Search

ObjectivePrevious studies describing menses duration and heaviness of flow during the menopausal transition (MT) have been short in duration and limited to white women. We estimated the frequency of and risk factors for prolonged bleeding, spotting and heavy bleeding during the MT in an ethnically diverse population.DesignProspective community-based cohort study.Setting usasoutheastern Michigan, northern California and Los Angeles, California.PopulationA total of 1320 midlife women who participated in the Study of Women's Health Across the Nation (SWAN) Menstrual Calendar Substudy. Participants included African-American, white, Chinese, and Japanese women.MethodsWomen completed daily menstrual calendars from 1996 to 2006, and provided information on hormone therapy, smoking and physical activity. Annual measures included height and weight. Kaplan-Meier survival analysis and multivariable regression were used to analyse the data.Main outcome measuresMenses of 10+ days, spotting of 6+ days, heavy bleeding of 3+ days.ResultsAt least three occurrences of menses 10+ days was reported by 77.7% (95% confidence interval [95% CI] 56.7-93.2), of 6+ days of spotting by 66.8% (95% CI 55.2-78.0) and of 3+ days of heavy bleeding by 34.5% (95% CI 30.2-39.2) of women. Menses of 10+ days, 6+ days of spotting, and 3+ days of heavy bleeding were associated with MT stage, uterine fibroids, hormone use and ethnicity. Body mass index was associated with 3+ days of heavy bleeding.ConclusionsThese data provide clinicians and women with important information about the expected frequency of prolonged and heavy bleeding and spotting during the menopausal transition that may facilitate clinical decision making.

CONTEXT: Until recently, the reproductive health agenda has focused on a restricted number of morbidity indicators, particularly those associated with life-threatening diseases. However, gynecologic morbidities that are a source of pelvic pain,although not life-threatening,do impose a substantial burden because of their potential to reduce women's overall well-being. METHODS: In 2005,a cross-sectional population-based study was conducted in Hermosillo, Mexico, to assess self reported pelvic pain conditions in a random sample of 1,307 women aged 25-54. The 12-month prevalence of each condition was calculated,and logistic regression was used to assess the association between pelvic pain and social, demographic, anthropometric and reproductive characteristics, and other medical conditions. RESULTS: The 12-month prevalence of pelvic pain during menstruation among 1,007 menstruating women was 40%. Pelvic pain during or after sexual intercourse was reported by 12% of the 1,183 sexually active respondents. Among 1,201 nonpregnant women, 6% reported chronic pelvic pain. In adjusted analyses,younger age (25-34 years) and having a history of STIs or pelvic inflammatory disease (PID)were associated with an increased risk of pain during menstruation and chronic pelvic pain (odds ratios, 1.6-3.1). An interaction term for younger age and history of STIs or PID was associated with an elevated risk of intercourse-related pelvic pain (6.4). Chronic pelvic pain and pain during menstruation were more frequently reported as interfering with daily activities than was intercourse-related pelvic pain. The proportion of women who had talked with a physician about their condition was highest among those with chronic pelvic pain (40%). CONCLUSION: Pelvic pain associated with menstruation, pelvic pain during or after sexual intercourse,and chronic pelvic pain are common complaints among Mexican women of reproductive age. Health care providers should pay greater attention to these conditions. [ABSTRACT FROM AUTHOR]

To compare the characteristics of and baseline factors associated with prevalent and incident urinary incontinence in a diverse cohort of midlife women, the authors analyzed the baseline and first five annual follow-up visits of the Study of Women's Health Across the Nation (SWAN), 1995-2001. From responses to annual questionnaires, the authors defined prevalent incontinence as at least monthly incontinence reported at baseline and incident incontinence as at least monthly incontinence first reported over follow-up. They used multiple logistic regression for their comparison. The mean age of their cohort at baseline was 45.8 (standard deviation: 2.7) years. Prevalent incontinence was 46.7%, and the average incidence was 11.1% per year. Most women reported stress, but a higher proportion developed urge incontinence (15.9% vs. 7.6% at baseline). African Americans (29.5%) and Hispanics (27.5%) had the lowest prevalence of incontinence; African Americans (11.6%) and Caucasians (13.4%) had the highest average annual incidence. Parity, diabetes, fibroids, and poor social support were associated with prevalent incontinence, while high body mass index, high symptom sensitivity, and poor health were associated with incident incontinence. In midlife women, incident incontinence is mild with different characteristics and baseline risk factors; overweight women have a higher risk of developing incontinence. [ABSTRACT FROM AUTHOR]

Previous epidemiologic studies evaluating risk factors for lower urinary tract symptoms (LUTS) have focused on White populations. Between September 1996 and January 1998, in a population-based sample of African-American men aged 40-79 years in Flint, Michigan, the authors assessed the role of putative sociodemographic, lifestyle, and medical history risk factors in moderate to severe LUTS, including the subcategories of obstructive and irritative symptoms. After the exclusion of men with prostate cancer or prior prostate surgery and men who were taking alpha-blockers for urinary tract symptoms, 708 participants provided responses to a structured interviewer-administered questionnaire. After multivariable adjustment, current and former smokers were at increased risk of moderate to severe LUTS, including obstructive symptoms. Heavy alcohol consumption and a history of hypertension or diabetes were positively associated with LUTS, and high income (>/=$30,000) was inversely associated with LUTS and with obstructive and irritative symptoms. A history of heart disease was positively associated with LUTS and with irritative symptoms. To the authors' knowledge, this was the first population-based study undertaken in African-American men to evaluate putative risk factors for moderate to severe LUTS, including subcategories of obstructive and irritative urinary symptoms. These results describe associations with specific lifestyle and medical history risk factors. [ABSTRACT FROM AUTHOR]

Several studies suggest that toxic chemicals in hair products may be absorbed through the scalp in sufficient amounts to increase the risks of adverse health effects in women or their infants. This case-control study of 525 Black women from three counties in North Carolina who had delivered a singleton, liveborn infant examined whether exposure to chemicals used in hair straightening and curling increased the odds that the infant was preterm or low birth weight. Cases consisted of 188 preterm and 156 low birth weight births (for 123 women, their infant was both low birth weight and preterm). Controls were 304 women who delivered term and normal birth weight infants. Women who used a chemical hair straightener at any time during pregnancy or within 3 months prior to conception had an adjusted odds ratios (OR) of 0.7 (95% confidence interval (CI) 0.4-1.1) for preterm birth and 0.6 (95% CI 0.4-1.1) for low birth weight. Exposure to chemical curl products was also not associated with preterm delivery (adjusted OR = 0.9, 95% CI 0.5-1.8) or low birth weight (adjusted OR = 1.0, 95% CI 0.5-1.9). Despite this failure to find an association, continued search for risk factors to which Black women are uniquely exposed is warranted. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study examined the effect of working conditions, occupational stress, and antenatal leave on risk of small-for-gestational age and premature births in Mexico City. METHODS: Over a 3-month period, 2663 (96.2%) of 2767 women who gave birth at three major hospitals and worked at least 3 months during pregnancy were interviewed shortly after delivery. After the exclusion of multiple gestations and birth defects, 261 (10.0%) small-for-gestational-age and 288 (11.0%) preterm births were identified. RESULTS: For small-for-gestational-age births, working more than 50 hours a week (odds ratio [OR] = 1.59), standing more than 7 hours a day (OR = 1.40), and no antenatal leave (OR = 1.55) were associated with an increased risk. Women with no antenatal leave were also much more likely to give birth prematurely (OR = 3.04). CONCLUSIONS: In this study, arduous working conditions and lack of antenatal leave benefits were found to increase the risk of poor birth outcome in Mexican women. Enforcement of existing antenatal leave laws and provision of comparable benefits for the uninsured may reduce the incidence of small-for-gestational-age births and prematurity. [ABSTRACT FROM AUTHOR]

