Irregular Cycles, Ovulatory Disorders, and Cardiometabolic Conditions in a US-Based Digital Cohort.

Importance: Polycystic ovary syndrome (PCOS), characterized by irregular menstrual cycles and hyperandrogenism, is a common ovulatory disorder. Having an irregular cycle is a potential marker for cardiometabolic conditions, but data are limited on whether the associations differ by PCOS status or potential interventions. Objective: To evaluate the association of PCOS, time to regularity since menarche (adolescence), and irregular cycles (adulthood) with cardiometabolic conditions. Design, Setting, and Participants: This cross-sectional study used a large, US-based digital cohort of users of the Apple Research application on their iPhone. Eligibility criteria were having ever menstruated, living in the US, being at age of consent of at least 18 years (or 19 years in Alabama and Nebraska or 21 years in Puerto Rico), and being able to communicate in English. Participants were enrolled between November 14, 2019, and December 13, 2022, and completed relevant surveys. Exposures: Self-reported PCOS diagnosis, prolonged time to regularity (not spontaneously establishing regularity within 5 years of menarche), and irregular cycles. Main Outcomes and Measures: The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, heart attack, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis, and pulmonary embolism measured using descriptive statistics and logistic regression to estimate prevalence odds ratios (PORs) and 95% CIs. Effect modification by lifestyle factors was also estimated. Results: The study sample (N = 60 789) had a mean (SD) age of 34.5 (11.1) years, with 12.3% having PCOS and 26.3% having prolonged time to regularity. Among a subset of 25 399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles. In covariate-adjusted logistic regression models, PCOS was associated with a higher prevalence of all metabolic and several cardiovascular conditions, eg, arrhythmia (POR, 1.37; 95% CI, 1.20-1.55), coronary artery disease (POR, 2.92; 95% CI, 1.95-4.29), heart attack (POR, 1.79; 95% CI, 1.23-2.54), and stroke (POR, 1.66; 95% CI, 1.21-2.24). Among participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (POR, 1.24; 95% CI, 1.05-1.46), hypertension (POR, 1.09; 95% CI, 1.01-1.19), arrhythmia (POR, 1.20; 95% CI, 1.06-1.35), and TIA (POR, 1.33; 95% CI, 1.01-1.73), and having irregular cycles was associated with type 2 diabetes (POR, 1.36; 95% CI, 1.08-1.69), high cholesterol (POR, 1.17; 95% CI, 1.05-1.30), arrhythmia (POR, 1.21; 95% CI, 1.02-1.43), and TIA (POR, 1.56; 95% CI, 1.06-2.26). Some of these associations were modified by high vs low body mass index or low vs high physical activity. Conclusions and Relevance: These findings suggest that PCOS and irregular cycles may be independent markers for cardiometabolic conditions. Early screening and intervention among individuals with irregular menstrual cycles may be beneficial.

Environmental phenol exposures in 6- to 12-week-old infants: The Infant Feeding and Early Development (IFED) study.

BACKGROUND: Exposure to phenols, endocrine-disrupting chemicals used in personal care and consumer products, is widespread. Data on infant exposures are limited despite heightened sensitivity to endocrine disruption during this developmental period. We aimed to describe distributions and predictors of urinary phenol concentrations among U.S. infants ages 6-12 weeks. METHODS: The Infant Feeding and Early Development (IFED) study is a prospective cohort study of healthy term infants enrolled during 2010-2013 in the Philadelphia region. We measured concentrations of seven phenols in 352 urine samples collected during the 6- or 8- and/or 12-week study visits from 199 infants. We used linear mixed models to estimate associations of maternal, sociodemographic, infant, and sample characteristics with natural-log transformed, creatinine-standardized phenol concentrations and present results as mean percent change from the reference level. RESULTS: Median concentrations (µg/L) were 311 for methylparaben, 10.3 for propylparaben, 3.6 for benzophenone-3, 2.1 for triclosan, 1.0 for 2,5-dichlorophenol, 0.7 for BPA, and 0.3 for 2,4-dichlorophenol. Geometric mean methylparaben concentrations were approximately 10 times higher than published estimates for U.S. children ages 3-5 and 6-11 years, while propylparaben concentrations were 3-4 times higher. Infants of Black mothers had higher concentrations of BPA (83%), methylparaben (121%), propylparaben (218%), and 2,5-dichorophenol (287%) and lower concentrations of benzophenone-3 (-77%) and triclosan (-53%) than infants of White mothers. Triclosan concentrations were higher in breastfed infants (176%) and lower in infants whose mothers had a high school education or less (-62%). Phenol concentrations were generally higher in summer samples. CONCLUSIONS: Widespread exposure to select environmental phenols among this cohort of healthy U.S. infants, including much higher paraben concentrations compared to those reported for U.S. children, supports the importance of expanding population-based biomonitoring programs to infants and toddlers. Future investigation of exposure sources is warranted to identify opportunities to minimize exposures during these sensitive periods of development.

