obese women and to vigorous PA in women overall. PA may influence fecundability through altered endocrine function. Studies evaluating this association have primarily utilized Internet-based recruitment and self-report for pregnancy assessment and have yielded conflicting results. STUDY DESIGN, SIZE, Duration: This is a secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a multisite, randomized controlled trial of preconception-initiated low-dose aspirin. PARTICIPANTS/MATERIALS, SETTING, Healthy women (n = 1214), aged 18-40 and with 1-2 prior pregnancy losses, were recruited from four US medical centers. Participants were followed for up to six menstrual cycles while attempting pregnancy and through pregnancy for those who became pregnant. Time to hCG detected pregnancy was assessed using discrete-time Cox proportional hazard models to estimate fecundability odds ratios (FOR) adjusted for covariates, accounting for left truncation and right censoring. Main The association of walking with fecundability varied significantly by BMI (P-interaction = 0.01). Among overweight/obese women, walking ≥10 min at a time was related to improved fecundability (FOR = 1.82, 95% CI: 1.19, 2.77). In adjusted models, women reporting >4 h/wk of vigorous activity had significantly higher fecundability (FOR = 1.69, 95% CI: 1.24, 2.31) compared to no vigorous activity. Associations of vigorous activity with fecundability were not significantly different by BMI (P-interaction = 0.9). Moderate activity, sitting, and International Physical Activity Questionnaire (IPAQ) categories were not associated with fecundability overall or in BMI-stratified analyses. LIMITATIONS, Some misclassification of PA levels as determined by the short form of the IPAQ is likely to have occurred, and may have led to non-differential misclassification of exposure in our study. Information on diet and change in BMI was not collected and may have contributed to some residual confounding in our results. The generalizability of our results may be limited as our population consisted of women with a history of one or two pregnancy losses. These findings provide positive evidence for the benefits of PA in women attempting pregnancy, especially for walking among those with higher BMI. Further study is necessary to clarify possible mechanisms through which walking and vigorous activity might affect time-to-pregnancy. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors report no conflicts of interest in this work. #NCT00467363.
Although maternal nutrition may affect fecundity, associations between preconception micronutrient levels and time to pregnancy (TTP) have not been examined. We assessed the relationship between preconception fat-soluble micronutrient concentrations and TTP among women with 1-2 prior pregnancy losses. This was a prospective cohort study of 1,228 women set within the Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial (United States, 2007-2011), which assessed the association of preconception-initiated daily low-dose aspirin with reproductive outcomes. We measured preconception levels of zeaxanthin, cryptoxanthin, lycopene, αand β-carotene, and αand γ-tocopherol in serum. We used discrete Cox regression models, accounting for left-truncation and right-censoring, to calculate fecundability odds ratios and 95% confidence intervals. The models adjusted for age, body mass index, race, smoking, alcohol, physical activity, income, vitamin use, cholesterol, treatment arm, and study site. Serum α-carotene levels (per log unit (μg/dL) increase, fecundability odds ratio (FOR) = 1.17, 95% confidence interval (CI): 1.00, 1.36) and serum α-carotene concentrations at or above the US average (2.92 μg/dL) versus below the average (FOR = 1.21, 95% CI: 1.02, 1.44) were associated with shorter TTP. Compared with levels below the US average (187 μg/dL), γ-tocopherol concentrations at or above the average were associated with longer TTP (FOR = 0.83, 95% CI: 0.69, 1.00). The potential for these nutrients to influence fecundability deserves further exploration.
Environmental Exposures · Personal Care and Household Products
Jiang C et al., 2018·BMC Pregnancy Childbirth·
Open Access
Limited evidences were reported about the risk of pre-pregnancy hair dye use or irregular menstruation with abnormal birth weight during pregnancy, and their joint effects were also unknown. The aim of our study was to explore whether the pre-pregnancy exposure of hair dye and irregular menstruation were associated with the risk of abnormal birth weight. We conducted a nested case-control study from a prospective cohort of 6203 pregnant women. Low birth weight study included 315 mother-infant pairs (105 LBW cases and 210 matched controls), and macrosomia study included 381 mother-infant pairs (127 macrosomia cases and 254 matched controls). Meanwhile, lifestyle information including hair dying custom and menstrual history were collected by face-to-face questionnaires and birth outcomes were extracted from the medical records. The logistic regressions models were used to analyze the join effect of irregular menstruation and hair dye use. Pre-pregnancy hair dye use was associated with increased risk of LBW (adjusted OR = 1.71, 95% CI: 1.01-2.92, P = 0.048). Irregular menstruation had high risk of LBW (adjusted OR = 2.79, 95% CI: 1.53-5.09, P = 0.001) and macrosomia (adjusted OR = 1.93, 95% CI: 1.09-3.44, P = 0.023). Additionally, in the LBW study, women who used hair dye with pre-pregnancy BMI < 18.5 kg/m(2) had higher OR than those with only one risk factor (3.07 vs 2.53, P (trend) = 0.015), and women with both hair dye use and irregular menstruation also had higher risk than those with only one factor (4.53 vs 2.07, P (trend) = 0.05). Moreover, in macrosomia study, women with irregular menstruation and pre-pregnancy BMI ≥ 24 kg/m(2) had higher risk than those with one factor (13.31 vs 2.09, P (trend) = 0.001). Our study showed that either pre-pregnancy hair dye use or irregular menstruation was associated with abnormal birth weight, especially, their joint effects could furthermore increase the risk of low birth weight infants when these two factors existed simultaneously.
Harris HR et al., 2018·Human reproduction (Oxford, England)·
Open Access
Is there an association between intake of fruits and vegetables and risk of laparoscopically confirmed endometriosis? Higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis. Two case-control studies have examined the associations between fruit and vegetable intake and endometriosis risk with contrasting results. Diets rich in fruits and vegetables include higher levels of pro-vitamin A nutrients (alpha-carotene, beta-carotene, beta-cryptoxanthin) and women with endometriosis have been reported to have lower intake of vitamin A than women without endometriosis. STUDY DESIGN SIZE, A prospective cohort study using data collected from 70 835 premenopausal women from 1991 to 2013 as part of the Nurses' Health Study II cohort. PARTICIPANTS/MATERIALS, SETTING, Diet was assessed with a validated food frequency questionnaire (FFQ) every 4 years. Cases were restricted to laparoscopically confirmed endometriosis. Cox proportional hazards models were used to calculate rate ratios (RR) and 95% CI. MAIN During 840 012 person-years of follow-up, 2609 incident cases of laparoscopically confirmed endometriosis were reported (incidence rate = 311 per 100 000 person-years). We observed a non-linear inverse association between higher fruit consumption and risk of laparoscopically confirmed endometriosis (Psignificance of the curve = 0.005). This inverse association was particularly evident for citrus fruits. Women consuming ≥1 servings of citrus fruits/day had a 22% lower endometriosis risk (95% CI = 0.69-0.89; Ptrend = 0.004) compared to those consuming <1 serving/week. No association was observed between total vegetable intake and endometriosis risk. However, women consuming ≥1 servings/day cruciferous vegetables had a 13% higher risk of endometriosis (95% CI = 0.95-1.34; Ptrend = 0.03) compared to those consuming <1 serving/week. Of the nutrients examined, only beta-cryptoxanthin intake was significantly associated with lower endometriosis risk (RR fifth quintile = 0.88; 95% CI = 0.78-1.00; Ptrend = 0.02). LIMITATIONS Some error in the self-reporting of dietary intake is expected, however, use of a validated FFQ and examining diet prospectively across multiple time points, make it unlikely that this non-differential misclassification strongly influenced the results. Our findings suggest that a higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis, and beta-cryptoxanthin in these foods may partially explain this association. In contrast to what we hypothesized, consumption of some vegetables increased endometriosis risk which may indicate a role of gastrointestinal symptoms in both the presentation and exacerbation of endometriosis-related pain; however, it is not clear what components of these foods might underlie the observed associations. Future studies examining dietary patterns that consider different combinations of food intake may help clarify these associations. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by research grants HD4854, HD52473 and HD57210 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and grant P30 DK046200 from the National Institute of Diabetes and Digestive and Kidney Diseases. The Nurses' Health Study II is supported by the Public Health Service grant UM1 CA176726 from the National Cancer Institute, National Institutes of Health. HRH is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). No competing interests. n/a.
Rooney KL et al., 2018·Dialogues in clinical neuroscience
The relationship between stress and infertility has been debated for years. Women with infertility report elevated levels of anxiety and depression, so it is clear that infertility causes stress. What is less clear, however, is whether or not stress causes infertility. The impact of distress on treatment outcome is difficult to investigate for a number of factors, including inaccurate self-report measures and feelings of increased optimism at treatment onset. However, the most recent research has documented the efficacy of psychological interventions in lowering psychological distress as well as being associated with significant increases in pregnancy rates. A cognitive-behavioral group approach may be the most efficient way to achieve both goals. Given the distress levels reported by many infertile women, it is vital to expand the availability of these programs.
Kristensen DM et al., 2018·Proc Natl Acad Sci U S A·
Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.
The incidence of metabolic disorders like type 2 diabetes and obesity continues to increase. In addition to the well-known contributors to these disorders, such as food intake and sedentary lifestyle, recent research in the exposure science discipline provides evidence that exposure to endocrine-disrupting chemicals like bisphenol A and phthalates via multiple routes (e.g., food, drink, skin contact) also contribute to the increased risk of metabolic disorders. Endocrine-disrupting chemicals (EDCs) can disrupt any aspect of hormone action. It is becoming increasingly clear that EDCs not only affect endocrine function but also adversely affect immune system function. In this review, we focus on human, animal, and in vitro studies that demonstrate EDC exposure induces dysfunction of the immune system, which, in turn, has detrimental effects on metabolic health. These findings highlight how the immune system is emerging as a novel player by which EDCs may mediate their effects on metabolic health. We also discuss studies highlighting mechanisms by which EDCs affect the immune system. Finally, we consider that a better understanding of the immunomodulatory roles of EDCs will provide clues to enhance metabolic function and contribute toward the long-term goal of reducing the burden of environmentally induced diabetes and obesity.
Stress and Allostatic Load · Cortisol and the Adrenal Axis
Joseph DN et al., 2017·International journal of molecular sciences
An organism's reproductive fitness is sensitive to the environment, integrating cues of resource availability, ecological factors, and hazards within its habitat. Events that challenge the environment of an organism activate the central stress response system, which is primarily mediated by the hypothalamic-pituitary-adrenal (HPA) axis. The regulatory functions of the HPA axis govern the cardiovascular and metabolic system, immune functions, behavior, and reproduction. Activation of the HPA axis by various stressors primarily inhibits reproductive function and is able to alter fetal development, imparting a biological record of stress experienced in utero. Clinical studies and experimental data indicate that stress signaling can mediate these effects through direct actions in the brain, gonads, and embryonic tissues. This review focuses on the mechanisms by which stress activation of the HPA axis impacts fertility and fetal development.
Khayat S et al., 2017·Journal of clinical and diagnostic research : JCDR·
Open Access
Micronutrients (include vitamins and minerals) are essential for normal function, growth and development. Minerals have important effects on the health of the mother and foetus. But biological mechanisms of minerals are not completely understood. Micronutrient deficiency during pregnancy can lead to anaemia, hypertension, obstetric complications and even maternal death and in foetus lead to a fail in growth and development. Mineral deficiency during pregnancy, particularly exist in developing countries. During pregnancy due to the increased demands caused by physiological changes, deficiency is exaggerated and as a result its complications occur. Thus, ensuring to receive enough macronutrients and micronutrients before and during pregnancy, is important. Nevertheless, there are controversies regarding administrating supplements. There are not enough studies about some of the minerals and the challenges remain. Regarding the importance of minerals in pregnancy and lactation, in this review we will analyze the role of them in pregnancy and lactation.
Gaskins AJ et al., 2017·Am J Obstet Gynecol·
Open Access
The literature on the relationship between diet and human fertility has greatly expanded over the last decade, resulting in the identification of a few clear patterns. Intake of supplemental folic acid, particularly at doses higher than those recommended for the prevention of neural tube defects, has been consistently related to lower frequency of infertility, lower risk of pregnancy loss, and greater success in infertility treatment. On the other hand and despite promising evidence from animal models, vitamin D does not appear to exert an important role in human fertility in the absence of deficiency. Antioxidant supplementation does not appear to offer any benefits to women undergoing infertility treatment, but it appears to be beneficial when it is the male partner who is supplemented. However, the available evidence does not allow discerning which specific antioxidants, or at which doses, are responsible for this benefit. Long-chain omega-3 fatty acids appear to improve female fertility, although it remains unclear to what extent contamination of shared food sources, such as fish with high levels of environmental toxicants, can dampen this benefit. Lastly, adherence to healthy diets favoring seafood, poultry, whole grains, fruits, and vegetables are related to better fertility in women and better semen quality in men. The cumulative evidence has also piled against popular hypotheses. Dairy and soy, once proposed as reproductive toxicants, have not been consistently related to poor fertility. In fact, soy and soy supplements appear to exert a beneficial effect among women undergoing infertility treatment. Similarly, because data from large, high-quality studies continue to accumulate, the evidence of a potentially deleterious effect of moderate alcohol and caffeine intake on the ability to become pregnant seems less solid than it once did. While a complete picture of the role of nutrition on fertility is far from complete, much progress has been made. The most salient gaps in the current evidence include jointly considering female and male diets and testing the most consistent findings in randomized trials.
Pizzino G et al., 2017·Oxid Med Cell Longev·
Open Access
Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress). Several antioxidants have been exploited in recent years for their actual or supposed beneficial effect against oxidative stress, such as vitamin E, flavonoids, and polyphenols. While we tend to describe oxidative stress just as harmful for human body, it is true as well that it is exploited as a therapeutic approach to treat clinical conditions such as cancer, with a certain degree of clinical success. In this review, we will describe the most recent findings in the oxidative stress field, highlighting both its bad and good sides for human health.
Chiang C et al., 2017·Semin Reprod Med·
Open Access
This review article summarizes the epidemiological findings published between 2011 and 2016 concerning bisphenol A (BPA), phthalates, dioxins, pesticides, air pollution, fracking chemicals, triclosan, and parabens and fertility parameters in men (i.e., semen volume, sperm concentration, sperm motility, and sperm morphology) as well as fertility parameters in women (i.e., cyclicity, fertility treatment outcomes), pregnancy outcomes (i.e., preterm birth,miscarriage), and reproductive disorders (i.e., polycystic ovary syndrome, endometriosis, and uterine fibroids). Overall, this review indicates that several environmental toxicants are significantly associated with reduced fertility parameters in men and women as well as several reproductive disorders in women. Although many studies reported that the selected exposures are associated with adverse fertility outcomes, several studies reported null associations. Thus, future studies are still needed to better elucidate the associations and potential mechanisms between these environmental chemicals and fertility outcomes in men and women.
Rattan S et al., 2017·Journal of Endocrinology·
Open Access
Endocrine disrupting chemicals are ubiquitous chemicals that exhibit endocrine disrupting properties in both humans and animals. Female reproduction is an important process, which is regulated by hormones and is susceptible to the effects of exposure to endocrine disrupting chemicals. Disruptions in female reproductive functions by endocrine disrupting chemicals may result in subfertility, infertility, improper hormone production, estrous and menstrual cycle abnormalities, anovulation, and early reproductive senescence. This review summarizes the effects of a variety of synthetic endocrine disrupting chemicals on fertility during adult life. The chemicals covered in this review are pesticides (organochlorines, organophosphates, carbamates, pyrethroids, and triazines), heavy metals (arsenic, lead, and mercury), diethylstilbesterol, plasticizer alternatives (di-(2-ethylhexyl) phthalate and bisphenol A alternatives), 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated biphenyls, triclosan, and parabens. This review focuses on the hypothalamus, pituitary, ovary, and uterus because together they regulate normal female fertility and the onset of reproductive senescence. The literature shows that several endocrine disrupting chemicals have endocrine disrupting abilities in females during adult life, causing fertility abnormalities in both humans and animals.
Environmental Exposures · Solvents and Industrial Chemicals
The aim of this study was to assess whether higher plasma formaldehyde concentration existed in women diagnosed with miscarriage and whether it contributed to higher risk of miscarriage in Chinese women.A case-control study was conducted in 118 women with a diagnosed miscarriage at the first trimester and 191 healthy women who delivered at term. Plasma levels of formaldehyde were measured by gas chromatography in conjunction with mass spectrometry after derivatization of the formaldehyde to the pentafluorophenylhydrazone and characteristics of the subjects including age, education level, occupation, family income, home decoration status, and exposure to second-hand smoke were recorded. Logistic regression analyses were performed to investigate the relationship between miscarriage and levels of formaldehyde.Women with miscarriage were comparable to controls in terms of age, education level, occupation, family income, and home decoration status. They were, however, more likely to be exposed to second-hand smoke. Plasma levels of formaldehyde were significantly higher in women with miscarriage (0.0944 ± 0.0105 vs. 0.0239 ± 0.0032 μg/mL, P < .001). Multivariate logistic regression showed that higher level of formaldehyde (odds ratio [OR]: 8.06, 95% confidence interval [CI]: 4.96-13.09) and exposure to second-hand smoke (OR: 3.60, 95% CI: 1.58-8.20) were independently and significantly associated with higher risk of miscarriage.Plasma levels of formaldehyde were significantly higher in women who were diagnosed with miscarriage than those who delivered at term and higher levels of formaldehyde was an independent risk factor for miscarriage, with higher levels being associated with higher risk of miscarriage.
Our objective was to describe patterns and predictors of sedentary behavior (sitting time) over 10 years among a large Canadian cohort. Data are from the Canadian Multicentre Osteoporosis Study, a prospective study of women and men randomly selected from the general population. Respondents reported socio-demographics, lifestyle behaviors and health outcomes in interviewer-administered questionnaires; weight and height were measured. Baseline data were collected between 1995 and 1997 (n = 9418; participation rate = 42%), and at 5- (n = 7648) and 10-year follow-ups (n = 5567). Total sitting time was summed across domain-specific questions at three time points and dichotomized into "low" (≤ 7 h/day) and "high" (> 7 h/day), based on recent meta-analytic evidence on time sitting and all-cause mortality. Ten-year sitting patterns were classified as "consistently high", "consistently low", "increased", "decreased", and "mixed". Predictors of sedentary behavior patterns were explored using chi-square tests, ANOVA and logistic regression. At baseline (mean age = 62.1 years ± 13.4) average sitting was 6.9 h/day; it was 7.0 at 5and 10-year follow-ups (p for trend = 0.12). Overall 23% reported consistently high sitting time, 22% consistently low sitting, 14% decreased sitting, 17% increased sitting with 24% mixed patterns. Consistently high sitters were more likely to be men, university educated, full-time employed, obese, and to report consistently low physical activity levels. This is one of the first population-based studies to explore patterns of sedentary behavior (multi-domain sitting) within men and women over years. Risk classification of sitting among many adults changed during follow-up. Thus, studies of sitting and health would benefit from multiple measures of sitting over time.
Domingo JL et al., 2017·Journal of Agricultural and Food Chemistry
Because of the important environmental presence and the potential human toxicity of per- and polyfluorinated alkyl substances (PFASs), in recent years the social and scientific interest in these compounds has notably increased. Special attention has been paid to perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), the most extensively investigated PFASs. Although human exposure to PFASs may occur through different pathways, dietary intake seems to be the main route of exposure to these compounds. In 2012, we published a wide revision on the state of the science regarding the concentrations of PFASs in foodstuffs, the human dietary exposure to these compounds, and their health risks. In the present review, we have updated the information recently (2011-2016) published in the scientific literature. As in our previous review, we have also observed considerable differences in the PFASs detected-and their concentrations-in the food items analyzed in samples from a number of regions and countries. However, fish and other seafood seem to be the food group in which more PFASs are detected and where the concentrations of these compounds are higher. On the basis of the recommendations of the EFSA on the maximum dietary intakes of PFOS and PFOA, human health risks would not be of concern for nonoccupationally exposed populations, at least in the very limited countries for which recent data are available.
Amoako AA et al., 2017·Advances in experimental medicine and biology
The periconception period starts 6 months before conception and lasts until the tenth week of gestation. In this chapter, we will focus on epigenetic modifications to DNA and gene expression within this period and during assisted reproduction. There are two critical times during the periconception window when significant epigenetic 'reprogramming' occur: one during gametogenesis and another during the pre-implantation embryonic stage. Furthermore, assisted conception treatments, laboratory protocols and culture media can affect the embryo development and birth weights in laboratory animals. There is, however, an ongoing debate as to whether epigenetic changes in humans, causing embryo mal-development, placenta dysfunction and birth defects, result from assisted reproductive technologies or are consequences of pre-existing medical and/or genetic conditions in the parents. The periconception period starts from ovarian folliculogenesis, through resumption of oogenesis, fertilisation, peri-implantation embryo development, embryogenesis until the end of organogenesis. In men, it is the period from spermatogenesis to epididymal sperm storage and fertilisation. Gametes and developing embryos are sensitive to environmental factors during this period, and epigenetic modifications can occur in response to adverse lifestyles and environmental factors. We now know that lifestyle factors such as advanced parentage age, obesity or undernutrition, smoking, excessive alcohol and caffeine intake and recreational drugs used during gamete production and embryogenesis could induce epigenetic alterations, which could impact adversely on pregnancy outcomes and health of the offspring. Furthermore, these can also result in a permanent and irreversible effect in a dose-dependent manner, which can be passed on to the future generations.
Nutrition and Metabolic Health · Blood Sugar and Insulin
Alvarado JL et al., 2016·Biomed Res Int·
Open Access
Delphinidin anthocyanins have previously been associated with the inhibition of glucose absorption. Blood glucose lowering effects have been ascribed to maqui berry (Aristotelia chilensis) extracts in humans after boiled rice consumption. In this study, we aimed to explore whether a standardized delphinidin-rich extract from maqui berry (Delphinol) affects glucose metabolism in prediabetic humans based on glycemia and insulinemia curves obtained from an oral glucose tolerance test (OGTT) after a challenge with pure glucose. Volunteers underwent four consecutive OGTTs with at least one week washout period, in which different doses of Delphinol were administered one hour before glucose intake. Delphinol significantly and dose-dependently lowered basal glycemia and insulinemia. Lower doses delayed postprandial glycemic and insulinemic peaks, while higher doses reversed this tendency. Glycemia peaks were dose-dependently lowered, while insulinemia peaks were higher for the lowest dose and lower for other doses. The total glucose available in blood was unaffected by treatments, while the total insulin availability was increased by low doses and decreased by the highest dose. Taken together, these open exploratory results suggest that Delphinol could be acting through three possible mechanisms: by inhibition of intestinal glucose transporters, by an incretin-mediated effect, or by improving insulin sensitivity.
Sleep and Circadian Health · Shift Work and Light Exposure
Goldstein CA et al., 2016·Current Sleep Medicine Reports
Adequate sleep is crucial for general health and wellbeing. Although the neuronal control of the reproductive axis and sleep-generating neurons share an anatomical location, little is known regarding the impact of sleep and circadian disruption on fertility in women. Animal models have established clear circadian control of the pre-ovulatory luteinizing hormone surge. Additionally, disruption of the circadian timing system by exposure to abnormal light-dark cycles or mutations of core clock genes results in diminished reproductive capacity in animals. Abnormalities in menstruation, fertility, and early pregnancy maintenance in female shift workers provide evidence for a role of circadian rhythms in the reproductive health of women. Reproductive hormones may modify sleep, and the relationship is bidirectional such that sleep disruption may alter the profile of reproductive hormone secretion. Therefore, sleep, apart from its circadian timing, may also have relevance in attaining pregnancy. Additionally, infertility is associated with psychological distress which may result in poor quality sleep. The interaction between psychological distress and disturbed sleep in reproduction has garnered minimal attention and may be a crucial factor to consider during the evaluation and treatment of infertility. This work reviews animal models and evidence in women that suggest a role for sleep and circadian rhythms in reproductive health and reveals areas that require future investigation.
Purdue-Smithe AC et al., 2016·The American journal of clinical nutrition·
Open Access
Clinically significant premenstrual syndrome (PMS) affects 15-20% of premenopausal women, substantially reducing quality of life. Women with PMS often are counseled to minimize caffeine intake, although only limited evidence supports this recommendation. We evaluated the association between total caffeine, coffee, and tea intake and the development of PMS in a case-control study nested within the prospective Nurses' Health Study II. All participants were free from PMS at baseline (1991). PMS cases reported a new clinician-made diagnosis of PMS on biennial questionnaires between 1993 and 2005, and then confirmed symptom timing and moderate-to-severe impact and severity of symptoms with the use of a retrospective questionnaire (n = 1234). Controls did not report PMS and confirmed experiencing no symptoms or few mild symptoms with limited personal impact (n = 2426). Caffeine, coffee, and tea intake was measured by food-frequency questionnaires every 4 y, and data on smoking, body weight, and other factors were updated every 2-4 y. Logistic regression was used to evaluate the associations of total caffeine intake and frequency of coffee and tea consumption with PMS. After adjustment for age, smoking, and other factors, total caffeine intake was not associated with PMS. The OR comparing women with the highest (quintile median = 543 mg/d) to the lowest (quintile median = 18 mg/d) caffeine intake was 0.79 (95% CI: 0.61, 1.04; P-trend = 0.31). High caffeinated coffee intake also was not associated with risk of PMS or specific symptoms, including breast tenderness (OR for ≥4 cups/d compared with <1/mo: 0.73; 95% CI: 0.48, 1.12; P-trend = 0.44). Our findings suggest that caffeine intake is not associated with PMS, and that current recommendations for women to reduce caffeine intake may not help prevent the development of PMS.
Schliep KC et al., 2016·Am J Clin Nutr·
Open Access
Clinicians often recommend limiting caffeine intake while attempting to conceive; however, few studies have evaluated the associations between caffeine exposure and menstrual cycle function, and we are aware of no previous studies assessing biological dose via well-timed serum measurements. We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race. Participants (n = 259) were followed for ≤2 menstrual cycles and provided fasting blood specimens ≤8 times/cycle. Linear mixed models were used to estimate associations between serum caffeine biomarkers and geometric mean reproductive hormones, whereas Poisson regression was used to assess risk of sporadic anovulation. The highest compared with the lowest serum caffeine tertile was associated with lower total testosterone [27.9 ng/dL (95% CI: 26.7, 29.0 ng/dL) compared with 29.1 ng/dL (95% CI: 27.9, 30.3 ng/dL), respectively] and free testosterone [0.178 ng/mL (95% CI: 0.171, 0.185 ng/dL) compared with 0.186 ng/mL (95% CI: 0.179, 0.194 ng/dL), respectively] after adjustment for age, race, percentage of body fat, daily vigorous exercise, perceived stress, depression, dietary factors, and alcohol intake. The highest tertiles compared with the lowest tertiles of caffeine and paraxanthine were also associated with reduced risk of anovulation [adjusted RRs (aRRs): 0.39 (95% CI: 0.18, 0.87) and 0.40 (95% CI: 0.18, 0.87), respectively]. Additional adjustment for self-reported coffee intake did not alter the reproductive hormone findings and only slightly attenuated the results for serum caffeine and paraxanthine and anovulation. Although reductions in the concentrations of total testosterone and free testosterone and decreased risk of anovulation were greatest in Asian women, there was no indication of effect modification by race. Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women.
Environmental Exposures · Personal Care and Household Products
Pan S et al., 2016·Environmental Health Perspectives
Xenoestrogens are synthetic compounds that mimic endogenous estrogens by binding to and activating estrogen receptors. Exposure to estrogens and to some xenoestrogens has been associated with cell proliferation and an increased risk of breast cancer. Despite evidence of estrogenicity, parabens are among the most widely used xenoestrogens in cosmetics and personal-care products and are generally considered safe. However, previous cell-based studies with parabens do not take into account the signaling cross-talk between estrogen receptor α (ERα) and the human epidermal growth factor receptor (HER) family.
We investigated the hypothesis that the potency of parabens can be increased with HER ligands, such as heregulin (HRG).
The effects of HER ligands on paraben activation of c-Myc expression and cell proliferation were determined by real-time polymerase chain reaction, Western blots, flow cytometry, and chromatin immunoprecipitation assays in ERα- and HER2-positive human BT-474 breast cancer cells.
Butylparaben (BP) and HRG produced a synergistic increase in c-Myc mRNA and protein levels in BT-474 cells. Estrogen receptor antagonists blocked the synergistic increase in c-Myc protein levels. The combination of BP and HRG also stimulated proliferation of BT-474 cells compared with the effects of BP alone. HRG decreased the dose required for BP-mediated stimulation of c-Myc mRNA expression and cell proliferation. HRG caused the phosphorylation of serine 167 in ERα. BP and HRG produced a synergistic increase in ERα recruitment to the c-Myc gene.
Our results show that HER ligands enhanced the potency of BP to stimulate oncogene expression and breast cancer cell proliferation in vitro via ERα, suggesting that parabens might be active at exposure levels not previously considered toxicologically relevant from studies testing their effects in isolation.
Pan S, Yuan C, Tagmount A, Rudel RA, Ackerman JM, Yaswen P, Vulpe CD, Leitman DC. 2016. Parabens and human epidermal growth factor receptor ligand cross-talk in breast cancer cells. Environ Health Perspect 124:563-569; http://dx.doi.org/10.1289/ehp.1409200.
Ziv-Gal A et al., 2016·Reproductive toxicology (Elmsford, N.Y.)
During the menopausal transition, a woman's reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45-54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)=1.07-1.96), hot flashes in the past 30days (OR=1.43; 95%CI=1.04-1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06-2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women.
Vitamin D is associated with markers of ovarian reserve in women of advanced reproductive age and
in vitro
studies suggest that vitamin D may influence anti‐mullerian hormone (AMH). Higher vitamin D levels are also associated with improved IVF outcomes in some studies. However, less is understood regarding associations with ovarian reserve or time to pregnancy among younger women or women without a history of infertility. Our purpose was to assess the relationships between vitamin D and AMH and fecundability among women with proven fecundity.