Objectives: The hypothesis that informal jobs, which imply absence of formal labour contracts, instability and the absence of fringe benefits, are positively associated with psychiatric symptoms was evaluated in a poor urban area of Brazil.Methods: With data from a cross-sectional study, the association between informal jobs and high number of psychological symptoms was estimated. The study population was composed of 327 women randomly selected from a community in the city of Salvador, Brazil. Women who reported having a job without a formal contract were classified as informal workers. Psychological symptoms were collected through a validated questionnaire, the QMPA.Results: A positive association between informal work and a high number of psychological symptoms was found (crude prevalence ratio = 1.88, 95% confidence interval [CI]: 1.24-2.85). More than 4 hours of housework a day and being a family head were confounders, although adjustment for these variables did not significantly change the results (adjusted prevalence ratio = 1.97, 95% CI: 1.26-3.09).Conclusions: These findings are suggestive that informal work may be a risk for mental symptoms. Reinforcement of universal labour rights coverage and improvement in housework sharing are recommended. [ABSTRACT FROM AUTHOR]

Importance: Fibroids are benign neoplasms associated with severe gynecologic morbidity. There are no strategies to prevent fibroid development., Objective: To examine associations of hypertension, antihypertensive treatment, anthropometry, and blood biomarkers with incidence of reported fibroid diagnosis in midlife., Design, Setting, and Participants: The Study of Women's Health Across the Nation is a prospective, multisite cohort study in the US. Participants were followed-up from enrollment (1996-1997) through 13 semiannual visits (1998-2013). Participants had a menstrual period in the last 3 months, were not pregnant or lactating, were aged 42 to 52 years, were not using hormones, and had a uterus and at least 1 ovary. Participants with prior fibroid diagnoses were excluded. Data analysis was performed from November 2022 to February 2024., Exposures: Blood pressure, anthropometry, biomarkers (cholesterol, triglycerides, and C-reactive protein), and self-reported antihypertensive treatment at baseline and follow-up visits were measured. Hypertension status (new-onset, preexisting, or never [reference]) and hypertension treatment (untreated, treated, or no hypertension [reference]) were categorized., Main Outcomes and Measures: Participants reported fibroid diagnosis at each visit. Discrete-time survival models estimated hazard ratios (HRs) and 95% CIs for associations of time-varying hypertension status, antihypertensive treatment, anthropometry, and biomarkers with incident reported fibroid diagnoses., Results: Among 2570 participants without a history of diagnosed fibroids (median [IQR] age at screening, 45 [43-48] years; 1079 [42.1%] college educated), 526 (20%) reported a new fibroid diagnosis during follow-up. Risk varied by category of hypertension treatment: compared with those with no hypertension, participants with untreated hypertension had a 19% greater risk of newly diagnosed fibroids (HR, 1.19; 95% CI, 0.91-1.57), whereas those with treated hypertension had a 20% lower risk (HR, 0.80; 95% CI, 0.56-1.15). Among eligible participants with hypertension, those taking antihypertensive treatment had a 37% lower risk of newly diagnosed fibroids (HR, 0.63; 95% CI, 0.38-1.05). Risk also varied by hypertension status: compared with never-hypertensive participants, participants with new-onset hypertension had 45% greater risk of newly diagnosed fibroids (HR, 1.45; 95% CI, 0.96-2.20). Anthropometric factors and blood biomarkers were not associated with fibroid risk., Conclusions and Relevance: Participants with untreated and new-onset hypertension had increased risk of newly diagnosed fibroids, whereas those taking antihypertensive treatment had lower risk, suggesting that blood pressure control may provide new strategies for fibroid prevention.

Background: Intimate partner violence affects about a third of women in their lifetimes and can result in short- and long-term health consequences, including less favorable performance on measures of cognitive function., Objectives: We assess whether experiencing physical intimate partner violence in midlife was associated with steeper declines in subsequent tests of cognitive performance., Design: This study used data from 1713 women in the longitudinal cohort Study of Women's Health Across the Nation to relate baseline information on physical intimate partner violence to declines in scores from the Symbol Digit Modalities Test, the East Boston Memory Test and the Digit Span Backwards spanning follow-up visits 7 through 15., Methods: Separate linear mixed models were constructed for each cognitive test outcome. Analyses were adjusted for race-ethnicity, education, financial strain, depressive symptoms, trouble sleeping, and bodily pain., Results: At Study of Women's Health Across the Nation baseline, 3.1% of participants reported experiencing physical intimate partner violence in the prior year. In adjusted models, women who reported violence evidenced a statistically significant greater annualized decline (-0.17 points, 95% CI: -0.28, -0.06) in working memory (Digit Span Backwards test), compared to women who had not reported prior-year violence at baseline., Conclusion: Midlife women with a history of physical intimate partner violence exhibited a persistent decrease in the trajectory of working memory. These longitudinal findings extend previous cross-sectional reports which found that physical intimate partner violence had detrimental effects on working memory. These findings provide additional evidence that intimate partner violence is associated with decreases in working memory performance. They underscore the importance of further research into intimate partner violence and cognition during middle age, a particularly understudied life stage.