Environmental Phenols and Growth in Infancy: The Infant Feeding and Early Development Study.

CONTEXT: Higher mean and rapid increases in body mass index (BMI) during infancy are associated with subsequent obesity and may be influenced by exposure to endocrine-disrupting chemicals such as phenols. OBJECTIVE: In a prospective US-based cohort conducted 2010-2014, we investigated associations between environmental phenol exposures and BMI in 199 infants. METHODS: We measured seven urinary phenols at ages 6-8 and 12 weeks and assessed BMI z-score at up to 12 study visits between birth and 36 weeks. We examined individual and joint associations of averaged early infancy phenols with level of BMI z-score using mean differences (ß [95% confidence intervals (CI)]) and with BMI z-score trajectories using relative risk ratios (RR [95% CI]). RESULTS: Benzophenone-3, methyl and propyl paraben, and all phenols jointly were positively associated with higher mean BMI z-score (0.07 [-0.05, 0.18], 0.10 [-0.08, 0.27], 0.08 [-0.09, 0.25], 0.17 [-0.08, 0.43], respectively). Relative to a Stable trajectory, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and all phenols jointly were positively associated with risk of a Rapid Increase trajectory (1.46 [0.89, 2.39], 1.33 [0.88, 2.01], 1.66 [1.03, 2.68], 1.41 [0.71, 2.84], respectively). CONCLUSION: Early phenol exposure was associated with a higher mean and rapid increase in BMI z-score across infancy, signaling potential long-term cardiometabolic consequences of exposure.

Family History and Uterine Fibroid Development in Black and African American Women.

Importance: Uterine fibroids are an understudied condition, with earlier onset in Black than White women. Prior studies of the importance of family history on fibroid development are limited by reliance on hospital-based participant selection, poorly defined measures of family history, and nonsystematic fibroid assessment. Objective: To examine whether family history is a risk factor for fibroid development using prospective ultrasonography data to identify incident fibroids and measure fibroid growth and standardized methods to ascertain family history. Design, Setting, and Participants: This prospective community cohort of Black and African American women from the Detroit, Michigan, area was conducted from January 1, 2010, to December 31, 2018, using 4 standardized ultrasonographic examinations during 5 years to detect fibroids 0.5 cm or larger in diameter and measure fibroid growth. Data analysis was performed between May 2022 and January 2024. Exposures: Maternal fibroid history data were gathered directly from participants' mothers when possible (1425/1628 [88%]), and 2 exposure variables were created: maternal history of fibroids (diagnosed vs not diagnosed) and age at maternal fibroid diagnosis (20-29, 30-39, or ≥40 years vs not diagnosed). Main Outcomes and Measures: Fibroid incidence was assessed using multivariable Cox proportional hazards regression models; fibroid growth was calculated as change in log-volume per 18 months for fibroids matched at successive ultrasonograms. Results: A total of 1610 self-identified Black and/or African American women aged 23 to 35 years (mean [SD] age, 29.2 [3.4] years) with no prior clinical diagnosis of fibroids at enrollment were available for analysis. Of 1187 fibroid-free participants at enrollment, 442 (37%) had mothers who were diagnosed with fibroids. Compared with participants without a maternal history of fibroids, those reporting maternal history had an adjusted hazard ratio (AHR) of 1.21 (95% CI, 0.96-1.52). Risk was strongest in those whose mothers were diagnosed at a younger age (20-29 years: AHR, 1.56; 95% CI, 1.11-2.21; 30-39 years: AHR, 1.03; 95% CI, 0.71-1.49; ≥40 years: AHR, 1.11; 95% CI, 0.81-1.52; P = .053 for trend). Fibroid growth rates were higher when mothers were diagnosed with fibroids vs not diagnosed (8.0% increased growth; 95% CI, -1.2% to 18.0%). Conclusions and Relevance: In this prospective cohort study, results supported maternal history of fibroids as a risk factor for incident fibroids, especially when mothers were diagnosed at a younger age. Maternal history was also associated with increased fibroid growth. Asking patients about their family history of fibroids could encourage patient self-advocacy and inform care.