Secondary analysis of the EAGeR Trial, a multicenter, block‐randomized, double‐blind, placebo‐controlled clinical trial to evaluate the effect of preconception‐initiated daily low dose aspirin on reproductive outcomes in women with a history of pregnancy loss and normal fecundity. Participants were attempting pregnancy, aged 18–40 years, with 1–2 prior pregnancy losses and no history of infertility. We assessed 25‐OH vitamin D and AMH in serum at baseline (not pregnant) among 1185 women. AMH levels were log‐transformed for normality. Linear regression was used to estimate associations between vitamin D and AMH concentrations adjusting for age, body mass index, race, season, physical activity, and number of prior losses. Time to hCG detected pregnancy was assessed using Cox proportional hazard regression models for discrete survival time, accounting for left truncation and right censoring, to estimate fecundability odds ratios (FOR), adjusting for the same factors. A total of 163 women (13.8%) had deficient vitamin D levels (<20 ng/mL). Overall, vitamin D levels were not associated with AMH (percent change −1.6, 95% confidence interval [CI] −5.3%, 2.3% per 10 ng/mL). Vitamin D deficiency was also not associated with AMH (deficient: adjusted geometric mean AMH 2.51, 95% CI 2.20, 2.85 vs. inadequate/sufficient: 2.74, 95% CI 2.60, 2.89). There also were no significant associations observed between overall vitamin D levels or deficiency and fecundability (FOR 1.09, 95% CI 0.84, 1.42 comparing deficient vs. inadequate/sufficient) after adjustment. Vitamin D was not associated with AMH, time to pregnancy, or fecundability among women with proven fecundity. These results suggest that vitamin D is not associated with ovarian reserve or fecundability and that vitamin D supplementation may offer little clinical benefit for improving markers of ovarian reserve and fecundity.
Support or Funding Information
Intramural Research Program, DIPHR, NICHD, NIH
We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk.
Evidence is growing that the equilibrium between reactive oxygen species and antioxidants plays a vital role in women's reproductive health. The objective of this study was to evaluate variations in serum antioxidant concentrations across the menstrual cycle and associations between antioxidants and reproductive hormones and anovulation among healthy women. The BioCycle Study, a prospective cohort, followed 259 women aged 18-44 y for up to 2 menstrual cycles. Serum fat-soluble vitamin and micronutrient (α-tocopherol, γ-tocopherol, retinol, lutein, lycopene, and β-carotene), ascorbic acid, and reproductive hormone concentrations were measured 5-8 times/cycle. We used weighted linear mixed models to assess associations between antioxidants and hormone concentrations, after adjustment for age, race, body mass index, parity, sleep, pain medication use, total energy intake, concurrent hormones, serum cholesterol, F2-isoprostanes, and other antioxidants. Generalized linear models were used to identify associations with anovulation. Serum antioxidant concentrations varied across the menstrual cycle. Retinol and α-tocopherol were associated with higher estradiol [RR: 1.00 pg/mL (95% CI: 0.67, 1.34 pg/mL); RR: 0.02 pg/mL (95% CI: 0.003, 0.03 pg/mL), respectively] and testosterone [RR: 0.61 ng/dL (95% CI: 0.44, 0.78 ng/dL); RR: 0.01 ng/dL (95% CI: 0.001, 0.01 ng/dL), respectively]. Ascorbic acid was associated with higher progesterone (RR: 0.15 ng/mL; 95% CI: 0.05, 0.25 ng/mL) and with lower follicle-stimulating hormone (RR: -0.06 mIU/mL; 95% CI: -0.09, -0.03 mIU/mL). The ratio of αto γ-tocopherol was associated with an increased risk of anovulation (RR: 1.03; 95% CI: 1.01, 1.06). These findings shed new light on the intricate associations between serum antioxidants and endogenous hormones in healthy premenopausal women and support the hypothesis that concentrations of serum vitamins affect steroidogenesis even after adjustment for oxidative stress.
Trivedi MS et al., 2015·Nutr Metab (Lond)·
Open Access
Casein-free, gluten-free diets have been reported to mitigate some of the inflammatory gastrointestinal
and behavioral traits associated with autism, but the mechanism for this palliative effect has not been elucidated. We
recently showed that the opioid peptide beta-casomorphin-7, derived from bovine (bBCM7) milk, decreases cysteine
uptake, lowers levels of the antioxidant glutathione (GSH) and decreases the methyl donor S-adenosylmethionine
(SAM) in both Caco-2 human GI epithelial cells and SH-SY5Y human neuroblastoma cells. While human breast milk
can also release a similar peptide (hBCM-7), the bBCM7 and hBCM-7 vary greatly in potency; as the bBCM-7 is highly
potent and similar to morphine in it's effects. Since SAM is required for DNA methylation, we wanted to further
investigate the epigenetic effects of these food-derived opioid peptides. In the current study the main objective was
to characterize functional pathways and key genes responding to DNA methylation effects of food-derived opioid
peptides. SH-SY5Y neuroblastoma cells were treated with 1 μM hBCM7 and bBCM7 and RNA and DNA were isolated
after 4 h with or without treatment. Transcriptional changes were assessed using a microarray approach and CpG
methylation status was analyzed at 450,000 CpG sites. Functional implications from both endpoints were evaluated via
Ingenuity Pathway Analysis 4.0 and KEGG pathway analysis was performed to identify biological interactions between
transcripts that were significantly altered at DNA methylation or transcriptional levels (p < 0.05, FDR <0.1). Here we show that hBCM7 and bBCM7, as well as morphine, cause epigenetic changes affecting gene
pathways related to gastrointestinal disease and inflammation. These epigenetic consequences exhibited the same
potency order as opiate inhibition of cysteine uptake insofar as hBCM7 was less potent than bBCM7, which was less
potent than morphine. Our findings indicate that epigenetic effects of milk-derived opiate peptides may contribute to GI
dysfunction and inflammation in sensitive individuals. While the current study was performed using SH-SY5Y
neuronal cellular models, similar actions on other cells types might combine to cause symptoms of intolerance. These
actions may provide a potential contributing mechanism for the beneficial effects of a casein-free diet in alleviating
gastrointestinal symptoms in neurological conditions including autism and other conditions. Lastly, our study also
contributes to the evolving awareness of a “gut-brain connection”.
Keywords: Epigenetics, Gluten free casein free diet, Autism, Glutathione, Gastrointestinal, Inflammation
Stevenson M et al., 2015·J Occup Environ Med·
Open Access
Adverse health outcomes related to exposure to endocrine disrupting chemicals, including increased incidences of coronary heart disease, prostate and testicular cancers, and congenital disabilities, have been reported in firefighters or their offspring. We, therefore, measured the estrogenic and antiestrogenic activity of extracts of used firefighter gear to assess exposure to these agents. Extracts and known chemical contaminants were examined for estrogenicity and antiestrogenicity in yeast cells expressing the estrogen receptor. Most extracts of used gear and phthalate diesters detectable on this gear displayed strong antiestrogenic effects. Notably, new glove and hood extracts showed significant estrogenic activity. Overall, our data suggest that firefighters are exposed to both estrogenic and antiestrogenic agents, possibly phthalates that may lead to health risks observed in this occupation as a result of perturbation of hormone homeostasis.
Choi BO et al., 2015·Korean journal of family medicine
Although several risk factors associated with reduced age at natural menopause (ANM) have been investigated, the results are inconsistent. Excessive stress, which leads to elevation of stress hormones, can also negatively affect reproductive ability, including by accelerating menopause. However, a direct association between stress level and ANM has not yet been demonstrated. Therefore, the object of this study was to investigate the association between stress level and ANM in Korean women. Study participants were Korean women between 40 and 70 years old who were in natural menopause during the 5th Korean National Health and Nutrition Examination Survey (n=3,176). The level of stress in daily life was estimated based on data from the mental health topics of the survey. We used the t-test and one-way analysis of variance to analyze the correlation between stress level and ANM. Regression (β) coefficients calculated by multiple regression analysis were used to estimate various factors affecting ANM. Women who experienced a high level of stress in daily life had a lower mean ANM than women with a low stress level (50.17±3.7 and 50.58±3.5 years, respectively), with a statistically significant correlation (P<0.05). This correlation was still observed after adjusting for age, body mass index, menstrual regularity, and personal income (P<0.05 for variables). In Korean women between 40 and 70 years of age who are in natural menopause, there is a statistically significant correlation between stress level and ANM. In particular, women who experience a high level of stress in daily life have reduced ANM.
Limited data are available from controlled studies on biomarkers of maternal vitamin B-12 status. We sought to quantify the effects of pregnancy and lactation on the vitamin B-12 status response to a known and highly controlled vitamin B-12 intake. As part of a 10-12 wk feeding trial, pregnant (26-29 wk gestation; n = 26), lactating (5 wk postpartum; n = 28), and control (nonpregnant, nonlactating; n = 21) women consumed vitamin B-12 amounts of ∼8.6 μg/d [mixed diet (∼6 μg/d) plus a prenatal multivitamin supplement (2.6 μg/d)]. Serum vitamin B-12, holotranscobalamin (bioactive form of vitamin B-12), methylmalonic acid (MMA), and homocysteine were measured at baseline and study-end. All participants achieved adequate vitamin B-12 status in response to the study dose. Compared with control women, pregnant women had lower serum vitamin B-12 (-21%; P = 0.02) at study-end, whereas lactating women had higher (P = 0.04) serum vitamin B-12 throughout the study (+26% at study-end). Consumption of the study vitamin B-12 dose increased serum holotranscobalamin in all reproductive groups (+16-42%; P ≤ 0.009). At study-end, pregnant (vs. control) women had a higher holotranscobalamin-to-vitamin B-12 ratio (P = 0.04) with ∼30% (vs. 20%) of total vitamin B-12 in the bioactive form. Serum MMA increased during pregnancy (+50%; P < 0.001) but did not differ by reproductive state at study-end. Serum homocysteine increased in pregnant women (+15%; P = 0.009) but decreased in control and lactating women (-16-17%; P < 0.001). Despite these changes, pregnant women had ∼20% lower serum homocysteine than the other 2 groups at study-end (P ≤ 0.02). Pregnancy and lactation alter vitamin B-12 status in a manner consistent with enhanced vitamin B-12 supply to the child. Consumption of the study vitamin B-12 dose (∼3 times the RDA) increased the bioactive form of vitamin B-12, suggesting that women in these reproductive states may benefit from vitamin B-12 intakes exceeding current recommendations. This trial was registered at clinicaltrials.gov as NCT01127022.
Cigarette smoking, one of the main causes of preventable morbidity and mortality, has a multitude of well-known side effects. The relationship between cigarette smoking and infertility has been studied for decades; however, large-scale, population-wide prospective studies are lacking. The majority of the current literature is in the form of retrospective studies focused on the effects of smoking on semen analyses. This article discusses the results of these studies and reviews the postulated mechanisms. The effects of smoking on assisted reproduction and in vitro fertilization outcomes are noted. The consequences of smoking while pregnant on future fertility as well as the outcomes of second-hand smoke are analyzed. The current evidence suggests that men should be advised to abstain from smoking in order to improve reproductive outcomes.
Traditional environmental risk factors in inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), were examined as part of the retrospective epidemiologic study conducted in Vukovar-Srijem County, north-eastern Croatia in 2010. The geographical variations in the frequency of IBD in Croatia have been observed, which is also the trend in the Central Eastern European region and Europe as a whole, indicating the influence of environmental and lifestyle factors. However, the data on the spread of environmental IBD risk factors are still limited. The purpose of this study was to analyse the traditional environmental risk factors in IBD on our cohort sample, including measles virus infection and vaccination (MMR vaccine-Mumps, Measles, Rubella), tonsillectomy, appendectomy, current and former cigarette smoking and use of oral contraceptives in women. This retrospective, case-control study was performed as a part of a wider epidemiologic study aimed at assessing the incidence, prevalence and clinical expression of IBD, in Vukovar-Srijem County ( population: 204,768; 2001), which is a lesser developed part of the continental Croatia that experienced deep demographic changes in the recent past. IBD patients were identified according to the hospital's patient records. There were 119 UC patients and 31 CD patients of a total of 150 patients in the cohort. A total of 150 individuals, volunteers, not having a diagnosis of IBD, ageand sex-matched, were used as the control group. Information on examined risk factors were obtained from all subjects in a previously conducted interview. Patients were contacted personally or by phone and interviewed by a gastroenterologist. There were no differences in the number of smokers, former smokers and non-smokers, between UC and CD patients and the controls, nor in the duration of smoking (years), in current smokers and ex-smokers. Only marginally significant longer time of non-smoking, in ex-smokers was found in IBD patients, compared to the controls, more pronounced in CD patients (p = 0.05). No difference was found in relation to tonsillectomy and risk of IBD. There was no difference in the number of female IBD patients and women from the controls using oral contraceptives. Duration (years) of oral contraceptives use was longer in women from the controls than in female IBD patients (p < 0.001). Frequency of appendectomy was the lowest in UC patients, compared to the controls and CD patients (3.4, 12.0 and 38.7%, respectively) (p < 0.001). No difference was found in relation to measles virus infection and risk of IBD. MMR vaccination rates were higher in CD patients (90.3%), compared to UC patients and the controls (74.8 and 67.3%, respectively) (p = 0.026). No association was found between smoking and tonsillectomy and risk of IBD. Our results do not support the idea of oral contraceptives use as a risk factor for IBD. Frequency of appendectomy was the lowest in UC patients, suggesting that appendectomy decreases the risk of UC, contributing the earlier results. MMR vaccination seemed to be associated with Crohn's disease. These results can add value to our understanding of the increasing incidence of IBD in Croatia and other Central Eastern European countries and can be introductory to future large-scale research.
Pfeiffer CM et al., 2015·The Journal of nutrition·
Open Access
Serum total folate consists mainly of 5-methyltetrahydrofolate (5-methylTHF). Unmetabolized folic acid (UMFA) may occur in persons consuming folic acid-fortified foods or supplements. We describe serum 5-methylTHF and UMFA concentrations in the US population ≥1 y of age by demographic variables and fasting time, stratified by folic acid-containing dietary supplement use. We also evaluate factors associated with UMFA concentrations >1 nmol/L. Serum samples from the cross-sectional NHANES 2007-2008 were measured for 5-methylTHF (n = 2734) and UMFA (n = 2707) by HPLC-tandem mass spectrometry. In supplement users compared with nonusers, we found significantly higher geometric mean concentrations of 5-methylTHF (48.4 and 30.7 nmol/L, respectively) and UMFA (1.54 and 0.794 nmol/L, respectively). UMFA concentrations were detectable (>0.3 nmol/L) in >95% of supplement users and nonusers, regardless of demographic or fasting characteristics; concentrations differed significantly by age and fasting time, but not by sex and race-ethnicity, both in supplement users and nonusers. The prevalence of UMFA concentrations >1 nmol/L was 33.2% overall and 21.0% in fasting (≥8 h) adults (≥20 y of age). Using multiple logistic regression analysis, UMFA concentrations >1 nmol/L were associated with being older, non-Hispanic black, nonfasting (<8 h), having smaller body surface area, higher total folic acid intake (diet and supplements), and higher red blood cell folate concentrations. In fasting adults, a decrease in the mean daily alcohol consumption was also associated with increased odds of UMFA concentrations >1 nmol/L. UMFA detection was nearly ubiquitous, and concentrations >1 nmol/L were largely but not entirely explained by fasting status and by total folic acid intake from diet and supplements. These new UMFA data in US persons ≥1 y of age provide much-needed information on this vitamer in a fortified population with relatively high use of dietary supplements.
Afeiche MC et al., 2014·The Journal of nutrition·
Open Access
Emerging literature suggests that men's diets may affect spermatogenesis as reflected in semen quality indicators, but literature on the relation between meat intake and semen quality is limited. Our objective was to prospectively examine the relation between meat intake and indicators of semen quality. Men in subfertile couples presenting for evaluation at the Massachusetts General Hospital Fertility Center were invited to participate in an ongoing study of environmental factors and fertility. A total of 155 men completed a validated food-frequency questionnaire and subsequently provided 338 semen samples over an 18-mo period from 2007-2012. We used linear mixed regression models to examine the relation between meat intake and semen quality indicators (total sperm count, sperm concentration, progressive motility, morphology, and semen volume) while adjusting for potential confounders and accounting for within-person variability across repeat semen samples. Among the 155 men (median age: 36.1 y; 83% white, non-Hispanic), processed meat intake was inversely related to sperm morphology. Men in the highest quartile of processed meat intake had, on average, 1.7 percentage units (95% CI: -3.3, -0.04) fewer morphologically normal sperm than men in the lowest quartile of intake (P-trend = 0.02). Fish intake was related to higher sperm count and percentage of morphologically normal sperm. The adjusted mean total sperm count increased from 102 million (95% CI: 80, 131) in the lowest quartile to 168 million (95% CI: 136, 207) sperm in the highest quartile of fish intake (P-trend = 0.005). Similarly, the adjusted mean percentages of morphologically normal sperm for men in increasing quartiles of fish intake were 5.9 (95% CI: 5.0, 6.8), 5.3 (95% CI: 4.4, 6.3), 6.3 (95% CI: 5.2, 7.4), and 7.5 (95% CI: 6.5, 8.5) (P-trend = 0.01). Consuming fish may have a positive impact on sperm counts and morphology, particularly when consumed instead of processed red meats.
Bentov Y et al., 2014·Clin Med�Insights�Reprod�Health·
Open Access
The age-related reduction in live-birth rate is attributed to a high rate of aneuploidy and follicle depletion. We showed in an animal model that treatment with Coenzyme Q10 (CoQ10) markedly improved reproductive outcome. The aim of this study was to compare the post-meiotic oocyte aneuploidy rate in in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) patients treated with CoQ10 or placebo.
We conducted a double blind placebo controlled randomized trial that included IVF-ICSI patients 35-43 years of age. The patients were treated with either 600 mg of CoQ10 or an equivalent number of placebo caps. We compared the post-meiotic aneuploidy rate using polar body biopsy (PBBX) and comparative genomic hybridization (CGH). According to the power calculation, 27 patients were needed for each arm.
Owing to safety concerns regarding the effects of polar body biopsy on embryo quality and implantation, the study was terminated before reaching the target number of participants. A total of 39 patients were evaluated and randomized (17 CoQ10, 22 placebo), 27 were given the study medication (12 CoQ10, 15 placebo), and 24 completed an IVF-ICSI cycle including PBBX and embryo transfer (10 CoQ10, 14 placebo). Average age, base line follicle stimulating hormone (FSH), peak estradiol and progesterone serum level, as well as the total number of human menopausal gonadotropin (hMG) units-did not differ between the groups. The rate of aneuploidy was 46.5% in the CoQ10 group compared to 62.8% in the control. Clinical pregnancy rate was 33% for the CoQ10 group and 26.7% for the control group.
No significant differences in outcome were detected between the CoQ10 and placebo groups. However, the final study was underpowered to detect a difference in the rate of aneuploidy.
To evaluate the association between physical activity (PA) across the menstrual cycle and reproductive function. The BioCycle Study (2005-2007) followed 259 healthy premenopausal women not using hormonal contraceptives for up to two menstrual cycles (N = 509 cycles). Serum leptin, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and testosterone were measured five to eight times per cycle. Linear mixed models were used to estimate the effect of past-week PA (measured four times during each cycle) on hormone levels. Past-week PA was categorized into tertiles based on metabolic equivalent of task hours per week (cut-points were 15.3 and 35.7). Risk ratios for sporadic anovulation were estimated using generalized linear models. Analyses adjusted for habitual PA (assessed at baseline), body mass index, race, age, and perceived stress. Linear mixed models used inverse probability weights to control for concurrent reproductive hormones and caloric intake. High past-week PA was inversely associated with leptin (-6.6%; 95% confidence interval, -10.6 to -2.5) and luteal phase progesterone (-22.1%; -36.2 to -4.7) as compared with low past-week PA. High past-week PA was not significantly associated with sporadic anovulation (adjusted risk ratio, 1.5; 0.6 to 3.4). High levels of PA were modestly associated with changes in select hormones but not sporadic anovulation among moderate to highly active premenopausal women.
Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal balance and may exert adverse consequences on humans. The male reproductive system may be susceptible to the effects of such environmental toxicants. This review discusses the recent progress in scientific data mainly from epidemiology studies on the associations between EDCs and male reproductive health and our understanding of possible mechanisms associated with the effects of EDCs on male reproductive health. Finally, the review provides recommendations on future research to enhance our understanding of EDCs and male reproductive health. The review highlights the need for (1) well-defined longitudinal epidemiology studies, with appropriately designed exposure assessment to determine potential causal relationships; (2) chemical and biochemical approaches aimed at a better understanding of the mechanism of action of xenoestrogens with regard to low-dose effects, and assessment of identify genetic susceptibility factors associated with the risk of adverse effects following exposure to EDCs.
Pollack AZ et al., 2013·Reprod Toxicol·
Open Access
There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18-44 years were recruited into an operative cohort, along with 131 similarly aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research.
Ruth MR et al., 2013·J Animal Sci Biotechnol·
Open Access
The intestine and the gut-associated lymphoid tissue (GALT) are essential components of whole body immune defense, protecting the body from foreign antigens and pathogens, while allowing tolerance to commensal bacteria and dietary antigens. The requirement for protein to support the immune system is well established. Less is known regarding the immune modifying properties of individual amino acids, particularly on the GALT. Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake, but the availability of specific dietary amino acids (in particular glutamine, glutamate, and arginine, and perhaps methionine, cysteine and threonine) are essential to optimizing the immune functions of the intestine and the proximal resident immune cells. These amino acids each have unique properties that include, maintaining the integrity, growth and function of the intestine, as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers, specific T cell functions, and the secretion of IgA by lamina propria cells. Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters. Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.
Filiberto AC et al., 2013·Fertil Steril·
Open Access
To assess the association of total isoflavone intake with ovulatory function, including sporadic anovulation in healthy premenopausal women.
Prospective cohort study.
University. PATIENT(S): Participants included 259 healthy regularly menstruating women aged 18-44 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum concentrations of E2, free E2, P, LH, FSH, and SHBG and sporadic anovulation in healthy premenopausal women. RESULT(S): Isoflavone intake was not associated with E2, free E2, P, LH, and FSH concentrations. Consumption in the highest quartile (Q4: 1.6-78.8 mg/d) was significantly associated with greater SHBG concentrations (β = 0.09; 95% confidence interval [CI] 0.02-0.16), compared with the first quartile (Q1: 0.0-0.3 mg/d). CONCLUSION(S): Isoflavone intake was not associated with sporadic anovulation (Q4 vs. Q1: odds ratio 0.87, 95% CI 0.32-1.66). Dietary isoflavone intake among young premenopausal women was not related to sex hormone concentrations or anovulation, but was associated with minimally increased SHBG concentrations. These results suggest potential endocrine effects with no subsequent effects on ovulation, easing concerns regarding their impacts on fertility.
Nutrition and Metabolic Health · Body Weight and Composition
Increasing 25-hydroxyvitamin D serum levels can prevent a wide range of diseases. There is a concern about increasing kidney stone risk with vitamin D supplementation. We used GrassrootsHealth data to examine the relationship between vitamin D status and kidney stone incidence. The study included 2012 participants followed prospectively for a median of 19 months. Thirteen individuals self-reported kidney stones during the study period. Multivariate logistic regression was applied to assess the association between vitamin D status and kidney stones. We found no statistically significant association between serum 25-hydroxyvitamin D and kidney stones (P = .42). Body mass index was significantly associated with kidney stone risk (odds ratio = 3.5; 95% confidence interval = 1.1, 11.3). We concluded that a serum 25-hydroxyvitamin D level of 20 to 100 nanograms per milliliter has no significant association with kidney stone incidence.
Imbard A et al., 2013·International journal of environmental research and public health
Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.
Langsetmo L et al., 2013·J Clin Endocrinol Metab·
Open Access
Calcium and vitamin D are recommended for bone health, but there are concerns about adverse risks. Some clinical studies suggest that calcium intake may be cardioprotective, whereas others report increased risk associated with calcium supplements. Both low and high serum levels of 25-hydroxyvitamin D have been associated with increased mortality. The purpose of this study was to determine the association between total calcium and vitamin D intake and mortality and heterogeneity by source of intake. The Canadian Multicentre Osteoporosis Study cohort is a population-based longitudinal cohort with a 10-year follow-up (1995-2007). This study included randomly selected community-dwelling men and women. A total of 9033 participants with nonmissing calcium and vitamin D intake data and follow-up were studied. Exposure: Total calcium intake (dairy, nondairy food, and supplements) and total vitamin D intake (milk, yogurt, and supplements) were recorded. Outcome: The outcome variable was all-cause mortality. There were 1160 deaths during the 10-year period. For women only, we found a possible benefit of higher total calcium intake, with a hazard ratio of 0.95 (95% confidence interval, 0.89-1.01) per 500-mg increase in daily calcium intake and no evidence of heterogeneity by source; use of calcium supplements was also associated with reduced mortality, with hazard ratio of 0.78 (95% confidence interval, 0.66-0.92) for users vs nonusers with statistically significant reductions remaining among those with doses up to 1000 mg/d. These associations were not modified by levels of concurrent vitamin D intake. No definitive associations were found among men. Calcium supplements, up to 1000 mg/d, and increased dietary intake of calcium may be associated with reduced risk of mortality in women. We found no evidence of mortality benefit or harm associated with vitamin D intake.
Hansen SO et al., 2013·Eur J Obstet Gynecol Reprod Biol·
To review the literature on the effects of diet on endometriosis and dysmenorrhoea. A systematic search for trials investigating a relationship between diet and endometriosis/dysmenorrhoea was undertaken, and 23 studies were included in this review. Data on the relationship between diet and endometriosis were limited to 12 trials, three of which were animal studies, resulting in a total of 74,708 women. One large study (n=70,709) found a relatively strong association between endometriosis and trans-fatty acid consumption, and a lower risk of endometriosis with increased consumption of long-chain omega-3 fatty acids. The latter finding was also supported by smaller studies. No further dietary recommendations for reducing the risk of endometriosis were possible, and results for intake of vegetable, fibre and fruit were equivocal. The relationship between diet and dysmenorrhoea was investigated in 11 trials with different designs, including a total of 1433 women. Intake of fish oil seemed to reduce dysmenorrhoea. The literature on endometriosis and dysmenorrhoea in relation to diet is sparse, yielding equivocal results on specific elements. Overall, however, the literature suggests that specific types of dietary fats are associated with endometriosis and/or dysmenorrhoea, thereby indicating that there may be modifiable risk factors. Further research is recommended on both subjects.
Kerdivel G et al., 2013·International Journal of Endocrinology
In all vertebrate species, estrogens play a crucial role in the development, growth, and function of reproductive and nonreproductive tissues. A large number of natural or synthetic chemicals present in the environment and diet can interfere with estrogen signaling; these chemicals are called endocrine disrupting chemicals (EDCs) or xenoestrogens. Some of these compounds have been shown to induce adverse effects on human and animal health, and some compounds are suspected to contribute to diverse disease development. Because xenoestrogens have varying sources and structures and could act in additive or synergistic effects when combined, they have multiple mechanisms of action. Consequently, an important panel of in vivo and in vitro bioassays and chemical analytical tools was used to screen, evaluate, and characterize the potential impacts of these compounds on humans and animals. In this paper, we discuss different molecular actions of some of the major xenoestrogens found in food or the environment, and we summarize the current models used to evaluate environmental estrogens.
Total daily intakes of diethyl phthalate (DEP), di(n-butyl) phthalate (DnBP), di(isobutyl) phthalate (DiBP), butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) were calculated from phthalate metabolite levels measured in the urine of 431 Danish children between 3 and 6 years of age. For each child the intake attributable to exposures in the indoor environment via dust ingestion, inhalation and dermal absorption were estimated from the phthalate levels in the dust collected from the child's home and daycare center. Based on the urine samples, DEHP had the highest total daily intake (median: 4.42 µg/d/kg-bw) and BBzP the lowest (median: 0.49 µg/d/kg-bw). For DEP, DnBP and DiBP, exposures to air and dust in the indoor environment accounted for approximately 100%, 15% and 50% of the total intake, respectively, with dermal absorption from the gas-phase being the major exposure pathway. More than 90% of the total intake of BBzP and DEHP came from sources other than indoor air and dust. Daily intake of DnBP and DiBP from all exposure pathways, based on levels of metabolites in urine samples, exceeded the Tolerable Daily Intake (TDI) for 22 and 23 children, respectively. Indoor exposures resulted in an average daily DiBP intake that exceeded the TDI for 14 children. Using the concept of relative cumulative Tolerable Daily Intake (TDI(cum)), which is applicable for phthalates that have established TDIs based on the same health endpoint, we examined the cumulative total exposure to DnBP, DiBP and DEHP from all pathways; it exceeded the tolerable levels for 30% of the children. From the three indoor pathways alone, several children had a cumulative intake that exceeded TDI(cum). Exposures to phthalates present in the air and dust indoors meaningfully contribute to a child's total intake of certain phthalates. Such exposures, by themselves, may lead to intakes exceeding current limit values.
Braun JM et al., 2013·Current Opinion in Pediatrics
Phthalates are multifunctional chemicals used in personal care products, medications, and plastics. We reviewed the epidemiological literature examining the relationship between early life phthalate exposure and pediatric health outcomes.
Five studies from Asia, Europe, and the United States suggest that childhood exposure to di-2-ethylhexyl phthalate (DEHP) and butylbenzyl phthalate (BBzP) may increase the risk of allergic diseases including asthma and eczema. Six studies from four different prospective cohorts report that gestational BBzP, DEHP, di-butyl phthalate (DBP), and di-ethyl phthalate (DEP) exposures are associated with alterations in infant/toddler physical development as well as parent-reported externalizing, internalizing, and autistic-like child behavior. However, there are inconsistencies related to the specific phthalates and behavioral domains. Two small studies report shorter anogenital distance among male infants with higher gestational phthalate exposure.
Several epidemiological studies suggest fetal and childhood exposure to some phthalates may perturb normal development, with several studies consistently reporting increased risk of allergic diseases with DEHP and BBzP exposure. Although anticipatory guidance is not evidence-based at this time, providers can counsel concerned patients to reduce phthalate exposures in order to protect the developing fetus and child from potential adverse health outcomes.
Buck Louis GM et al., 2013·Fertil Steril·
Open Access
To assess in utero exposures and the odds of an endometriosis diagnosis.
Matched cohort design.