Background: Shorter average lifespans for minoritized populations are hypothesized to stem from 'weathering' or accelerated health declines among minoritized individuals due to systemic marginalization. However, evidence is mixed on whether racial/ethnic differences exist in reproductive ageing, potentially due to selection biases in cohort studies that may systematically exclude 'weathered' participants. This study examines racial/ethnic disparities in the age of menopause after accounting for differential selection 'into' (left truncation) and 'out of' (right censoring) a cohort of midlife women., Methods: Using data from the Study of Women's Health Across the Nation (SWAN) cross-sectional screener (N = 15 695) and accompanying ∼20-year longitudinal cohort (N = 3302) (1995-2016), we adjusted for potential selection bias using inverse probability weighting (left truncation) to account for socio-demographic/health differences between the screening and cohort study, and multiple imputation (right censoring) to estimate racial/ethnic differences in age at menopause (natural and surgical)., Results: Unadjusted for selection, no Black/White differences in menopausal timing [hazard ratio (HR)=0.98 (0.86, 1.11)] were observed. After adjustment, Black women had an earlier natural [HR = 1.13 (1.00, 1.26)] and surgical [HR= 3.21 (2.80, 3.62)] menopause than White women with natural menopause-corresponding to a 1.2-year Black/White difference in menopause timing overall., Conclusions: Failure to account for multiple forms of selection bias masked racial/ethnic disparities in the timing of menopause in SWAN. Results suggest that there may be racial differences in age at menopause and that selection particularly affected the estimated menopausal age for women who experienced earlier menopause. Cohorts should consider incorporating methods to account for all selection biases, including left truncation, as they impact our understanding of health in 'weathered' populations., (© The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Racial/ethnic disparities in hypertension are a pressing public health problem. The contribution of environmental pollutants including PFAS have not been explored, even though certain PFAS are higher in Black population and have been associated with hypertension., Objectives: We examined the extent to which racial/ethnic disparities in incident hypertension are explained by racial/ethnic differences in serum PFAS concentrations., Methods: We included 1058 hypertension-free midlife women with serum PFAS concentrations in 1999-2000 from the multi-racial/ethnic Study of Women's Health Across the Nation with approximately annual follow-up visits through 2017. Causal mediation analysis was conducted using accelerated failure time models. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures., Results: During 11,722 person-years of follow-up, 470 participants developed incident hypertension (40.1 cases per 1000 person-years). Black participants had higher risks of developing hypertension (relative survival: 0.58, 95% CI: 0.45-0.76) compared with White participants, which suggests racial/ethnic disparities in the timing of hypertension onset. The percent of this difference in timing that was mediated by PFAS was 8.2% (95% CI: 0.7-15.3) for PFOS, 6.9% (95% CI: 0.2-13.8) for EtFOSAA, 12.7% (95% CI: 1.4-22.6) for MeFOSAA, and 19.1% (95% CI: 4.2, 29.0) for PFAS mixtures. The percentage of the disparities in hypertension between Black versus White women that could have been eliminated if everyone's PFAS concentrations were dropped to the 10th percentiles observed in this population was 10.2% (95% CI: 0.9-18.6) for PFOS, 7.5% (95% CI: 0.2-14.9) for EtFOSAA, and 17.5% (95% CI: 2.1-29.8) for MeFOSAA., Conclusions: These findings suggest differences in PFAS exposure may be an unrecognized modifiable risk factor that partially accounts for racial/ethnic disparities in timing of hypertension onset among midlife women. The study calls for public policies aimed at reducing PFAS exposures that could contribute to reductions in racial/ethnic disparities in hypertension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sleep disturbances are common and may impact fracture risk directly by influencing bone turnover or indirectly through shared risk factors or mediators. To investigate the association between self-reported sleep disturbances across the menopausal transition (MT) and fractures, we prospectively studied 3101 women enrolled in the Study of Women's Health Across the Nation (SWAN). At each of 14 study visits spaced approximately 18 months apart, a standardized validated scale ascertained trouble falling asleep, waking up several times during the night, and waking up earlier than planned. Two time-varying exposures were modeled: presence of any of the three disturbances at least three times per week and waking up several times during the night at least three times per week. Base models adjusted for fixed (race/ethnicity, study site) and time-varying characteristics (age, body mass index, and MT stage). Fully adjusted models also included time-varying bone beneficial and detrimental medications, smoking, alcohol, physical activity, diabetes, depression and sleep medications, and depressive symptoms. Women who experienced a fracture were more likely to report a greater frequency of having trouble falling asleep, waking up several times, and/or waking up earlier: 35% versus 30% at baseline, p  = 0.02. In the base models, women who had any of the three sleep disturbances at least three times per week had a higher risk of any fracture, odds ratio (OR) = 1.23 (95% confidence intervals, 1.02, 1.48) and nontraumatic fracture, OR = 1.36 (1.03, 1.80). These associations were largely attenuated to nonsignificance in the fully adjusted model. Sensitivity analyses limiting our sample to 2315 SWAN women enrolled in the bone mineral density (BMD) centers yielded similar results. Additional adjustment for femoral neck BMD had no effect on our results. In conclusion, self-reported sleep disturbances were associated with an increased risk of fractures, but these associations likely reflect shared risk factors or factors in the causal pathway. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: JAC, HMK, KR, YL, MH, SDH, JSF, and have no conflicts., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Phthalates, ubiquitous endocrine-disrupting chemicals, may affect ovarian folliculogenesis and steroidogenesis. We examined the associations of urinary phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH), and timing of natural menopause in midlife women. Data were from 1189 multiracial/multiethnic women aged 45 to 56 years without hormone therapy from the Study of Women's Health Across the Nation (SWAN). Urinary concentrations of 12 phthalate metabolites and hormones were repeatedly measured in 1999 to 2000 and 2002 to 2003, resulting in a total of 2111 observations. Linear mixed-effect models were used to calculate percentage differences (%D) and 95% CIs in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause. We observed statistically significant associations of phthalate metabolites with lower testosterone concentrations: MCOP with testosterone (%D: -2.08%; 95% CI, -3.66 to -0.47) and MnBP with testosterone (%D: -1.99%; 95% CI, -3.82 to -0.13), after adjusting for multiple comparisons with false discovery rates less than 5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%; 95% CI, -24.10 to -3.14), MEHHP (%D: -15.58%; 95% CI, -24.59 to -5.50), and MEOHP (%D: -13.50%; 95% CI, -22.93 to -2.90). No associations were observed for other hormones or timing of natural menopause. These results suggest that exposure to phthalates may affect circulating levels of testosterone and diminish the ovarian reserve in midlife women. Given the widespread exposure, reduced exposure to phthalates may be a key step to prevent reproductive effects of phthalates., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Exposure to heavy metals may alter the circulating levels of sex hormones. However, epidemiologic studies on heavy metals and sex hormones have been limited, and results have been inconsistent. We assessed the associations of heavy metals assayed in urine, including arsenic, cadmium, lead, and mercury, with repeated measures of serum estradiol (E 2 ), follicle-stimulating hormone (FSH), testosterone, and sex hormone-binding globulin (SHBG) levels in the Study of Women's Health Across the Nation Multi-Pollutant Study. The sample included 1355 White, Black, Chinese, and Japanese women, aged 45-56 years at baseline (1999-2000), whose serum hormone levels were repeatedly measured through 2017. Urinary metal concentrations were measured at baseline. Linear mixed effect models were used to calculate percent changes in serum hormone levels per doubling of urinary metal concentrations, adjusting for demographics, socioeconomic status, lifestyle, health-related factors, and urinary creatinine. After multivariable adjustment, a doubling of urinary metal concentration was associated with lower E 2 levels by 2.2% (95% CI: 4.0%, -0.3%) for mercury and 3.6% (95% CI: 5.7%, -1.6%) for lead; higher FSH levels by 3.4% (95% CI: 0.9%, 5.9%) for lead; and higher SHBG levels by 3.6% (95% CI: 1.3%, 5.9%) for cadmium. The overall joint effect using the Bayesian kernel machine regression showed that metal mixtures were inversely associated with E 2 and positively associated with FSH levels. No association was found between metals and testosterone levels. Results from this prospective cohort study demonstrate that environmental heavy metal exposures, including cadmium, mercury, and lead, may disturb circulating levels of E 2 , FSH, and SHBG in midlife women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Importance: Racial disparities in cardiometabolic health are consistently observed in cohort studies. However, most studies neither evaluate differences in age at onset nor account for systematic exclusion stemming from "weathering" (accelerated health declines for minoritized groups due to structural social and economic marginalization)., Objective: To evaluate racial or ethnic disparities in age at onset of 4 cardiometabolic outcomes (hypertension, isolated systolic hypertension [ISH], insulin resistance [IR], and diabetes), accounting for multiple forms of potential selection bias., Design, Setting, and Participants: This cohort study used data from the Study of Women's Health Across the Nation longitudinal cohort (1995-2016) and a cross-sectional screening sample (1995-1997). Data were analyzed from July 2019 to October 2021. Participants were eligible for the cohort if they were aged 42 to 52 years, had not received hormone therapy in the past 3 months, were not pregnant, had an intact uterus and at least 1 ovary, and were premenopausal or early perimenopausal (most recent menses ≤3 months)., Exposures: Self-reported racial or ethnic group (Black, Chinese, Hispanic, Japanese, or White)., Main Outcomes and Measures: The main outcomes were hypertension (systolic blood pressure [BP] ≥140 mm Hg and diastolic BP ≥90 mm Hg or use of antihypertensive medication), ISH (systolic BP ≥140 mm Hg and diastolic BP <90 mm Hg or use of antihypertensive medication), IR (homeostasis model assessment for IR value >5.9 or insulin use), and diabetes (fasting serum glucose level ≥126 mg/dL [to convert to mmol/L, multiply by 0.0555], use of insulin or oral antidiabetic medication, or physician diagnosis). Selection into the cohort was addressed via inverse probability weighting and interval-censored survival models and selection out via multiple imputation. Accelerated failure time models were used to examine racial or ethnic differences in age at disease onset and estimate the median age at onset., Results: A total of 3302 women were included in the study, with a median age of 46.2 years (range, 42-52 years) at baseline. In the sample, 42.6% had a bachelor's degree or higher and 36.3% self-rated their health as "very good" at baseline; 23.9% had hypertension, 43.7% had ISH, 13.5% had IR, and 4.6% had diabetes at baseline. Hypertension occurred a median of 5.0 years (95% CI, 5.4-5.5 years) earlier and metabolic outcomes (diabetes and IR) a median of 11.3 years (95% CI, 9.7-12.9 years) earlier for Black and Hispanic women vs White women; ISH occurred a median of 7.7 years (95% CI, 7.3-8.1 years) earlier for Black women vs White women. Adjustment for selection was associated with a mean 20-year decrease in estimated median age at onset, with greater decreases among Black and Hispanic women., Conclusions and Relevance: In this multiracial cohort of midlife women, failure to account for selection biases, especially at study onset, was associated with falsely high estimates of age at cardiometabolic onset, with greater misestimation among Black and Hispanic women. The results suggest that hypertension and metabolic interventions, particularly for Black and Hispanic women, should be targeted to women aged as young as 30 years for hypertension and 40 years for metabolic interventions. Considering the timing of disease and fully addressing inherent selection biases in research are critical to understanding aging and disease risk, especially for racial and ethnic minoritized populations.