Per- and polyfluoroalkyl substances (PFAS), perceived stress, and depressive symptoms in a prospective cohort study of black women.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals with neurotoxic properties. PFAS have been associated with depressive symptoms among women in some studies, but little research has evaluated the effects of PFAS mixtures. Further, no study has investigated interactions of PFAS-depression associations by perceived stress, which has been shown to modify the effects of PFAS on other health outcomes. OBJECTIVE: In a prospective cohort study of reproductive-aged Black women, we investigated associations between PFAS and depressive symptoms and the extent to which perceived stress modified these associations. METHODS: We analyzed data from 1499 participants (23-35 years) in the Study of Environment, Lifestyle, and Fibroids. We quantified concentrations of nine PFAS in baseline plasma samples using online solid-phase extraction-liquid chromatography-isotope dilution tandem mass spectrometry. Participants reported perceived stress via the Perceived Stress Scale (PSS-4; range = 0-16) at baseline and depressive symptoms via the Center for Epidemiologic Studies Depression Scale (CESD; range = 0-44) at the 20-month follow-up visit. We used Bayesian Kernel Machine Regression to estimate associations between PFAS concentrations, individually and as a mixture, and depressive symptoms, and to assess effect modification by PSS-4 scores, adjusting for confounders. RESULTS: Baseline perfluorodecanoic acid concentrations were associated with greater depressive symptoms at the 20-month follow-up, but associations for other PFAS were null. The PFAS were not associated with depressive symptoms when evaluated as a mixture. The association between the 90th percentile (vs. 50th percentile) of the PFAS mixture with CES-D scores was null at the 10th (ß = 0.03; 95 % CrI = 0.20, 0.25), 50th (ß = 0.02; 95 % CrI = -0.16, 0.19), and 90th (ß = 0.01; 95 % CrI = 0.18, 0.20) percentiles of PSS-4 scores, suggesting perceived stress did not modify the PFAS mixture. CONCLUSION: In this prospective cohort study, PFAS concentrations-assessed individually or as a mixture-were not appreciably associated with depressive symptoms, and there was no evidence of effect modification by perceived stress.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. CONCLUSION: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

Perceived childhood neighborhood safety and sleep health during childhood and adulthood among a cohort of African American women.

OBJECTIVE: To investigate associations between perceived childhood neighborhood safety and sleep over the life course. METHODS: Among a cohort of 1693 Black/African American women aged 23-35 years at enrollment (2010-2012), participants recalled neighborhood safety (safe vs. unsafe) when they were 5, 10, and 15 years old. Participants' mothers/caregivers and participants reported sleep-related health behaviors at age 5. We used ordinal logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for sleep-related health behaviors (i.e., rarely/never or sometimes vs. mostly/always going to bed by 8:00 p.m., bed in a quiet room, bed in a dimly lit or unlit room), separately. Adulthood sleep duration and insomnia symptoms were reported at enrollment and over three follow-up periods. We applied generalized estimating equations to log binomial regression models to estimate relative risks (RR) for adulthood sleep characteristics. RESULTS AND CONCLUSIONS: Four percent of participants reported an unsafe neighborhood at age 5 years, only, and 12% reported an unsafe neighborhood at all ages. Participants in perceived unsafe vs. safe neighborhoods at age 5 had higher odds of poor sleep-related health behaviors (e.g., rarely/never or sometimes going to bed in a quiet room: OR = 1.73 [1.27-2.35]). Participants in perceived unsafe vs. safe neighborhoods throughout childhood had higher risk of short sleep (RR = 1.10 [1.02-1.18]) and insomnia symptoms (RR = 1.07 [1.00-1.15]) during adulthood after adjustment for life course socioeconomic characteristics and adulthood health behaviors and characteristics. Perceived unsafe childhood neighborhood was associated with poorer sleep over the life course and may serve as an early intervention target.