Fourteen participating clinical centers in geographically defined areas in Utah and California. PATIENT(S): Operative cohort comprised 473 women undergoing laparoscopy/laparotomy, and an ageand residence-matched population cohort comprising 127 women undergoing pelvic magnetic resonance imaging (MRI), 2007-2009. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Women completed standardized interviews before surgery or MRI regarding in utero exposures: mothers' lifestyle during the index pregnancy, and the index woman's gestation and birth size. Endometriosis was defined as visually confirmed disease in the operative cohort, and MRI visualized disease in the population cohort. The odds of an endometriosis diagnosis and corresponding 95% confidence intervals (CI) were estimated for each exposure by cohort using logistic regression and adjusting for current smoking, age at menarche, body mass index, and study site. RESULT(S): Endometriosis was diagnosed in 41% and 11% of women in the operative and population cohorts, respectively. In the primary analysis, adjust odds ratios (AORs) were elevated for maternal vitamin usage (1.27; 95% CI, 0.85-1.91), maternal cigarette smoking (1.16; 95% CI = 0.61-2.24), and low birth weight (1.1; 95% CI, 0.92-1.32). Reduced odds were observed for maternal usage of caffeine (0.99; 95% CI, 0.64-1.54), alcohol (0.82; 95% CI, 0.35-1.94), paternal cigarette smoking (0.72; 95% CI, 0.43-1.19), and preterm delivery (0.98; 95% CI, 0.47-2.03). Sensitivity analyses mostly upheld the primary results except for a decreased AOR for preterm birth (0.41; 95% CI, 0.18-0.94) when restricting to visualized and histologically confirmed endometriosis in the operative cohort. CONCLUSION(S): In utero exposures were not statistically significantly associated with the odds of an endometriosis diagnosis in either cohort.
Marques-Pinto A et al., 2013·Endocrine connections
Over recent decades, epidemiological studies have been reporting worrisome trends in the incidence of human infertility rates. Extensive detection of industrial chemicals in human serum, seminal plasma and follicular fluid has led the scientific community to hypothesise that these compounds may disrupt hormonal homoeostasis, leading to a vast array of physiological impairments. Numerous synthetic and natural substances have endocrine-disruptive effects, acting through several mechanisms. The main route of exposure to these chemicals is the ingestion of contaminated food and water. They may disturb intrauterine development, resulting in irreversible effects and may also induce transgenerational effects. This review aims to summarise the major scientific developments on the topic of human infertility associated with exposure to endocrine disruptors (EDs), integrating epidemiological and experimental evidence. Current data suggest that environmental levels of EDs may affect the development and functioning of the reproductive system in both sexes, particularly in foetuses, causing developmental and reproductive disorders, including infertility. EDs may be blamed for the rising incidence of human reproductive disorders. This constitutes a serious public health issue that should not be overlooked. The exposure of pregnant women and infants to EDs is of great concern. Therefore, precautionary avoidance of exposure to EDs is a prudent attitude in order to protect humans and wildlife from permanent harmful effects on fertility.
Environmental Exposures · Radiation and Electromagnetic Exposure
Stone MB et al., 2013·Environ Health Perspect·
Open Access
Above-ground and underground nuclear weapon detonation at the Nevada Test Site (1951-1992) has resulted in radioiodine exposure for nearby populations. Although the long-term effect of environmental radioiodine exposure on thyroid disease has been well studied, little is known regarding the effect of childhood radioiodine exposure on subsequent fertility. We investigated early childhood thyroid radiation exposure from nuclear testing fallout (supplied predominantly by radioactive isotopes of iodine) and self-reported lifetime incidence of male or female infertility or sterility. Participants were members of the 1965 Intermountain Fallout Cohort, schoolchildren at the time of exposure who were reexamined during two subsequent study phases to collect dietary and reproductive histories. Thyroid radiation exposure was calculated via an updated dosimetry model. We used multivariable logistic regression with robust sandwich estimators to estimate odds ratios for infertility, adjusted for potential confounders and (in separate models) for a medically confirmed history of thyroid disease. Of 1,389 participants with dosimetry and known fertility history, 274 were classified as infertile, including 30 classified as sterile. Childhood thyroid radiation dose was possibly associated with infertility [adjusted odds ratio (AOR) = 1.17; 95% CI: 0.82, 1.67 and AOR = 1.35; 95% CI: 0.96, 1.90 for the middle and upper tertiles vs. the first tertile of exposure, respectively]. The odds ratios were attenuated (AOR = 1.08; 95% CI: 0.75, 1.55 and AOR = 1.29; 95% CI: 0.91, 1.83 for the middle and upper tertiles, respectively) after adjusting for thyroid disease. There was no association of childhood radiation dose and sterility. Our findings suggest that childhood radioiodine exposure from nuclear testing may be related to subsequent adult infertility. Further research is required to confirm this.
Environmental chemicals may be associated with endometriosis. No published research has focused on the possible role of perfluorochemicals (PFCs) despite their widespread presence in human tissues. We formulated two samples. The first was an operative sample comprising 495 women aged 18-44 years scheduled for laparoscopy/laparotomy at one of 14 participating clinical sites in the Salt Lake City or San Francisco area, 2007-2009. The second was a population-based sample comprising 131 women matched to the operative sample on age and residence within a 50-mile radius of participating clinics. Interviews and anthropometric assessments were conducted at enrollment, along with blood collection for the analysis of nine PFCs, which were quantified using liquid chromatography-tandem mass spectrometry. Endometriosis was defined based on surgical visualization (in the operative sample) or magnetic resonance imaging (in the population sample). Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for each PFC (log-transformed), adjusting for age and body mass index, and then parity. Serum perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17-3.06]) and perfluorononanoic acid (2.20 [1.02-4.75]) were associated with endometriosis in the operative sample; findings were moderately attenuated with parity adjustment (1.62 [0.99-2.66] and 1.99 [0.91-4.33], respectively). Perfluorooctane sulfonic acid (1.86 [1.05-3.30]) and PFOA (2.58 [1.18-5.64]) increased the odds for moderate/severe endometriosis, although the odds were similarly attenuated with parity adjustment (OR = 1.50 and 1.86, respectively). Select PFCs were associated with an endometriosis diagnosis. These associations await corroboration.
We tested the hypothesis that 75 g of whole-shelled walnuts/day added to the Western-style diet of healthy young men would beneficially affect semen quality. A randomized, parallel two-group dietary intervention trial with single-blind masking of outcome assessors was conducted with 117 healthy men, age 21-35 yr old, who routinely consumed a Western-style diet. The primary outcome was improvement in conventional semen parameters and sperm aneuploidy from baseline to 12 wk. Secondary endpoints included blood serum and sperm fatty acid (FA) profiles, sex hormones, and serum folate. The group consuming walnuts (n = 59) experienced improvement in sperm vitality, motility, and morphology, but no change was seen in the group continuing their usual diet but avoiding tree nuts (n = 58). Comparing differences between the groups from baseline, significance was found for vitality (P = 0.003), motility (P = 0.009), and morphology (normal forms; P = 0.04). Serum FA profiles improved in the walnut group with increases in omega-6 (P = 0.0004) and omega-3 (P = 0.0007) but not in the control group. The plant source of omega-3, alpha-linolenic acid (ALA) increased (P = 0.0001). Sperm aneuploidy was inversely correlated with sperm ALA, particularly sex chromosome nullisomy (Spearman correlation, -0.41, P = 0.002). Findings demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility, and morphology.
Gaskins AJ et al., 2012·Human reproduction (Oxford, England)·
Open Access
Are different dietary patterns associated with semen parameters in young men? The consumption of a Prudent dietary pattern was significantly associated with higher progressive sperm motility and unrelated to sperm concentration and morphology. The consumption of a Western dietary pattern was unrelated to conventional semen quality parameters. Over the past decades there has been evidence of a concomitant decline in sperm and diet quality. Yet whether diet composition influences semen quality remains largely unexplored. STUDY DESIGN, SIZE, The Rochester Young Men's Study (n= 188) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS, SETTING, Men aged 18-22 years were included in this analysis. Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Linear regression was used to analyze the relation between diet patterns and conventional semen quality parameters (sperm concentration, progressive motility and morphology) adjusting for abstinence time, multivitamin use, race, smoking status, BMI, recruitment period, moderate-to-intense exercise and total calorie intake. Two dietary patterns were identified by factor analysis. The 'Western' pattern was characterized by high intake of red and processed meat, refined grains, pizza, snacks, high-energy drinks and sweets. The 'Prudent' pattern was characterized by high intake of fish, chicken, fruit, vegetables, legumes and whole grains. The Prudent pattern was positively associated with percent progressively motile sperm in multivariate models (P-trend = 0.04). Men in the highest quartile of the Prudent diet had 11.3% (95% CI 1.3, 21.3) higher % progressively motile sperm compared with men in the lowest quartile. The Prudent pattern was unrelated to sperm concentration and morphology. The Western pattern was not associated with any semen parameter. This was a cross-sectional and observational study, which limited our ability to determine causality of diet on semen quality parameters. Our findings support the suggestion that a diet rich in fruits, vegetables, chicken, fish and whole grains may be an inexpensive and safe way to improve at least one measure of semen quality. The authors are supported by NIH grant T32DK007703-16 and P30DK46200 and European Union DEER Grant 212844. The authors have no competing interests to declare.
To design and perform a case-control study of multiple sclerosis (MS) in Crete, an island of 0.6 million people, that has experienced profound socioeconomic changes in recent decades. All MS cases occurring on Crete from 1980 to 2008 were ascertained. To search for putative risk factors, a structured questionnaire of 71 variables was employed, with patients with MS (n = 657) being compared to random controls (n = 593) matched for age, gender, and current place of residence. MS incidence rose markedly on Crete over the past 3 decades. This increase was associated with a major shift in MS distribution among genders (1980: F/M = 0.9; 2008: F/M = 2.1), with females living in towns or having relocated at a young age from the countryside to urban centers being mainly affected. In rural Crete, MS showed lesser increases and gender preference. Of the major changes that accompanied urbanization, smoking among women with MS increased dramatically, while imported pasteurized cow milk virtually replaced fresh goat milk produced locally. Compared to controls, female patients with MS more often used contraceptives and were older at first childbirth. Besides smoking, alcohol drinking and vitamin intake was more common among female patients with MS. Also, the distribution of childhood diseases and chronic medical conditions differed significantly between patients with MS and controls. MS incidence rose markedly over 3 decades in a genetically stable population in tandem with a transition from rural to urban living, thus possibly implicating environmental factors introduced by urbanization.
Buck Louis GM et al., 2012·Environ Health Perspect·
Open Access
An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies. We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort. Using a matched cohort design, we assembled an operative cohort of women 18-44 years of age undergoing laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009 and a population-based cohort matched on age and residence within a 50-mile catchment area of the clinical centers. Endometriosis was defined as visualized disease in the operative cohort and as diagnosed by magnetic resonance imaging in the population cohort. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an endometriosis diagnosis, with separate models run for each medium (omental fat in the operative cohort, serum in both cohorts) and cohort. Adjusted models included age, body mass index, breast-feeding conditional on parity, cotinine, and lipids. Concentrations were higher in omental fat than in serum for all POPs. In the operative cohort, γ-hexachlorocyclohexane (γ-HCH) was the only POP with a significant positive association with endometriosis [per 1-SD increase in log-transformed γ-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; β-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed β-HCH: AOR = 1.72; 95% CI: 1.09, 2.72). Using a matched cohort design, we found that cohort-specific and biological-medium-specific POPs were associated with endometriosis, underscoring the importance of methodological considerations when interpreting findings.
Tam C et al., 2012·Obstetrics and gynecology international
There are increasing concerns that exposure to unmetabolized folic acid, which results from folic acid intakes that overwhelm the liver's metabolic capacity, may be associated with adverse effects. In this paper, we examined the folic acid status of women of reproductive age in relation to dietary intake and the effect of folic acid supplementation (1.1 mg or 5 mg). Plasma unmetabolized folic acid was not significantly correlated with folate intake estimated by food frequency questionnaire or biomarkers. The proportion of women with detectable levels of unmetabolized folic acid increased from 65% to 100% after twelve weeks of supplementation (P < 0.05); however, the increase in concentrations did not reach statistical significance and the effect was not sustained. Moreover, there were no significant differences between the two doses. This suggests that there are mechanisms by which the body adapts to high folic acid intakes to limit exposure to unmetabolized folic acid.
Background and
Persistent organic pollutants (POPs) have been associated with endometriosis, though with equivocal results possibly reflecting choice of biospecimen. We sought to assess this ...
Stress and Allostatic Load · Cortisol and the Adrenal Axis
Ranabir S et al., 2011·Indian J Endocrinol Metab·
Open Access
In the modern environment one is exposed to various stressful conditions. Stress can lead to changes in the serum level of many hormones including glucocorticoids, catecholamines, growth hormone and prolactin. Some of these changes are necessary for the fight or flight response to protect oneself. Some of these stressful responses can lead to endocrine disorders like Graves' disease, gonadal dysfunction, psychosexual dwarfism and obesity. Stress can also alter the clinical status of many preexisting endocrine disorders such as precipitation of adrenal crisis and thyroid storm.
Twin studies provide insight into the complex interaction between genetic and environmental factors in the development of inflammatory bowel disease (IBD). We assessed associations between childhood environmental factors and development of Crohn's disease (CD) and ulcerative colitis (UC) in twins. Questionnaires on clinical demographics and exposure to environmental factors were sent to twins with IBD, their healthy co-twins, and their doctors. Kappa statistics were used to examine agreement between twin pairs and odds ratios were calculated by conditional logistic regression. In all, 250 IBD twin pairs (122 CD; 125 UC; 3 CD/UC; 28 concordant pairs) were analyzed. Concordant monozygotic twins with CD showed good agreement for disease location (κ 0.88; 95% confidence interval [CI]: 0.45-1.00), disease behavior (κ 1.00; 95% CI: 0.43-1.00), and moderate agreement for age at diagnosis and need for medical and surgical therapy. Concordant monozygotic twins with UC showed good agreement for disease extent (κ 0.60; CI 0.13-1.00) and use of thiopurines (κ 0.73; CI 0.10-1.00). In discordant twins, symptomatic childhood mumps infection (odds ratio [OR], 3.8; 95% CI, 1.2-11.3) and oral contraceptives (OR, 4.0; 1.1-14.2) were associated with CD. Smoking was associated with CD (OR, 4.3; 95% CI, 1.9-9.8) but inversely associated with UC (OR, 0.3; 95% CI, 0.1-0.9). Both CD and UC twins had suffered more "gastroenteritis" and spent more time with animals than their co-twins. Disease phenotype in CD and disease extent in UC appeared to be genetically influenced. Smoking is a risk factor for CD but is protective for UC. Early exposure to "infections" during childhood may be associated with the development of IBD.
Studies indicate that intake of vitamin D in the range from 1,100 to 4,000 IU/d and a serum 25-hydroxyvitamin D concentration [25(OH)D] from 60-80 ng/ml may be needed to reduce cancer risk. Few community-based studies allow estimation of the dose-response relationship between oral intake of vitamin D and corresponding serum 25(OH)D in the range above 1,000 IU/d. A descriptive study of serum 25(OH)D concentration and self-reported vitamin D intake in a community-based cohort (n = 3,667, mean age 51.3 ± 13.4 y). Serum 25(OH)D rose as a function of self-reported vitamin D supplement ingestion in a curvilinear fashion, with no intakes of 10,000 IU/d or lower producing 25(OH)D values above the lower-bound of the zone of potential toxicity (200 ng/ml). Unsupplemented all-source input was estimated at 3,300 IU/d. The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d. Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.
Periconceptional intake of folic acid is known to reduce a woman's risk of having an infant affected by a neural tube birth defect (NTD). National programs to mandate fortification of food with folic acid have reduced the prevalence of NTDs worldwide. Uncertainty surrounding possible unintended consequences has led to concerns about higher folic acid intake and food fortification programs. This uncertainty emphasizes the need to continually monitor fortification programs for accurate measures of their effect and the ability to address concerns as they arise. This review highlights the history, effect, concerns, and future directions of folic acid food fortification programs.
To determine whether urine bisphenol-A (BPA) levels are associated with lower semen quality. Cohort study. Four regions in China where high exposure to BPA in the workplace existed. PATIENT(S): 218 men with and without BPA exposure in the workplace. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen parameters. RESULT(S): After adjustment for potential confounders using linear regression, increasing urine BPA level was statistically significantly associated with [1] decreased sperm concentration, [2] decreased total sperm count, [3] decreased sperm vitality, and [4] decreased sperm motility. Compared with men who did not have detectable urine BPA levels, those with detectable urine BPA had more than three times the risk of lowered sperm concentration and lower sperm vitality, more than four times the risk of lower sperm count, and more than twice the risk of lower sperm motility. The urine BPA level was not associated with semen volume or abnormal sperm morphology. Similar dose-response associations were observed among men with environmental BPA exposure at levels comparable with those in the U.S population. Despite a markedly reduced sample size, the inverse correlation between increased urine BPA levels and decreased sperm concentration and total sperm count remained statistically significant. CONCLUSION(S): These results provide the first epidemiologic evidence of an adverse effect of BPA on semen quality.
Environmental Exposures · Radiation and Electromagnetic Exposure
Agarwal A et al., 2011·International braz j urol : official journal of the Brazilian Society of Urology
Cell phones have become a vital part of everyday life. However, the health risks associated with their usage are often overlooked. Recently, evidence from several studies supports a growing claim that cell phone usage may have a detrimental effect on sperm parameters leading to decreased male fertility. Nonetheless, other studies showed no conclusive link between male infertility and cell phone usage. The ambiguity of such results is attributed to the lack of a centralized assay for measuring inflicted damage caused by cell phones. Study design, ethics, and reproducibility are all aspects which must be standardized before any conclusions can be made.
Mulligan ML et al., 2010·American journal of obstetrics and gynecology
Vitamin D is an essential fat soluble vitamin and a key modulator of calcium metabolism in children and adults. Because calcium demands increase in the third trimester of pregnancy, vitamin D status becomes crucial for maternal health, fetal skeletal growth, and optimal maternal and fetal outcomes. Vitamin D deficiency is common in pregnant women (5-50%) and in breastfed infants (10-56%), despite the widespread use of prenatal vitamins, because these are inadequate to maintain normal vitamin D levels (>or=32 ng/mL). Adverse health outcomes such as preeclampsia, low birthweight, neonatal hypocalcemia, poor postnatal growth, bone fragility, and increased incidence of autoimmune diseases have been linked to low vitamin D levels during pregnancy and infancy. Studies are underway to establish the recommended daily doses of vitamin D in pregnant women. This review discusses vitamin D metabolism and the implications of vitamin D deficiency in pregnancy and lactation.
Nutrition and Metabolic Health · Eating Disorders and Underfueling
Cross-sectional studies have found associations among elevated cognitive dietary restraint (CDR), increased ovulatory disturbances, and lower bone mass, possibly mediated by cortisol. To determine whether healthy young women with higher CDR have more menstrual cycles with subclinical ovulatory disturbances (SOD), elevated 24-h urinary free cortisol (UFC), and less positive 2-yr areal bone mineral density change (Delta-aBMD). DESIGN, SETTING, We conducted a 2-yr longitudinal study of 123 healthy, community-dwelling, nonobese, regularly menstruating women aged 19-35 yr. Key variables were Three Factor Eating Questionnaire Restraint score, percent of cycles with anvoluation and/or luteal phase length <10 d (%SOD), UFC, and Delta-aBMD at the lumbar spine (L1-L4), total hip, and whole body. Anthropometrics, general stress, physical activity, and energy intake were measured. Adjusting for potential confounders, differences were examined by general linear modeling using median split of CDR score and %SOD. Women with higher CDR had higher %SOD (56 vs. 34%, P < 0.001) and higher UFC (28.0 vs. 24.0 microg/d, P = 0.021). Delta-aBMD did not differ by CDR. Women with higher %SOD had less positive Delta-aBMD at L1-L4 (0.7 vs. 1.9%, P = 0.034) and hip (-0.6 vs. 0.9%, P = 0.001), and higher CDR score (8.7 vs. 7.1, P = 0.04). Physical activity, general stress, body mass index, and energy intake did not explain differences by CDR or %SOD. UFC was not associated with %SOD or Delta-aBMD. Women with more frequent SOD reported higher CDR and experienced less positive Delta-aBMD. Although women with higher CDR had higher UFC, the mechanism linking CDR, SOD, and aBMD is not clear.
Nutrition and Metabolic Health · Eating Disorders and Underfueling
Cognitive dietary restraint (CDR) is the
perception
of limiting food intake to achieve/maintain a perceived ideal body weight. The objective of this 2‐yr prospective study was to determine if women with higher CDR have more subclinical ovulation disturbances (SOD; anovulation or luteal phase <10 d), elevated cortisol excretion and less positive changes in areal bone mineral density over two years (ΔaBMD). Participants were 123 healthy, non‐obese, regularly menstruating women aged 19–35. Annually participants completed questionnaires (Three Factor Eating Questionnaire, physical activity, general stress, dietary intake), anthropometrics and 24‐hr urine collections for measurement of 24‐hr urinary free cortisol (UFC). At baseline and final follow‐up, dual energy x‐ray absorptiometry scans measured ΔaBMD at the lumbar spine (L1‐4), hip and total body. Quantitative waking temperature was used to determine SOD frequency. SOD correlated positively with CDR and inversely with hip ΔaBMD but not with UFC. CDR and UFC were not associated with each other or ΔaBMD. Women with higher CDR had more SOD. Women with more SOD had less positive ΔaBMD and higher CDR. Physical activity, general stress, body mass and energy intake did not explain differences by CDR or SOD. In conclusion, CDR was the only study variable associated with SOD which was associated with less positive ΔaBMD. Canadian Institutes of Health Research 79563.
Grant Funding Source
: Canadian Institute of Health Research
Langsetmo L et al., 2010·BMC Musculoskelet Disord·
Open Access
Previous research has shown that underlying dietary patterns are related to the risk of many different adverse health outcomes, but the relationship of these underlying patterns to skeletal fragility is not well understood. The objective of the study was to determine whether dietary patterns in men (ages 25-49, 50+) and women (pre-menopause, post-menopause) are related to femoral neck bone mineral density (BMD) independently of other lifestyle variables, and whether this relationship is mediated by body mass index. We performed an analysis of 1928 men and 4611 women participants in the Canadian Multicentre Osteoporosis Study, a randomly selected population-based longitudinal cohort. We determined dietary patterns based on the self-administered food frequency questionnaires in year 2 of the study (1997-99). Our primary outcome was BMD as measured by dual x-ray absorptiometry in year 5 of the study (2000-02). We identified two underlying dietary patterns using factor analysis and then derived factor scores. The first factor (nutrient dense) was most strongly associated with intake of fruits, vegetables, and whole grains. The second factor (energy dense) was most strongly associated with intake of soft drinks, potato chips and French fries, certain meats (hamburger, hot dog, lunch meat, bacon, and sausage), and certain desserts (doughnuts, chocolate, ice cream). The energy dense factor was associated with higher body mass index independent of other demographic and lifestyle factors, and body mass index was a strong independent predictor of BMD. Surprisingly, we did not find a similar positive association between diet and BMD. In fact, when adjusted for body mass index, each standard deviation increase in the energy dense score was associated with a BMD decrease of 0.009 (95% CI: 0.002, 0.016) g/cm(2) for men 50+ years old and 0.004 (95% CI: 0.000, 0.008) g/cm(2) for postmenopausal women. In contrast, for men 25-49 years old, each standard deviation increase in the nutrient dense score, adjusted for body mass index, was associated with a BMD increase of 0.012 (95% CI: 0.002, 0.022) g/cm(2). In summary, we found no consistent relationship between diet and BMD despite finding a positive association between a diet high in energy dense foods and higher body mass index and a strong correlation between body mass index and BMD. Our data suggest that some factor related to the energy dense dietary pattern may partially offset the advantages of higher body mass index with regard to bone health.
Nutrition and Metabolic Health · Body Weight and Composition
Recent studies have shown that both female and male obesity may delay time-to-pregnancy (TTP). Little is known about central adiposity or weight gain and fecundability in women. We examined the association between anthropometric factors and TTP among 1651 Danish women participating in an internet-based prospective cohort study of pregnancy planners (2007-2008). We categorized body mass index (BMI = kg/m(2)) as underweight (<20), normal weight (20-24), overweight (25-29), obese (30-34) and very obese (> or =35). We used discrete-time Cox regression to estimate fecundability ratios (FRs) and 95% confidence intervals (CI), controlling for potential confounders. We found longer TTPs for overweight (FR = 0.83, 95% CI = 0.70-1.00), obese (FR = 0.75, 95% CI = 0.58-0.97), and very obese (FR = 0.61, 95% CI = 0.42-0.88) women, compared with normal weight women. After further control for waist circumference, FRs for overweight, obese, and very obese women were 0.72 (95% CI = 0.58-0.90), 0.60 (95% CI = 0.42-0.85) and 0.48 (95% CI = 0.31-0.74), respectively. Underweight was associated with reduced fecundability among nulliparous women (FR = 0.82, 95% CI = 0.63-1.06) and increased fecundability among parous women (FR = 1.61, 95% CI = 1.08-2.39). Male BMI was not materially associated with TTP after control for female BMI. Compared with women who maintained a stable weight since age 17 (-5 to 4 kg), women who gained > or =15 kg had longer TTPs (FR = 0.72, 95% CI = 0.59-0.88) after adjustment for BMI at age 17. Associations of waist circumference and waist-to-hip ratio with TTP depended on adjustment for female null associations were observed before adjustment for BMI and weakly positive associations were observed after adjustment for BMI. Our results confirm previous studies showing reduced fertility in overweight and obese women. The association between underweight and fecundability varied by parity.
The role of environmental factors in the risk for Crohn's disease (CD), an inflammatory bowel disease (IBD), was investigated in a North Island-based New Zealand case-control cohort. A total of 315 CD patients and 536 controls were recruited through various sources to the Auckland CD Risk Factor Study. As well as demographic characteristics, the self-reported questionnaire included (1) smoking and drinking alcohol, (2) breastfeeding in infancy, (3) early life exposures to allergens and microbes, (4) health conditions lasting 6 months or longer and (5) taking antibiotics and any medications. There was strong evidence for familial associations of the disease, and minor effects of birth order and number of siblings. Being a smoker, especially over a long time period, and exposure to smoking during childhood and adolescence periods increased risk, whereas drinking alcohol at least once per week showed a slight protective effect. Long term use of the oral contraceptive pill increased the risk of developing CD, but breastfeeding and immunisation during infancy showed no significant association. Long term and debilitating illness (lasting 6 months or more), taking antibiotics prior to developing CD, or taking four or more antibiotics or any regular medication in a year during adolescence substantially increased the CD risk. Having a pet during childhood was a protective factor, but regularly feeding an animal was not sufficient to protect. Many of these significant factors are likely to impact on the colonic microflora and/or immune system. We conclude that, in addition to strong evidence for genetic associations, factors likely to impact on immune response or reduce early exposure to microbes provide a main risk factor for CD in this New Zealand population.
Baccarelli A et al., 2009·Current opinion in pediatrics·
Open Access
Epigenetics investigates heritable changes in gene expression occurring without changes in DNA sequence. Several epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA expression, can change genome function under exogenous influence. Here, we review current evidence indicating that epigenetic alterations mediate toxicity from environmental chemicals. In-vitro, animal, and human investigations have identified several classes of environmental chemicals that modify epigenetic marks, including metals (cadmium, arsenic, nickel, chromium, and methylmercury), peroxisome proliferators (trichloroethylene, dichloroacetic acid, and TCA), air pollutants (particulate matter, black carbon, and benzene), and endocrine-disrupting/reproductive toxicants (diethylstilbestrol, bisphenol A, persistent organic pollutants, and dioxin). Most studies conducted so far have been centered on DNA methylation, whereas only a few investigations have studied environmental chemicals in relation to histone modifications and microRNA. For several exposures, it has been proved that chemicals can alter epigenetic marks, and that the same or similar epigenetic alterations can be found in patients with the disease of concern or in diseased tissues. Future prospective investigations are needed to determine whether exposed individuals develop epigenetic alterations over time and, in turn, which such alterations increase the risk of disease. Also, further research is needed to determine whether environmental epigenetic changes are transmitted transgenerationally.
Environmental Exposures · Radiation and Electromagnetic Exposure
To investigate the effect of cell phone use on various markers of semen quality. Observational study. Infertility clinic. PATIENT(S): Three hundred sixty-one men undergoing infertility evaluation were divided into four groups according to their active cell phone use: group A: no use; group B: <2 h/day; group C: 2-4 h/day; and group D: >4 h/day. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm parameters (volume, liquefaction time, pH, viscosity, sperm count, motility, viability, and morphology). RESULT(S): The comparisons of mean sperm count, motility, viability, and normal morphology among four different cell phone user groups were statistically significant. Mean sperm motility, viability, and normal morphology were significantly different in cell phone user groups within two sperm count groups. The laboratory values of the above four sperm parameters decreased in all four cell phone user groups as the duration of daily exposure to cell phones increased. CONCLUSION(S): Use of cell phones decrease the semen quality in men by decreasing the sperm count, motility, viability, and normal morphology. The decrease in sperm parameters was dependent on the duration of daily exposure to cell phones and independent of the initial semen quality.
Chavarro JE et al., 2007·Obstetrics and gynecology
To evaluate the relation of a dietary pattern and other lifestyle practices to risk of ovulatory disorder infertility. We followed a cohort of 17,544 women without a history of infertility for 8 years as they tried to become pregnant or became pregnant. A dietary score based on factors previously related to lower ovulatory disorder infertility (higher consumption of monounsaturated rather than trans fats, vegetable rather than animal protein sources, low glycemic carbohydrates, high fat dairy, multivitamins, and iron from plants and supplements) and other lifestyle information was prospectively related to the incidence of infertility. Increasing adherence to a "fertility diet" pattern was associated with a lower risk of ovulatory disorder infertility. The multivariable-adjusted relative risk of ovulatory disorder infertility comparing women in the highest with women in the lowest quintile of the "fertility diet" pattern score was 0.34 (95% confidence interval 0.23-0.48; P for trend<.001). This inverse relation was similar in subgroups defined by women's age, parity, and body weight. A combination of five or more low-risk lifestyle factors, including diet, weight control, and physical activity was associated with a 69% lower risk of ovulatory disorder infertility and an estimated population attributable risk of 66% (95% confidence interval 29-86%). Following a "fertility diet" pattern may favorably influence fertility in otherwise healthy women. Further, the majority of infertility cases due to ovulation disorders may be preventable through modifications of diet and lifestyle. II.
Plasma 25-hydroxyvitamin D was measured in 40 healthy, mostly Black, mother-infant pairs. Although a majority of mothers received a daily prenatal multivitamin, vitamin D deficiency (<30 nmol/L), was found in 50% of mothers and 65% of their newborn infants, with a positive correlation between maternal and infant plasma 25-hydroxyvitamin D concentrations. Maternal vitamin D deficiency may represent an important risk factor for the development of rickets in children.
