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.
PMID 35512771 35512771 DOI 10.1080/07315724.2022.2040399 10.1080/07315724.2022.2040399 Aguree et al. 2022, Aguree 2022
Cite this article
Aguree, S., Murray-Kolb, L. E., Diaz, F., & Gernand, A. D. (2023). Menstrual Cycle-Associated Changes in Micronutrient Biomarkers Concentration: A Prospective Cohort Study. Journal of the American Nutrition Association, 42(4), 339-348. https://doi.org/10.1080/07315724.2022.2040399
Aguree S, Murray-Kolb LE, Diaz F, Gernand AD. Menstrual Cycle-Associated Changes in Micronutrient Biomarkers Concentration: A Prospective Cohort Study. J Am Nutr Assoc. 2023;42(4):339-348. doi:10.1080/07315724.2022.2040399
Aguree, Sixtus, et al. "Menstrual Cycle-Associated Changes in Micronutrient Biomarkers Concentration: A Prospective Cohort Study." Journal of the American Nutrition Association, vol. 42, no. 4, 2023, pp. 339-348.
Keywords
Estrogen and Micronutrient, Biomarkers Mass, Micronutrient Deficiencies, Plasma Volume, Progesterone and Micronutrient
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.
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.
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.
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.