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are ubiquitous synthetic chemicals that may disrupt blood pressure controls; however, human evidence to support this hypothesis is scant. We examined the association between serum concentrations of PFAS and risks of developing hypertension., Methods: This study included 1058 midlife women initially free of hypertension from the multiracial and multiethnic SWAN (Study of Women's Health Across the Nation) with annual follow-up visits between 1999 and 2017. Hypertension was defined as blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic or receiving antihypertensive treatment. Cox proportional hazards models were utilized to calculate hazard ratios and 95% CIs. Quantile g-computation was implemented to evaluate the joint effect of PFAS mixtures., Results: During 11 722 person-years of follow-up, 470 participants developed incident hypertension (40.1 cases per 1000 person-years). Compared with the lowest tertile, women in the highest tertile of baseline serum concentrations had adjusted hazard ratios of 1.42 (95% CI, 1.19-1.68) for perfluorooctane sulfonate ( P trend=0.01), 1.47 (95% CI, 1.24-1.75) for linear perfluorooctanoate ( P trend=0.01), and 1.42 (95% CI, 1.19-1.70) for 2-(N-ethyl-perfluorooctane sulfonamido) acetate ( P trend=0.01). No significant associations were observed for perfluorononanoate and perfluorohexane sulfonate. In the mixture analysis, women in the highest tertile of overall PFAS concentrations had a hazard ratio of 1.71 (95% CI, 1.15-2.54; P trend=0.008), compared with those in the lowest tertile., Conclusions: Several PFAS showed positive associations with incident hypertension. These findings suggest that PFAS might be an underappreciated contributing factor to women's cardiovascular disease risk.