Chavarro JE et al., 2007·The American Journal of Clinical Nutrition
Pharmacologic activation of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) improves ovulatory function in women with polycystic ovary syndrome, and specific dietary fatty acids can affect PPAR-gamma activity. The objective of the study was to assess whether the intakes of total fat, cholesterol, and major types of fatty acids affect the risk of ovulatory infertility. We conducted a prospective cohort study of 18 555 married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999. Diet was assessed twice during follow-up by using a food-frequency questionnaire. During follow-up, 438 incidents of ovulatory infertility were reported. In logistic regression analyses, intakes of total fat, cholesterol, and most types of fatty acids were not related to ovulatory infertility. Each 2% increase in the intake of energy from trans unsaturated fats, as opposed to that from carbohydrates, was associated with a 73% greater risk of ovulatory infertility after adjustment for known and suspected risk factors for this condition [relative risk (RR) = 1.73; 95% CI: 1.09, 2.73]. Obtaining 2% of energy intake from trans fats rather than from n-6 polyunsaturated fats was associated with a similar increase in the risk of ovulatory infertility (RR = 1.79; 95% CI: 1.11, 2.89). In addition, obtaining 2% of energy from trans fats rather than from monounsaturated fats was associated with a more than doubled risk of ovulatory infertility (RR = 2.31; 95% CI: 1.09, 4.87).Conclusiontrans Unsaturated fats may increase the risk of ovulatory infertility when consumed instead of carbohydrates or unsaturated fats commonly found in nonhydrogenated vegetable oils.
Hauser R et al., 2006·Epidemiology (Cambridge, Mass.)
Phthalates are multifunctional chemicals used in a variety of consumer, medical, and personal care products. Previously, we reported dose-response associations of decreased semen quality with urinary concentrations of monobutyl phthalate (MBP) and monobenzyl (MBzP) phthalate, which are metabolites of dibutyl phthalate and butylbenzyl phthalate, respectively. The present study extends our work in a larger sample of men and includes measurements of di(2-ethylhexyl) phthalate (DEHP) oxidative metabolites. Between January 2000 and May 2004, we recruited 463 male partners of subfertile couples who presented for semen analysis to the Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values for sperm concentration (<20 million/mL) and motility (<50% motile) and the Tygerberg Kruger Strict criteria for morphology (<4% normal). The comparison group was men with all 3 semen parameters above the reference values. In a single spot urine sample from each man, phthalate metabolites were measured using solid-phase extraction coupled to high-performance liquid chromatography isotope-dilution tandem mass spectrometry. There were dose-response relationships of MBP with low sperm concentration (odds ratio per quartile adjusted for age, abstinence time, and smoking status = 1.00, 3.1, 2.5, 3.3; P for trend = 0.04) and motility (1.0, 1.5, 1.5, 1.8; P for trend = 0.04). There was suggestive evidence of an association between the highest MBzP quartile and low sperm concentration (1.00, 1.1, 1.1, 1.9; P for trend = 0.13). There were no relationships of monoethyl phthalate, monomethyl phthalate, and the DEHP metabolites with these semen parameters. The present study confirms previous results on the relationship of altered semen quality with exposure to MBP at general population levels. We did not find associations between semen parameters and 3 DEHP metabolites.
Genetics and environmental factors are implicated in the etiology of inflammatory bowel disease (IBD). We studied environmental factors in a population-based Swedish-Danish twin cohort using the co-twin control method. A questionnaire was sent to 317 twin pairs regarding markers of exposures in the following areas: infections/colonization and diet as well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were calculated by conditional logistic regression. When confounding appeared plausible, multivariate conditional logistic regression was added. The questions were also divided into topic groups, and adjustment was made for multiple testing within each of the groups. The response rate to the questionnaire was 83%. In consideration of the study design, only discordant pairs were included (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92). Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and associated with CD (OR, 2.9; 95% CI, 1.2-7.1). The observed associations indicate that markers of possible infectious events may influence the risk of IBD. Some of these effects might be mediated by long-term changes in gut flora or alterations in reactivity to the flora. The influence of smoking in IBD was confirmed.
Chen C et al., 2005·Environ Health Perspect·
Open Access
Our recent study showed a dose-response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E1C levels in a +/-10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E1C levels (beta = -0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (beta = -0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E1C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E1C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY·
Physiological and psychological stress disrupts hypothalamic GnRH pulsatility via CRH-cortisol pathways, producing downstream impairments in LH and FSH secretion that manifest as anovulation, delayed ovulation, follicular phase prolongation, or luteal phase deficiency -- all of which are documented cycle-by-cycle on the CrMS chart. NaProTECHNOLOGY addresses stress-induced HPO axis dysfunction by identifying the specific cycle-level disorder through charting and targeted hormone profiling, then applying cycle-appropriate ovulation induction and cooperative hormone support alongside correction of the underlying physical or psychological stressor.
Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. In regions of combined severe iodine and selenium deficiency, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid hormone economy may develop under conditions of special dietary regimens such as long-term total parenteral nutrition, phenylketonuria diet, cystic fibrosis, or may be the result of imbalanced nutrition in children, elderly people, or sick patients.
Environmental Exposures · Personal Care and Household Products
Zonana-Nacach A et al., 2002·Salud Publica Mex·
Open Access
To assess risk factors associated with systemic lupus erythematosus (SLE) in the Mexican population. MATERIAL AND A case-control study was conducted on June 1996, at the Reumathology Clinic of Hospital de Especialidades del Centro Médico Nacional Siglo XXI (HE CMN), Instituto Mexicano del Seguro Social, in Mexico City. Cases were one hundred thirty subjects with four or more SLE criteria and disease evolution of +/- 5 years. Controls were hospitalized patients with acute diseases but without autoimmune diseases. Cases and controls were matched 1:1 by age and gender; both groups were evaluated by direct interview through a structured questionnaire. The following risk factors were assessed: genetic family history of SLE and connective tissue disease; socioedemographic (ethnicity, geographic distribution, education, monthly income); hormonal (use of oral contraceptives, replacement therapy and gynecoobstetric background); environmental (use of hair products, living with dogs, bacterial/viral infections, and allergies). Statistical analysis consisted of odd ratios (OR) with 95% confidence intervals (CI) and multivariate analysis using logistic regression. The multivariate model showed association with family history of SLE (OR 4.2, CI 95% 1.17-15.2), family history of connective tissue disorder (OR 2.6, CI 95% 1.15-4.5), use of oral contraceptives for more than one year (OR 2.1, CI 95% 1.13-4.3), repetitive pharyngitis (OR 2.1, CI 95% 1.18-3.6), and use of medications (OR 5.0 IC 95% 1.62-21.6). No association was found with socieconomic status, hair dye products, asthma, or allergies. Genetic factors, such as family history of SLE and connective tissue disease in first-degree relatives, persist as important factors in the development of SLE. Other factors, such as use of some drugs, oral contraceptives, and repetitive pharyngitis, may also favor the onset of disease in genetically susceptible hosts. The English version of this paper is available at: http://www.insp.mx/salud/index.html.
Nutrition and Metabolic Health · Eating Disorders and Underfueling
Women with high scores for dietary restraint have been found to have higher 24-h urinary cortisol excretion and a higher prevalence of subclinical ovulatory disturbances, both of which may be risk factors for bone loss. The purpose of this study was to explore relationships between dietary restraint and bone health in regularly menstruating young women. 62 women (age: 21.7 +/- 2.5 yr) had body composition and total body and lumbar spine bone mineral density (BMD) and content (BMC) assessed using dual-energy x-ray absorptiometry. Dietary restraint was assessed using the restraint subscale from the Three-Factor Eating Questionnaire: 29 women had low restraint (LR; restraint score 0--5), 33 had high restraint (HR; restraint score 13--21). Exercise (h x wk(-1)) was assessed by questionnaire on two occasions. LR and HR women were similar in age and body composition (fat mass = 15.0 +/- 4.7 kg, lean mass = 40.9 +/- 4.9 kg), but HR women exercised more (3.4 +/- 1.7 vs 2.2 +/- 1.8 h x wk(-1), P < 0.05). Exercise was correlated with BMD and BMC, and when it was included as a covariate, total body BMC was significantly lower in HR than LR women. In multiple regression analysis, weekly hours of exercise and restraint score were significant predictors of total body BMD and BMC. The observations of this cross-sectional study suggest that high levels of cognitive dietary restraint, or associated factors such as higher cortisol, may attenuate the positive effects of exercise on bone in young women.
Roberts SB et al., 2001·J Gerontol A Biol Sci Med Sci·
Caloric restriction (CR) reduces the rate of aging and increases life span in all small animal species studied to date, but the effects of CR in humans remain uncertain. This review summarizes current knowledge of the effects of CR in nonhuman primates and humans. The results suggest that CR has a range of beneficial effects in nonhuman primates studied under laboratory conditions, and short-term markers of CR seen in animal models appear to occur in humans subject to CR also. However, the overall benefit of CR in human populations remains to be established, and studies in human populations are needed.
Cognitive dietary restraint, assessed by the Three-Factor Eating Questionnaire restraint subscale, is associated with subclinical menstrual cycle disturbances. This association may be mediated by stress-activated cortisol release. We assessed whether 24-h urinary cortisol excretion differs between women with high and low restraint scores.
Participants (aged 21.6+/-2.5 y; n = 62) with normal-length menstrual cycles and high (n = 33) or low (n = 29) restraint scores completed a questionnaire describing weight history, dietary practices, and exercise. Cortisol, calcium, and creatinine were measured in urine collected over 24 h on a day when all food and beverages were provided and measured. Previously, 3-d food records and anthropometric measurements were obtained. Age, height, weight, body mass index, and length of menstrual cycle were similar between groups. The reported amount of exercise was higher (3.4+/-1.7 compared with 2.2+/-1.8 h/wk; P<0.05) and energy intakes (assessed from 3-d and 24-h food records) were lower in the highthan in the low-restraint group. Ratios of urinary cortisol (nmol) to creatinine (mmol) were higher in the high-restraint than in the low-restraint group (42.9+/-12.9 compared with 36.3+/-8.9; P<0.05), whereas ratios of urinary calcium (mmol) to creatinine were lower (0.3+/-0.1 compared with 0.4+/-0.2; P<0.05) in the high-restraint group. Urinary cortisol was not associated with exercise, nutrient intakes, or anthropometric measurements. High dietary restraint scores are associated with urinary cortisol, a biological marker of stress, and high cortisol excretion may affect bone health. Our results suggest that further research is warranted to clarify these associations and to determine whether they persist over time.
Nutrition and Metabolic Health · Eating Disorders and Underfueling
Peripheral metabolism of thyroid hormones is a critical component of the impact these hormones have on intracellular function. Thyroid hormones can be metabolized in peripheral tissue by deiodination, conjugation, deamination, and decarboxylation enzyme reactions. Therefore, alterations in these metabolic pathways might significantly impact the quantity of specific thyroid hormone metabolites influencing function at the cellular level. Available evidence also suggests that, under some circumstances, the activity of hepatic antioxidant enzyme systems and lipid peroxidation might influence the peripheral metabolism of thyroid hormones. Several syndromes, such as "euthyroid sick syndrome" and "low T3 syndrome," have been classified within the medical literature. The common feature of these disorders is a low level of circulating T3, with generally normal to slightly elevated blood T4 levels and either normal or slightly suppressed TSH levels. This pattern of altered thyroid hormone levels is generally agreed to be a result of impairment in extra-thyroidal peripheral metabolism. Hepatic and renal pathology, as well as catabolic states such as those induced subsequent to severe injury, illness, or trauma result in consistent shifts in the thyroid hormone profile, secondary to their impact on peripheral enzyme pathways. Lifestyle factors, such as stress, caloric restriction, and exercise, influence peripheral metabolism of thyroid hormones. Exposure to toxic metals, chemical poisons, and several drugs can also influence the peripheral fate of thyroid hormones. While the role of vitamins, minerals, and botanical extracts in thyroid hormone metabolism requires further elucidation, current evidence supports a role for selenium in the hepatic 5'-deiodination enzyme.
Nutrition and Metabolic Health · Eating Disorders and Underfueling
We assessed the relationship between dietary restraint and menstrual cycle characteristics in 27 ovulatory women, previous participants in a longitudinal study of spinal cancellous bone mineral density (BMD). Subjects completed the restraint scale of the Three Factor Eating Questionnaire, recorded basal temperature and exercise for at least three menstrual cycles, and completed a 3-d food record. Cycle lengths of women in the upper and lower tertiles of scores for restraint were similar [27.8 +/- 1.0 (mean +/- SE) vs 27.6 +/- 0.8 d], but luteal phase length was shorter in the former group (8.6 +/- 0.9 vs 10.8 +/- 0.5 d, P < 0.05). Age, body mass index, percent body fat, waist-hip ratio, reported energy intake, and activity were similar between groups. Because the previous longitudinal study found associations between ovulatory disturbances and bone loss, we assessed spinal BMD using dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). BMD of women in upper and lower restraint tertiles, respectively, did not differ: DXA, 1.15 +/- 0.05 vs 1.20 +/- 0.06 g/cm2; and QCT, 140 +/- 7 vs 133 +/- 7 mg/cm3. Additional prospective studies, however, appear warranted. In conclusion, this study's results provide evidence that high dietary restraint is associated with a shortened luteal phase length.
We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives.
An adaptive model for the evolution of reproductive failure predicted psychosocial stress to increase as anatomic causes of infertility decrease. The nonanatomic infertility group in our study reported greater psychosocial stress than intermediate (P < 0.008) or anatomic groups (P < 0.0005). Controls, women with nonanatomic etiologies who were not attempting pregnancy, also reported higher psychosocial stress than the anatomic group (P < 0.007). Results are consistent with the hypothesis that psychosocial distress contributes significantly to the etiology of some forms of infertility.
We report a patient with fatal acute arsenic poisoning presenting as vomiting and diarrhea with the finding of intra-abdominal radiopacities on radiographs. These represent the classic features of acute arsenic toxicity and are detailed here as a reminder to others facing a similar puzzling patient with this potentially treatable poisoning.
Two runners who were not aware they had conceived continued their intense running regimens during the first and second trimesters of pregnancy. Both women assumed that their amenorrhea was due to endurance training. When their pregnancies were diagnosed, both women markedly reduced their training mileage during the third trimester because they feared that intense exercise might harm the fetus. Retrospective data were collected on their antenatal and intrapartum courses. Both women delivered healthy infants of normal weight. Although these two cases suggest that strenuous anaerobic exercise during pregnancy is not harmful, more studies are needed to determine if these cases are isolated.
Domingo JL, 1989·Reviews of Environmental Contamination and Toxicology
Cobalt is an essential trace element which is widely distributed in nature. Most of cobalt consumed is used in the manufacture of alloys, and although not released extensively in the environment, it may represent a hazard to human health. In addition, excess dietary cobalt produces toxic effects in animals. Polycythemia and hyperglycemia with transitory damage to pancreatic alpha-cells have been widely reported after cobalt administration. Cobalt salts induce respiratory deficiency in yeast. CoCl2 increased sister chromatid exchange (SCE) in P388D1 cells and in lymphocytes from two donors. So far it has not been possible to induce cancer in experimental animals using cobalt by any other route than by injection. Ingestion of cobalt may lead to reproductive changes in the male rat such as loss of testicular volume and darkening of testicle color. On the other hand, oral administration of cobalt did not produce teratogenicity or significant fetotoxicity in the rat at daily doses as high as 100 mg CoCl2/kg. However, cobalt affected the period of late gestation as well as the postnatal development of the pups. Occupational toxicology of cobalt, hygienic and epidemiologic aspects, and treatment of cobalt poisoning are also topics of special interest. Cobalt is a metal with marked allergenic potential. Asthma, interstitial lung disease and combined asthma and alveolitis have been described as occupational health hazards. EDTA, DTPA, and N-acetyl-L-cysteine have been suggested as possible antidotes in cobalt intoxication.
A central, reversible decrease in male sexual function appears related to some aspect of obstructive sleep apnoea (OSA). Lower serum testosterone (T) levels were documented in 15 men with OSA versus nine snorers (no OSA), (9.18 +/- 0.92 vs 11.55 +/- 0.90 nmol/l, mean +/- SEM), P less than 0.05 in a consecutive case series of 24 men referred for diagnostic overnight sleep studies. Gonadotrophins did not differ between the two groups. Although the men with OSA did not differ in body mass index (BMI) or weight from the snorers, they were older (51 +/- 3.9 vs 44 +/- 3.1 years), P less than 0.02. Serum T did not correlate with age, but was correlated with minimum nocturnal arterial oxygen saturation (Min SaO2) (r = 0.589), P less than 0.02. A prospective controlled trial of uvulopalatopharyngoplasty therapy (UPP) for OSA in 12 subsequent subjects showed reproductive improvement which was parallel with improved apnoea at 3 months postsurgery. T increased (13.31 +/- 1.07 to 16.59 +/- 0.72 nmol/l), P less than 0.02, without significant changes in BMI, serum PRL, LH or FSH. All seven of the men who reported decreased sexual interest prior to surgery felt their libido and sexual functioning had returned to normal 3 months following UPP. Some aspect of OSA in men appears to produce a reversible hypothalamic-pituitary reproductive dysfunction.
Nielsen FH et al., 1987·FASEB journal : official publication of the Federation of American Societies for Experimental Biology
A study was done to examine the effects of aluminum, magnesium, and boron on major mineral metabolism in postmenopausal women. This communication describes some of the effects of dietary boron on 12 women between the ages of 48 and 82 housed in a metabolic unit. A boron supplement of 3 mg/day markedly affected several indices of mineral metabolism of seven women consuming a low-magnesium diet and five women consuming a diet adequate in magnesium; the women had consumed a conventional diet supplying about 0.25 mg boron/day for 119 days. Boron supplementation markedly reduced the urinary excretion of calcium and magnesium; the depression seemed more marked when dietary magnesium was low. Boron supplementation depressed the urinary excretion of phosphorus by the low-magnesium, but not by the adequate-magnesium, women. Boron supplementation markedly elevated the serum concentrations of 17 beta-estradiol and testosterone; the elevation seemed more marked when dietary magnesium was low. Neither high dietary aluminum (1000 mg/day) nor an interaction between boron and aluminum affected the variables presented. The findings suggest that supplementation of a low-boron diet with an amount of boron commonly found in diets high in fruits and vegetables induces changes in postmenopausal women consistent with the prevention of calcium loss and bone demineralization.
Exercise is commonly listed as a remedy for the premenstrual syndrome (PMS), although no study has proven that it is an effective therapy. Numerous reports have suggested that exercise is associated with improved mood and symptoms. In those reports, however, the diagnosis of PMS was not clearly documented, nor was the exercise carefully controlled. Preliminary evidence suggests that exercise training in ovulatory, sedentary women and intensified training in women athletes decrease mild premenstrual symptoms. Although conditioning exercise is associated with short luteal phase and anovulatory cycles, decreases in mild premenstrual symptoms occur prior to menstrual cycle changes. Controlled studies of PMS and exercise training may not only document an effective, nonpharmacologic therapy for PMS but also clarify the hormonal etiology of this complex biobehavioral phenomenon.
Six months of exercise training was associated with decreased premenstrual symptoms in two groups of women. There was no change in symptoms in nontraining women. Eight sedentary (ST) women increased running from 0 to 76 +/- 26 km/cycle (mean +/- standard deviation) over 6 months and seven runners (MT) trained for a marathon (42.2 km). Six normally active, nontraining (C-NT) women kept their activity constant. Each subject completed monthly intensity-graded questionnaires or kept daily symptoms diaries concerning premenstrual symptoms. All monitored basal body temperature, weight, and exercise. Gonadal steroids were measured in ST women. For ST subjects, breast (P = 0.005), fluid (P = 0.01), and personal stress (P = 0.025) decreased. MT women experienced decreased fluid (P = 0.034) and depression (P = 0.014). Anxiety tended to decrease (P = 0.087). ST and MT subjects experienced decreases in premenstrual symptoms without documented hormonal, menstrual cycle, or weight changes. These symptom changes appear to be the earliest evidence of the effects of conditioning exercise on the reproductive system.
Neubert D et al., 1986·Environ Health Perspect·
Open Access
Examples of a combined approach using in vivo as well as in vitro methods for the assessment of prenatal toxicity are presented. The topics discussed include the analysis of the possible embryotoxic potential of valproic acid (VPA), female sex hormones, bis(tri-n-butyltin) oxide (TBTO), and acyclovir and the problem of supplementing in vitro systems with drug-metabolizing activity.
Vessey M et al., 1986·Br Med J (Clin Res Ed)·
Open Access
Since the start in 1968 of the Oxford Family Planning Association contraceptive study 31 women have developed ulcerative colitis and 18 have developed Crohn's disease, giving incidences of 0.15 and 0.09/1000 woman years respectively. The incidence of ulcerative colitis in women who were non-smokers on entry to the study was 0.17/1000 woman years and the incidence in smokers was 0.11/1000 woman years. The findings for Crohn's disease were entirely different, the corresponding incidences being 0.05 and 0.17/1000 woman years respectively. Both ulcerative colitis and Crohn's disease were more common among women currently using oral contraceptives than among those not doing so. Incidences per 1000 woman years for ulcerative colitis were 0.26 in users and 0.11 in non-users; for Crohn's disease the incidences were 0.13 and 0.07 respectively. Though the association between the use of oral contraceptives and chronic inflammatory bowel disease cannot be regarded as established, the effects of smoking have been shown consistently in many studies. This observation provides an important clue to the aetiology of chronic inflammatory bowel disease.
Prior JC et al., 1986·Eur J Appl Physiol Occup Physiol·
Conditioning exercise decreased premenstrual symptoms during 3 months of a prospective controlled training study. Eight women with normal ovulatory menstrual cycles began a running exercise training programme while completing intensity-graded questionnaires concerning molimina. Six sedentary control women followed the same protocol for 3 months but did not exercise. Oral basal temperatures evaluated by mean temperature analysis were obtained for all cycles. Exercise distance and time, average exercise heart rate, basal and maximal heart rate and body weights were recorded prospectively and evaluated during the control (0) and 3rd month of the study. Mid-luteal phase progesterone and estrogen levels were sampled during the analyzed cycles for the exercise group. Molimina did not change over 3 months time in the control group. The exercise group, after increasing distance run to 51.0 +/- 18.1 km/cycle at 3 months, showed decreases in overall molimina (scores on a 9-point scale) 6.5 +/- 1.8 to 3.5 +/- 0.9, p less than 0.01). Breast symptoms decreased from 8.3 +/- 0.7, p less than 0.005. Fluid symptoms also decreased from 7.3 +/- 1.8 to 5.5 +/- 0.9, p less than 0.025. Menstrual cycle intervals, luteal lengths, body weights and mid-luteal estrogen and progesterone levels were normal and unchanged. Moderate exercise training without major weight, hormonal or menstrual cycle alteration significantly decreased premenstrual symptoms.
Nutrition and Metabolic Health · Body Weight and Composition
The onset and progression through the various stages of puberty are influenced by a number of factors (Fig. 2). In both animals and humans, the age of puberty appears to be related more to body weight than to chronologic age. Undernutrition and low body fat, or an altered ratio of lean mass to body fat, seem to delay the adolescent spurt and to retard the onset of menarche. According to Frisch, a minimum level of fatness (17% of body weight) is associated with menarche; however, a heavier minimum weight for height, representing an increased amount of body fat (22%), appears necessary for the onset and maintenance of regular menstrual cycles in girls over 16 years of age. This critical amount of body fat implies that a particular body composition, in addition to other environmental and psychosocial factors, is important in triggering and maintaining the pubertal process.
Molloy AM et al., 1985·Archives of disease in childhood·
Open Access
Serum folate and vitamin B12 concentrations in early pregnancy were compared for 32 mothers with pregnancies affected by neural tube defects and 395 randomly selected pregnant control women from the same maternity hospitals. No significant differences were found between the affected mothers and the controls in the median values and frequency distributions of either vitamin. Sixteen of the samples from mothers whose infants had neural tube defects were taken between 9 and 13 weeks' gestation and 11 of these had both serum folate and vitamin B12 concentrations within the normal ranges for our laboratory. These findings are discussed in relation to the concept of folate deficiency as a major factor in the aetiology of neural tube defects.
The principal function of muscular tissue is contraction. This is also true for the uterus this function begins with sexual maturation. During pregnancy special conditions are brought about by the increasing distention of the uterine cavity. For clinical practice, external tocography is of importance for the recognition of uterine motility Data in the literature on the normal frequency of contractions during pregnancy vary greatly and caused us to study this topic. Moreover, most cases of prematurity independent of other causes suppose a prematurely increased uterine motility. In order to register this activity a portable recording apparatus was developed. We studied in particular the question for how long and how often uterine contractions should be recorded. A one hour daily recording was found to be sufficient. In order to gain information on the average number of contractions it suffices to record during one week. In 26 healthy primiparous and 28 multiparous women the number of contractions from the 25th to 41st gestation week was recorded. A notable finding was the frequency peak about the 32nd week. The number of pregnancy contractions as a sole parameter for the recognition of impending premature delivery is not sufficient. However, the information may be important when taking in conjunction with the previous history and the state of the cervix. We considered tocolysis indicated when as a weekly average there are more than two contractions per hour with beginning cervical dilation or more than three contractions per hour regardless of cervical findings.(ABSTRACT TRUNCATED AT 250 WORDS)
We describe seven adults who had ataxia and severe sensory-nervous-system dysfunction after daily high-level pyridoxine (vitamin B6) consumption. Four were severely disabled; all improved after withdrawal. Weakness was not a feature of this condition, and the central nervous system was clinically spared. Although consumption of large doses of pyridoxine has gained wide public acceptance, this report indicates that it can cause sensory neuropathy or neuronopathy syndromes and that safe guidelines should be established for the use of this widely abused vitamin.
The premenstrual symptom complex many women experience in a moderate to severe form can be divided into four subgroups. Because there is more than one syndrome and nervous tension is one of the most common symptoms, the term premenstrual tension syndromes (PMTS) is used. The most common subgroup, PMT-A, consists of premenstrual anxiety, irritability and nervous tension, sometimes expressed in behavior patterns detrimental to self, family and society. Elevated blood estrogen and low progesterone have been observed in this subgroup. Administration of vitamin B6 at doses of 200-800 mg/day reduces blood estrogen, increases progesterone and results in improved symptoms under double-blind conditions. Women in this subgroup consume an excessive amount of dairy products and refined sugar, and progesterone may be of value in them. The second-most-common subgroup, PMT-H, is associated with symptoms of water and salt retention, abdominal bloating, mastalgia and weight gain. The severe form of PMT-H is associated with elevated serum aldosterone. Vitamin B6 at high dosage suppresses aldosterone and results in diuresis and clinical improvement. Vitamin E helps the breast symptoms. Methylxanthines and nicotine should be curtailed and sodium limited to 3 gm/day. PMT-C is characterized by premenstrual craving for sweets, increased appetite and indulgence in eating refined sugar followed by palpitation, fatigue, fainting spells, headache and sometimes the shakes. PMT-C patients have increased carbohydrate tolerance and low red-cell magnesium. Adequate magnesium replacement results in improved glucose tolerance tests and decreased PMT-C symptoms. Deficiency of the prostaglandin PGE1 may also be involved in PMT-C. PMT-D is the least common but most dangerous because suicide is most frequent in this subgroup. The symptoms are depression, withdrawal, insomnia, forgetfulness and confusion. In ten PMT-D patients the mean blood estrogen was lower and the mean blood progesterone higher than normal during the midluteal phase. Elevated adrenal androgens are observed in some hirsute PMT-D patients. Two PMT-D patients with normal blood progesterone and estrogens had high lead levels in hair tissue and chronic lead intoxication. This subgroups needs careful medical attention when the symptoms are severe. Therapy should be individualized according to the results of the evaluation.
The human individual responds as an entire organism to the effect of endurance training. Exercise physiologists have long documented cardiovascular, musculo-skeletal and metabolic effects of conditioning. Only recently are we beginning to understand that there are hormonal and hypothalamic changes which occur with conditioning. These hormonal changes probably serve similar adaptive functions as do the other conditioning responses. Careful controlled studies need to be performed of individuals prior to, early in conditioning, and following extended periods of conditioning looking at hypothalamic function, body morphometric characteristics, psychiatric and psychological testing and menstrual cycle data in order to better understand hormonal conditioning. When hormone changes occurring with endurance training are approached in this light, the complex inter-related alterations will begin to form a pattern. Further studies are needed to document the dynamic and reversible nature of these hormonal adaptations.
In a cohort of 50,282 pregnancies 19 children with cardiovascular defects were born to 1042 women who received female hormones during early pregnancy (18.2 per 1000). Among 49,240 children not exposed in utero to these agents there were 385 with cardiovascular malformations (7.8 per 1000). Six children with cardiovascular defects were born to a sub-group of 278 women who used oral contraceptives during early pregnancy (21.5 per 1000). After the data were controlled for a wide variety of potentially confounding factors by multivariate methods, the association between in utero exposure to female hormones and cardiovascular birth defects was statistically significant.
Since in utero exposure to diethylstilbestrol (DES) is known to cause abnormalities of the female genital tract later in life, exposed male offspring were located, surveyed by mail, and compared with unexposed male offspring from the same period and medical practices. The exposed and unexposed respondents appeared comparable and did not differ in their response to most medical questions. However, a larger proportion of exposed than of unexposed boys had experienced problems in passing urine (12.9% vs. 1.8%, P = .0003) and abnormalities of the penile urethra (4.4% vs. 0%; P = .017).
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Thyroid and Metabolic Function · Insulin and Metabolism
Polycystic ovary syndrome (PCOS) is a widespread and complex endocrine disorder affecting women of childbearing potential, characterized by reproductive dysfunction, hyperandrogenism, and metabolic disorders, including insulin resistance. Insulin resistance is a key pathogenetic factor contributing to ovarian dysfunction and reduced fertility. Myo-inositol (MI), a ubiquitous polyol, has earned a reputation as a promising dietary supplement due to its vital role in insulin signaling pathways. This scoping review aimed to map the available scientific literature on the effects of MI supplementation in women with PCOS, with particular emphasis on fertility and ovarian function, and to identify gaps in the current evidence base. This scoping review was conducted in accordance with the methodology developed by the Joanna Briggs Institute (JBI) and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines. A literature search was conducted against six electronic databases: PubMed, Scopus, Web of Science, EBSCO (MEDLINE Complete), Cochrane Library and Google Scholar. Searches were conducted between 10 January and 20 February 2026. Eligibility sources included original articles (observational and randomized controlled trials), meta-analyses, systematic and narrative reviews, published in English with full text available, focusing on adult women with PCOS. Data extraction was performed independently by two reviewers using the Population-Concept-Context (PCC) framework. In accordance with the scope review methodology, no formal critical appraisal of study quality and no quantitative synthesis were performed. This is consistent with JBI methodology, which does not require critical appraisal for scoping reviews unless explicitly justified. Of the 77 records initially identified, 13 studies were included in the review, and no duplicates were found. These potential benefits should be interpreted cautiously, as the available evidence is heterogeneous and varies across study designs. Potential benefits were also reported for hormonal and metabolic parameters, including reductions in hyperandrogenism and the improvement of insulin sensitivity. Some studies suggest benefits for oocyte and embryo quality, but results remain inconsistent. MI supplementation may support PCOS management, particularly in fertility-related outcomes. Its ability to improve ovulation, increase pregnancy rates, optimize ART outcomes, and mitigate the risk of OHSS highlights its clinical utility. However, the evidence remains heterogeneous, and some outcomes, particularly oocyte and embryo quality, remain inconclusive.