Body Mass Index and Uterine Fibroid Development: A Prospective Study.

OBJECTIVE: Fibroids are hormonally dependent uterine tumors. The literature on adiposity and fibroid prevalence is inconsistent. Previous work usually combined all those with body mass indexes (BMIs) ≥30kg/m2 into a single category and relied on clinically diagnosed fibroids which misclassifies the many women with undiagnosed fibroids. We used a prospective cohort design with periodic ultrasound screening to investigate associations between repeated measures of BMI and fibroid incidence and growth assessed at each follow-up ultrasound. METHODS: The Study of Environment, Lifestyle & Fibroids (SELF) followed 1,693 Black/African American women, ages 23-35 from Detroit, Michigan with ultrasound every 20 months for 5 years. Measured height and repeated weight measures were used to calculate BMI. Fibroid incidence was modeled using Cox models among those who were fibroid-free at the enrollment ultrasound. Fibroid growth was estimated for individual fibroids matched across visits as the difference in log-volume between visits and was modeled using linear mixed models. All models used time-varying BMI and adjusted for time-varying covariates. RESULTS: Compared to BMI <25kg/m2 those with BMI 30-<35kg/m2 had increased fibroid incidence (adjusted hazard ratio (aHR) 1.37, (95% Confidence Interval (CI): 0.96-1.94)), those with BMI ≥40kg/m2 had reduced incidence (aHR 0.61, (95% CI: 0.41-0.90)). Fibroid growth had mostly small magnitude associations with BMI. CONCLUSION: BMI has a non-linear association with fibroid incidence that could be driven by effects of BMI on inflammation and reproductive hormones. More detailed measures of visceral and subcutaneous adiposity and their effects on hormones, DNA damage, and cell death are needed.

Personal Care Products, Socioeconomic Status, and Endocrine-Disrupting Chemical Mixtures in Black Women.

Personal care products (PCPs) are sources of exposure to endocrine-disrupting chemicals (EDCs) among women, and socioeconomic status (SES) may influence these exposures. Black women have inequitable exposure to EDCs from PCP use, but no study has investigated how exposure to EDCs through PCPs may vary by SES, independent of race. Using data from the Study of Environment, Lifestyle, and Fibroids, a cohort of reproductive-aged Black women (n = 751), we quantified associations between PCPs and urinary biomarker concentrations of EDC mixtures (i.e., phthalates, phenols, parabens) within SES groups, defined using k-modes clustering based on education, income, marital status, and employment. Information about PCP use and SES was collected through questionnaires and interviews. We used principal component analysis to characterize the EDC mixture profiles. Stratified linear regression models were fit to assess associations between PCP use and EDC mixture profiles, quantified as mean differences in PC scores, by SES group. Associations between PCP use and EDC mixture profiles varied by SES group; e.g., vaginal powder use was associated with a mixture of phenols among lower SES women, whereas this association was null for higher SES women. Findings suggest that SES influences PCP EDC exposure in Black women, which has implications for public health interventions.

Association between serum 25-hydroxyvitamin D and antimüllerian hormone levels in a cohort of African-American women.