Aims/hypothesis: Diabetogenic effects of per- and polyfluoroalkyl substances (PFAS) have been suggested. However, evidence based on prospective cohort studies is limited. We examined the association between serum PFAS concentrations and incident diabetes in the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS)., Methods: We included 1237 diabetes-free women aged 45-56 years at baseline (1999-2000) who were followed up to 2017. At each follow-up visit, women with incident diabetes were identified by the presence of one or more of the following conditions: (1) use of a glucose-lowering medication at any visit; (2) fasting glucose ≥7 mmol/l on two consecutive visits while not on steroids; and (3) any two visits with self-reported diabetes and at least one visit with fasting blood glucose ≥7 mmol/l. Serum concentrations of 11 PFAS were quantified by online solid-phase extraction-HPLC-isotope dilution-tandem MS. Seven PFAS with high detection rates (>96%) (n-perfluorooctanoic acid [n-PFOA], perfluorononanoic acid [PFNA], perfluorohexane sulfonic acid [PFHxS], n-perfluorooctane sulfonic acid [n-PFOS], sum of perfluoromethylheptane sulfonic acid isomers [Sm-PFOS], 2-[N-methyl-perfluorooctane sulfonamido] acetic acid [MeFOSAA] and 2-[N-ethyl-perfluorooctane sulfonamido] acetic acid) were included in data analysis. Cox proportional hazards models were used to compute HRs and 95% CIs. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures., Results: After adjustment for race/ethnicity, site, education, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status and BMI, the HR (95% CI) comparing the lowest with the highest tertile was 1.67 (1.21, 2.31) for n-PFOA (p trend  = 0.001), 1.58 (1.13, 2.21) for PFHxS (p trend  = 0.003), 1.36 (0.97, 1.90) for Sm-PFOS (p trend  = 0.05), 1.85 (1.28, 2.67) for MeFOSAA (p trend  = 0.0004) and 1.64 (1.17, 2.31) for the sum of four common PFAS (n-PFOA, PFNA, PFHxS and total PFOS) (p trend  = 0.002). Exposure to seven PFAS as mixtures was associated with an HR of 2.62 (95% CI 1.12, 6.20), comparing the top with the bottom tertiles for all seven PFAS., Conclusions/interpretation: This study suggests that PFAS may increase diabetes risk in midlife women. Reduced exposure to these 'forever and everywhere chemicals' may be an important preventative approach to lowering population-wide diabetes risk., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Morphological parameters measured for the second metacarpal from hand radiographs are used clinically for assessing bone health during growth and aging. Understanding how these morphological parameters relate to metacarpal strength and strength at other anatomical sites is critical for providing informed decision-making regarding treatment strategies and effectiveness. The goals of this study were to evaluate the extent to which 11 morphological parameters, nine of which were measured from hand radiographs, relate to experimentally measured whole-bone strength assessed at multiple anatomical sites and to test whether these associations differed between men and women. Bone morphology and strength were assessed for the second and third metacarpals, radial diaphysis, femoral diaphysis, and proximal femur for 28 white male donors (18-89 years old) and 35 white female donors (36-89+ years old). The only morphological parameter to show a significant correlation with strength without a sex-specific effect was cortical area. Dimensionless morphological parameters derived from hand radiographs correlated significantly with strength for females, but few did for males. Males and females showed a significant association between the circularity of the metacarpal cross-section and the outer width measured in the mediolateral direction. This cross-sectional shape variation contributed to systematic bias in estimating strength using cortical area and assuming a circular cross-section. This was confirmed by the observation that use of elliptical formulas reduced the systematic bias associated with using circular approximations for morphology. Thus, cortical area was the best predictor of strength without a sex-specific difference in the correlation but was not without limitations owing to out-of-plane shape variations. The dependence of cross-sectional shape on the outer bone width measured from a hand radiograph may provide a way to further improve bone health assessments and informed decision making for optimizing strength-building and fracture-prevention treatment strategies. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been associated with earlier natural menopause; however, the underlying mechanisms are not well understood, particularly the extent to which this relationship is mediated by sex hormones. We analyzed data (1999-2017) on 1,120 premenopausal women from the Study of Women's Health Across the Nation (SWAN). Causal mediation analysis was applied to quantify the degree to which follicle-stimulating hormone (FSH) and estradiol levels could mediate the associations between PFAS and incident natural menopause. Participants with higher PFAS concentrations had shorter times to natural menopause, with a relative survival of 0.82 (95% confidence interval (CI): 0.69, 0.96) for linear perfluorooctane sulfonate (n-PFOS), 0.84 (95% CI: 0.69, 1.00) for sum of branched-chain perfluorooctane sulfonate (Sm-PFOS), 0.79 (95% CI: 0.66, 0.93) for linear-chain perfluorooctanoate (n-PFOA), and 0.84 (95% CI: 0.71, 0.97) for perfluorononanoate (PFNA), comparing the highest tertile of PFAS concentrations with the lowest. The proportion of the effect mediated through FSH was 8.5% (95% CI: -11.7, 24.0) for n-PFOS, 13.2% (95% CI: 0.0, 24.5) for Sm-PFOS, 26.9% (95% CI: 15.6, 38.4) for n-PFOA, and 21.7% (6.8, 37.0) for PFNA. No significant mediation by estradiol was observed. The effect of PFAS on natural menopause may be partially explained by variations in FSH concentrations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Question: Can additional genetic variants for circulating anti-Müllerian hormone (AMH) levels be identified through a genome-wide association study (GWAS) meta-analysis including a large sample of premenopausal women?, Summary Answer: We identified four loci associated with AMH levels at P < 5 × 10-8: the previously reported MCM8 locus and three novel signals in or near AMH, TEX41 and CDCA7., What Is Known Already: AMH is expressed by antral stage ovarian follicles in women, and variation in age-specific circulating AMH levels has been associated with disease outcomes. However, the physiological mechanisms underlying these AMH-disease associations are largely unknown., Study Design, Size, Duration: We performed a GWAS meta-analysis in which we combined summary statistics of a previous AMH GWAS with GWAS data from 3705 additional women from three different cohorts., Participants/materials, Setting, Methods: In total, we included data from 7049 premenopausal female participants of European ancestry. The median age of study participants ranged from 15.3 to 48 years across cohorts. Circulating AMH levels were measured in either serum or plasma samples using different ELISA assays. Study-specific analyses were adjusted for age at blood collection and population stratification, and summary statistics were meta-analysed using a standard error-weighted approach. Subsequently, we functionally annotated GWAS variants that reached genome-wide significance (P < 5 × 10-8). We also performed a gene-based GWAS, pathway analysis and linkage disequilibrium score regression and Mendelian randomization (MR) analyses., Main Results and the Role of Chance: We identified four loci associated with AMH levels at P < 5 × 10-8: the previously reported MCM8 locus and three novel signals in or near AMH, TEX41 and CDCA7. The strongest signal was a missense variant in the AMH gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among single nucleotide polymorphisms for AMH levels and for age at menopause (rg = 0.82, FDR = 0.003). Exploratory two-sample MR analyses did not support causal effects of AMH on breast cancer or polycystic ovary syndrome risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored., Large Scale Data: The full AMH GWAS summary statistics will made available after publication through the GWAS catalog (https://www.ebi.ac.uk/gwas/)., Limitations, Reasons for Caution: Whilst this study doubled the sample size of the most recent GWAS, the statistical power is still relatively low. As a result, we may still lack power to identify more genetic variants for AMH and to determine causal effects of AMH on, for example, breast cancer. Also, follow-up studies are needed to investigate whether the signal for the AMH gene is caused by reduced AMH detection by certain assays instead of actual lower circulating AMH levels., Wider Implications of the Findings: Genes mapped to the MCM8, TEX41 and CDCA7 loci are involved in the cell cycle and processes such as DNA replication and apoptosis. The mechanism underlying their associations with AMH may affect the size of the ovarian follicle pool. Altogether, our results provide more insight into the biology of AMH and, accordingly, the biological processes involved in ovarian ageing., Study Funding/competing Interest(s): Nurses' Health Study and Nurses' Health Study II were supported by research grants from the National Institutes of Health (CA172726, CA186107, CA50385, CA87969, CA49449, CA67262, CA178949). The UK Medical Research Council and Wellcome (217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the listed authors, who will serve as guarantors for the contents of this article. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). Funding for the collection of genotype and phenotype data used here was provided by the British Heart Foundation (SP/07/008/24066), Wellcome (WT092830M and WT08806) and UK Medical Research Council (G1001357). M.C.B., A.L.G.S. and D.A.L. work in a unit that is funded by the University of Bristol and UK Medical Research Council (MC&#95;UU&#95;00011/6). M.C.B.'s contribution to this work was funded by a UK Medical Research Council Skills Development Fellowship (MR/P014054/1) and D.A.L. is a National Institute of Health Research Senior Investigator (NF-0616-10102). A.L.G.S. was supported by the study of Dynamic longitudinal exposome trajectories in cardiovascular and metabolic non-communicable diseases (H2020-SC1-2019-Single-Stage-RTD, project ID 874739). The Doetinchem Cohort Study was financially supported by the Ministry of Health, Welfare and Sports of the Netherlands. The funder had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Ansh Labs performed the AMH measurements for the Doetinchem Cohort Study free of charge. Ansh Labs was not involved in the data analysis, interpretation or reporting, nor was it financially involved in any aspect of the study. R.M.G.V. was funded by the Honours Track of MSc Epidemiology, University Medical Center Utrecht with a grant from the Netherlands Organization for Scientific Research (NWO) (022.005.021). The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women's Health (ORWH) (U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495). The SWAN Genomic Analyses and SWAN Legacy have grant support from the NIA (U01AG017719). The Generations Study was funded by Breast Cancer Now and the Institute of Cancer Research (ICR). The ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent official views of the funders. The Sister Study was funded by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (Z01-ES044005 to D.P.S.); the AMH assays were supported by the Avon Foundation (02-2012-065 to H.B. Nichols and D.P.S.). The breast cancer genome-wide association analyses were supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the 'Ministère de l'Économie, de la Science et de l'Innovation du Québec' through Genome Québec and grant PSR-SIIRI-701, The National Institutes of Health (U19 CA148065, X01HG007492), Cancer Research UK (C1287/A10118, C1287/A16563, C1287/A10710) and The European Union (HEALTH-F2-2009-223175 and H2020 633784 and 634935). All studies and funders are listed in Michailidou et al. (Nature, 2017). F.J.M.B. has received fees and grant support from Merck Serono and Ferring BV. D.A.L. has received financial support from several national and international government and charitable funders as well as from Medtronic Ltd and Roche Diagnostics for research that is unrelated to this study. N.S. is scientific consultant for Ansh Laboratories. The other authors declare no competing interests., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Age at final menstrual period (FMP) and the accompanying hormone trajectories across the menopause transition do not occur in isolation, but likely share molecular pathways. Understanding the genetics underlying the endocrinology of the menopause transition may be enhanced by jointly analyzing multiple interrelated traits., Methods: In a sample of 347 White and 164 Black women from the Study of Women's Health Across the Nation (SWAN), we investigated pleiotropic effects of 54 candidate genetic regions of interest (ROI) on 5 menopausal traits (age at FMP and premenopausal and postmenopausal levels of follicle stimulation hormone and estradiol) using multivariate kernel regression (Multi-SKAT). A backward elimination procedure was used to identify which subset of traits were most strongly associated with a specific ROI., Results: In White women, the 20 kb ROI around rs10734411 was significantly associated with the multivariate distribution of age at FMP, premenopausal estradiol, and postmenopausal estradiol (omnibus p-value = .00004). This association did not replicate in the smaller sample of Black women., Conclusion: This study using a region-based, multiple-trait approach suggests a shared genetic basis among multiple facets of reproductive aging., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Study Objectives: Polysomnography (PSG) is considered the "gold standard" for assessing sleep, but cost and burden limit its use. Although wrist actigraphy and self-report diaries are feasible alternatives to PSG, few studies have compared all three modalities concurrently across multiple nights in the home to assess their relative validity across multiple sleep outcomes. This study compared sleep duration and continuity measured by PSG, actigraphy, and sleep diaries and examined moderation by race/ethnicity., Methods: Participants from the Study of Women's Health Across the Nation (SWAN) Sleep Study included 323 White ( n = 147), African American ( n = 120), and Chinese ( n = 56) middle-aged community-dwelling women (mean age: 51 years, range: 48-57). PSG, wrist actigraphy (AW-64; Philips Respironics, McMurray, PA), and sleep diaries were collected concurrently in participants' homes over three consecutive nights. Multivariable repeated-measures linear models compared time in bed (TIB), total sleep time (TST), sleep efficiency (SE), sleep latency (SL), and wake after sleep onset (WASO) across modalities., Results: Actigraphy and PSG produced similar estimates of sleep duration and efficiency. Diaries yielded higher estimates of TIB, TST, and SE versus PSG and actigraphy, and lower estimates of SL and WASO versus PSG. Diary SL was shorter than PSG SL only among White women, and diary WASO was lower than PSG and actigraphy WASO among African American versus White women., Conclusions: Given concordance with PSG, actigraphy may be preferred as an alternative to PSG for measuring sleep in the home. Future research should consider racial/ethnic differences in diary-reported sleep continuity., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society.)