Self-reported dietary intake varies across menstrual cycle phases, but objective assessments of dietary intake together with appetite and resting metabolic rate (RMR) are limited. This study aimed to assess differences in dietary intake, appetite, and RMR during two hormonally-distinct menstrual cycle phases in laboratory and free-living settings. Healthy premenopausal females with predictable normal-length menstrual cycles completed two study visits: one in the late-follicular and one in the mid-luteal phase. Menstrual cycle phases were assessed using urinary luteinizing hormone surge and prospective cycle days. Participants consumed a 2-day energyand macronutrient-balanced run-in diet prior to each visit. RMR was measured with indirect calorimetry, followed by appetite ratings before and after a standardized breakfast, and a food cravings questionnaire. Appetite was also tracked for 2.5 days post-visit in a free-living environment. Ad libitum energy and macronutrient intakes were measured using pre-weighed plus weighing of uneaten food at an in-laboratory lunch meal, as well as during the 2.5-day free-living period. Eighteen participants were included (age: 21 ± 4 years; body mass index: 21.2 ± 1.5 kg/m2). There were no differences between in-laboratory ad libitum energy or macronutrient intakes, appetite, or food cravings between phases. RMR did not differ between phases, although the mid-luteal phase RMR tended to be higher (104 ± 218 kcal/day higher; P = 0.074). No main or interaction effects for phase or time were observed for free-living dietary intake nor appetite ratings. Although RMR tended to be increased during the luteal phase, comprehensive appetite and energy intake assessments showed no significant cycle-phase differences in these 18 participants.
Declining fertility, overlooked mental health, and reduced life expectancy underscore the urgent need for renewed attention to men's health. A semen analysis, traditionally used to assess fertility, holds untapped potential as a tool for promoting lifestyle changes and preventing chronic diseases in men. Spermatogenesis is highly sensitive to environmental and lifestyle factors and can be an early indicator of overall health. Disruptions in this process can signal underlying systemic issues and predict long-term health risks, including cardiovascular disease and metabolic disorders. An increasing number of men seek to engage in preconception care, as fertility is closely tied to a man's sense of masculinity, identity and aspirations for fatherhood. In this context, a semen analysis can be a powerful motivator to encourage healthy behaviours and proactive health management. By incorporating semen analysis into primary care, health care providers can leverage men's desire for fatherhood as an entry point to discuss broader health concerns, such as mental well-being, nutrition and physical activity. This approach would address immediate reproductive health, and also promote long-term wellness, helping to reduce the burden of chronic disease in men.
Johnson J et al., 2025·Journal of Assisted Reproduction and Genetics
The human placenta plays an important role in pregnancy and offspring health. The paternal genome contributes significantly to placental growth and development. While the maternal factors affecting gestational health are thoroughly investigated, the paternal factors are often overlooked. Thus, it is important to understand various paternal factors affecting placental development and function. To assess the effect of various paternal factors on placental development, function, and pregnancy-related disorders. This review was registered in PROSPERO (Registration number CRD420250634649). Literatures across databases like JSTOR, Scopus, Google Scholar, ScienceDirect, and PubMed were screened through a set of criteria. Forty-eight studies were selected that included low-to-moderate risk paternal factors like age, smoking, race/ethnicity/location, genetic, epigenetic factors, exposure to chemicals, seminal plasma, and lifestyle factors. Increased paternal age was reported to contribute towards higher risks of preeclampsia, spontaneous abortions, preterm birth, stillbirth, and higher placental and fetal birth weight. Paternal smoking, on the other hand, was found to be an associated risk factor for placental abruption and stillbirth. Exposure to various chemicals was found to be associated with changes in sperm epigenome and placental dysfunction. Discussion and Paternal health, lifestyle, and exposure to chemicals may affect placental development and pregnancy. Paternal factors may alter seminal plasma proteome, cytokine profile, and abnormal sperm DNA methylation of imprinted genes which is associated with adverse pregnancy outcomes. Pre-conceptional health assessment of prospective fathers might be helpful in ensuring optimal placental development in pregnancies to follow, in addition to newborn health.
Guidelines by Clinical Area · Obstetric Guidelines
Davenport MH et al., 2025·British journal of sports medicine
This consensus aims to provide guidance for postpartum women and people, healthcare providers and exercise professionals on physical activity, sedentary behaviour and sleep throughout the first year postpartum. The development of this guideline followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and the Appraisal of Guidelines for Research and Evaluation II instrument. The Guideline Consensus Panel consisted of representatives from key professional groups, researchers and methodological experts. Literature was retrieved through searches of 12 online databases, and articles on maternal physical activity, sedentary behaviour or sleep in the first year after childbirth were eligible for inclusion if they reported on any of 21 maternal or infant health outcomes, which were prioritised considering the preferences and values of postpartum individuals. There was no restriction on language, and all study designs were eligible except for case studies. The certainty of evidence was rated using GRADE. This evidence review produced seven systematic reviews, which informed this consensus statement. A Delphi process was conducted to identify relative contraindications to postpartum moderate-intensity to vigorous-intensity physical activity, which informed the development of the Get Active Questionnaire for Postpartum. Evidence to decision tables were developed, and feedback on the recommendations was solicited from end users (healthcare providers, exercise professionals, researchers, policy organisations and postpartum women and people). Adhering to these consensus recommendations for postpartum women and people is likely to result in large improvements in psychological well-being, as well as pelvic, musculoskeletal and cardiometabolic health, and reduced fatigue, while not experiencing adverse events (moderate certainty evidence). Most end users indicated that following these recommendations would be feasible, acceptable and equitable, and likely to require minimal resources from individual and health systems perspectives. PROSPERO registration number CRD42022359282.
Self-reported dietary intake varies across menstrual cycle phases, but objective assessments of dietary intake together with appetite and resting metabolic rate (RMR) are limited. This study aimed to assess differences in appetite, dietary intake, and RMR during two hormonally-distinct menstrual cycle phases in laboratory and free-living settings. Healthy premenopausal females with predictable normal-length menstrual cycles completed two study visits: one in the late-follicular and one in the mid-luteal phase. Menstrual cycle phases were identified using urinary luteinizing hormone surge and cycle days. Participants consumed a 2-day energy- and macronutrient-balanced run-in diet prior to each visit. RMR was measured with indirect calorimetry, followed by appetite ratings before and after a standardized breakfast, and completed a food cravings questionnaire. Appetite was also tracked for 2.5 days post-visit in a free-living environment. Ad libitum energy and macronutrient intake were measured using pre-weighed plus weighing of uneaten food at an in-laboratory lunch meal, as well as during the 2.5-day free-living period. Eighteen participants were included (age: 21±4 years; body mass index: 21.2±1.5 kg/m 2 ). There were no differences between in-laboratory ad libitum energy or macronutrient intakes, appetite, or food cravings between phases. RMR did not differ between phases, although the mid-luteal phase RMR trended toward higher (104±218 kcal/day higher ; P =0.074). No main nor interaction effects for phase and time were observed for free-living dietary intake nor appetite ratings. Accurate measurements show no differences in appetite or energy intake between menstrual cycle phases, though RMR may be slightly elevated in the luteal phase.
Are serum vitamin D levels associated with the incidence of endometrial polyps (EPs) in infertile patients? Serum 25(OH)D levels were nonlinearly correlated with the incidence of EPs in infertile women. EPs are a common condition that may affect the receptivity of the endometrium in women of reproductive age. Vitamin D regulates cell proliferation and differentiation, apoptosis, angiogenesis, anti-inflammation, and immunomodulation, in addition to its well-known functions in balancing calcium and phosphorus. Previous studies have shown that vitamin D concentrations are associated with reproductive outcomes, and that low vitamin D levels are associated with the incidence of colorectal polyps and nasal polyps. There is little evidence regarding the relationship between EPs and serum vitamin D levels. STUDY DESIGN, SIZE, We conducted a cross-sectional study using data from Guangdong Women and Children Hospital from January 2019 to October 2023, enrolling 3107 patients. PARTICIPANTS/MATERIALS, SETTING, A total of 3107 infertile patients who underwent hysteroscopy were included in this study; 642 patients had endometrial polyps and 2465 had a normal uterine cavity. Hysteroscopy findings included risk of EPs, polyp size, percentage of multiple polyps, and incidence of chronic endometritis (CE). Serum vitamin D were assessed by measuring total 25(OH)D using chemiluminescence. According to international guideline recommendations for vitamin D deficiency, patients were divided into two groups: the <50 nmol/l group and the ≥50 nmol/l group. Univariable and multivariable logistic regression models, stratified analyses, and smooth curve fitting were used to examine the relationship between serum 25(OH)D levels and risk of EPs. MAIN Of all patients, 23.8% (740/3107) were vitamin D deficient (<50 nmol/l). The incidence of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group (24.9% vs 19.3%; P = 0.001). However, there were no differences in polyp size, proportion of multiple polyps, and presence of CE between the two groups. After controlling for confounders, 25(OH)D ≥ 50 nmol/l (compared with <50 nmol/l) was negatively associated with risk of EPs (adjusted OR, 0.733; 95% CI, 0.598-0.898). Other variables that had an impact on polyp incidence included BMI, type of infertility, CA125, and CD138-positive plasma cells. In addition, a linear regression model between age and serum 25(OH)D levels showed a positive linear association. Subgroup analyses were performed for different age groups, and the risk of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group, both in the younger subgroup (23.8% vs 19.1%) and in the older subgroup (28.0% vs 19.9%). The smooth curve fitting model showed a nonlinear correlation between 25(OH)D levels and risk of EPs (nonlinear P-value = 0.020), with an optimal threshold of 51.8 nmol/l for 25(OH)D levels. Moreover, subgroup smooth curve fitting models showed a nonlinear correlation between 25(OH)D levels and polyp risk in patients aged <35 years (nonlinear P-value = 0.010), whereas a linear correlation between 25(OH)D levels and polyp risk was found in patients aged ≥35 years (nonlinear P-value = 0.682). LIMITATIONS, Caution should be exercised in interpreting our findings as this is a correlational study and causality cannot be inferred from our results. In addition, because of strict inclusion and exclusion criteria, our results may not be generalizable to unselected populations, including premenopausal women or women of other races. This study demonstrated for the first time that vitamin D deficiency is an independent risk factor for the incidence of EPs in infertile patients. Identifying modifiable risk factors (e.g. vitamin D deficiency) can help in the development of new strategies for treating polyps or to protect against polyp development. Further clinical intervention trials and laboratory studies are needed to evaluate the effect of vitamin D on the development of EPs and to elucidate the mechanisms. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the National Natural Science Foundation of China (82101718) and Natural Science Foundation of Guangdong Province, China (2022A1515010776). No competing interest was involved in this study. N/A.
Young-Wolff KC et al., 2024·JAMA internal medicine
Many studies have evaluated whether in utero cannabis exposure is associated with fetal and neonatal outcomes, yet little is known about whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. To evaluate whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. DESIGN, SETTING, This population-based retrospective cohort study included pregnancies in Northern California from January 2011 to December 2019 that lasted 20 weeks or longer and were screened for prenatal cannabis use. Prenatal cannabis use was defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening at entrance to prenatal care (approximately 8-10 weeks' gestation). Self-reported frequency of use (daily, weekly, monthly or less, never, unknown), use defined only by self-report, and use defined only by toxicology test results were examined. Electronic health record data were used to define the following outcomes: gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity. Adjusted risk ratios (aRRs) were calculated using a modified Poisson regression. The sample (n = 316 722 pregnancies; 250 221 unique individuals) included 84 039 (26.5%) Asian/Pacific Islander, 20 053 (6.3%) Black, 83 145 (26.3%) Hispanic, and 118 333 (37.4%) White individuals; the mean (SD) age was 30.6 (5.4) years. Overall, 20 053 (6.3%) screened positive for prenatal cannabis use; 2.9% were positive by self-report, 5.3% by toxicology testing, and 1.8% by both. The frequency of cannabis use was 1930 (0.6%) daily, 2345 (0.7%) weekly, 4892 (1.5%) monthly or less, and 10 886 (3.4%) unknown. Prenatal cannabis use was associated with greater risk of gestational hypertension (aRR, 1.17; 95% CI, 1.13-1.21), preeclampsia (aRR, 1.08; 95% CI, 1.01-1.15), weight gain less than (aRR, 1.05; 95% CI, 1.01-1.08) and greater than (aRR, 1.09; 95% CI, 1.08-1.10) guidelines, and placental abruption (aRR, 1.19; 95% CI, 1.05-1.36). The pattern of results was similar when defining prenatal cannabis use only by self-report or only by toxicology testing, and associations between the frequency of prenatal cannabis use and outcomes varied with outcome. The results of this cohort study suggest that prenatal cannabis use was associated with several adverse maternal health outcomes during pregnancy. Continued research is needed to understand whether characteristics of prenatal cannabis use (eg, dose, mode, and timing) moderate these associations.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Practice Committee of the American Society for Reproductive Medicine, 2024·Fertility and Sterility
In the United States, approximately 21% of adults report some form of tobacco use, although 18% report marijuana use. Although the negative impact of tobacco use in pregnancy is well documented, the impact of tobacco and marijuana on fertility and reproduction is less clear. This committee opinion reviews the potential deleterious effects of tobacco, nicotine, and marijuana use on conception, ovarian follicular dynamics, sperm parameters, gamete mutations, early pregnancy, and assisted reproductive technology outcomes. It also reviews the current status of tobacco smoking cessation strategies. This document replaces the 2018 American Society for Reproductive Medicine Practice Committee document entitled Smoking and Infertility: a committee opinion (Fertil Steril 2018).
Studies have shown that the occurrence and development of endometriosis are closely linked to long-term psychological stress. The specific contribution of chronic stress to the metabolic adaptations in patients with endometriosis is still unknown. Lesions were removed from ten endometriosis patients during an operation, and the participants were divided into two groups using a psychological questionnaire. An mRNA Human Gene Expression Microarray analysis was applied to compare the mRNA expression profiles between the chronic stress group and the control group. In addition, the reliability of the mRNA Human Gene Expression Microarray analysis was verified by using research on metabolites based on both the liquid chromatography (LC-MS/MS) technique and quantitative reverse transcription polymerase chain reaction (RT-PCR). A microarray analysis of significantly up-regulated, differentially expressed genes between the chronic stress and the control groups showed genes that were principally related to metabolism-related processes and immune-related processes, such as the immune response process, negative regulation of T cell proliferation, the leucine metabolic process, and the L-cysteine metabolic process (p < 0.05). LC-MS showed that the differential metabolites were primarily concerned with arginine and proline metabolism, D-glutamine and D-glutamate metabolism, aspartate metabolism, glycine, serine metabolism, and tyrosine metabolism (p < 0.05). The possibility of chronic stress blocks the endometriosis immune response through metabolic reprogramming. Chronic stress reduces the supply of energy substrates such as arginine and serine, down-regulates T immune cell activation, and affects the anti-tumor immune response, thereby promoting the migration and invasion of endometriosis lesions in patients with chronic stress.
Mengelkoch S et al., 2024·Brain, behavior, and immunity
Women using hormonal contraceptives (HCs) exhibit numerous signs of chronic inflammation, including elevated C-reactive protein levels and greater risk of developing mood and autoimmune disorders. However, users and non-users of HCs often have similar circulating proinflammatory cytokine levels, making the mechanism of association unclear. One possible explanation for this paradox is that HC users exhibit differences in their inflammatory responses to psychosocial stress that, over time, could contribute to chronic inflammation and its pathologies. Here, we tested this possibility by examining women's glucocorticoid, inflammatory, and psychological responses to the Trier Social Stress Test (TSST) in 67 naturally cycling (NC) and 60 oral HC-using women (Mage = 19.31, SDage = 1.95). As hypothesized, HC users and NC women exhibited different glucocorticoid and proinflammatory cytokine responses to the TSST. For NC women, TSST-induced increases in glucocorticoids were uncommon, and increases in glucocorticoids were accompanied by elevations in IL-6. In contrast, for women using HCs, increases in glucocorticoids in response to the TSST were common, and increases in glucocorticoids were accompanied by increases in TNF-α. HC users and NC women also differed in their psychological responses to the TSST, with HC users reporting elevated stress levels compared to NC women. Together, these results suggest that HC use impacts women's glucocorticoid, inflammatory, and psychological responses to psychosocial stress, potentially contributing to observed differences in these women's mental and physical health.
Thyroid and Metabolic Function · Insulin and Metabolism
Dhar S et al., 2024·Journal of human reproductive sciences
Zinc is an essential micronutrient, a vital stabiliser and a cofactor in many enzymes such as superoxide dismutase and phospholipase C and also acts as an antioxidant by protecting the sulfhydryl groups of different proteins and enzymes against free radicals. It is unclear if serum zinc levels are correlated with polycystic ovary syndrome (PCOS) and its pathophysiology, although relation between diabetes and insulin resistance has been established. This study aimed to investigate circulating serum zinc levels in PCOS subjects compared with non-PCOS subjects. In this cohort study, PCOS subjects were compared with normal subjects aged between 18 and 35. All the included subjects underwent measurement of anthropometric parameters, fasting insulin, luteinising hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, progesterone, oestrogen and serum zinc levels. These values were taken on days 2-5 of the menstrual cycle. Univariate analysis and linear regression were performed for serum zinc levels and fasting insulin levels in PCOS subjects and non-PCOS subjects using SPSS (version 21) and Microsoft Excel (2019). Serum zinc levels in the PCOS group were lower than in the control group (P = 0.012). Fasting insulin levels in the PCOS group were higher than in non-PCOS subjects (P = 0.001). We found a negative correlation between zinc and fasting insulin (r = -0.580, P < 0.0001) in the normal group and (r = -0.332, P = 0.019) in the PCOS group. A positive correlation was found between body mass index (BMI) and fasting insulin levels in both the PCOS group (r = 0.227, P = 0.112) and normals (r = 0.612, P < 0.0001). A negative statistically significant correlation between BMI and zinc in both the PCOS group (r = -0.378, P = 0.007) and the non-PCOS group (r = -0.7452, P < 0.0001) was seen. The data suggest that serum zinc levels were found to be lower in PCOS subjects as compared to normal controls and evaluation of these levels may indicate that zinc has a vital role in PCOS pathophysiology.
Deepak Kumar K et al., 2023·Journal of human nutrition and dietetics : the official journal of the British Dietetic Association
One in seven couples are impacted by infertility in the UK, and female infertility is often associated with several health conditions impacted by nutrition. Despite many studies aimed at identifying the critical role of nutrition in infertility, there is currently no screening tool that identifies nutritional risk factors for infertility. To propose a self-administered screening tool to identify women who would benefit from nutritional intervention to promote fertility. A narrative review was carried out to identify and summarise modifiable nutritional risk factors that can influence female fertility, including comorbidities that can influence nutrition intake, absorption, and metabolism. A nutrition screening tool outlining modifiable nutrition risk factors potentially improving female fertility has been proposed, comprising of BMI, medical history and quality of diet and lifestyle which would aid in designing evidence based dietetic services for female infertility.
Zańko A et al., 2022·International journal of environmental research and public health
Infertility is a problem that affects millions of couples around the world. It is known as a disease of couples, not individuals, which makes diagnosis difficult and treatment unclear. Male infertility can have many causes, from mechanical ones to abnormal spermatogenesis or spermiogenesis. Semen quality is determined by a number of factors, including those dependent on men themselves, with the number of infertile men growing every year. These include, e.g., diet, physical activity, sleep quality, stress, among many others. As these factors co-exist with insulin resistance, which is a disease closely related to lifestyle, it has been singled out in the study due to its role in affecting semen quality. In order to examine connections between lifestyle, insulin resistance, and semen quality, a review of literature published from 1989 to 2020 in the following databases PubMed/Medline, EMBASE (Elsevier), Scopus, Web of Science, and Google Scholar was performed. Hence, semen quality, environment, and insulin resistance are interrelated, thus it is difficult to indicate which aspect is the cause and which is the effect in a particular relationship and the nature of possible correlations. Since the influence of lifestyle on semen quality has been extensively studied, it is recommended that more thorough research be done on the relationship between insulin resistance and semen quality, comparing the semen quality of men with and without insulin resistance.
Prescribing Safety · Medication Safety in Pregnancy
Brennan PA et al., 2022·Res Child Adolesc Psychopathol·
Open Access
Prenatal antidepressant exposure has been associated with increased risk for neurodevelopmental disorders in childhood, including autism spectrum disorder (ASD). The current study utilized multi-cohort data from the Environmental influences on Child Health Outcomes (ECHO) program (N = 3129) to test for this association, and determine whether the association remained after adjusting for maternal prenatal depression and other potential confounders. Antidepressants and a subset of selective serotonin reuptake inhibitors (SSRIs) were examined in relation to binary (e.g., diagnostic) and continuous measures of ASD and ASD related traits (e.g., social difficulties, behavior problems) in children 1.5 to 12 years of age. Child sex was tested as an effect modifier. While prenatal antidepressant exposure was associated with ASD related traits in univariate analyses, these associations were statistically non-significant in models that adjusted for prenatal maternal depression and other maternal and child characteristics. Sex assigned at birth was not an effect modifier for the prenatal antidepressant and child ASD relationship. Overall, we found no association between prenatal antidepressant exposures and ASD diagnoses or traits. Discontinuation of antidepressants in pregnancy does not appear to be warranted on the basis of increased risk for offspring ASD.
Infertility Distress · Anxiety and Depression in Infertility
What is the association between perceived stress during peri-conception and early pregnancy and pregnancy loss among women who have experienced a prior pregnancy loss? Daily perceived stress above the median is associated with over a 2-fold risk of early pregnancy loss among women who have experienced a prior loss. WHAT IS KNOWN ALREADY? Women who have experienced a pregnancy loss may be more vulnerable to stress while trying to become pregnant again. While prior research has indicated a link between psychological stress and clinically confirmed miscarriages, research is lacking among a pre-conceptional cohort followed prospectively for the effects of perceived stress during early critical windows of pregnancy establishment on risk of both hCG-detected pregnancy losses and confirmed losses, while considering important time-varying confounders. STUDY DESIGN, SIZE, Secondary data analysis of the EAGeR trial (2007-2011) among women with an hCG-detected pregnancy (n = 797 women). PARTICIPANTS/MATERIALS, SETTING, Women from four US clinical centers enrolled pre-conceptionally and were followed ≤6 cycles while attempting pregnancy and, as applicable, throughout pregnancy. Perceived stress was captured via daily diaries and end-of-month questionnaires. Main outcome measures include hCG-detected and clinically recognized pregnancy losses. MAIN Among women who had an hCG-confirmed pregnancy, 188 pregnancies (23.6%) ended in loss. Women with high (>50th percentile) versus low (≤50th percentile) peri-implantation or early pregnancy weekly perceived stress had an elevated risk of experiencing any pregnancy loss (hazard ratio (HR): 1.69, 95% CI: 1.13, 2.54) or clinical loss (HR: 1.58, 95% CI: 0.96, 2.60), with higher risks observed for women experiencing an hCG-detected loss (HR: 2.16, 95% CI: 1.04, 4.46). Models accounted for women's age, BMI, employment, marital status, income, education, race, parity, prior losses, exercise and time-varying nausea/vomiting, caffeine, alcohol and smoking. LIMITATIONS, We were limited in our ability to clearly identify the mechanisms of stress on pregnancy loss due to our sole reliance on self-reported perceived stress, and the lack of biomarkers of different pathways of stress. This study provides new insight on early pregnancy perceived stress and risk of pregnancy loss, most notably hCG-detected losses, among women with a history of a prior loss. Our study is an improvement over past studies in its ability to account for time-varying early pregnancy symptoms, such as nausea/vomiting, and lifestyle factors, such as caffeine, alcohol and smoking, which are also risk factors for psychological stress and pregnancy loss. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract numbers: HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I). Additionally, K.C.S. was supported by the National Institute on Aging of the National Institutes of Health under Award Number K01AG058781. The authors have no conflicts of interest to disclose. #NCT00467363.
Guidelines by Clinical Area · Obstetric Guidelines
Adams JB et al., 2022·Maternal health, neonatology and perinatology
The blood levels of most vitamins decrease during pregnancy if un-supplemented, including vitamins A, C, D, K, B1, B3, B5, B6, folate, biotin, and B12. Sub-optimal intake of vitamins from preconception through pregnancy increases the risk of many pregnancy complications and infant health problems. In the U.S., dietary intake of vitamins is often below recommended intakes, especially for vitamin D, choline and DHA. Many studies suggest that insufficient vitamin intake is associated with a wide range of pregnancy complications (anemia, Cesarean section, depression, gestational diabetes, hypertension, infertility, preeclampsia, and premature rupture of membranes) and infant health problems (asthma/wheeze, autism, low birth weight, congenital heart defects, intellectual development, intrauterine growth restriction, miscarriage, neural tube defects, orofacial defects, and preterm birth). The primary goal of this paper is to review the research literature and propose evidence-based recommendations for the optimal level of prenatal supplementation for each vitamin for most women in the United States. A secondary goal was to compare these new recommendations with the levels of vitamins in over 180 commercial prenatal supplements. The analysis found that prenatal supplements vary widely in content, often contained only a subset of essential vitamins, and the levels were often below our recommendations. This suggests that increasing prenatal vitamin supplementation to the levels recommended here may reduce the incidence of many pregnancy complications and infant health problems which currently occur.
Vigil P et al., 2022·Front Glob Womens Health·
Open Access
Stress is known to be associated with adverse health outcomes. The COVID-19 pandemic and its associated lockdowns are examples of chronic stressors. Lockdown measures inadvertently caused significant psychological distress and became a powerful source of anxiety/stress, sleep disturbances, nutritional changes and weight gain. Stress is known to impact women's health specifically, through hypothalamic-pituitary-gonadal (HPG) axis dysfunction and resultant ovulatory dysfunction. Such dysfunction may manifest in menstrual irregularities and/or infertility due to hypothalamic hypogonadism. Here, we review the key physiological mediators of stress and associated ovulatory dysfunction. The kisspeptinergic system is comprised of sets of neurons located in the hypothalamus, the rostral periventricular region of the third ventricle (RP3V) and the arcuate nucleus (ARC). This system links nutrition, reproductive signals and stress. It plays a key role in the function of the HPG axis. During chronic stress, the kisspeptinergic system affects the HPG axis, GnRH pulsatility, and, therefore, ovulation. Leptin, insulin and corticotrophin-releasing hormone (CRH) are thought to be additional key modulators in the behavioral responses to chronic stress and may contribute to stress-related ovulatory dysfunction. This mini-review also summarizes and appraises the available evidence on the negative impact of chronic stress as a result of the COVID-19 pandemic lockdowns. It proposes physiological mechanisms to explain the observed effects on women's reproductive health and well-being. The review suggests areas for future research.
Male infertility is an increasing and serious medical concern, though the mechanism remains poorly understood. Impaired male reproductive function affects approximately half of infertile couples worldwide. Multiple factors related to the environment, genetics, age, and comorbidities have been associated with impaired sperm function. Present-day clinicians rely primarily on standard semen analysis to diagnose male reproductive potential and develop treatment strategies. To address sperm quality assessment bias and enhance analysis accuracy, the World Health Organization (WHO) has recommended standardized sperm testing; however, conventional diagnostic and therapeutic options for male infertility, including physical examination and semen standard analysis, remain ineffective in relieving the associated social burden. Instead, assisted reproductive techniques are becoming the primary therapeutic approach. In the post-genomic era, multiomics technologies that deeply interrogate the genome, transcriptome, proteome, and/or the epigenome, even at single-cell level, besides the breakthroughs in robotic surgery, stem cell therapy, and big data, offer promises towards solving semen quality deterioration and male factor infertility. This review highlights the complex etiology of male infertility, especially the roles of lifestyle and environmental factors, and discusses advanced technologies/methodologies used in characterizing its pathophysiology. A comprehensive combination of these innovative approaches in a global and multi-centric setting and fulfilling the suitable ethical consent could ensure optimal reproductive and developmental outcomes. These combinatorial approaches should allow for the development of diagnostic markers, molecular stratification classes, and personalized treatment strategies. Since lifestyle choices and environmental factors influence male fertility, their integration in any comprehensive approach is required for safe, proactive, cost-effective, and noninvasive precision male infertility theranostics that are affordable, accessible, and facilitate couples realizing their procreation dream.
