Kim, K., Wactawski-Wende, J., Michels, K. A., Schliep, K. C., Plowden, T. C., Chaljub, E. N., & Mumford, S. L. (2018). Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles. The British journal of nutrition, 120(1), 81-89. https://doi.org/10.1017/S0007114518000818
Kim K, Wactawski-Wende J, Michels KA, Schliep KC, Plowden TC, Chaljub EN, et al. Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles. Br J Nutr. 2018;120(1):81-89. doi:10.1017/S0007114518000818
Kim, K., et al. "Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles." The British journal of nutrition, vol. 120, no. 1, 2018, pp. 81-89.
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Eunice Kennedy Shriver National Institute of Child Health and Human Development04byxyr05
Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.01y64my43
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RRM Academy Synopsis
Low dietary sodium and manganese linked to skipped ovulation
Women with low sodium or low manganese intake were more likely to have cycles without ovulation. This cohort followed 259 healthy women with regular cycles for up to two cycles. None took mineral supplements. The other minerals measured showed no association with ovulatory function.
Key Findings
The BioCycle Study followed 259 healthy, regularly menstruating women aged 18–44. Researchers counted 42 of 509 cycles (8.3%) as anovulatory, meaning no ovulation occurred.
Sodium intake below the recommended dietary allowance carried a risk ratio of 2.70 (95% CI 1.00, 7.31) for anovulation, compared with higher intake.
Manganese intake below the recommended dietary allowance carried a risk ratio of 2.00 (95% CI 1.02, 3.94) for anovulation, compared with higher intake.
Low sodium intake also went with higher FSH (about a fifth higher) and higher LH (about a third higher). Luteal-phase progesterone was about a third lower.
The authors detected no associated hormone changes with manganese. The other minerals measured showed no association with ovulatory function.
Interpretation
The BioCycle Study is an observational cohort. It shows associations and cannot show that low intake caused skipped ovulation. Food recalls estimated intake, and the sodium figure leaves out table salt, so the authors note misclassification is possible. The sodium interval starts at 1.00, and the authors call the work exploratory. Several other hormone links lost significance after adjustment for multiple comparisons. The results cover healthy, regularly menstruating women not taking supplements. The authors add that excessive sodium relates to high blood pressure and heart disease, so the result should be interpreted carefully.
RRM Context
Restorative reproductive medicine treats ovulation as a vital sign and looks for the cause when it is missing. The study judged ovulation from progesterone and LH measured across each cycle. Diet is one candidate contributor to examine beside cycle data. The study recorded the women's usual diets.
Our editorial summary of this paper, not the article's abstract.
Abstract
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.
Schliep KC et al., 2026·J Gynecol Obstet Hum Reprod·Free full text on PubMed Central
Endometriosis has been linked to cardiometabolic alterations, but whether these associations vary by disease severity or phenotype is unclear. We examined lipid profiles across endometriosis diagnosis, stage, and typology. Data came from 476 women in the NICHD ENDO cohort. Endometriosis was confirmed laparoscopically and staged using the rASRM criteria (I-IV). Typology was categorized as superficial endometriosis (SE), ovarian endometrioma (OE), deep infiltrating endometriosis (DE), and OE+DE. We compared endometriosis status, stage (I/II vs III/IV), and typology to no endometriosis using adverse lipid thresholds (total cholesterol ≥200 mg/dL, HDL <50 mg/dL, LDL ≥100 mg/dL, triglycerides ≥175 mg/dL, non-HDL ≥130 mg/dL, VLDL ≥30 mg/dL, ApoA1 <125 mg/dL, and ApoB ≥120 mg/dL). Adjusted prevalence ratios (aPR) and 95 % CIs were estimated via generalized linear models, controlling for age, race/ethnicity, BMI, income, marital status, and serum cotinine. Endometriosis diagnosis alone was not associated with adverse lipid profiles. In contrast, moderate/severe disease showed higher prevalence of elevated triglycerides (aPR= 2.27; 95 % CI: 1.18,4.35) and VLDL (aPR= 2.41; 95 % CI: 1.50, 3.85). Typology revealed stronger patterns: OE and OE+DE were associated with adverse profiles across multiple markers (aPRs 1.59-4.09), particularly ApoB and triglycerides. Minimal/mild disease and SE were not associated. The metabolic signal was phenotype-driven rather than diagnosis-driven, with severe stage and OE/OE+DE showing clear associations with adverse lipid profiles. These findings suggest lipid profiles may serve as markers of phenotype severity or shared biological milieu. Replication in larger cohorts is needed.