This paper reviews differences in the experience of the menopause transition and midlife health outcomes between Black and White women who participated in the Study of Women's Health Across the Nation (SWAN), a 25-year, longitudinal, multi-racial/ethnic cohort study. We identify health disparities, i.e., instances in which Black women's outcomes are less favorable than those of White women, and consider whether structural racism may underlie these disparities. Although SWAN did not explicitly assess structural racism, Black women in SWAN grew up during the Jim Crow era in the United States, during which time racism was legally sanctioned. We consider how we might gain insight into structural racism by examining proxy exposures such as socioeconomic characteristics, reports of everyday discrimination, and a range of life stressors, which likely reflect the longstanding, pervasive and persistent inequities that have roots in systemic racism in the US. Thus, this paper reviews the presence, magnitude, and longitudinal patterns of racial disparities observed in SWAN in six areas of women's health - menopause symptoms, sleep, mental health, health related quality of life, cardio-metabolic health, and physical function -and elucidates the contextual factors that are likely influencing these disparities. We review the strengths and weaknesses of SWAN's design and approach to analysis of racial disparities and use this as a springboard to offer recommendations for future cohort studies., (© 2022. The Author(s).)

Background: Exposure to metals and metal mixtures may influence ovarian aging. However, epidemiologic evidence of their potential impact is lacking., Objective: We prospectively examined the associations of 15 urinary metal concentrations and their mixtures with natural menopause in the Study of Women's Health Across the Nation Multi-Pollutant Study., Methods: The study population consisted of 1082 premenopausal women from multiple racial/ethnic groups, aged 45-56 years at baseline (1999-2000), with the median follow-up of 4.1 years. Urinary concentrations of 15 metals, including arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc, were measured at baseline. Natural menopause was defined as the final bleeding episode prior to at least 12 months of amenorrhea, not due to surgery or hormone therapy. Cox proportional hazards models were used to examine associations between individual metal concentrations and timing of natural menopause. The associations between metal mixtures and natural menopause were evaluated using elastic net penalized Cox regression, and an environmental risk score (ERS) was computed to represent individual risks of natural menopause related to metal mixtures., Results: The median age at natural menopause was 53.2 years. Using the Cox proportional hazards models, the adjusted hazard ratio (HR) (and its 95% confidence interval (CI)) for natural menopause was 1.32 (1.03, 1.67) for arsenic and 1.36 (1.05, 1.76) for lead, comparing the highest with the lowest quartiles of metal concentrations. The predicted ages at natural menopause in the highest and lowest quartiles were 52.7 and 53.5 years for arsenic; and 52.9 and 53.8 years for lead. A significant association between ERS and menopause was also observed. Women in the highest vs. the lowest quartiles of ERS had an HR of 1.71 (1.36, 2.15), equivalent to a 1.6 year earlier median time to natural menopause., Conclusion: This study suggests that arsenic, lead, and metal mixtures are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Environmental phenols have been suggested as diabetogens but evidence from prospective cohort studies is limited. We examined associations between urinary concentrations of phenols and parabens, assessed at two time-points, and incident diabetes in the Study of Women's Health Across the Nation (SWAN)., Methods: We examined 1,299 women, aged 45-56 years, who were diabetes-free at baseline of the SWAN Multi-Pollutant Study (MPS) (1999-2000) and were followed through January 2017. Urinary concentrations of bisphenol-A, bisphenol-F, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, benzophenone-3, methyl-paraben, ethyl-paraben, propyl-paraben, and butyl-paraben were measured twice at MPS baseline and 3 years later (2002-2003), and the two average concentrations were used as exposure variables. Associations of incident diabetes with individual phenols and parabens were examined using Cox regression. We evaluated the overall joint effects using quantile-based g-computation., Results: Adjusted hazard ratios (HRs) for incident diabetes of the third tertile compared with the first tertile of urinary concentrations were 0.40 (95% confidence interval [CI] = 0.29, 0.56) for methyl-paraben; 0.42 (0.30, 0.58) for propyl-paraben; 0.53 (0.38, 0.75) for 2,5-diclrorophenol; and 0.55 (0.39, 0.80) for benzophenone-3. Nonlinear associations were found for bisphenol-A and 2,4-dichlorophenol (significant positive associations in the second tertile but no associations in the third tertile compared with the first tertile). No significant associations were observed for the other individual chemicals or the joint effect of mixtures., Conclusions: Our findings do not support diabetogenic effects of urinary parabens which were inversely associated with incident diabetes among mid-life women. Epidemiologic findings for biomarkers with short half-lives and high within-person variability need to be interpreted with caution., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report. Acknowledgments Clinical Centers: University of Michigan, Ann Arbor—Siobán Harlow, PI 2011–present, MaryFran Sowers, PI 1994–2011; Massachusetts General Hospital, Boston, MA—Joel Finkelstein, PI 1999–present; Robert Neer, PI 1994–1999; Rush University, Rush University Medical Center, Chicago, IL—Howard Kravitz, PI 2009–present; Lynda Powell, PI 1994–2009; University of California, Davis/Kaiser—Ellen Gold, PI; University of California, Los Angeles—Gail Greendale, PI; Albert Einstein College of Medicine, Bronx, NY—Carol Derby, PI 2011–present, Rachel Wildman, PI 2010–2011; Nanette Santoro, PI 2004–2010; University of Medicine and Dentistry—New Jersey Medical School, Newark—Gerson Weiss, PI 1994–2004; and the University of Pittsburgh, Pittsburgh, PA—Karen Matthews, PI. NIH Program Office: National Institute on Aging, Bethesda, MD—Chhanda Dutta 2016–present; Winifred Rossi 2012–2016; Sherry Sherman 1994–2012; Marcia Ory 1994–2001; National Institute of Nursing Research, Bethesda, MD—Program Officers. Central Laboratory: University of Michigan, Ann Arbor—Daniel McConnell (Central Ligand Assay Satellite Services). SWAN Repository: University of Michigan, Ann Arbor—Siobán Harlow 2013–Present; Dan McConnell 2011–2013; MaryFran Sowers 2000–2011. Coordinating Center: University of Pittsburgh, Pittsburgh, PA—Maria Mori Brooks, PI 2012–present; Kim Sutton-Tyrrell, PI 2001–2012; New England Research Institutes, Watertown, MA—Sonja McKinlay, PI 1995–2001. Steering Committee: Susan Johnson, Current Chair; Chris Gallagher, Former Chair. We thank the study staff at each site and all the women who participated in SWAN., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