To evaluate variations in micronutrient biomarker concentrations and deficiencies across the menstrual cycle in a cohort of healthy women. This prospective cohort study was conducted among healthy women of reproductive age living in the State College area, Pennsylvania, (n = 45). Data collection occurred at the early follicular phase, the late follicular phase, and the midluteal phase. Fasting blood samples were collected to measure micronutrient biomarkers. At the early follicular phase, the mean ± SD concentrations for zinc, copper, magnesium, and retinol were 81.8 ± 16.2 µg/dL, 80.1 ± 12.8 µg/dL, 17.9 ± 1.4 mg/L, and 39.4 ± 9.3 µg/dL, respectively. The geometric mean (95% CI) for manganese, iron and ferritin concentrations were 1.51 [1.21, 1.87] µg/L, 106.7 [90.8, 125.4] µg/dL, and 26.4 [20.5, 34.0] µg/L, respectively. Mean concentrations of zinc and magnesium declined by 6.6% (p = 0.009) and 4.6% (p < 0.001) from the early follicular phase to the midluteal phase, respectively. Other biomarkers remained relatively constant across the cycle. At the early follicular phase, the prevalence of low serum concentrations for zinc, copper, magnesium, manganese, iron, and ferritin was 22%, 7%, 29%, 13%, 14%, and 28%, respectively. Also, in early follicular phase, 36% had anemia, and 13% specifically had iron deficiency anemia. The prevalence of magnesium deficiency was significantly higher at the midluteal phase vs. the early follicular phase (p = 0.025). Our study suggests that while many micronutrient concentrations are relatively constant across the menstrual cycle in healthy women, zinc and magnesium decline, and the prevalence of magnesium deficiency increases. Supplemental data for this article is available online at.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Polycystic ovary syndrome (PCOS) often coexists with a wide spectrum of dysglycemic conditions, ranging from impaired glucose tolerance to type 2 diabetes mellitus (T2D), which occur to a greater extent compared to healthy body mass index-matched women. This concurrence of disorders is mainly attributed to common pathogenetic pathways linking the two entities, such as insulin resistance. However, due to methodological flaws in the available studies and the multifaceted nature of the syndrome, there has been substantial controversy as to the exact association between T2D and PCOS which has not yet been elucidated. The aim of this review is to present the best available evidence regarding the epidemiology of dysglycemia in PCOS, the unique pathophysiological mechanisms underlying the progression of dysglycemia, the most appropriate methods for assessing glycemic status and the risk factors for T2D development in this population, as well as T2D risk after transition to menopause. Proposals for application of a holistic approach to enable optimal management of T2D risk in PCOS are also provided. Specifically, adoption of a healthy lifestyle with adherence to improved dietary patterns, such the Mediterranean diet, avoidance of consumption of endocrine-disrupting foods and beverages, regular exercise, and the effect of certain medications, such as metformin and glucagon-like peptide 1 receptor agonists, are discussed. Furthermore, the maintenance of a healthy weight is highlighted as a key factor in achievement of a significant reduction of T2D risk in women with PCOS.
Iwasa T et al., 2022·Reproductive medicine and biology
It is known that metabolic and nutritional disturbances induce reproductive dysfunction in females. The main cause of these alterations is reduced gonadotrophin-releasing hormone (GnRH) secretion from the hypothalamus, and the underlying mechanisms have gradually been elucidated. The present review summarizes current knowledge about the effects of nutrition/metabolism on reproductive functions, especially focusing on the GnRH regulation system. Various central and peripheral factors are involved in the regulation of GnRH secretion, and alterations in their activity combine to affect GnRH neurons. Satiety-related factors, i.e., leptin, insulin, and alpha-melanocyte-stimulating hormone, directly and indirectly stimulate GnRH secretion, whereas orexigenic factors, i.e., neuropeptide Y, Agouti-related protein, orexin, and ghrelin, attenuate GnRH secretion. In addition, kisspeptin, which is a potent positive regulator of GnRH, expression is reduced by metabolic and nutritional disturbances. These neuroendocrine systems may be defensive mechanisms, which help organisms to survive adverse conditions by temporarily suppressing reproduction.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Practice Committee of the American Society for Reproductive Medicine, 2022·Fertility and Sterility
This committee opinion provides practitioners with suggestions for optimizing the likelihood of achieving pregnancy in couples or individuals attempting conception who have no evidence of infertility. This document replaces the document of the same name previously published in 2013 (Fertil Steril 2013;100:631-7).
Thyroid and Metabolic Function · Insulin and Metabolism
Cabre HE et al., 2022·Deutsche Zeitschrift fur Sportmedizin
If athletes develop low energy availability (LEA), it can lead to a Relative Energy Deficiency in Sport (RED-S) syndrome which has severe health consequences if not treated. A narrative review of the most recent and pertinent literature on the topic, with special emphasis on women. In assessing the current literature, we have synthesized: i) the scientific implications of LEA and RED-S, ii) the clinical manifestations of the conditions currently available for detection, as well as iii) the practical implications for healthcare and support for female athletes and teams in planning intervention or prevention strategies (maintaining EA >45 kcal/kg FFM/day). The 'Female Athlete Triad" emerged in the 1990s as researchers understood more of the etiological adaptation of female athlete health to sports training. In the last 10 years, the scientific community has recognized that the 'Triad' approach was too narrow in focus, and the broader concept of RED-S emerged. Both the Triad and RED-S are consequences of a frequently prevalent LEA in athletes (<30 kcal/kg FFM/day). Developing LEA and RED-S compromises training adaptation, performance capacity, and health in athletes. For these reasons, it is critical that an athlete's support team recognize the behaviors that may indicate RED-S evolution. In this way, we can assist female athletes in reaching their full potential in sports while protecting their health. Kommt es bei männlichen oder weiblichen Athleten zu einer dauerhaft niedrigen Energieverfügbarkeit (low energy availability, LEA), steigt das Risiko eines Relative Energy Deficiency in Sports (RED-S) Syndroms, welches unbehandelt schwerwiegende kurz- wie langfristige gesundheitliche Konsequenzen haben kann. Ein narratives Review der aktuellsten und relevantesten Literatur mit besonderem Fokus auf weibliche Betroffene. Aus der verfügbaren Literatur haben wir i) wissenschaftliche Implikationen von LEA und RED-S, ii) klinische Manifestationen und iii) praktische Implikationen für die medizinische Behandlung, Unterstützung betroffener Teams, sowie präventive Strategien herausgearbeitet. In den 1990er Jahren erfasste mit zunehmendem Verständnis um die frauen-spezifischen Anpassungen an sportliche Aktivität das Phänomen der “Female Athlete Triad” die Aufmerksamkeit von Wissenschaftlern und Medizinern. In der vergangenen 10 Jahren zeigte sich, dass der “Triad”-Ansatz zu kurz greift und es wurde stattdessen das breiter gefasste Konzept des RED-S etabliert. Sowohl die “Female Athlete Triad”, als auch RED-S sind letztendlich Konsequenzen der häufig prävalenten LEA in Athletinnen mit weitreichenden Konsequenzen auf die Trainingsadaptation, Wettkampfleistung und kurz-, wie langfristige Gesundheit der Betroffenen. Aus diesem Grund ist das Erkennen von Verhaltensweisen, welche auf ein RED-S hindeuten durch Trainer und weiterer Stakeholder einer Athletin beziehungsweise eines Teams essenziell für eine gesundheitsund leistungserhaltende Betreuung von betroffenen Athletinnen.
Prescribing Safety · Medication Safety in Pregnancy
Bauer AZ et al., 2021·Nature reviews. Endocrinology
Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.
Thyroid and Metabolic Function · Insulin and Metabolism
Westerman R et al., 2021·Reprod Biomed Soc Online·
Open Access
Metabolic risk factors such as obesity are considered major obstacles to female fertility. Chronic infertility imposes psychological and social burdens on women because infertility violates societal gender roles. Although the prevalence of obesity among women is expected to increase in the future, the relevance of metabolic status for fertility is still underestimated. However, the assessment of metabolic risk factors is highly relevant for understanding fertility disorders and improving infertility treatment. This narrative review discusses the associations of metabolic risk factors (e.g. obesity, female athlete triad, oxidative stress) with significant infertility. An electronic search was conducted for studies published between 2006 and 2020 in Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, PubMed, Scopus, Google Scholar and related databases. In total, this search identified 19,309 results for polycystic ovary syndrome, 28,969 results for endometriosis, and only 1611 results for idiopathic and/or unknown infertility. For the present narrative review, 50 relevant studies were included: 19 studies were on obesity, 24 studies investigated the female athlete triad, and seven studies addressed other risk factors, including reactive oxygen species. This narrative review confirms the direct impact of obesity on female infertility, while the effect of other risk factors needs to be confirmed by large-scale population studies.
Başar Gökcen B et al., 2020·Gynecological Endocrinology
Data on eating disorders in women with PCOS is insufficient. The objective of this case study was to examine the hypothesis that women with PCOS exhibit more impaired eating than healthy women. Women diagnosed with PCOS under the 2003 Rotterdam Diagnostic Criteria (n = 40) were compared with a healthy control group (n = 40). The groups also were divided into two as normal body weight and overweight/obese. The Eating Disorders Assessment Questionnaire (EDE-Q) and the Three Factor Eating Questionnaire (TFEQ-R21), were completed by all participants in order to evaluate eating behaviors in addition to eating disorders. Among the overweight/obese group, the average total and subscale scores of the EDE-Q as well as the total and sub-factor scores of the TFEQ-R21 were higher in women with PCOS compared to controls (p < .05). However, this statistically significant result was not shown among the women with normal weight (p > .05). In comparison to the controls, the PCOS women displayed higher values of the tool scores indicating abnormal restraint eating, body shape concern and weight concern subscale scores (p < .05). This result suggests that the evaluation of eating disorders should be added to routine screening and the monitoring of women with PCOS.
Michels KA et al., 2020·Chronobiol Int·
Open Access
Despite research indicating that sleep disorders influence reproductive health, the effects of sleep on reproductive hormone concentrations are poorly characterized. We prospectively followed 259 regularly menstruating women across one to two menstrual cycles (the BioCycle Study, 2005-2007), measuring fasting serum hormone concentrations up to eight times per cycle. Women provided information about daily sleep in diaries and chronotype and night/shift work on a baseline questionnaire. We evaluated percent differences in mean hormone concentrations, the magnitude of shifts in the timing and amplitude of hormone peaks, and the risk for sporadic anovulation associated with self-reported sleep patterns and night/shift work. We estimated chronotype scores - categorizing women below and above the interquartile range (IQR) as "morning" and "evening" chronotypes, respectively. For every hour increase in daily sleep duration, mean estradiol concentrations increased by 3.9% (95% confidence interval [CI] 2.0, 5.9%) and luteal phase progesterone by 9.4% (CI 4.0, 15.2%). Receiving less than 7 hours of sleep per day was associated with slightly earlier rises in peak levels for several hormones. Women reporting night/shift work (n = 77) had lower testosterone relative to women employed without night/shift work (percent difference: -9.9%, CI -18.4, -0.4%). Women with morning chronotypes (n = 47) had earlier rises in estradiol during their cycles and potentially an earlier rise in luteinizing hormone. Compared to those who had intermediate chronotypes, women with evening chronotypes (n = 42) had a later luteinizing hormone peak of borderline statistical significance. A reduced risk for sporadic anovulation was suggested, but imprecise, for increasing hours of daily sleep leading up to ovulation (risk ratio 0.79, CI 0.59, 1.06), while an imprecise increased risk was observed for women with morning chronotypes (risk ratio 2.50, CI 0.93, 6.77). Sleep-related hormonal changes may not greatly alter ovarian function in healthy women, but have the potential to influence gynecologic health.
Thyroid and Metabolic Function · Insulin and Metabolism
Roseff S et al., 2020·International journal of endocrinology
The aim of this paper is to critically analyze the composition of many inositol-based products currently used to treat Polycystic Ovary Syndrome (PCOS). Several different combinations of myo-inositol and D-chiro-inositol, with and without additional compounds such as micro- and macroelements, vitamins, and alpha-lipoic acid, have been formulated over the years. Such therapeutic proposals do not take various features of inositol stereoisomers into consideration. As an example, it is important to know that D-chiro-inositol treatment may be beneficial when administered in low doses, yet the progressive increase of its dosage results in the loss of its advantageous effects on the reproductive performance of women and a deterioration in the quality of blastocysts created via in vitro fertilization (IVF). In addition, we have to consider that the intestinal absorption of myo-inositol is reduced by the simultaneous administration of D-chiro-inositol since the two stereoisomers compete with each other for the same transporter that has similar affinity for each of them. A decrease in myo-inositol absorption is also found when it is coadministered with inhibitors of sugar intestinal absorption and/or types of sugars such as sorbitol, maltodextrin, and sucralose. The combination of these may require higher amounts of myo-inositol in order to reach a therapeutic dosage compared to inositol administration alone, a particularly important fact when physicians strive to obtain a specific plasma level of the stereoisomer. Finally, we must point out that D-chiro-inositol was found to be an aromatase inhibitor which increases androgens and may have harmful consequences for women. Therefore, the inositol supplements used in PCOS treatment must be carefully defined. Clinical evidence has demonstrated that the 40 : 1 ratio between myo-inositol and D-chiro-inositol is the optimal combination to restore ovulation in PCOS women. Therefore, it is quite surprising to find that inositol-based treatments for PCOS seem to be randomly chosen and are often combined with useless or even counterproductive molecules, all of which can weaken myo-inositol's efficacy. Such treatments clearly lack therapeutic rationale.
Harville EW et al., 2019·Paediatr Perinat Epidemiol·
Open Access
Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature. The consortium will investigate the effects of preconception exposures on four sets of outcomes: (1) fertility and miscarriage; (2) pregnancy-related conditions; (3) perinatal and child health; and (4) adult health outcomes. A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation. The included studies are a mix of studies following women or couples intending to conceive, general-health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages. Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors. Twenty-three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general-population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data. The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy.
Wassef A et al., 2019·Journal of psychosomatic obstetrics and gynaecology
Iron-deficiency and anaemia are common in pregnant and postpartum women because of increasing iron demand and blood loss. Many women also enter pregnancy with pre-depleted iron stores. We reviewed the evidence linking anaemia and/or iron-deficiency to postpartum depression (PPD). We identified seventeen studies in four databases including randomized-controlled trials (RCTs) and observational studies assessing the impact of anaemia, iron-deficiency and iron supplementation on the risk of PPD. We extracted data on sample size, geographical region, obstetrical complications, measures of depression, haemoglobin, iron levels and intake of iron supplementation and critically appraised the results from the studies. Eight out of ten studies found higher risk for PPD (r - 0.19 to -0.43 and ORs 1.70-4.64) in anaemic women. Low ferritin in the postpartum period but not during pregnancy was associated with increased risk of PPD. Iron supplementation in the postpartum period decreased risk of PPD in four out of five studies, whereas it did not protect from PPD if given during pregnancy. Limitations include study heterogeneity, discrepancy of prevalence of PPD and usage of a screening tool for evaluation of PPD. Anaemia and/or iron-deficiency may contribute to PPD in at-risk women. Further studies should elucidate the association between these entities.
Thyroid and Metabolic Function · Insulin and Metabolism
Abedini M et al., 2019·Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
Several studies have investigated serum zinc levels in patients with polycystic ovarian syndrome (PCOS), but the results of these studies remain inconclusive. Therefore, to derive a more precise estimation, we conducted a meta-analysis to investigate serum zinc concentrations in women with PCOS in comparison with healthy subjects. Electronic search was performed in PubMed, Scopus, and Google scholar up to April; 4, 2018 without any restriction. Eligible studies that evaluated the levels of zinc status in subjects with PCOS were included. Weighted mean differences (WMDs) with corresponding 95% CIs in serum zinc levels were initially estimated using a random-effects model. Eight studies, measuring circulating zinc levels in 552 PCOS and 464 control subjects, were included. Pooled effect size suggested that serum zinc levels in women with PCOS were not statistically different than their controls (WMD = -4.43 mg/dL; 95% CI = [-10.30, 1.44]; P = 0.139). Exclusion of one study revealed that women with PCOS significantly have lower serum zinc levels compared to healthy controls (WMD: -6.60 mg/dL; 95% CI = [-12.43, -0.76], P = 0.027). Our study indicated that circulating zinc levels in women with PCOS were significantly lower than those in healthy controls when detailed analysis is conducted. Large scale studies are needed to elucidate clear relation between zinc status and etiology of PCOS.
Amini S et al., 2019·Critical reviews in food science and nutrition
Postpartum depression (PPD) is a prevalent mood disorder estimated to affect 20%-40% of women worldwide after childbirth. In recent studies, the effect of vitamin D on prevention of mood disorders and depression has been investigated, but it is still unclear how vitamin D may affect PPD. The evidence on the relevance between vitamin D deficiency and PPD is inconsistent, and assessment of the recent literature has not previously been carried out. Moreover, there are few clinical studies on PPD and vitamin D supplementation. Five studies have so far assessed the relationship between the levels of vitamin D and PPD. Findings from cohort studies suggest that vitamin-D deficiency is related to the incidence of PPD and vitamin D may play a significant role in the recovery of women with PPD, but it is uncertain whether these actions are the effect of vitamin D on the function of hypothalamic-pituitary-adrenal (HPA) axis, the levels of estradiol, serotonin, pro-inflammatory cytokines, and/or of other mechanisms involved in PPD.
Hajhashemi M et al., 2019·Caspian journal of internal medicine
Uterine leiomyomas (fibroids) are the most common benign pelvic tumors in women of reproductive age with an incidence ranging from 5.4% to 77%, Also, there is a high prevalence of vit D deficiency in Iran and there are the numbers of in vivo and vitro biological studies on the relationship of vitamin D and uterine leiomyomas. The aim of this study was to evaluate the effect of vit D supplementation on the size of uterine leiomyoma in women with vit D deficiency. This double-blind prospective clinical trial was performed on 69 patients with uterine leiomyomas who had vit D deficiency. Group A (n=35) was treated with vit D 50,000 IU every 2 weeks for 10 weeks, while group B (n=34) received placebo with same color and shape. Finally, the leiomyoma size in both groups was compared (IRCT: 20160521027998N5). After a 10-week intervention, 25-hydroxyvitamin D3 levels were significantly higher in group receiving vitamin D (36.08 vs 16.25 ng/ml). (P<0.001) Leiomyomas size in vit D group significantly decreased as compared to placebo group (52.58 vs 61.11 mm, respectively). Our results showed that administration of vit D3 may reduce the size of leiomyoma. It seems that vitamin D administration is the effective way to treat leiomyoma.
Disorders of bone density are especially prevalent among athletic women. The severity of bone loss ranges from osteopenia to frank osteoporosis. In female athletes, a higher incidence of osteoporosis is due to a decreased rate of bone accretion in youth, often as a result of hormonal deficiency and/or excessive exercise. Low bone mass poses a particular challenge for athletes because it predisposes to stress-related bone injuries and increases the risk of osteoporosis and insufficiency fractures with aging. This article reviews the pathophysiology of bone thinning in premenopausal and postmenopausal women, the impact of exercise, and the treatment options presently available.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
The aim of the present study was to demonstrate that the use of inositol and folic acid from the first trimester of pregnancy, counteracts the onset of gestational diabetes mellitus (GDM) in women at risk, preserving the infants from macrosomia, hypoglycemia and preterm delivery. The authors collected data from the pregnant women at the laboratory (Unit of Cytogenic and Molecular Genetics), from January 2014 to April 2016, all with first trimester fasting plasma glucose (FPG) >92 mg/dl. A total of 40 women were treated with 250 mg/day D-chiro-inositol, 1.75 g/day D-myo-inositol, 12.5 mg/day zinc, 10 mg/day methylsulfonylmethane, 400 µg/day 5-methyltetrahydrofolic acid. The other 43 women (control group) were treated with only 400 µg/day folic acid. The primary outcome measure was the incidence of maternal GDM. The secondary outcome measures were the incidence of fetal macrosomia, preterm delivery and neonatal hypoglycemia. At the 24th week of pregnancy, the incidence of maternal GDM was recorded in 18 women in the control group and in 5 women in the treated group [relative risk (RR)=3.35; 95% confidence interval (CI)=1.37-8.17; P=0.0028). A significant difference was observed between treated and control groups in terms of risk of macrosomia. A total of seven infants in the control group, and two in the treated group, weighed >4,000 g (RR=5,12; 95% CI=1.21-21.68; P=0.0099). No significant difference was identified between two groups, regarding the other two secondary outcomes, neonatal hypoglycemia (RR=4.650; 95% CI=0.57-38.11; P=0.1086) and preterm delivery (RR=1.74; 95% CI=0.83-3.66; P=0.1301). The current study demonstrated the potential benefit of supplementation with the association of D-chiro-inositol and D-myo-inositol in pregnant 'at risk' women, with first trimester FPG >92 mg/dl, in preventing the onset of maternal GDM and macrosomia in newborns.
How are concentrations of plasma homocysteine and serum folate associated with reproductive hormones and anovulation in regularly menstruating women? Higher homocysteine was associated with sporadic anovulation and hormonal changes that may be indicative of impaired ovulatory function, but higher serum folate was associated only with higher luteal phase progesterone. Higher folate levels as well as some variants in genes relevant to one-carbon metabolism, are associated with improved reproductive outcomes and responses to fertility treatment, but only a few small studies have explored the relationship between markers of one-carbon metabolism and menstrual cycle characteristics. STUDY DESIGN, SIZE, Duration: The BioCycle Study (2005-2007) is a prospective, longitudinal cohort of 259 regularly menstruating women not using hormonal contraceptives or dietary supplements who were followed for up to two menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, Serum folate and reproductive hormones were measured up to eight times per cycle and plasma homocysteine up to three times. Linear mixed models were used to estimate associations between serum folate or plasma homocysteine and log-transformed reproductive hormone levels while accounting for multiple observations and cycles per woman. Generalized estimating equations were used to examine risk of sporadic anovulation. All models were adjusted for age, race, body mass index, cigarette and alcohol use, and energy and fiber intake. Main Higher plasma homocysteine concentrations were associated with lower total estradiol across the cycle (adjusted percent change per unit increase in homocysteine [aPC] -2.3%, 95% CI: -4.2, -0.03), higher follicle stimulating hormone around the time of expected ovulation (aPC 2.4%, 95% CI: 0.2, 4.7) and lower luteal phase progesterone (aPC -6.5%, 95% CI: -11.1, -1.8). Higher serum folate concentrations were associated with higher luteal phase progesterone (aPC per unit increase in folate 1.0%, 95% CI: 0.4, 1.6). Higher homocysteine concentrations at expected ovulation were associated with a 33% increased risk of sporadic anovulation. We observed no risk associated with decreased folate concentrations, but a higher ratio of folate to homocysteine at ovulation was associated with a 10% decreased risk of anovulation. LIMITATIONS, Our results are generalizable to healthy women with adequate serum folate levels. The independent influence of homocysteine should be confirmed in larger cohorts and among women with folate deficiency or increased risks of anovulation. If these findings are confirmed, it is possible that lowering homocysteine with B-vitamins through diet or supplementation could improve ovulatory function in some women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Contract numbers: HHSN275200403394C, HHSN275201100002I and Task one HHSN27500001). None of the authors has any conflicts of interest to disclose.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
This Committee Opinion provides practitioners with suggestions for optimizing the likelihood of achieving pregnancy in couples/individuals attempting conception who have no evidence of infertility. This document replaces the document of the same name previously published in 2013, Fertil Steril 2013;100(3):631-7.
The aim of this study was to evaluate the effect of vitamin D supplementation in women with hypovitaminosis D and "small burden" uterine fibroids.This study focused on 208 women diagnosed with uterine fibroids and concomitant hypovitaminosis D, from January to December 2014. One hundred eight women of the initial study population were diagnosed with "small burden" uterine fibroids. Among them, those who underwent a proper vitamin D supplementation constituted the "study group" (n = 53), while women who spontaneously refused the therapy or did not perform it properly, constituted the "control group" (n = 55). The characteristics of uterine fibroids, the fibroid-related symptoms, and the vitamin D serum levels were evaluated 12 months after the initial diagnosis.In women with uterine fibroids, a negative correlation emerged between the baseline 25-hydroxy-cholecalciferol (25-OH-D3) concentration and both the volume of the largest fibroid (r = -0.18, P = 0.01) and the total volume of fibroids (r = -0.19, P = 0.01). No correlation was found between the baseline 25-OH-D3 levels and the number of fibroids per patient (r = -0.10, P = 0.16). In women of the "study group," a significant increase in the 25-OH-D3 serum level was observed after 12 months of supplementation, and a lower rate of surgical or medical treatment due to the "progression to extensive disease" was reported (13.2% vs 30.9%, P = 0.05).Supplementation therapy with 25-OH-D3 restores normal vitamin D serum levels in women with "small burden" fibroids. In these women, vitamin D supplementation seems to reduce the progression to an extensive disease, and thus the need of conventional surgical or medical therapy.
Porucznik CA et al., 2016·Environ Health·
Open Access
To examine transient environmental exposures and their relationship with human fecundity, exposure assessment should occur optimally at the time of conception in both members of the couple. We performed an observational, prospective cohort study with biomonitoring in both members of a heterosexual couple trying to conceive. Couples collected urine, saliva, and semen specimens for up to two menstrual cycles on days corresponding to the time windows of fertilization, implantation, and early pregnancy, identified based on the woman's observations of her cervical fluid. Three hundred nine eligible couples were screened between 2011 and 2015, of which 183 enrolled. Eleven couples (6.0 %) withdrew or were lost to follow up. The most successful and cost effective recruiting strategies were word of mouth (40 % of participating couples), posters and flyers (37 %), and targeted Facebook advertising (13 %) with an overall investment of $37.35 spent on recruitment per couple. Both men and women collected ≥97.2 % of requested saliva samples, and men collected ≥89.9 % of requested semen samples. Within the periovulatory days (±3 days), there was at least one urine specimen collected by women in 97.1 % of cycles, and at least one by men in 91.7 % of cycles. Daily compliance with periovulatory urine specimens ranged from 66.5 to 92.4 % for women and from 55.7 to 75.0 % for men. Compliance was ≥88 % for questionnaire completion at specified time points. Couples planning to conceive can be recruited successfully for periconceptional monitoring, and will comply with intensive study protocols involving home collection of biospecimens and questionnaire data.
Brents LK, 2016·The Yale journal of biology and medicine
Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Tolerance to these effects has been shown in rhesus monkeys, but the effects of chronic marijuana use on human female reproduction are largely unknown. Marijuana-induced analgesia, drug reinforcement properties, tolerance, and dependence are influenced by ovarian hormones, with estrogen generally increasing and progesterone decreasing sensitivity to marijuana. Carefully controlled regulation of the Endocannabinoid System (ECS) is required for successful reproduction, and the exogenous cannabinoids in marijuana may disrupt the delicate balance of the ECS in the female reproductive system.
Studies with animals of both sexes show that the adrenal glands release progesterone in addition to cortisol in response to stress. However, little is known about the progesterone response to stress in naturally cycling women. We investigated the effect of stress on estradiol, progesterone, and cortisol levels in women during the follicular phase of the menstrual cycle. We found that physical stress (the cold pressor test) had no effect on estradiol levels, but increased progesterone and cortisol. We also found positive correlations between baseline progesterone and cortisol levels, as well as between the change in progesterone and cortisol before and after water exposure in both the stress and control sessions. Mediation analyses revealed during the stress session, the change in progesterone from baseline to 42-min post-stress onset was mediated by the magnitude of change in cortisol levels across the same time span. Overall, these findings reveal that progesterone released in response to stress as observed in animals and men extends to women during the low ovarian output follicular phase of the menstrual cycle, and that the mechanism of release may be similar to the mechanism of cortisol release.
Jamilian M et al., 2016·Biological trace element research
The current study was conducted to evaluate the effects of zinc supplementation on endocrine outcomes, biomarkers of inflammation, and oxidative stress in patients with polycystic ovary syndrome (PCOS). This study was a randomized double-blind, placebo-controlled trial. Forty-eight women (18-40 years) with PCOS diagnosed according to Rotterdam criteria were randomly assigned to receive either 220 mg zinc sulfate (containing 50 mg zinc) (group 1; n = 24) and/or placebo (group 2; n = 24) for 8 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were measured at study baseline and after 8-week intervention. After 8 weeks of intervention, alopecia (41.7 vs. 12.5%, P = 0.02) decreased compared with the placebo. Additionally, patients who received zinc supplements had significantly decreased hirsutism (modified Ferriman-Gallwey scores) (-1.71 ± 0.99 vs. -0.29 ± 0.95, P < 0.001) and plasma malondialdehyde (MDA) levels (-0.09 ± 1.31 vs. +2.34 ± 5.53 μmol/L, P = 0.04) compared with the placebo. A trend toward a significant effect of zinc intake on reducing high-sensitivity C-reactive protein (hs-CRP) levels (P = 0.06) was also observed. We did observe no significant changes of zinc supplementation on hormonal profiles, inflammatory cytokines, and other biomarkers of oxidative stress. In conclusion, using 50 mg/day elemental zinc for 8 weeks among PCOS women had beneficial effects on alopecia, hirsutism, and plasma MDA levels; however, it did not affect hormonal profiles, inflammatory cytokines, and other biomarkers of oxidative stress.
Santamaria A et al., 2015·J Matern Fetal Neonatal Med·
To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women. In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and < 30 kg/m(2)). The primary outcome was the incidence of GDM. From January 2012 to December 2014, 220 pregnant women were randomized at two Italian University hospitals, 110 to myo-inositol and 110 to placebo. The incidence of GDM was significantly lower in the myo-inositol group compared to the placebo group (11.6% versus 27.4%, respectively, p = 0.004). Myo-inositol treatment was associated with a 67% risk reduction of developing GDM (OR 0.33; 95% CI 0.15-0.70). Myo-inositol supplementation, administered since early pregnancy, reduces GDM incidence in overweight non-obese women.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Ethics Committee of the American Society for Reproductive Medicine, 2015·Fertility and Sterility
The purpose of this ASRM Practice Committee report is to provide clinicians with principles and strategies for the evaluation and treatment of couples with infertility associated with obesity. This revised document replaces the Practice Committee document titled, "Obesity and reproduction: an educational bulletin," last published in 2008 (Fertil Steril 2008;90:S21-9).
Schliep KC et al., 2015·Am J Clin Nutr·
Open Access
Although habitual low-to-moderate alcohol intake has been linked with reduced all-cause mortality and morbidity, the effect of recent alcohol intake on female reproductive function has not been clearly established. We assessed the relation between acute alcohol consumption, reproductive hormones, and markers of menstrual cycle dysfunction including sporadic anovulation, irregular cycle length, luteal phase deficiency, long menses, and heavy blood loss.
A total of 259 healthy, premenopausal women from Western New York were followed for ≤2 menstrual cycles (2005-2007) and provided fasting blood specimens during ≤8 visits/cycle and four 24-h dietary recalls/cycle. Linear mixed models were used to estimate associations between previous day's alcohol intake and hormone concentrations, whereas Poisson regression was used to assess RR of cycle-average alcohol intake and menstrual cycle function. For every alcoholic drink consumed, the geometric mean total and free estradiol, total and free testosterone, and luteinizing hormone were higher by 5.26% (95% CI: 1.27%, 9.41%), 5.82% (95% CI: 1.81%, 9.99%), 1.56% (95% CI: 0.23%, 2.90%), 1.42% (95% CI: 0.02%, 2.84%), and 6.18% (95% CI: 2.02%, 10.52%), respectively, after adjustment for age, race, percentage of body fat, perceived stress, pain-medication use, sexual activity, caffeine, and sleep. Binge compared with nonbinge drinking (defined as reporting ≥4 compared with <4 drinks/d, respectively) was associated with 64.35% (95% CI: 18.09%, 128.71%) and 63.53% (95% CI: 17.41%, 127.73%) higher total and free estradiol. No statistically significant associations were shown between cycle-average alcohol intake and menstrual cycle function. Although recent moderate alcohol intake does not appear to have adverse short-term effects on menstrual cycle function, including sporadic anovulation, potential protective and deleterious long-term effects of alterations in reproductive hormones on other chronic diseases warrant additional investigation.