OBJECTIVE: To examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and ovarian reserve as measured using antimüllerian hormone (AMH) levels. DESIGN: Cross-sectional study. SETTING: Detroit, Michigan area. PATIENTS: Data were obtained from a prospective cohort of self-identified Black or African American women aged 23-35 years at the time of enrollment (N = 1,593), who had no prior diagnosis of polycystic ovary syndrome, were not currently pregnant, and were not missing AMH or 25(OH)D level measures. INTERVENTION: Serum 25(OH)D. MAIN OUTCOME MEASURE(S): The serum AMH level was the main outcome. Linear regression was used to examine the associations between categorical 25(OH)D levels (<12, 12-<20, 20-<30, and ≥30 ng/mL) and continuous natural log-transformed AMH levels. Associations between 25(OH)D and high (upper 10th percentile: >7.8 ng/mL) or low AMH (<0.7 ng/mL) levels were estimated with logistic regression. Models were adjusted for age, age-squared, body mass index (kg/m2), hormonal contraceptive use, smoking, and exercise. RESULTS: The 25(OH)D levels were low; 70% of participants were below 20 ng/mL. In fully adjusted models, compared with 25(OH)D levels <12 ng/mL, those with 25(OH)D levels of 12-<20, 20-<30, and ≥30 ng/mL had an AMH level that was 7% (95% confidence interval [CI]: -4, 20), 7% {95% CI: -6, 22}, or 11% {95% CI: -7, 34} higher, respectively. Moreover, these groups had lower odds of having low AMH levels (odds ratio [95% CI]: 0.63 {0.40, 0.99}, 0.60 {0.34, 1.07}, and 0.76 {0.35, 1.65}, respectively), and the highest category of 25(OH)D levels had higher odds of having high AMH levels (odds ratio [95% CI]: 1.42 {0.74, 2.72}). Exclusion of participants with either irregular cycles or very high AMH (>25 ng/mL) levels did not alter the associations. CONCLUSION: Taken together, these results indicate that higher levels of 25(OH)D are associated with slightly higher AMH levels, lower odds of low AMH levels, and higher odds of high AMH levels. This evidence is weak, however, because only a small percentage of participants had high 25(OH)D levels. Future studies should examine populations with a wide distribution of 25(OH)D levels (both high and low), with a clinical trial design, or with longitudinal measures of both 25(OH)D and AMH levels.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

Systematic evidence mapping informs a class-based approach to assessing personal care products and pubertal timing.

BACKGROUND: Personal care products (PCPs) contain many different compounds and are a source of exposure to endocrine disrupting chemicals (EDCs), including phthalates and phenols. Early-life exposure to EDCs commonly found in PCPs has been linked to earlier onset of puberty. OBJECTIVE: To characterize the human and animal evidence on the association between puberty-related outcomes and exposure to PCPs and their chemical constituents and, if there is sufficient evidence, identify groups of chemicals and outcomes to support a systematic review for a class-based hazard or risk assessment. METHODS: We followed the OHAT systematic review framework to characterize the human and animal evidence on the association between puberty-related health outcomes and exposure to PCPs and their chemical constituents. RESULTS: Ninety-eight human and 299 animal studies that evaluated a total of 96 different chemicals were identified and mapped by key concepts including chemical class, data stream, and puberty-related health outcome. Among these studies, phthalates and phenols were the most well-studied chemical classes. Most of the phthalate and phenol studies examined secondary sex characteristics and changes in estradiol and testosterone levels. Studies evaluating PCP use and other chemical classes (e.g., parabens) had less data. CONCLUSIONS: This systematic evidence map identified and mapped the published research evaluating the association between exposure to PCPs and their chemical constituents and puberty-related health outcomes. The resulting interactive visualization allows researchers to make evidence-based decisions on the available research by enabling them to search, sort, and filter the literature base of puberty-related studies by key concepts. This map can be used by researchers and regulators to prioritize and target future research and funding to reduce uncertainties and address data gaps. It also provides information to inform a class-based hazard or risk assessment on the association between phthalate and phenol exposures and puberty-related health outcomes.

Associations of reproductive and breastfeeding history with anti-Müllerian hormone concentration among African-American women of reproductive age.