[Figure: see text].

Background: To assess whether Healing in Harmony (HiH), a form of music therapy, improved women's mental health following conflict-related trauma and sexual violence in the Democratic Republic of Congo., Methods: This study used a step-wedged design and included 167 women, who completed up to two pre-tests, a post-test, and up to two follow-up interviews at 3 and 6 months after completing the program. The Hopkins Symptoms Checklist was used to measure anxiety and depression. The Harvard Trauma Questionnaire was used to measure post-traumatic stress disorder (PTSD). Generalized estimating equations with unstructured covariance were used to estimate mean change in mental health scores and relative risks (RRs) for screening positive., Results: Prior to starting the HiH program, 73.9, 84.2, and 68.5% screened positive with median scores being 2.20, 2.70, and 2.06 for depression, anxiety, and PTSD, respectively. The RR for screening positive declined significantly (RR = 0.49 for depression, 0.61 for anxiety, and 0.54 for PTSD) and mean scores declined significantly by -0.54, -0.67, and -0.53 points, respectively, from the pre- to the post-test, declines that were sustained at the 3-month and 6-month follow-up interviews., Conclusion: The HiH program was associated with significant improvement in women's mental health that was sustained up to 6 months post completion of the program despite instability in the region and evidence of continued experience of conflict-related trauma during the study. These data support the value of providing psychological care in the context of ongoing humanitarian crises., Competing Interests: JBB, AB, AM, MMH, PMS, BM, and SDH have no conflicts of interest. JC is currently employed by MakeMusicMatter to implement the HiH program globally (https://makemusicmatter.org/healing-in-harmony/)., (© The Author(s) 2021.)