Eisenberg ML, 2015·American journal of epidemiology
Approximately 15% of all couples are unable to conceive after a year and are labeled infertile. In recent years, increasing attention has been given to lifestyle factors that may impact fertility. In the United States, it is estimated that there are more than 17 million current users of marijuana with 4.6 million using marijuana almost daily. Although common, to date, little data exist on the impact of marijuana use on male fertility. In the current issue of the Journal, Gundersen et al. (Am J Epidemiol. 2015;182(6):473-481) provide data examining the relationship between marijuana use and semen quality from young men recruited out of the general Danish population. Men who reported daily marijuana use displayed significant lower sperm concentration and sperm counts compared with nonusers, while testosterone levels were higher. The current report provides important information for patients and providers regarding the negative association of marijuana use on semen quality. Although the benefit of marijuana cessation on recovery is uncertain, further study on the impact of marijuana use on male reproductive health is warranted as more states explore marijuana legalization.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
To evaluate whether myo-inositol supplementation, an insulin sensitizer, reduces the rate of gestational diabetes mellitus (GDM) and lowers insulin resistance in obese pregnant women. In an open-label, randomized trial, myo-inositol (2 g plus 200 micrograms folic acid twice a day) or placebo (200 micrograms folic acid twice a day) was administered from the first trimester to delivery in pregnant obese women (prepregnancy body mass index 30 or greater. We calculated that 101 women in each arm would be required to demonstrate a 65% GDM reduction in the myo-inositol group with a statistical power of 80% (α=0.05). The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test. From January 2011 to April 2014, 220 pregnant women at 12-13 weeks of gestation were randomized at two Italian university hospitals, 110 to myo-inositol and 110 to placebo. Most characteristics were similar between groups. The GDM rate was significantly reduced in the myo-inositol group compared with the control group, 14.0% compared with 33.6%, respectively (P=.001; odds ratio 0.34, 95% confidence interval 0.17-0.68). Furthermore, women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group, -1.0±3.1 compared with 0.1±1.8 (P=.048). Myo-inositol supplementation, started in the first trimester, in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance. CLINICAL ClinicalTrials.gov, www.clinicaltrials.gov, NCT01047982.
Pizzorno L, 2015·Integrative medicine (Encinitas, Calif.)
The trace mineral boron is a micronutrient with diverse and vitally important roles in metabolism that render it necessary for plant, animal, and human health, and as recent research suggests, possibly for the evolution of life on Earth. As the current article shows, boron has been proven to be an important trace mineral because it (1) is essential for the growth and maintenance of bone; (2) greatly improves wound healing; (3) beneficially impacts the body's use of estrogen, testosterone, and vitamin D; (4) boosts magnesium absorption; (5) reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α); (6) raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase; (7) protects against pesticide-induced oxidative stress and heavy-metal toxicity; (8) improves the brains electrical activity, cognitive performance, and short-term memory for elders; (9) influences the formation and activity of key biomolecules, such as S-adenosyl methionine (SAM-e) and nicotinamide adenine dinucleotide (NAD(+)); (10) has demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin's lymphoma; and (11) may help ameliorate the adverse effects of traditional chemotherapeutic agents. In none of the numerous studies conducted to date, however, do boron's beneficial effects appear at intakes > 3 mg/d. No estimated average requirements (EARs) or dietary reference intakes (DRIs) have been set for boron-only an upper intake level (UL) of 20 mg/d for individuals aged ≥ 18 y. The absence of studies showing harm in conjunction with the substantial number of articles showing benefits support the consideration of boron supplementation of 3 mg/d for any individual who is consuming a diet lacking in fruits and vegetables or who is at risk for or has osteopenia; osteoporosis; osteoarthritis (OA); or breast, prostate, or lung cancer.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Foroozanfard F et al., 2015·Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
This study was conducted to evaluate the effects of zinc supplementation on glucose homeostasis parameters and lipid concentrations in PCOS women. We are aware of no study evaluating the effects of zinc supplementation on metabolic profiles of patients with polycystic ovary syndrome (PCOS). This randomized, double-blind, placebo-controlled trial was conducted among 52 women diagnosed with PCOS and aged 18-40 years old. Participants were randomly divided into 2 groups to receive 220 mg zinc sulfate (containing 50 mg zinc) supplements (n=26) or placebo (n=26) per day for 8 weeks. Fasting blood samples were taken at baseline and after 8 weeks' intervention to quantify glucose, insulin and lipid concentrations. After 8 weeks of intervention, subjects who received zinc supplements had significantly increased serum zinc levels (+15.6±21.8 vs. -4.1±16.7 mg/dL, P=0.001) compared with placebo. In addition, zinc-supplemented patients had reduced fasting plasma glucose (FPG) (-4.3±9.6 vs. +0.5±6.0 mg/dL, P=0.03), serum insulin levels (-3.0±2.9 vs. +1.5±8.4 µIU/mL, P=0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (-0.8±0.8 vs. +0.3±1.9, P=0.006), homeostatic model assessment-Beta cell function (HOMA-B) (-10.6±9.5 vs. +4.9±32.1, P=0.02) and increased quantitative insulin sensitivity check index (QUICKI) (+0.02±0.02 vs. -0.004±0.05, P=0.03) compared with placebo. Additionally, a significant reduction in serum triglycerides (-15.6±40.3 vs. +14.5±25.3 mg/dL, P=0.002) and VLDL-cholesterol concentrations (-3.2±8.1 vs. +2.9±5.1 mg/dL, P=0.002) was observed following the administration of zinc supplements compared with placebo. Taken together, 220 mg zinc sulfate supplementation per day for 8 weeks among PCOS women had beneficial effects on metabolic profiles.
Schliep KC et al., 2015·Fertil Steril·
Open Access
To assess the effects of both male and female body mass index (BMI), individually and combined, on IVF outcomes.
Prospective cohort study.
University fertility center. PATIENT(S): All couples undergoing first fresh IVF cycles, 2005-2010, for whom male and female weight and height information were available (n = 721 couples). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryologic parameters, clinical pregnancy, and live birth incidence. RESULT(S): The average male BMI among the study population was 27.5 ± 4.8 kg/m(2) (range, 17.3-49.3 kg/m(2)), while the average female BMI (n = 721) was 25.2 ± 5.9 kg/m(2) (range, 16.2-50.7 kg/m(2)). Neither male nor female overweight (25-29.9 kg/m(2)), class I obese (30-34.9 kg/m(2)), or class II/III obese (≥35 kg/m(2)) status was significantly associated with fertilization rate, embryo score, or incidence of pregnancy or live birth compared with normal weight (18.5-24.9 kg/m(2)) status after adjusting for male and female age, partner BMI, and parity. Similar null findings were found between combined couple BMI categories and IVF success. CONCLUSION(S): Our findings support the notion that weight status does not influence fecundity among couples undergoing infertility treatment. Given the limited and conflicting research on BMI and pregnancy success among IVF couples, further research augmented to include other adiposity measures is needed.
Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for unfavorable pregnancy outcomes. Prevalence of vitamin D deficiency is highly prevalent among women with GDM. This study was designed to assess the effect of vitamin D supplementation on pregnancy outcomes of pregnant women with GDM who were not on oral hypoglycemic agents. This randomized controlled clinical trial was performed among 45 pregnant women diagnosed with GDM at 24-28 weeks' gestation. Subjects were randomly assigned to consume either vitamin D supplements (cholecalciferol) or placebo. Individuals in the vitamin D group (n=22) received 50 000 IU vitamin D3 pearl 2 times during the study: at study baseline and day 21 of intervention and those in placebo group (n=23) received 2 placebos at the mentioned times. Fasting blood samples were taken at baseline to measure fasting plasma glucose. Participants underwent a 3-h oral glucose tolerance tests (OGTT) and the blood samples were collected at time 60, 120, and 180 min to measure plasma glucose levels. Newborn's weight, height, head circumference, Apgar score, and hyperbilirubinemia were determined. Taking vitamin D supplements, compared with placebo, resulted in improved pregnancy outcomes; such that those in the vitamin D group had no case of polyhydramnios, while 17.4% of subjects in placebo group had this condition (p=0.04). In addition, newborn's hyperbilirubinemia was significantly lower in vitamin D group than that in placebo group (27.3% vs. 60.9%, p=0.02). In conclusion, vitamin D supplementation for 6 weeks among pregnant women with GDM resulted in decreased maternal polyhydramnios and infant hyperbilirubinemia compared with placebo. Clinical trial registration number www.irct.ir:IRCT201305115623N7.
To summarize the role of melatonin and circadian rhythms in determining optimal female reproductive physiology, especially at the peripheral level. Databases were searched for the related English-language literature published up to March 1, 2014. Only papers in peer-reviewed journals are cited. Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Melatonin treatment, alterations of the normal light:dark cycle and light exposure at night. MAIN OUTCOME MEASURE(S): Melatonin levels in the blood and in the ovarian follicular fluid and melatonin synthesis, oxidative damage and circadian rhythm disturbances in peripheral reproductive organs. RESULT(S): The central circadian regulatory system is located in the suprachiasmatic nucleus (SCN). The output of this master clock is synchronized to 24 hours by the prevailing light-dark cycle. The SCN regulates rhythms in peripheral cells via the autonomic nervous system and it sends a neural message to the pineal gland where it controls the cyclic production of melatonin; after its release, the melatonin rhythm strengthens peripheral oscillators. Melatonin is also produced in the peripheral reproductive organs, including granulosa cells, the cumulus oophorus, and the oocyte. These cells, along with the blood, may contribute melatonin to the follicular fluid, which has melatonin levels higher than those in the blood. Melatonin is a powerful free radical scavenger and protects the oocyte from oxidative stress, especially at the time of ovulation. The cyclic levels of melatonin in the blood pass through the placenta and aid in the organization of the fetal SCN. In the absence of this synchronizing effect, the offspring may exhibit neurobehavioral deficits. Also, melatonin protects the developing fetus from oxidative stress. Melatonin produced in the placenta likewise may preserve the optimal function of this organ. CONCLUSION(S): Both stable circadian rhythms and cyclic melatonin availability are critical for optimal ovarian physiology and placental function. Because light exposure after darkness onset at night disrupts the master circadian clock and suppresses elevated nocturnal melatonin levels, light at night should be avoided.
Infertility remains a common and often unresolved condition afflicting certain couples. Numerous animal studies have demonstrated that alterations in the light-dark cycle can affect reproduction as mediated by the pineal gland and its hormone, melatonin. To examine whether a similar disruption could affect human fertility, a pilot study was conducted with infertile women enrolled in a Natural Family Planning program.
Thyroid and Metabolic Function · Insulin and Metabolism
Guler I et al., 2014·Biological trace element research
In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.
Metabolic and Endocrine Agents · Thyroid Replacement
Selenium supplementation in people with Hashimoto's thyroiditis might reduce antibody levels and result in a decreased dosage of levothyroxine (LT4) and may provide other beneficial effects (e.g. on mood and health-related quality of life). The aim of our systematic review was to assess the effects of selenium supplementation on Hashimoto's thyroiditis. We searched The Cochrane Library, MEDLINE, EMBASE and Web of Science for randomized controlled trials. Study selection, data extraction, assessment of risk of bias and analyses were carried out by two independent review authors. We assessed the quality of the evidence of included studies using GRADE. Four studies rated at unclear to high risk of bias comprising 463 participants were included. One study at high risk of bias showed statistically significant improvement in subjective well-being with sodium selenite 200 μg plus titrated LT4 compared with placebo plus titrated LT4 (RR 4.67, 95% CI 1.61-13.50). Selenomethionine 200 μg as a single treatment or combined with LT4 reduced the serum levels of anti-thyroid peroxidase antibodies compared with placebo (or placebo plus LT4) in three studies (p < 0.001). Although the changes from baseline were statistically significant in these three studies, their clinical relevance is unclear. In conclusion, the results of these four studies, assessed at unclear to high risk of bias, show that evidence to support or refute the efficacy of selenium supplementation in people with Hashimoto's thyroiditis is incomplete and not reliable to help inform clinical decision making.
Algars M et al., 2014·Journal of psychosomatic research
The relation between eating disorders and menstrual function has been widely studied, but it is unknown whether the behavior of binge eating itself is related to menstrual dysfunction. The 11,503 women included in this study were from the Swedish Twin study of Adults: Genes and Environment. The associations between menstrual dysfunction and binge eating were analyzed using logistic regression or multiple linear regression models with generalized estimation equations. Women who reported lifetime binge eating were more likely to report either amenorrhea or oligomenorrhea than women who reported no binge eating. These results persisted when controlling for compensatory behaviors including self-induced vomiting, laxative use, and diuretic use. No differences between women with and without a history of binge eating were observed for age at menarche. Even when controlling for the effect of compensatory behaviors, the behavior of binge eating is associated with menstrual dysfunction. Metabolic and endocrinological factors could underlie this association. Careful evaluation of menstrual status is warranted for women with all eating disorders, not just anorexia nervosa.
Zhou W et al., 2013·J Musculoskelet Neuronal Interact·
Our objective was to study changes in calcium and vitamin D intakes over time, and their cross-sectional and longitudinal associations with bone mineral density (BMD). We followed 9382 women and men aged ≥25 and 899 aged 16-24, for 10 and 2 years respectively. Calcium and vitamin D intakes increased over time in adults, but decreased in women aged 16-18. The increased intakes in adults were largely attributable to the increased use of calcium and/or vitamin D supplements. Both the percentage of supplement users and average dose among users increased over time. There was nevertheless a high prevalence of calcium and vitamin D intake below the estimated average requirement. At baseline, higher calcium and vitamin D intakes were associated with higher total hip and femoral neck BMD in young men, and cumulatively high levels of calcium and vitamin D intakes over time contributed to better BMD maintenance at lumbar spine and hip sites in adult women. Although total intakes, particularly of vitamin D, frequently fell below the Institute of Medicine recommendations despite an increase over time in supplement use, we found some positive associations between total calcium and vitamin D intake and bone health.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Several inositol isomers and in particular myo-inositol (MI) and D-chiro-inositol (DCI), were shown to possess insulin-mimetic properties and to be efficient in lowering post-prandial blood glucose. In addition, abnormalities in inositol metabolism are associated with insulin resistance and with long term microvascular complications of diabetes, supporting a role of inositol or its derivatives in glucose metabolism. The aim of this review is to focus on the potential benefits of a dietary supplement of myo-inositol, by far the most common inositol isomer in foodstuffs, in human disorders associated with insulin resistance (polycystic ovary syndrome, gestational diabetes mellitus or metabolic syndrome) or in prevention or treatment of some diabetic complications (neuropathy, nephropathy, cataract). The relevance of such a nutritional strategy will be discussed for each context on the basis of the clinical and/or animal studies. The dietary sources of myo-inositol and its metabolism from its dietary uptake to its renal excretion will be also covered in this review. Finally, the actual insights into inositol insulin-sensitizing effects will be addressed and in particular the possible role of inositol glycans as insulin second messengers.
Dupont C et al., 2013·Asian journal of andrology·
Open Access
There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index (BMI). A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling (TUNEL) assay, we observed an increased rate of sperm DNA damage in obese men (odds ratio (95% confidence interval): 2.5 (1.2-5.1)).
Kamath R et al., 2013·Indian J Community Med·
Open Access
Cancer has become one of the ten leading causes of death in India. Breast cancer is the most common diagnosed malignancy in India, it ranks second to cervical cancer. An increasing trend in incidence is reported from various registries of national cancer registry project and now India is a country with largest estimated number of breast cancer deaths worldwide. To study the factors associated with breast cancer. To study the association between breast cancer and selected exposure variables and to identify risk factors for breast cancer. A hospital based Case control study was conducted at Shirdi Sai Baba Cancer Hospital and Research Center, Manipal, Udupi District. Total 188 participants were included in the study, 94 cases and 94 controls. All the study participants were between 25 to 69 years of age group. The cases and controls were matched by ± 2 years age range. Non vegetarian diet was one of the important risk factors (OR 2.80, CI 1.15-6.81). More than 7 to 12 years of education (OR 4.84 CI 1.51-15.46) had 4.84 times risk of breast cancer as compared with illiterate women. The study suggests that non vegetarian diet is the important risk factor for Breast Cancer and the risk of Breast Cancer is more in educated women as compared with the illiterate women. This is a Hospital based study so generalisability of the findings could be limited.
Sermondade N et al., 2013·Human reproduction update·
Open Access
BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.
Vitamin D deficiency is common in women with polycystic ovary syndrome (PCOS), with the 67-85% of women with PCOS having serum concentrations of 25-hydroxy vitamin D (25OHD) <20 ng/ml. Vitamin D deficiency may exacerbate symptoms of PCOS, with observational studies showing lower 25OHD levels were associated with insulin resistance, ovulatory and menstrual irregularities, lower pregnancy success, hirsutism, hyperandrogenism, obesity and elevated cardiovascular disease risk factors. There is some, but limited, evidence for beneficial effects of vitamin D supplementation on menstrual dysfunction and insulin resistance in women with PCOS. Vitamin D deficiency may play a role in exacerbating PCOS, and there may be a place for vitamin D supplementation in the management of this syndrome, but current evidence is limited and additional randomized controlled trials are required to confirm the potential benefits of vitamin D supplementation in this population.
The female athlete triad (the triad) is an interrelationship of menstrual dysfunction, low energy availability (with or without an eating disorder), and decreased bone mineral density; it is relatively common among young women participating in sports. Diagnosis and treatment of this potentially serious condition is complicated and often requires an interdisciplinary team. Articles from 1981 to present found on PubMed were selected for review of major components of the female athlete triad as well as strategies for diagnosis and treatment of the conditions. The main goal in treatment of young female athletes with the triad is a natural return of menses as well as enhancement of bone mineral density. While no specific drug intervention has been shown to consistently improve bone mineral density in this patient population, maximizing energy availability and optimizing vitamin D and calcium intake are recommended. Treatment requires a multidisciplinary approach involving health care professionals as well as coaches and family members. Prevention of this condition is important to minimize complications of the female athlete triad.
Berger C et al., 2012·J Bone Miner Res·
Open Access
Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels.
Gonzales GF, 2012·Evidence-based complementary and alternative medicine : eCAM
Lepidium meyenii (maca) is a Peruvian plant of the Brassicaceae family cultivated for more than 2000 years, which grows exclusively in the central Andes between 4000 and 4500 m altitude. Maca is used as a food supplement and also for its medicinal properties described traditionally. Since the 90s of the XX century, an increasing interest in products from maca has been observed in many parts of the world. In the last decade, exportation of maca from Peru has increased from 1,415,000 USD in 2001 to USD 6,170,000 USD in 2010. Experimental scientific evidence showed that maca has nutritional, energizer, and fertility-enhancer properties, and it acts on sexual dysfunctions, osteoporosis, benign prostatic hyperplasia, memory and learning, and protects skin against ultraviolet radiation. Clinical trials showed efficacy of maca on sexual dysfunctions as well as increasing sperm count and motility. Maca is a plant with great potential as an adaptogen and appears to be promising as a nutraceutical in the prevention of several diseases.
Physical activity (PA) is an important modifiable risk factor for both bone mineral density (BMD) and body mass index (BMI). However, BMI is itself strongly predictive of BMD. Our aim was to determine the association between PA and BMD, with consideration of BMI as a potential mediating factor. The Canadian Multicentre Osteoporosis Study (CaMos) is a population-based prospective cohort study of Canadian women and men. PA was determined from interviewer-administered questionnaires at baseline and Year 5 and summarized as daily energy expenditure in total metabolic equivalents of the task multiplied by minutes/day (MET*m/d). Height, weight, and total hip and lumbar spine BMD were measured at baseline and Year 5. General linear models assessed relationships between PA and BMD, both cross-sectionally (baseline PA with baseline BMD) and longitudinally (average PA and change in PA with change in BMD). BMI was considered as a mediating factor. Potential confounders included age, center, education, caffeine intake, alcohol exposure, smoking history, history of weight-cycling, age at menarche, past use of oral contraceptives, history of >3 months missed menstruation, menopausal status, and antiresorptive use, as relevant. The study included 2855 men and 6442 women. PA was inversely associated with BMI at baseline, and an increase in PA between baseline and Year 5 was associated with a decrease in BMI, with 0.41 (95% CI: 0.22, 0.60) kg/m(2) loss per 1000 MET*m/d increase (in men) and 0.40 (95% CI: 0.23, 0.57) kg/m(2) loss per 1000 MET*m/d increase (in women). BMI was strongly associated with BMD, both cross-sectionally and longitudinally. However, increased PA was associated with a small increase in total hip BMD, 0.004 (95% CI: 0.000-0.008) g/cm(2) per 1000 MET*m/d (in men) and 0.003 (95% CI: 0.000-0.007) g/cm(2) per 1000 MET*m/d (in women). Average PA was associated with an increase in lumbar spine BMD in women, but not in men; it was not associated with change in total hip BMD in either sex. Increased PA is associated with an increase in BMD and a concomitant decrease in BMI. These findings suggest that population-level interventions to increase PA would favorably impact bone and other health outcomes.
Langsetmo L et al., 2010·Am J Clin Nutr·
Open Access
Previous research has shown that dietary patterns are related to the risk of several adverse health outcomes, but the relation of these patterns to skeletal fragility is not well understood. Our objective was to determine the relation between dietary patterns and incident fracture and possible mediation of this relation by body mass index, bone mineral density, or falls.
We performed a retrospective cohort study based on the Canadian Multicentre Osteoporosis Study-a randomly selected population-based cohort. We assessed dietary patterns by using self-administered food-frequency questionnaires in year 2 of the study (1997-1999). Our primary outcome was low-trauma fracture occurring before the 10th annual follow-up (2005-2007). We identified 2 dietary patterns by using factor analysis. The first factor (nutrient dense) was strongly associated with intake of fruit, vegetables, and whole grains. The second factor (energy dense) was strongly associated with intake of soft drinks, potato chips, French fries, meats, and desserts. The nutrient-dense factor was associated with a reduced risk of fracture per 1 SD in men overall [hazard ratio (HR): 0.83; 95% CI: 0.64, 1.08] and in women overall (HR: 0.86; 95% CI: 0.76, 0.98). An age trend (P = 0.03) was observed, which yielded an HR of 0.97 in younger women (age < 70 y) compared with an HR of 0.82 in older women (age ≥ 70 y). The associations were independent of body mass index, bone mineral density, falls, and demographic variables. The energy-dense pattern was not related to fracture. A diet high in vegetables, fruit, and whole grains may reduce the risk of low-trauma fracture, particularly in older women.
To test consumables and other products used during oocyte collection, sperm preparation, IUI, embryo culture, and IVF-embryo transfer for their possible reprotoxic properties. A prospective 4-year survey of reprotoxicity testing of consumables and other products used in assisted reproductive technologies (ART). Private infertility center in a university-affiliated teaching hospital. INTERVENTION(S): Thirty-six products of 72 different brands, including plastics, syringes, tubing, and surgical gloves were analyzed for their reprotoxicity in 350 human sperm survival tests (SpST). MAIN OUTCOME MEASURE(S): The SpST index: percentage progressive motility of test sample/percentage progressive motility of control sample after 24 and 96 hours. RESULT(S): Thirteen of 36 products were found to be reprotoxic: an SpST index <0.85 was noted 24 and 96 hours after exposure. These products included eight brands of unpowdered surgical gloves, two types of hysterometers and one type of tubing attached to the oocyte collection needle, one type of ovum pickup procedure needle, and one type of embryo transfer catheter. One type of condom used for ultrasound, one type of sterile Pasteur pipette and petri dish, as well as the cover of a specimen container, were reprotoxic. CONCLUSION(S): The SpST is an inexpensive, easy, and reliable method to identify potential reprotoxic products and consumables used in ART procedures. These data underline the importance of the inclusion of the SpST in a continuous quality control (QC) program of ART outcome.
Valeggia C et al., 2009·American journal of human biology : the official journal of the Human Biology Council
Lactation has long been recognized as a major determinant of interbirth intervals. The temporal pattern of nursing has been proposed as the mechanism behind lactational amenorrhea. We present a new model of the dynamic regulation of lactational amenorrhea that identifies maternal energy availability as the main determinant of ovarian resumption. Variation in the intensity of lactation remains a component of the model as a determinant of the absolute energetic cost of milk production. However, maternal energy supply determines net energy availability; a larger energy supply leaves a greater net energy surplus than a smaller energy supply (lactation costs being equal). We characterize the hormonal postpartum profile of 70 lactating Toba women of Argentina. We use C-peptide, which reflects maternal insulin production, as a measure of energy availability. Initially low, insulin production rises as the postpartum period progresses, reflecting the declining metabolic load of lactation. A short period of supernormal insulin production precedes menstrual resumption. The high levels of insulin may play a role in stimulating the resumption of ovarian activity, which in turn may help to resolve the transient period of insulin resistance. The dynamics of insulin sensitivity during lactation would aid in synchronizing the resumption of ovarian function with a reduction in the energy demands of milk production. This hypothesis is supported by the sustained weight gain experienced by lactating women during the months preceding the first postpartum menses. The link between fecundity and energy balance could serve as a mechanism for adjusting the duration of lactational amenorrhea to the relative metabolic load of lactation.
Golden NH et al., 2008·Annals of the New York Academy of Sciences
Menstrual irregularity is a common occurrence during adolescence, especially within the first 2-3 years after menarche. Prolonged amenorrhea, however, is not normal and can be associated with significant medical morbidity, which differs depending on whether the adolescent is estrogen-deficient or estrogen-replete. Estrogen-deficient amenorrhea is associated with reduced bone mineral density and increased fracture risk, while estrogen-replete amenorrhea can lead to dysfunctional uterine bleeding in the short term and predispose to endometrial carcinoma in the long term. In both situations, appropriate intervention can reduce morbidity. Old paradigms of whom to evaluate for amenorrhea have been challenged by recent research that provides a better understanding of the normal menstrual cycle and its variability. Hypothalamic amenorrhea is the most prevalent cause of amenorrhea in the adolescent age group, followed by polycystic ovary syndrome. In anorexia nervosa, exercise-induced amenorrhea, and amenorrhea associated with chronic illness, an energy deficit results in suppression of hypothalamic secretion of GnRH, mediated in part by leptin. Administration of recombinant leptin to women with hypothalamic amenorrhea has been shown to restore LH pulsatility and ovulatory menstrual cycles. The use of recombinant leptin may improve our understanding of the pathophysiology of hypothalamic amenorrhea in adolescents and may also have therapeutic possibilities.
Women with ovulatory menstrual cycles have a circadian rhythm superimposed on the menstrual-associated rhythm; in turn, menstrual events affect the circadian rhythm. In this paper, we review circadian rhythms in temperature, selected hormone profiles, and sleep-wake behavior in healthy women at different phases of the menstrual cycle. The effects on menstrual cycle rhythmicity of disrupted circadian rhythms, for example, with shiftwork and altered circadian rhythms in women with menstrual-related mood disturbances, are discussed. Compared to the follicular phase, in the post-ovulation luteal phase, body temperature is elevated, but the amplitude of the temperature rhythm is reduced. Evidence indicates that the amplitude of other rhythms, such as melatonin and cortisol, may also be blunted in the luteal phase. Subjective sleep quality is lowest around menses, but the timing and composition of sleep remains relatively stable across the menstrual cycle in healthy women, apart from an increase in spindle frequency activity and a minor decrease in rapid eye movement (REM) sleep during the luteal phase. Disruption of circadian rhythms is associated with disturbances in menstrual function. Female shiftworkers compared to non-shiftworkers are more likely to report menstrual irregularity and longer menstrual cycles. There also is accumulating evidence that circadian disruption increases the risk of breast cancer in women, possibly due to altered light exposure and reduced melatonin secretion. Further investigations into the biological consequences of circadian disruption in women will offer insight into some menstrual-associated disorders, including mood changes, as well as reproductive function and possible links with breast cancer.
Poyastro Pinheiro A et al., 2007·The International journal of eating disorders
To describe menstrual disturbance in eating disorders (ED). We describe menstrual history in 1,705 women and compare eating, weight, and psychopathological traits across menstrual groups. Menstrual dysfunction occurred across all eating disorder subtypes. Individuals with normal menstrual history and primary amenorrhea reported the highest and lowest lifetime body mass index (BMI), respectively. Normal menstruation and oligomenorrhea groups reported greater binge eating, vomiting, and appetite suppressant use. Amenorrhea was associated with lower caloric intake and higher exercise. Harm avoidance, novelty seeking, perfectionism, and obsessionality discriminated among menstrual status groups. No differences in comorbid Axis I and II disorders were observed. Menstrual dysfunction is not limited to any eating disorder subtype. BMI, caloric intake, and exercise were strongly associated with menstrual function. Menstrual status is not associated with comorbidity. Menstrual irregularity is an associated feature of all ED rather than being restricted to AN only.
Infertility Distress · Anxiety and Depression in Infertility
Cousineau TM et al., 2007·Best Practice & Research Clinical Obstetrics & Gynaecology·
The inability to conceive children is experienced as a stressful situation by individuals and couples all around the world. The consequences of infertility are manifold and can include societal repercussions and personal suffering. Advances in assisted reproductive technologies, such as IVF, can offer hope to many couples where treatment is available, although barriers exist in terms of medical coverage and affordability. The medicalization of infertility has unwittingly led to a disregard for the emotional responses that couples experience, which include distress, loss of control, stigmatization, and a disruption in the developmental trajectory of adulthood. Evidence is emerging of an association between stress of fertility treatment and patient drop-out and pregnancy rates. Fortunately, psychological interventions, especially those emphasizing stress management and coping-skills training, have been shown to have beneficial effects for infertility patients. Further research is needed to understand the association between distress and fertility outcome, as well as effective psychosocial interventions.