RESEARCH QUESTION: Are gravidity, parity and breastfeeding history associated with anti-Müllerian hormone concentration among African-American women of reproductive age? DESIGN: This study included baseline data from the Study of the Environment, Lifestyle and Fibroids, a 5-year longitudinal study of African-American women. Within this community cohort, data from 1392 women aged 25-35 years were analysed. The primary outcome was serum anti-Müllerian hormone concentration measured using the Ansh Labs picoAMH assay, an enzyme-linked immunosorbent assay. Multivariable linear regression models were used to estimate mean differences in anti-Müllerian hormone concentration (ß) and 95% CI by self-reported gravidity, parity and breastfeeding history, with adjustment for potential confounders. RESULTS: Of the 1392 participants, 1063 had a history of gravidity (76.4%). Of these, 891 (83.8%) were parous and 564 had breastfed. Multivariable-adjusted regression analyses found no appreciable difference in anti-Müllerian hormone concentration between nulligravid participants and those with a history of gravidity (ß = -0.025, 95% CI -0.145 to 0.094). Among participants with a history of gravidity, there was little difference in anti-Müllerian hormone concentration between parous and nulliparous participants (ß = 0.085, 95% CI -0.062 to 0.232). There was also little association between anti-Müllerian hormone concentration and breastfeeding history (ever versus never: ß = 0.009, 95% CI -0.093 to 0.111) or duration of breastfeeding (per 1-month increase: ß = -0.002, 95% CI -0.010 to 0.006). CONCLUSIONS: Gravidity, parity and breastfeeding history were not meaningfully associated with anti-Müllerian hormone concentration in this large sample of the Study of the Environment, Lifestyle and Fibroids cohort.

Association of genital talc and douche use in early adolescence or adulthood with uterine fibroids diagnoses.

BACKGROUND: Genital talc and douching are practices that can involve exposure to chemical compounds linked to certain gynecologic cancers. However, it is unclear if they are associated with fibroid risk or age at fibroid diagnosis among women. OBJECTIVE: This study aimed to evaluate the impact of early-adolescence genital talc use and douching on prevalence of fibroids diagnosed before the age of 35 and 50 years among Black/African American and non-Hispanic White women. STUDY DESIGN: Data were derived from the Sister Study (2003-2020), a prospective cohort of 50,884 US women aged 35 to 74 years at enrollment. Participants were asked if they ever had a fibroid diagnosis and at what age, and if they used genital talc and/or douched between the ages of 10 and 13 years or in the past 12 months. After applying predefined exclusion criteria, our analytical sample size was n=46,316 (Black, n=4310; non-Hispanic White, n=42,006). Multivariable logistic regression was used to compute adjusted odds ratios and 95% confidence intervals for having vs not having early-onset fibroids diagnosed before age 35 among women aged 35 to 74 years at enrollment, and fibroids diagnosed before age 50 among women aged 50 to 74 years at enrollment. We adjusted for early life factors (in utero diethylstilbestrol exposure, singleton or multiple birth, fed soy formula during infancy), childhood socioeconomic status, and relative weight and height compared with peers at age 10. We used multiple imputation (<10% missing in all analyses). Results were stratified by race/ethnicity given that Black women are more likely to develop fibroids at a younger age than non-Hispanic White women. RESULTS: Among Black/African American women, 29% had fibroids diagnosed before age 35. Both genital talc use at age 10 to 13 (adjusted odds ratio, 1.23; confidence interval, 1.06-1.41) and douching (adjusted odds ratio, 1.19; 95% confidence interval, 0.95-1.48) were associated with higher odds of having a fibroid diagnosed before age 35. Douching without talc use was not associated with increased odds, but combined use of genital talc and douche was associated with 52% increased odds of fibroids (confidence interval, 1.14-2.01). Among non-Hispanic White women, 9% reported fibroids diagnosed before age 35. Genital talc use (1.31; 1.20-1.44) but not douching (0.96; 0.77-1.20) at age of 10 to 13 years was associated with having a fibroid diagnosed before age 35. We observed similar patterns for non-Hispanic White women when we considered fibroids diagnosed before age 50, but neither practice was associated with fibroids diagnosed before age 50 in Black women. CONCLUSION: Genital talc use in early adolescence, alone and in combination with douching (but not douching alone), is associated with prevalence of fibroids diagnosed before age 35 among Black/African American women and before ages 35 and 50 among non-Hispanic White women. Early adolescence may be a window of susceptibility for fibroid development, suggesting that adolescent girls should be educated on abstention from or alternatives to talc use and douching.

