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Competing Interests: Declaration of competing interest This study received funding from Apple Inc. The funding source provided platforms and software for data collection and participated in writing the manuscript. It played no role in the analysis and interpretation of data or in the decision to submit. The research was also supported in part by the Intramural Research Program of the National Institutes of Health, Z01ES103333. Support for A.M.Z.J. was provided by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institute of Health. H.L., J.P.O., M.A.W., R.H., B.A.C., A.M.Z.J., and S.M. declare no support from any organization for the submitted work. C.L.C. and T.F.C. are employed by Apple Inc. and own Apple Inc. stock. No financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Purpose of Review: The aim of this review is to evaluate biological, life history, environmental, and lifestyle factors and exposures that cause variability in menstrual cycle length (MCL)., Recent Findings: Recent literature has detailed a number of factors that influence MCL, with particular emphasis placed on novel environmental exposures, such as air pollution and endocrine disrupting chemicals., Summary: MCL varies widely in response to intrinsic and extrinsic inputs and is a useful predictor of reproductive health and fecundability., Video Abstract: http://links.lww.com/COE/A28., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: This review seeks to evaluate the impact of environmental exposures on the menstrual cycle length detailing timing of exposure on pathophysiology., Recent Findings: Recent literature has examined the relationship between menstrual cycle length and environmental exposures including air pollutants, parabens, and polybrominated biphenyls., Summary: Research is limited but suggest importance of further research in evaluating environmental exposures and menstrual cycle length.

Purpose: The aim of this study was to evaluate the association between menstrual cycle characteristics in early life and adulthood and fecundability., Methods: Pregnancy Study Online (PRESTO) is an Internet-based preconception cohort study of pregnancy planners from the United States and Canada. During the preconception period, we enrolled 2189 female pregnancy planners aged 21-45 years who had been attempting conception for ≤6 cycles. Women self-reported menstrual cycle characteristics via an online baseline questionnaire, and pregnancy status was ascertained through bimonthly follow-up questionnaires. Proportional probabilities models were used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders., Results: Compared with usual menstrual cycle lengths of 27-29 days, cycle lengths of <25 (FR = 0.81, 95% CI: 0.54-1.22) and 25-26 days (FR = 0.92, 95% CI: 0.75-1.14) were associated with reduced fecundability. Compared with women who reached menarche at the age of 12-13 years, those who reached menarche at <12 years had reduced fecundability (FR = 0.87, 95% CI: 0.76-0.99). Women whose cycles never regularized after menarche (FR = 0.93, 95% CI: 0.81-1.06) had slightly reduced fecundability compared with women whose cycles regularized within 2 years of menarche. Bleed length and heaviness of bleeding were not appreciably associated with fecundability., Conclusions: Menstrual cycle characteristics, specifically cycle length and age at menarche, may act as markers of fertility potential among pregnancy planners., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Menstrual characteristics are important signs of women's health. Here we examine the variation of menstrual cycle length by age, ethnicity, and body weight using 165,668 cycles from 12,608 participants in the US using mobile menstrual tracking apps. After adjusting for all covariates, mean menstrual cycle length is shorter with older age across all age groups until age 50 and then became longer for those age 50 and older. Menstrual cycles are on average 1.6 (95%CI: 1.2, 2.0) days longer for Asian and 0.7 (95%CI: 0.4, 1.0) days longer for Hispanic participants compared to white non-Hispanic participants. Participants with BMI ≥ 40 kg/m2 have 1.5 (95%CI: 1.2, 1.8) days longer cycles compared to those with BMI between 18.5 and 25 kg/m2. Cycle variability is the lowest among participants aged 35–39 but are considerably higher by 46% (95%CI: 43%, 48%) and 45% (95%CI: 41%, 49%) among those aged under 20 and between 45–49. Cycle variability increase by 200% (95%CI: 191%, 210%) among those aged above 50 compared to those in the 35–39 age group. Compared to white participants, those who are Asian and Hispanic have larger cycle variability. Participants with obesity also have higher cycle variability. Here we confirm previous observations of changes in menstrual cycle pattern with age across reproductive life span and report new evidence on the differences of menstrual variation by ethnicity and obesity status. Future studies should explore the underlying determinants of the variation in menstrual characteristics. [ABSTRACT FROM AUTHOR]

COVID-19 vaccination may be associated with change in menstrual cycle length following vaccination. We estimated covariate-adjusted differences in mean cycle length (MCL), measured in days, between pre-vaccination cycles, vaccination cycles, and post-vaccination cycles within vaccinated participants who met eligibility criteria in the Apple Women's Health Study, a longitudinal mobile-application-based cohort of people in the U.S. with manually logged menstrual cycles. A total of 9652 participants (8486 vaccinated; 1166 unvaccinated) contributed 128,094 cycles (median = 10 cycles per participant; inter-quartile range: 4–22). Fifty-five percent of vaccinated participants received Pfizer-BioNTech's mRNA vaccine, 37% received Moderna's mRNA vaccine, and 8% received the Johnson & Johnson/Janssen (J&J) vaccine. COVID-19 vaccination was associated with a small increase in MCL for cycles in which participants received the first dose (0.50 days, 95% CI: 0.22, 0.78) and cycles in which participants received the second dose (0.39 days, 95% CI: 0.11, 0.67) of mRNA vaccines compared with pre-vaccination cycles. Cycles in which the single dose of J&J was administered were, on average, 1.26 days longer (95% CI: 0.45, 2.07) than pre-vaccination cycles. Post-vaccination cycles returned to average pre-vaccination length. Estimated follicular phase vaccination was associated with increased MCL in cycles in which participants received the first dose (0.97 days, 95% CI: 0.53, 1.42) or the second dose (1.43 days, 95% CI: 1.06, 1.80) of mRNA vaccines or the J&J dose (2.27 days, 95% CI: 1.04, 3.50), compared with pre-vaccination cycles. Menstrual cycle change following COVID-19 vaccination appears small and temporary and should not discourage individuals from becoming vaccinated. [ABSTRACT FROM AUTHOR]