Reeder MR et al., 2026·Fertil Steril·Free full text on PubMed Central
To examine birth outcomes between children conceived with in vitro fertilization (IVF) or intrauterine insemination (IUI) and sibling births from unassisted conceptions. Retrospective sibling cohort. Live born children conceived via IVF, with or without intracytoplasmic sperm injection, or IUI at the Utah Center for Reproductive Medicine, 1999-2018, and sibling births from unassisted conceptions (born 1985-2018). The main analysis included singleton births (460 IVF, 666 IUI, and 1,579 unassisted siblings). Exposure: In vitro fertilization, with or without intracytoplasmic sperm injection, or IUI. Preterm birth, low birth weight, small for gestational age, large for gestational age (LGA), and major congenital anomalies. Compared with unassisted siblings, singleton children conceived via IVF had gestational ages shorter by nearly half a week (95% confidence interval [CI], -0.6 to -0.3), birth weights of 72.1 g lower (95% CI, -118.8 to -25.4), and higher proportions of preterm birth (IVF, 11.1%; IUI, 8.7%; unassisted siblings, 6.8%), LGA (IVF, 9.1%; IUI, 4.5%; unassisted siblings, 5.9%), and major congenital anomalies (IVF, 3.7%; IUI, 2.0%; unassisted siblings, 1.4%). Models adjusted for maternal age, infant sex, infant birth year, previous pregnancy, and birth order showed that children conceived via IVF were more likely to be preterm (adjusted risk ratio [aRR], 1.6; 95% CI, 1.2-2.2; absolute difference, 4.3%) and LGA (aRR, 1.8; 95% CI, 1.2-2.5; absolute difference, 3.2%). Children conceived via IVF had a higher risk of major congenital anomalies than unassisted siblings adjusted for maternal age, infant sex, and birth order (aRR, 1.9; 95% CI, 1.0-3.8; absolute difference, 2.3%). Children conceived via IUI had birth weights 55.8 g lower (95% CI, -95.6 to -15.9) than unassisted siblings. We observed an increased risk of preterm birth, low birth weight, LGA, and major congenital anomalies among singleton children conceived with IVF compared with that among unassisted siblings; however, absolute differences remain small. For children conceived via IUI, lower birth weights were observed. These results suggest that treatment-related factors in addition to underlying subfertility may contribute to adverse birth outcomes.
Valenti M et al., 2026·Am J Obstet Gynecol·Free full text on PubMed Central
Endometriosis is a chronic, gynecologic condition in which tissue similar to the lining of the uterus implants throughout the body. Women with endometriosis have a higher prevalence of infertility and a greater risk of early natural menopause compared to those without endometriosis. This study aimed to evaluate preoperative serum AMH levels among women with and without incident endometriosis and to assess whether levels differ by surgical staging and typology. The ENDO (Endometriosis: Natural History, Diagnosis, and Outcomes) study was conducted between 2007 and 2009. The ENDO study consisted of an operative and population cohort (n=600). Only those in the ENDO operative cohort from the Utah site were used for this analysis, and included women aged 18 to 44 years who were scheduled for gynecologic surgery, irrespective of clinical indication (n=476). AMH levels were measured from stored serum collected before surgery using a quantitative enzyme-linked immunosorbent assay. After excluding participants with missing outcome data (n=51), unilateral oophorectomy (n=8), or those within the population cohort (n=69), 348 participants remained for the analysis. Surgically confirmed endometriosis diagnosis, staging (American Society for Reproductive Medicine I-IV), and typology (superficial, deep, ovarian) were ascertained by the operative report. Outliers for AMH (>14.0 ng/mL) were excluded from the analyses and AMH values were log-transformed. Multivariable linear regression models adjusted for age (squared and continuous), body mass index, serum cotinine levels, and exogenous hormonal contraceptive use were conducted. Percentage differences in AMH were calculated as (exp[β]-1)×100, and 95% confidence intervals were reported. Compared with no endometriosis, incident endometriosis diagnosis was associated with lower AMH levels (-19.8%; 95% confidence interval, -37.0 to 1.0); however, this association was not statistically significant. Stage III to IV disease was associated with 40.1% lower AMH levels (95% confidence interval, -58.9 to -12.7). Ovarian endometriomas were most strongly associated with lower AMH levels (-54.3%; 95% confidence interval, -69.4 to -31.8), with a more pronounced association among those with infertility (-72.6%; 95% confidence interval, -85.4 to -48.5). Deep (-24.1%; 95% confidence interval, -48.2 to 11.0) and superficial (-15.5%; 95% confidence interval, -34.6 to 9.3) endometriosis also showed a trend toward lower AMH levels, but these findings were not statistically significant. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis was associated with 26.8% lower AMH levels (95% confidence interval, -44.6 to -3.4). Stage III to IV disease was associated with 47.8% lower AMH levels (95% confidence interval, -65.8 to -23.2), and all subtypes of endometriosis were statistically significantly associated with lower levels of AMH compared with a postoperative diagnosis of a normal pelvis (ovarian: -60.8%; 95% confidence interval, -74.4 to -39.9; deep: -34.3%; 95% confidence interval, -56.2 to -1.4; superficial: -24.8%; 95% confidence interval, -43.9 to -0.8). Ovarian and moderate to severe (stage III-IV) endometriosis were associated with markedly lower AMH levels compared with no endometriosis. Compared with a postoperative diagnosis of a normal pelvis, incident endometriosis and moderate to severe stages (stage III-IV) were associated with statistically significantly lower AMH levels. Additionally, typology (deep, ovarian, or superficial) was associated with statistically significantly lower AMH levels. However, this association was likely driven by the presence of ovarian endometriomas across all subtypes. These findings are consistent with previous studies and demonstrate that endometriosis lesions themselves, independent of surgical intervention, influence AMH levels.