Early Life Disadvantage and the Risk of Depressive Symptoms among Young Black Women.

OVERVIEW: We examined the association between early-life socioeconomic disadvantage and depressive symptoms in adulthood and assessed whether social factors in adulthood modify the association. METHODS: The 11-item Center for Epidemiologic Studies-Depression Scale (CES-D) assessed adult depressive symptoms among 1612 Black women and other participants with a uterus (hereafter participants) in the Study of Environment, Lifestyle and Fibroids. Baseline self-reported childhood factors (i.e., parents in the household, mother's educational attainment, food insecurity, neighborhood safety, childhood income, and quiet bedroom for sleep) were included in a latent class analysis to derive an early life disadvantage construct. Multivariable log-binomial models estimated the association between early life disadvantage and adult depressive symptoms. Potential effect modifiers included adult educational attainment, social support, and financial difficulty. RESULTS: Participants classified as having high early life disadvantage had 1.34 times (95% CI: 1.20, 1.49) the risk of high depressive symptoms than those in the low early life disadvantage class after adjusting for age, first born status, and childhood health. Adult educational attainment and social support modified the association. CONCLUSION: Early life disadvantage increased the risk of depressive symptoms in adulthood. Participants with at least some college education and with high social support had greater risk than those with less than college education and low social support, respectively. Thus, the mental health of Black women and other participants with a uterus exposed to early life disadvantage do not necessarily benefit from higher education or from social support.

Menstrual cycle length variation by demographic characteristics from the Apple Women's Health Study.

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.

A prospective ultrasound study of cigarette smoking and uterine leiomyomata incidence and growth.

BACKGROUND: Uterine leiomyomata (fibroids) are common, benign neoplasms that contribute substantially to gynecologic morbidity. Some existing epidemiologic studies indicate that cigarette smoking is associated with lower uterine leiomyomata risk. However, no prospective studies have systematically screened an entire study population for uterine leiomyomata using transvaginal ultrasound or evaluated the association between cigarette smoking and uterine leiomyomata growth. OBJECTIVE: This study aimed to examine the association between cigarette smoking and uterine leiomyomata incidence and growth in a prospective ultrasound study. STUDY DESIGN: We enrolled 1693 residents from the Detroit metropolitan area into the Study of Environment, Lifestyle, and Fibroids during 2010 to 2012. Eligible participants were aged 23 to 34 years, had an intact uterus but no previous diagnosis of uterine leiomyomata, and self-identified as Black or African American. We invited participants to complete a baseline visit and 4 follow-up visits over approximately 10 years. At each visit, we used transvaginal ultrasound to assess uterine leiomyomata incidence and growth. Participants provided extensive self-reported data throughout follow-up including exposures to active and passive cigarette smoking in adulthood. We excluded participants who did not return for any follow-up visits (n=76; 4%). We fit Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals for the association between time-varying smoking history and incidence rates of uterine leiomyomata. We fit linear mixed models to estimate the percentage difference and 95% confidence intervals for the association between smoking history and uterine leiomyomata growth. We adjusted for sociodemographic, lifestyle, and reproductive factors. We interpreted our results based on magnitude and precision rather than binary significance testing. RESULTS: Among 1252 participants without ultrasound evidence of uterine leiomyomata at baseline, uterine leiomyomata were detected in 394 participants (31%) during follow-up. Current cigarette smoking was associated with a lower uterine leiomyomata incidence rate (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Associations were stronger among participants who had smoked for longer durations (≥15 years vs never: hazard ratio, 0.49; 95% confidence interval, 0.25-0.95). The hazard ratio for former smokers was 0.78 (95% confidence interval, 0.50-1.20). Among never smokers, the hazard ratio for current passive smoke exposure was 0.84 (95% confidence interval, 0.65-1.07). Uterine leiomyomata growth was not appreciably associated with current (percent difference, -3%; 95% confidence interval, -13% to 8%) or former (percent difference, -9%; 95% confidence interval, -22% to 6%) smoking. CONCLUSION: We provide evidence from a prospective ultrasound study that cigarette smoking is associated with lower uterine leiomyomata incidence.