Metabolic and Endocrine Agents · Thyroid Replacement
Supplemental vitamin D is available in 2 distinct forms: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Pharmacopoeias have officially regarded these 2 forms as equivalent and interchangeable, yet this presumption of equivalence is based on studies of rickets prevention in infants conducted 70 y ago. The emergence of 25-hydroxyvitamin D as a measure of vitamin D status provides an objective, quantitative measure of the biological response to vitamin D administration. As a result, vitamin D3 has proven to be the more potent form of vitamin D in all primate species, including humans. Despite an emerging body of evidence suggesting several plausible explanations for the greater bioefficacy of vitamin D3, the form of vitamin D used in major preparations of prescriptions in North America is vitamin D2. The case that vitamin D2 should no longer be considered equivalent to vitamin D3 is based on differences in their efficacy at raising serum 25-hydroxyvitamin D, diminished binding of vitamin D2 metabolites to vitamin D binding protein in plasma, and a nonphysiologic metabolism and shorter shelf life of vitamin D2. Vitamin D2, or ergocalciferol, should not be regarded as a nutrient suitable for supplementation or fortification.
Sallmén M et al., 2006·Epidemiology (Cambridge, Mass.)
Overweight and obese men have been reported to have lower sperm counts and hormonal changes, but data are lacking regarding effects on couple fertility. We examined the relationship between male body mass index (BMI) and infertility in couples enrolled in the Agricultural Health Study in the United States. The analysis sample was limited to couples (wife <40 years old) with an attempt at pregnancy in the last 4 years based on pregnancy and fertility data provided by wives. Infertility was defined as not conceiving a pregnancy after at least 12 months of unprotected intercourse regardless of whether or not a pregnancy ultimately occurred. Self-reported weight and height were used to calculate BMI (kg/m). Adjusted odds ratios (aORs) for infertility associated with increases in male BMI were calculated with logistic regression. Adjusting for potential confounders, a 3-unit increase in male BMI was associated with infertility (aOR = 1.12; 95% confidence interval = 1.01-1.25; n = 1329). There was a dose-response relationship, and the BMI effect was stronger when the data were limited to couples with the highest-quality infertility data. The association between BMI and infertility was similar for older and younger men, suggesting that erectile dysfunction in older men does not explain the association. This report of lower fertility in overweight and obese men needs replication. If the findings are robust, programs to prevent obesity may improve men's reproductive health and save medical costs for infertility treatment.
Amenorrhea is a diagnostic criterion for anorexia nervosa (AN), although menstrual cycles have been found to persist in some women with all the other features of AN. This study sought to determine factors that are associated with amenorrhea in 39 women with current primary spectrum AN. The use of exercise to control weight (odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.3-9.9; P = .02), low novelty seeking scores (OR = 0.7; 95% CI = 0.58-0.94; P = .02), and low systolic blood pressure (OR = 0.9; 95% CI = 0.84-0.99; P = .046) were predictors of amenorrhea independent of body mass index.
Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted beta-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15-1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13-1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52-2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27-2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.
Wade GN et al., 2004·American journal of physiology. Regulatory, integrative and comparative physiology
Natural selection has linked the physiological controls of energy balance and fertility such that reproduction is deferred during lean times, particularly in female mammals. In this way, an energetically costly process is confined to periods when sufficient food is available to support pregnancy and lactation. Even in the face of abundance, nutritional infertility ensues if energy intake fails to keep pace with expenditure. A working hypothesis is proposed in which any activity or condition that limits the availability of oxidizable fuels (e.g., undereating, excessive energy expenditure, diabetes mellitus) can inhibit both gonadotropin-releasing hormone (GnRH)/luteinizing hormone secretion and female copulatory behaviors. Decreases in metabolic fuel availability appear to be detected by cells in the caudal hindbrain. Hindbrain neurons producing neuropeptide Y (NPY) and catecholamines (CA) then project to the forebrain where they contact GnRH neurons both directly and also indirectly via corticotropin-releasing hormone (CRH) neurons to inhibit GnRH secretion. In the case of estrous behavior, the best available evidence suggests that the inhibitory NPY/CA system acts primarily via CRH or urocortin projections to various forebrain loci that control sexual receptivity. Disruption of these signaling processes allows normal reproduction to proceed in the face of energetic deficits, indicating that the circuitry responds to energy deficits and that no signal is necessary to indicate that there is an adequate energy supply. While there is a large body of evidence to support this hypothesis, the data do not exclude nutritional inhibition of reproduction by other pathways and processes, and the full story will undoubtedly be more complex than this.
Metabolic and Endocrine Agents · Thyroid Replacement
Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline. The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).
Tingen C et al., 2003·Environ Health Perspect·
Open Access
Although there has been growing concern about the effects of environmental exposures on human fertility, standard epidemiologic study designs may not collect sufficient data to identify subtle effects while properly adjusting for confounding. In particular, results from conventional time to pregnancy studies can be driven by the many sources of bias inherent in these studies. By prospectively collecting detailed records of menstrual bleeding, occurrences of intercourse, and a marker of ovulation day in each menstrual cycle, precise information on exposure effects can be obtained, adjusting for many of the primary sources of bias. This article provides an overview of the different types of study designs, focusing on the data required, the practical advantages and disadvantages of each design, and the statistical methods required to take full advantage of the available data. We conclude that detailed prospective studies allowing inferences on day-specific probabilities of conception should be considered as the gold standard for studying the effects of environmental exposures on fertility.
Buck GM et al., 2003·Environ Health Perspect·
Open Access
The determinants of successful human reproduction and development may act as early as periconceptionally, underscoring the need to capture exposures during these critical windows when assessing potential toxicants. To identify such toxicants, couples must be studied longitudinally prior to conception without regard to a couple's ability to ascertain a clinically recognized pregnancy. We examined the utility and feasibility of prospective pregnancy study designs by conducting a systematic review of the literature to summarize relevant information regarding the planning, implementation, and success of previously published prospective pregnancy studies. Information concerning design elements and participation was abstracted from 15 eligible studies (from a total of 20 identified studies) using a standardized form. The primary author of each study was contacted to review our summary of their work and obtain missing information. Our findings confirm the ability to recruit women/couples from diverse populations using a variety of recruitment strategies. Among the studies we reviewed, 4-97% of eligible individuals were successfully contacted, with enrollment rates ranging from 42 to 100%. Length of follow-up varied from 3 to 12 months. A high percentage of women provided urine (57-98%) and blood (86-91%) specimens and most male partners (94-100%) provided semen samples. These data support the feasibility of this design.
Exercise programs improve balance, strength and agility in elderly people and thus may prevent falls. However, specific exercise programs that might be widely used in the community and that might be "prescribed" by physicians, especially for patients with osteoporosis, have not been evaluated. We conducted a randomized controlled trial of such a program designed specifically for women with osteoporosis. We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise. Women who agreed to participate were randomly assigned to participate in a twice-weekly exercise class or to not participate in the class. We measured baseline data and, 20 weeks later, changes in static balance (by dynamic posturography), dynamic balance (by a timed figure-eight run) and knee extension strength (by dynamometry). Of 93 women who began the trial, 80 completed it. Before adjustment for covariates, the intervention group tended to have greater, although nonsignificant, improvements in static balance (mean difference 4.8%, 95% confidence interval [CI] -1.3% to 11.0%), dynamic balance (mean difference 3.3%, 95% CI -1.7% to 8.4%) and knee extension strength (mean difference 7.8%, 95% CI -5.4% to 21.0%). Mean crude changes in the static balance score were -0.85 (95% CI -2.91 to 1.21) for the control group and 1.40 (95% CI -0.66 to 3.46) for the intervention group. Mean crude changes in figure-eight velocity (dynamic balance) were 0.08 (95% CI 0.02 to 0.14) m/s for the control group and 0.14 (95% CI 0.08 to 0.20) m/s for the intervention group. For knee extension strength, mean changes were -0.58 (95% CI -3.02 to 1.81) kg/m for the control group and 1.03 (95% CI -1.31 to 3.34) kg/m for the intervention group. After adjustment for age, physical activity and years of estrogen use, the improvement in dynamic balance was 4.9% greater for the intervention group than for the control group (p = 0.044). After adjustment for physical activity, cognitive status and number of fractures ever, the improvement in knee extension strength was 12.8% greater for the intervention group than for the control group (p = 0.047). The intervention group also had a 6.3% greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis, but this difference was not significant (p = 0.06). Interpretation: Relative to controls, participants in the exercise program experienced improvements in dynamic balance and strength, both important determinants of risk for falls, particularly in older women with osteoporosis.
Carter ND et al., 2001·Br J Sports Med·
Open Access
To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis. Static balance was measured by computerised dynamic posturography (Equitest), dynamic balance by timed figure of eight run, and knee extension strength by dynamometry. Subjects were randomised to exercise intervention (twice weekly Osteofit classes for 10 weeks) or control groups. The outcome in 79 participants (39 exercise, 40 control) who were available for measurement 10 weeks after baseline measurement is reported. After confounding factors had been controlled for, the exercise group did not make significant gains compared with their control counterparts, although there were consistent trends toward greater improvement in all three primary outcome measures. Relative to the change in control subjects, the exercise group improved by 2.3% in static balance, 1.9% in dynamic balance, and 13.9% in knee extension strength. A 10 week community based physical activity intervention did not significantly reduce fall risk factors in women with osteoporosis. However, trends toward improvement in key independent risk factors for falling suggest that a study with greater power may show that these variables can be improved to a level that reaches statistical significance.
This 2-year prospective study examined associations among bone mineral acquisition and physical, maturational, and lifestyle variables during the pubertal transition in healthy girls. Forty-five girls, initially 10.5+/-0.6 years, participated. Body composition and bone mineral content (BMC) at the spine and total body (TB) were assessed at baseline and annually thereafter using dual-energy X-ray absorptiometry (DXA). Nutrient intakes were assessed using 3-day diet records and a calcium food frequency questionnaire (FFQ), physical activity by questionnaire, sexual maturation using Tanner's stages of breast and pubic hair maturation, growth by height and weight, and eating attitudes using the children's Eating Attitudes Test (Children's EAT). Mean children's EAT subscale scores (dieting, oral control [OC], and bulimia) were stable over time. Median split of OC subscale scores was used to form high and low OC groups. Groups had similar body composition, dietary intake, activity, and Tanner stage at baseline and 2 years. Using height, weight, and Tanner breast stage as covariates, girls with low OC scores had greater TB BMC at baseline (1452+/-221 g vs. 1387+/-197 g; p = 0.030) and 2 years (2003+/-323 g vs. 1909+/-299 g; p = 0.049) and greater lumbar spine (LS) BMC at 2 years (45.2+/-8.8 g vs. 41.2+/-9.6 g; p = 0.042). In multiple regression analysis, OC score predicted baseline, 2 years, and 2-year change in TB and spinal BMC, contributing 0.9-7.6% to explained variance. Calcium intake predicted baseline, 2 years, and 2-year change in TB BMC, explaining 1.6-5.3% of variance. We conclude that both OC and habitual calcium intake may influence bone mineral acquisition.
Of the few exercise intervention studies focusing on pediatric populations, none have confined the intervention to the scheduled physical education curriculum. To examine the effect of an 8-month school-based jumping program on the change in areal bone mineral density (aBMD), in grams per square centimeter, of healthy thirdand fourth-grade children. Ten elementary schools were randomized to exercise (n = 63) and control groups (n = 81). Exercise groups did 10 tuck jumps 3 times weekly and incorporated jumping, hopping, and skipping into twice weekly physical education classes. Control groups did regular physical education classes. At baseline and after 8 months of intervention, we measured aBMD and lean and fat mass by dual-energy x-ray absorptiometry (Hologic QDR-4500). Calcium intake, physical activity, and maturity were estimated by questionnaire. The exercise group showed significantly greater change in femoral trochanteric aBMD (4.4% vs 3.2%; P <.05). There were no group differences at other sites. Results were similar after controlling for covariates (baseline aBMD change in height, change in lean, calcium, physical activity, sex, and ethnicity) in hierarchical regression. An easily implemented school-based jumping intervention augments aBMD at the trochanteric region in the prepubertal and early pubertal skeleton.
Exercise is understood to exert positive effects on bone. However cancellous bone has not been shown to increase with exercise. Previous results of our 1-yr observational prospective study in ovulatory women related 20% of the change in cancellous spinal bone mineral density (BMD), measured by quantitative computed tomography (QCT), to luteal phase length (the time from ovulation to menstruation, LL). The 66 women who documented exercise daily included normally active women (N = 23) and those who ran consistently or were increasing running in preparation for a marathon (N = 43). Exercise did not affect BMD change in the women as a whole. We re-evaluated those data to determine whether exercise-related effects on spinal cancellous BMD change in regularly cycling premenopausal women were related to ovulatory characteristics. The potential relationship of exercise to BMD change was reanalyzed by stratifying women into tertiles according to average LL documented by quantitative basal temperature analysis. Repeated-measures ANOVA indicated independent positive effects of both luteal length (P = 0.001) and activity (P = 0.041). The 11 runners with LL > 10.9 d had a nonsignificant 0.5% increase in lumbar BMD while the 15 who averaged short LL (<9.9 d) experienced a significant 3.6% loss. In the runners as a group, however, kilometers run per week was negatively related to BMD change throughout (r = -0.347, P = 0.024). These data are the first to indicate that, in women with regular cycles, luteal length and exercise independently and positively affect change in spinal cancellous BMD.
To compare spinal bone mineral density (BMD) and 1-year BMD change between premenopausal vegetarian and nonvegetarian women.
Cross-sectional comparison of spinal BMD at baseline and prospective comparison of a subsample.
A western Canadian metropolitan area. Subjects/samples: Healthy vegetarian (n = 15 lacto-ovo-vegetarian, n = 8 vegan) and nonvegetarian (n = 22) women aged 20 to 40 years, with regular menstrual cycles and stable body weight completed baseline measurements. Twenty of these women (6 lacto-ovo-vegetarian, 5 vegan, 9 nonvegetarian) participated in repeat measurements at approximately 13 months. Statistical Analyses Performed: Descriptive statistics, independent sample and paired t tests, 1-way analysis of variance, correlation analysis, and stepwise multiple regression were used to compare groups and to assess associations with BMD. At baseline, subjects were 27.2 +/- 5.1 years old. Vegetarians had lower body mass index (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < .05) and percent body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P < .05); they also tended to have lower BMD (1.148 +/- 0.111 g/cm2 vs 1.216 +/- 0.132 g/cm2, P = .06), although this was not apparent with weight as a covariate (P = .14). Baseline BMD was predicted by vitamin B-12 intake and total body fat (R2 = .24, P = .001). Participants in the follow-up differed only in their being older than nonparticipants. Over 1 year, mean BMD increased significantly (1.1%): by diet group, nonvegetarians' BMD increased but vegetarians' BMD was unchanged. No other monitored variables were associated with BMD change. Applications/ Vegetarian women should be aware of links between low BMD and low body weight/body fat, and should maintain adequate intakes of nutrients believed to affect BMD.
Although numerous organic conditions may cause chronic pelvic pain (CPP), diagnostic laparoscopy reveals a normal pelvis in many patients with CPP. However, psychological studies yield a high frequency of psychopathology and increased prevalences of chronic stress and traumatic life events, ie, sexual and physical abuse, in women with CPP, suggesting a relationship between posttraumatic stress disorder (PTSD) and CPP. As chronic stress and PTSD have been associated with specific alterations of the hypothalamic-pituitary-adrenal (HPA) axis, we explored stress history, psychopathology and HPA axis alterations in women with CPP. We recruited 16 patients with CPP and 14 painfree, infertile controls from a general hospital where diagnostic laparoscopy was performed. Psychological assessment included standardized interviews on clinical symptoms, abuse experiences and major life events as well as psychometric testing for PTSD-like symptoms and depression. Endocrinological evaluation involved determinations of diurnal salivary cortisol levels and hormonal responses to a corticotropin-releasing factor (CRF) stimulation test (100 microg human CRF) and a low-dose dexamethasone suppression test (0.5 mg). We observed increased prevalences of abuse experiences and PTSD in women with CPP as well as a higher total number of major life events, whereas the mean extent of depression was within the normal range. With respect to endocrine measures, women with CPP demonstrated normal to low diurnal salivary cortisol levels, normal plasma-adrenocorticotropin (ACTH), but reduced salivary cortisol levels in the CRF stimulation test, and an enhanced suppression of salivary cortisol by dexamethasone. Women with CPP demonstrate HPA axis alterations, that partly parallel and partly contrast neuroendocrine correlates of PTSD, but show marked similarity to findings in patients with other stress-related bodily disorders. These findings suggest that a lack of protective properties of cortisol may be of relevance for the development of bodily disorders in chronically stressed or traumatized individuals.
Petit MA et al., 1997·Medicine & Science in Sports & Exercise·
Current concepts suggest that normal estrogen levels are necessary for exercise to have an osteogenic effect on bone. In a population of running and sedentary women Prior et al. (NEJM, 1990) have shown that consistent ovulation is necessary to prevent spinal cancellous bone loss. Change in spinal bone mineral density was measured by quantitative computed tomography (QCT) in running and sedentary women over one year, along with prospective documentation of dietary, menstrual cycle, hormonal, and exercise variables. Of the 66 women studied only 12 remained ovulatory throughout the year. Forty-two women were runners of which 6 were consistently ovulatory. We hypothesized that ovulation would interact with an exercise effect on cancellous bone. Analysis of the 42 runners showed an average loss in bone of 1.8%. Luteal phase index (r = 0.509) and average progesterone (r = 0.381) were correlated with change in QCT, but not estrogen, calcium, or any other hormonal, dietary, or morphometric variable. There was a negative association between change in QCT and number of km run/week (r = -0.319). In the 12 consistently ovulatory women, average cancellous bone increased in runners(≈2%) and decreased in nonrunners (N) by ≈1% (seefig.). These data are the first to show an increase in purely cancellous bone with moderate levels of aerobic activity. The results suggest that the presence of consistently ovulatory cycles, and thus progesterone in addition to estrogen, may be necessary for an osteogenic effect of low impact exercise (running) on cancellous bone.
Breast cancer incidence rates are high in societies with a Western lifestyle characterized by low levels of physical activity, and by an energy-dense diet rich in total and saturated fat and refined carbohydrates. Epidemiologic studies, so far mostly on postmenopausal women, have shown that breast cancer risk is increased in hyperandrogenic women, with decreased levels of plasma sex-hormone binding globulin, and with increased levels of testosterone and of free estrogens. This paper describes the role of hyperinsulinemia as a physiologic link between nutritional lifestyle factors, obesity, and the development of a hyperandrogenic endocrine profile, and reviews evidence that may or may not support the theory that chronic hyperinsulinemia is an underlying cause of breast cancer. An hypothesis is presented, stipulating that breast cancer risk is increased not only in hyperandrogenic postmenopausal women, but also in premenopausal women with mild hyperandrogenism and normal (ovulatory) menstrual cycles. The author suggests further investigation as to whether there is a positive association between risk of breast cancer before menopause and subclinical forms of the polycystic ovary syndrome (PCOS), and to what extent diet and physical activity during childhood, by modulating the degree of insulin resistance during adolescence, may or may not be determinants of a PCO-like hyperandrogenic endocrine profile persisting into adulthood.
Guidelines by Clinical Area · Bone and Endocrine Guidelines
To examine exercise as a therapy for people with osteoporosis. Options: Immobilization, standing low-load and high-load physical activities. Outcomes: Risk of injury, quality of life, risk of falls and fractures, strength and posture and pain management. Evidence: Relevant epidemiologic studies, clinical trials and reviews were examined, including the large-scale FICSIT trial in the United States, a prospective 4-year study of women enrolled in an exercise program in Toronto and the large-scale Study of Osteoporotic Fractures. Values: Minimizing risk of injury and increasing quality of life were given a high value. BENEFITS, HARMS, And Costs: Moderate physical activity in people with osteoporosis can reduce the risk of falls and fractures, decrease pain and improve fitness and overall quality of life. It may also stimulate bone gain and decrease bone loss. Its positive effects are an adjunct to other interventions, such as hormonal therapy. It may give patients the confidence to resume regular activity and can provide social interaction and support. During exercise programs, proper nutrition is necessary to prevent excessive weight loss and impaired immune function resulting from inadequate protein, vitamin and mineral intake. Recommendations: Immobilization should be avoided if possible in anyone with osteoporosis or at increased risk for osteoporosis. Regular, moderate physical activity is recommended for those with osteoporosis. Elderly people should be assessed for risk of falling to identify those in greatest need of an exercise program. Community group exercise programs are beneficial. Younger people with osteoporosis also need exercise that will preserve or improve bone mass, muscular strength, endurance and cardiovascular fitness. Weight loss as a result of physical activity should be avoided and adequate intake of protein, vitamins and minerals assured. Because the benefits of physical activity are independent of the effect of other therapies, physical activity is an essential adjunct to appropriate nutrition and other therapies. Validation: These recommendations were developed by the Scientific Advisory Board of the Osteoporosis Society of Canada at its 1995 Consensus Conference. They are in agreement with the position taken on osteoporosis and exercise by the United States Center for Disease Control and Prevention and the American College of Sports Medicine. Sponsors: Sponsors of the 1995 conference included the Dairy Farmers of Canada, Eli Lilly Canada, Inc., Hoffmann-La Roche Canada Ltd., Merck Frosst Canada Inc. and Procter & Gamble Pharmaceuticals Canada Inc.
O'Neill TW et al., 1996·J Epidemiol Community Health·
Open Access
To determine the risk factors associated with fracture of the distal forearm, and to evaluate the influence of falls on these risks.
This was a case-control study.
Manchester, UK. The cases were 62 white women aged 45-82 years who had sustained a fracture of the distal forearm and had attended local hospitals. Two control groups were studied - 50 women who had fallen onto the hand but had not sustained a fracture (recruited from the same source as those with fracture) and 116 women randomly selected from primary care age and sex registers in the catchment area of the hospitals. Both cases and controls were sent a letter inviting them to take part in the study. Data were collected by questionnaire completed by an interviewer. MAIN Compared with the population control group, those with fracture were more likely to walk at a brisk pace (odds ratio (OR) = 3.5; 95% confidence interval (CI) 1.3, 9.6) though they had undertaken less physical activity at home or work on a daily basis throughout life (OR = 0.4; 95% CI 0.2, 0.9). The risk associated with brisk walking was less marked when the cases were compared with fall controls. Other lifestyle factors including calcium intake, smoking, and alcohol consumption were not associated with fracture. Analysis of gynaecological and hormonal factors suggested that compared with population controls, those with fracture of the distal forearm had had fewer fertile years (OR = 0.4; 95% CI 0.1, 0.9) and were less likely to have used oral contraceptives (OR = 0.3; 95% CI 0.1, 0.9). The data highlight the need for caution when advising middle aged and elderly subjects about exercise. Such advice should be combined with practical information about the prevention of falls. Hormonal factors seem to be additional determinants of fracture. Other lifestyle interventions seem unlikely to play an important part in preventing distal forearm fracture.
Large-scale studies have demonstrated that obesity increases the risk of developing some forms of cancer. The association between obesity and cancer may result from factors such as fat distribution or sex hormone levels. Studies have also shown a relationship between a high-fat, low-fiber diet and cancer risk. High estrogen levels and low progesterone levels are associated with an increased risk of endometrial cancer. Obesity is known to raise estrogen levels and may lower progesterone levels. Obesity may increase the risk of breast cancer, but the evidence is less clear, since factors, such as age, country of origin, body-fat distribution, and family history, also play a major role in determining breast cancer risk. Sex hormones, insulin, and nutritional factors are also involved in the etiology of breast cancer. The incidence of lung cancer is inversely related to body weight.
We compared energy and macronutrient intakes across the menstrual cycle in participants (n = 42) in a study that assessed the frequency of ovulatory disturbances in regularly cycling vegetarians and nonvegetarians. Women kept daily basal body temperature records for six consecutive menstrual cycles and provided 3-d diet records near the beginning, middle, and end of different cycles. On completion of the study, temperature records were quantitatively analyzed to determine whether cycles were ovulatory, and if so, the date the luteal phase began. Diet records kept near the beginning and end of cycles were matched with temperature analysis results, and women were grouped according to whether the end-of-cycle record was kept during the luteal phase of an ovulatory cycle (group 1, n = 29), or during an anovulatory cycle or before luteal phase onset of a short luteal phase cycle (group 2, n = 13). Group 1 had higher energy intakes during the luteal than during the follicular phase (9.27 +/- 2.69 vs 8.01 +/- 2.36 MJ/d, P < 0.0001), whereas intakes of group 2 did not differ across the cycle (7.91 +/- 2.18 vs 8.20 +/- 1.48 MJ/d, NS). Both groups' macronutrient intakes were similar in records kept near the beginning and end of cycles. Documentation of ovulation is necessary in studies assessing premenopausal women's energy intakes.
Ovulatory function was prospectively assessed over 6 mo in 23 vegetarians and 22 nonvegetarians with clinically normal menstrual cycles. Subjects were 20-40 y of age, of stable weight (body mass index, in kg/m2, of 18-25), on current diets for > or = 2 y, and not using oral contraceptives. Quantitative analysis of basal body temperature records classified cycles as normally ovulatory, short luteal phase (< 10 d), or anovulatory. Subjects completed the Three-Factor Eating Questionnaire (subjects completed the Three-Factor Eating Questionnaire (subscales for restraint, hunger, and disinhibition) and kept three 3-d food records. Vegetarians had lower BMIs (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < 0.05), percentage body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P < 0.05), and restraint scores (6.4 +/- 4.4 vs 9.5 +/- 3.7, P < 0.05). Mean cycle lengths were similar, but vegetarians had longer luteal phase lengths (11.2 +/- 2.6 vs 9.1 +/- 3.8 d, P < 0.05). Cycle types also differed (chi 2 = 9.64, P < 0.01): vegetarians had fewer anovulatory cycles (4.6% vs 15.1% of cycles). Compared with those with restraint scores below the median, highly restrained women had fewer ovulatory cycles (3.6 +/- 2.3 vs 5.0 +/- 1.4, P < 0.05) and shorter mean luteal phase lengths (7.4 +/- 4.1 vs 10.7 +/- 3.1 d, P < 0.05). We conclude that ovulatory disturbances and restrained eating are less common among vegetarians, and that restraint influences ovulatory function.
We measured plasma Cu. Zn and Mg levels in 40 women suffering from premenstrual tension syndrome (PMTS) and in 20 control subjects by atomic absorption spectrophotometer. Mean plasma Cu, Zn and Mg levels, the Zn/Cu ratio were 80.2 +/- 6.00 micrograms/dl, 112.6 +/- 8.35 micrograms/dl, 0.70 +/- 0.18 mmol/l, and 1.40 +/- 0.10 in the PMTS group; and 77.0 +/- 4.50 micrograms/dl, 117.4 +/- 9.50 micrograms/dl, 0.87 +/- 0.10 mmol/l, and 1.51 +/- 0.05 in the control group respectively. The mean Mg level and the Zn/Cu ratio were significantly lower in PMTS patients than in the control group. Plasma Mg and Zn levels were diminished significantly during the luteal phase compared to the follicular phase in PMTS group. Mg deficiency may play a role in the etiology of PMTS.
A physically active and athletic lifestyle is not only a healthy but a fulfilling choice for women. Although there is extensive literature on 'athletic amenorrhoea' which implies that exercise causes loss of the menstrual cycle, there is inadequate scientific evidence for a causal relationship. The reproductive system adapts to environmental, nutritional, emotional and physical stressors or 'threats' by downward adjustment towards the premenarcheal pattern. The hormonal milieu of this adaptation is low gonadal steroid and high glucocorticoid levels which synergistically increase the risk for a negative bone balance. Athletic women may become amenorrhoeic if reproductive immaturity, emotional stress and undernutrition coexist with increasing exercise loads. Treatment for athletic women with menstrual cycle changes requires that hypothalamic stressors be identified and decreased. In addition, as progesterone deficiency (from disorders of ovulation, whether flow is regular or absent) is the most prevalent menstrual cycle change, treatment with medroxyprogesterone on days 16 to 25 of their cycle will not only provide regular flow (if estrogen levels are sufficient) but will also promote increased bone density.
Hypofolatemia can cause psychiatric disturbances of a depressive nature. Pregnancy and delivery are often associated with hypofolatemia. This study was conducted to determine if hypofolatemia at day 3 post partum is a risk factor for baby blues or post partum depression. To study this hypothesis, 131 post partum women were followed prospectively for the 3 months immediately following delivery. 19% were found to have 'baby blues', as defined by a score greater than 20 on Pitt's scale (Pitt, 1968, J. Psychiatry 114, 1325-1335) and 12% had post partum depression as defined by a score greater than 7 on QD2A scale (Pichot et al., 1984, Rev. Psycholog. App. 34, 229-250, 323-340), within the three months post partum. No relationship was observed between the serum or erythrocyte folate levels on the third day following delivery and the maternal post partum depression scores. A statistically significant correlation between post partum depression and previous psychiatric disturbance was, however, observed.
Reproductive change during conditioning exercise (physical training provides a model of hypothalamic adaptation to alterations in the external and internal environment. Parallels exist between the reproductive changes with exercise and those occurring with physical illness, undernutrition and psychological trauma. Although menstrual cyclicity may be disrupted in younger women, luteal phase shortening, anovulation and decreased premenstrual symptoms within normal ovulatory cycles are the most frequent observations noted. Baseline LH, prolactin and oestradiol tend to be lower, and other hormones unchanged, in trained women. Testosterone may be decreased within the normal range in men. Recent evidence shows that LH pulse frequency, amplitude and area under the LH curve are decreased in both female and male runners. Interrelationships between increases in central dopamine, endorphin and probably some hypothalamic message(s) relating to nutritional state appear to modulate these reproductive changes. The clinical and therapeutic response to reproductive alterations in the context of exercise differs when these are seen as adaptive and not as disease processes (Prior and Vigna, 1985b).
Fourteen normal women (self-selected from 180 women enrolled) in a marathon training clinic kept basal body temperature (BBT), mileage, and weight records for 48 cycles before the marathon. Entry criteria were: Age 20-45, gynecologic age greater than 5 years, no hormone use, or weight change in 3 months. The women were 35.2 +/- 5.6 years in age, 22.6 +/- 5.1 years gynecologic age, runners of 4.1 +/- 2.5 years with premenstrual symptoms, previous pregnancy 4/14, no infertility and 2/14 remote amenorrhea. BBT records were obtained and analyzed by Vollman's criteria (1977). There was no weight loss. 32/48 cycles were biphasic but only 16 were normal in the length of the premenstrual phase (PreM = luteal, nl 10 - 16 d) with a mean of 11.1 +/- 1.2 days. The other 16 biphasic cycles had short PreM phase of 6.4 +/- 1.8 days. Monophasic (M = anovulatory) cycles occurred in 16/48 records. Cycles which were abnormal (Short PreM and M) differed only in that usual run length was longer (9.6 - 9.9 miles) than in normal cycles (7.9 +/- 2.4 miles). Marathon training may be associated with normal length but M and short PreM type cycles.