Fertility and Outcomes · Conception After Excision
Hsu JZ et al., 2025·Eur J Obstet Gynecol Reprod Biol
Endometriosis is a chronic gynaecological condition affecting reproductive-aged women. It has been associated with infertility and potential risks for adverse pregnancy outcomes, although population-level evidence remains limited. This retrospective cohort study, including 147,950 pregnant women aged 20-45 years, used nationwide population-based data to compare the outcomes between women with (n = 11,400) and without (n = 136,550) endometriosis between 2000 and 2021. Baseline characteristics, comorbidities and pregnancy outcomes were compared between the groups. Multivariable regression analyses were performed to calculate adjusted relative risks (aRR) and 95 % confidence intervals (CI) for various pregnancy outcomes, and subgroup analyses were conducted by maternal age and infertility status. Among 147,950 pregnancies, women with endometriosis [mean ± standard deviation (SD) age 32.38 ± 4.51 years] had higher socio-economic status, more comorbidities, and more surgical history compared with women without endometriosis (mean ± SD age 30.06 ± 4.96 years). Women with endometriosis had increased risk of miscarriage (aRR 1.13, 95 % CI 1.03-1.24), preterm birth (aRR 1.31, 95 % CI 1.26-1.37), premature rupture of membranes (aRR 1.11, 95 % CI 1.06-1.16), placenta previa (aRR 1.63, 95 % CI 1.45-1.84), urinary tract infection (aRR 1.44, 95 % CI 1.31-1.59), and caesarean section (aRR 1.13, 95 % CI 1.11-1.16). Subgroup analysis revealed that risk of miscarriage was only higher in women aged 35-45 years and women without infertility. Risks of preterm birth, placenta previa and caesarean section were elevated across all subgroups, suggesting that endometriosis contributes independently to adverse pregnancy outcomes. Endometriosis is an independent risk factor for several pregnancy complications, supporting the need for tailored prenatal care and closer monitoring of affected women to improve maternal outcomes.
Filiberto AC et al., 2013·Fertil Steril·Free full text on PubMed Central
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.
Mumford SL et al., 2016·J Nutr·Free full text on PubMed Central
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.
Schliep KC et al., 2016·Am J Clin Nutr·Free full text on PubMed Central
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.
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.
Lifestyle and Environment › Nutrition and Metabolic Health › Dietary Patterns · Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances · Reproductive Endocrinology › Ovulation Physiology › Anovulation
Keewan Kim, Kara A Michels, Karen C Schliep, Torie Comeaux Plowden, Sunni L Mumford, Ellen N Chaljub, Jean Wactawski-Wende
K Kim, K Michels, K Schliep, T Plowden, S Mumford, E Chaljub, J Wactawski-Wende
PMID 29673411 29673411 DOI 10.1017/S0007114518000818 10.1017/S0007114518000818 Kim et al. 2018, Kim 2018
Cite this article
Kim, K., Wactawski-Wende, J., Michels, K. A., Schliep, K. C., Plowden, T. C., Chaljub, E. N., & Mumford, S. L. (2018). Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles. The British journal of nutrition, 120(1), 81-89. https://doi.org/10.1017/S0007114518000818
Kim K, Wactawski-Wende J, Michels KA, Schliep KC, Plowden TC, Chaljub EN, et al. Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles. Br J Nutr. 2018;120(1):81-89. doi:10.1017/S0007114518000818
Kim, K., et al. "Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles." The British journal of nutrition, vol. 120, no. 1, 2018, pp. 81-89.
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