Keloids, hypertrophic scars, and uterine fibroid development: a prospective ultrasound study of Black and African American women.

OBJECTIVE: To examine the association between keloids, hypertrophic scars, and uterine fibroid incidence as well as growth. Both keloids and fibroids are fibroproliferative conditions that have been reported to be more prevalent among Blacks than Whites, and they share similar fibrotic tissue structures, including extracellular matrix composition, gene expression, and protein profiles. We hypothesized that women with a history of keloids would have greater uterine fibroid development. DESIGN: A prospective community cohort study (enrollment 2010-2012) with 4 study visits over 5 years to conduct standardized ultrasounds to detect and measure fibroids ≥0.5 cm in diameter, assess the history of keloid and hypertrophic scars, and update covariates. SETTING: Detroit, Michigan area. PATIENTS: A total of 1,610 self-identified Black and/or African American women aged 23-35 years at enrollment without a previous clinical diagnosis of fibroids. EXPOSURE(S): Keloids (raised scars that grow beyond the margins of the original injury) and hypertrophic scars (raised scars that stay within the bounds of the original injury). Because of the difficulties in distinguishing keloids and hypertrophic scars, we separately examined the history of keloids and the history of either keloids or hypertrophic scars (any abnormal scarring) and their associations with fibroid incidence and growth. MAIN OUTCOME MEASURE(S): Fibroid incidence (new fibroid after a fibroid-free ultrasound at enrollment) was assessed using Cox proportional-hazards regression. Fibroid growth was assessed using linear mixed models. The estimates for the change in log volume per 18 months were converted to the estimated percentage difference in volume for scarring vs. no-scarring. Both incidence and growth models were adjusted for time-varying demographic, reproductive, and anthropometric factors. RESULT(S): Of the 1,230 fibroid-free participants, 199 (16%) reported ever having keloids, 578 (47%) reported keloids or hypertrophic scars, and 293 (24%) developed incident fibroids. Neither keloids (adjusted hazard ratio = 1.04; 95% confidence interval: 0.77, 1.40) nor any abnormal scarring (adjusted hazard ratio = 1.10; 95% confidence interval: 0.88, 1.38) were associated with fibroid incidence. Fibroid growth differed little by scarring status. CONCLUSION(S): Despite molecular similarities, self-reported keloid and hypertrophic scars did not show an association with fibroid development. Future research may benefit from the examination of dermatologist-confirmed keloids or hypertrophic scars; however, our data suggest little shared susceptibility for these 2 types of fibrotic conditions.

Early Life Anti-Müllerian Hormone Trajectories in Infant Girls.

BACKGROUND: Minipuberty is a period of increased reproductive axis activity in infancy, but the importance of this period is not well understood, especially in girls. Previous studies reported a peak in hormone concentrations at 3 to 4 months old. Our objective is to describe anti-Müllerian hormone (AMH) trajectories in the context of other minipuberty factors among healthy infant girls using longitudinal measures of AMH. METHODS: The Infant Feeding and Early Development study is a longitudinal cohort study of healthy infants, recruited from hospitals in the Philadelphia area during 2010 to 2013. We measured AMH in 153 girls who contributed 1366 serum samples across 11 study visits over 36 weeks. We also measured follicle stimulating hormone (FSH), estradiol, and ovarian characteristics. We used latent class mixed effects models to cluster trajectories of AMH concentration with age. Using linear mixed models, we estimated FSH and ovarian characteristic trajectories separately by AMH cluster. RESULTS: We classified infants into four clusters that represent patterns of AMH that were high and decreasing (decreasing), had a peak around 12 weeks or 20 weeks (early peak and middle peak), or were consistently low (low). Infants in these clusters differed in their FSH trajectories, timing of estradiol production, and ovarian characteristics. CONCLUSIONS: The AMH clusters identified suggest variation in the timing and the magnitude of the minipuberty response in infant girls. The decreasing and low clusters have not been described previously and should be further evaluated to determine whether they represent an opportunity for the early identification of later reproductive conditions.