Fetal development represents a time of potential vulnerability due to rapid cell division, organ development and limited fetal kidney/liver activity for detoxification and metabolism of exposures. Health effects of prenatal toxicant exposure have previously been described, but there is little cohesive evidence surrounding effects on ovarian function. Using bisphenol A (BPA) as a case study, we seek to examine whether a prominent prenatal environmental exposure can pose a real threat to human ovarian function. To do so, we broadly review human oogenesis and menstrual cycle biology. We then present available literature addressing prenatal bisphenol A and diverse outcomes at the level of the ovary. We highlight relevant human cohorts and mammalian models to review the existing data on prenatal exposures and ovarian disruption. Doing so suggests that while current exposures to BPA have not shown marked or consistent results, there is data sufficient to raise concerns regarding ovarian function. Challenges in the examination of this question suggest the need for additional models and pathways by which to expand these examinations in humans. [ABSTRACT FROM AUTHOR]

Background: Multimodal recruitment strategies are a novel way to increase diversity in research populations. However, these methods have not been previously applied to understanding the prevalence of menstrual disorders such as polycystic ovary syndrome. Objective: The purpose of this study was to test the feasibility of recruiting a diverse cohort to complete a web-based survey on ovulation and menstruation health. Methods: We conducted the Ovulation and Menstruation Health Pilot Study using a REDCap web-based survey platform. We recruited 200 women from a clinical population, a community fair, and the internet. Results: We recruited 438 women over 29 weeks between September 2017 and March 2018. After consent and eligibility determination, 345 enrolled, 278 started (clinic: n=43; community fair: n=61; internet: n=174), and 247 completed (clinic: n=28; community fair: n=60; internet: n=159) the survey. Among all participants, the median age was 25.0 (SD 6.0) years, mean BMI was 26.1 kg/m2 (SD 6.6), 79.7% (216/271) had a college degree or higher, and 14.6% (37/254) reported a physician diagnosis of polycystic ovary syndrome. Race and ethnicity distributions were 64.7% (176/272) White, 11.8% (32/272) Black/African American, 7.7% (21/272) Latina/Hispanic, and 5.9% (16/272) Asian individuals; 9.9% (27/272) reported more than one race or ethnicity. The highest enrollment of Black/African American individuals was in clinic (17/42, 40.5%) compared to 1.6% (1/61) in the community fair and 8.3% (14/169) using the internet. Survey completion rates were highest among those who were recruited from the internet (159/174, 91.4%) and community fairs (60/61, 98.4%) compared to those recruited in clinic (28/43, 65.1%). Conclusions: Multimodal recruitment achieved target recruitment in a short time period and established a racially diverse cohort to study ovulation and menstruation health. There were greater enrollment and completion rates among those recruited via the internet and community fair. J Med Internet Res 2021;23(4):e24716 doi:10.2196/24716 [ABSTRACT FROM AUTHOR]

[Display omitted] The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: −4.51%; 95% CI: −6.72%, −2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period. [ABSTRACT FROM AUTHOR]

Objective: Hirsutism, the presence of excess terminal hair in a male pattern, is a clinical marker of androgen excess in women. We used cross-sectional data from a North American preconception cohort study to evaluate the association between menstrual cycle characteristics and hirsutism.Study Design: Women aged 21-45 years were recruited to a North American cohort of pregnancy planners. On the baseline questionnaire, participants self-reported menstrual characteristics, which included menstrual regularity, cycle length, bleed length, and bleed heaviness. Participants provided a self-rating of hirsutism in nine distinct body areas using pictograms representing the modified Ferriman-Gallwey (mFG) score. Using their ratings, we calculated total mFG scores and defined hirsutism as mFG scores ≥8. We used log-binomial regression models to estimate prevalence ratios (PRs) for the association between menstrual characteristics and hirsutism assessed at baseline.Results: We included 5,542 women in the analytic cohort. Mean mFG score was 4.7, with 21.7 % reporting mFG scores ≥8. Compared with women with regular menstrual cycles, irregular cycles were positively associated with mFG ≥8 (PR 1.73, 95 % CI 1.56-1.91). Bleed lengths of ≥7 days compared with <3 days also showed a positive association with mFG score ≥8 (PR 1.59, 95 % CI 1.16-2.19), as did heavy bleeds (PR 1.42, 95 % CI 1.21-1.67) compared with moderate bleeds. Findings remained consistent when restricted to women without a prior diagnosis of polycystic ovary syndrome.Conclusions: In a population-based cohort of North American women, menstrual irregularity, increased cycle and bleeds lengths, and heavier menstrual bleeds were associated with self-reported hirsutism. [ABSTRACT FROM AUTHOR]