Background: Rates of statin use among minority women are unclear., Hypothesis: We hypothesized that statin use would vary by race/ethnicity with lower rates among minority women compared with Whites., Methods: Data from the study of women's health across the nation, a multiethnic cohort of women collected between 2009 to 2011 were used to examine reported statin use by race/ethnicity and risk profile. Multivariable logistic modeling was performed to estimate the odds ratio (OR) of statin treatment., Results: Of the 2399 women included, 234 had a diagnosis of atherosclerotic disease (ASCVD), 254 were diabetic (without ASCVD), 163 had an LDL ≥190 mg/dL, and 151 had a 10 year ASCVD pooled risk score ≥7.5%. Statins were used by 49.6% of women with CVD; 59.8% of women with diabetes without known ASCVD; 42.3% of women with an LDL ≥190 mg/dL; and 19.9% of women with an ASCVD risk ≥7.5%. Rates of statin use were 43.8% for women with ≥ two prior ASCVD events and 69.4% for women with ≥ one prior ASCVD event plus multiple high-risk conditions. Among women eligible for statins, Black women had a significantly reduced adjusted odds of being on a statin (OR 0.53, 95% confidence interval [CI] 0.36-0.78) compared with White women., Conclusions: In this cohort of multiethnic women, rates of statin use among women who would benefit were low, with Black women having lower odds of statin use than White women., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Epidemiologic studies on associations between metals and insulin resistance and β-cell dysfunction have been cross-sectional and focused on individual metals., Objective: We assessed the association of exposure to metal mixtures, based on assessment of 15 urinary metals, with both baseline levels and longitudinal changes in homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-β)., Methods: We examined 1262 women, aged 45-56 years at baseline (1999-2000), who were followed through 2015-2016, from the Study of Women's Health Across the Nation. Urinary concentrations of 15 metals (arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc) were determined at baseline. HOMA-IR and HOMA-β were repeatedly measured over 16 years of follow-up. A two-stage modeling was used to account for correlations in dependent and independent variables: In stage-1, linear mixed effects models were used to estimate the participant-specific baseline HOMA levels from random intercepts and participant-specific rates of changes from random slopes. In stage-2, adaptive elastic-net (AENET) models were fit to identify components of metal mixtures associated with participant-specific baseline levels and rates of changes in HOMA-IR and HOMA-β, respectively. An environmental risk score (ERS) was used to integrate metal mixture effects from AENET results., Results: In multivariable adjusted AENET models, urinary zinc was associated with higher HOMA-IR at baseline, whereas molybdenum was associated with lower HOMA-IR at baseline. The estimated changes in baseline HOMA-IR for one standard deviation increase in log-transformed urinary metal concentrations were 5.76% (3.05%, 8.55%) for zinc and -3.25% (-5.45%, -1.00%) for molybdenum, respectively. Urinary zinc was also associated with lower HOMA- β at baseline. Arsenic was associated with a slightly faster rate of decline in HOMA-β in the AENET model evaluating associations between metals and rate of changes. Significant associations of ERS with both HOMA-IR and HOMA-β at baseline were observed. ERS for the rate of changes was not calculated and examined in relation to rates of changes in HOMA-IR and HOMA-β because only a single metal was selected by AENET., Conclusion: Exposure to metal mixtures may be exerting effects on insulin resistance and β-cell dysfunction, which might be mechanisms by which metal exposures lead to elevated diabetes risks., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are found widespread in drinking water, foods, food packaging materials and other consumer products. Several PFAS have been identified as endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormonal signalling. Experimental models and epidemiologic studies suggest that PFAS exposures target the ovary and represent major risks for women's health., Objective and Rationale: This review summarises human population and toxicological studies on the association between PFAS exposure and ovarian function., Search Methods: A comprehensive review was performed by searching PubMed. Search terms included an extensive list of PFAS and health terms ranging from general keywords (e.g. ovarian, reproductive, follicle, oocyte) to specific keywords (including menarche, menstrual cycle, menopause, primary ovarian insufficiency/premature ovarian failure, steroid hormones), based on the authors' knowledge of the topic and key terms., Outcomes: Clinical evidence demonstrates the presence of PFAS in follicular fluid and their ability to pass through the blood-follicle barrier. Although some studies found no evidence associating PFAS exposure with disruption in ovarian function, numerous epidemiologic studies, mostly with cross-sectional study designs, have identified associations of higher PFAS exposure with later menarche, irregular menstrual cycles, longer cycle length, earlier age of menopause and reduced levels of oestrogens and androgens. Adverse effects of PFAS on ovarian folliculogenesis and steroidogenesis have been confirmed in experimental models. Based on laboratory research findings, PFAS could diminish ovarian reserve and reduce endogenous hormone synthesis through activating peroxisome proliferator-activated receptors, disrupting gap junction intercellular communication between oocyte and granulosa cells, inducing thyroid hormone deficiency, antagonising ovarian enzyme activities involved in ovarian steroidogenesis or inhibiting kisspeptin signalling in the hypothalamus., Wider Implications: The published literature supports associations between PFAS exposure and adverse reproductive outcomes; however, the evidence remains insufficient to infer a causal relationship between PFAS exposure and ovarian disorders. Thus, more research is warranted. PFAS are of significant concern because these chemicals are ubiquitous and persistent in the environment and in humans. Moreover, susceptible groups, such as foetuses and pregnant women, may be exposed to harmful combinations of chemicals that include PFAS. However, the role environmental exposures play in reproductive disorders has received little attention by the medical community. To better understand the potential risk of PFAS on human ovarian function, additional experimental studies using PFAS doses equivalent to the exposure levels found in the general human population and mixtures of compounds are required. Prospective investigations in human populations are also warranted to ensure the temporality of PFAS exposure and health endpoints and to minimise the possibility of reverse causality., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Objective: To examine associations between dietary intake of omega-3 (n-3; generally antiinflammatory) and omega-6 (n-6; generally proinflammatory) fatty acids and patient-reported outcomes in systemic lupus erythematosus (SLE)., Methods: This study was based on the population-based Michigan Lupus Epidemiology and Surveillance cohort. Estimates of n-3 and n-6 intake were derived from Diet History Questionnaire II items (past year with portion size version). Patient-reported outcomes included self-reported lupus activity (Systemic Lupus Activity Questionnaire [SLAQ]). Multivariable regression, adjusted for age, sex, race, and body mass index, was used to assess associations between absolute intake of n-3 and n-6, as well as the n-6:n-3 ratio, and patient-reported outcomes., Results: Among 456 SLE cases, 425 (93.2%) were female, 207 (45.4%) were African American, and the mean ± SD age was 52.9 ± 12.3 years. Controlling for potential confounders, the average SLAQ score was significantly higher by 0.3 points (95% confidence interval [95% CI] 0.1, 0.6; P = 0.013) with each unit increase of the n-6:n-3 ratio. Both lupus activity and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance scores were lower with each 1-gram/1,000 kcal increase of n-3 fatty acids (SLAQ regression coefficient β = -0.8 [95% CI -1.6, 0.0]; P = 0.055; PROMIS sleep β = -1.1 [95% CI -2.0, -0.2]; P = 0.017). Higher n-3 intakes were nonsignificantly associated with lower levels of depressive symptoms and comorbid fibromyalgia, and with higher quality of life, whereas results for the n6:n3 ratio trended in the opposite direction., Conclusion: This population-based study suggests that higher dietary intake of n-3 fatty acids and lower n-6:n-3 ratios are favorably associated with patient-reported outcomes in SLE, particularly self-reported lupus activity and sleep quality., (© 2019, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Introduction: Environmental exposure to metals may play a role in the pathogenesis of diabetes; however, evidence from human studies is limited. We prospectively evaluated the associations of 20 urinary metal concentrations and their mixtures with incident diabetes in the Study of Women's Health Across the Nation, a multisite, multiethnic cohort study of midlife women., Research Design and Methods: The sample included 1237 white, black, Chinese and Japanese-American women, aged 45-56 years, free of diabetes at baseline (1999-2000) who were followed through 2016. Concentrations of 20 metals (arsenic, barium, beryllium, cadmium, cobalt, chromium, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, uranium, vanadium, tungsten and zinc) were measured in urine specimens at baseline. Incident diabetes was identified annually by fasting glucose ≥126 mg/dL, self-reported doctor-diagnosed diabetes, or self-reported use of antidiabetic medications. A non-parametric clustering method, k-means clustering, was used to identify subgroups with different exposure patterns to metal mixtures., Results: After multivariable adjustment, the HR (95% CI) for diabetes associated with each doubling increase in urinary metal concentrations was 1.19 (1.10 to 1.30) for arsenic and 1.20 (1.05 to 1.37) for lead, in Cox proportional hazards models after controlling for multiple comparisons. A doubling in urinary excretion of zinc was associated with higher risk of diabetes (adjusted HR 1.31, 95% CI 1.11 to 1.53). Two distinct exposure patterns to metal mixtures-'high' versus 'low'-were identified. Participants assigned to the 'high' pattern had higher overall concentrations of all metals compared with those classified into the 'low' pattern. Adjusted HR for diabetes associated with 'high' pattern compared with 'low' was 1.42 (1.08 to 1.87)., Conclusions: Higher urinary concentrations of arsenic and lead, increased urinary excretion of zinc, as well as higher overall exposure to metal mixtures were associated with elevated risk of diabetes. Future studies should further investigate the underlying mechanisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Limited information exists regarding longitudinal trends in midlife women's exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS). Further, little is known about how patterns of exposure differ by race/ethnicity and reproductive characteristics including parity and menopause., Objective: We aimed to examine temporal variations in serum PFAS concentrations among midlife women from the Study of Women's Health Across the Nation., Methods: Serum concentrations of 11 PFAS homologues were measured in 75 White, Black and Chinese women with blood samples collected in 1999-2000, 2002-2003, 2005-2006, and 2009-2011. Rates of changes in PFAS concentrations were calculated assuming a first-order elimination model. Associations between PFAS concentrations and race/ethnicity, menstruation and parity were evaluated with linear mixed models, adjusting for age, body mass index and study site., Results: Serum concentrations of linear-chain perfluorooctanoic acid (n-PFOA), linear- and branched-chain perfluorooctane sulfonic acid (n-PFOS and sm-PFOS) decreased significantly (-6.0%, 95% CI: -8.3%, -3.6% per year for n-PFOA; -14.8%, 95% CI: -17.3%, -12.3% per year for n-PFOS; -16.9%, 95% CI: -19.1%, -14.6% per year for sm-PFOS); whereas perfluorononanoic acid (PFNA) increased (16.0%, 95% CI: 10.6%, 21.6% per year). Detection rates of perfluorodecanoic acid (PFDeA) and perfluoroundecanoic acid (PFUA) doubled. Temporal trends varied significantly by race/ethnicity. Chinese women tended to have consistently higher PFNA concentrations at each follow-up visit, compared with White and Black women. Serum PFHxS concentrations significantly decreased in White and Black women, but not in Chinese. Menstruating women consistently had lower concentrations. Parity was associated with lower concentrations at baseline but the differences between nulliparous and parous women became smaller over time., Conclusions: Our results suggest longitudinal declines in serum concentrations of legacy PFAS and increases in serum concentrations of emerging compounds from 1999 to 2011 in midlife women. Temporal trends in PFAS concentrations are not uniform across race/ethnicity and parity groups., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rheumatic diseases are a leading cause of chronic, noncancer pain. Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease characterized by periodic flares that can result in irreversible target organ damage, including end-stage renal disease. Both intermittent and chronic musculoskeletal pain, as well as fibromyalgia (considered a centralized pain disorder due to dysregulation of pain processing in the central nervous system), are common in SLE. Opioids are generally not indicated for long-term management of musculoskeletal pain or centralized pain (fibromyalgia) because of lack of efficacy, safety issues ranging from adverse medical effects to overdose, and risk for addiction (1,2). In this study of 462 patients with SLE from the population-based Michigan Lupus Epidemiology and Surveillance (MILES) Cohort and 192 frequency-matched persons without SLE, nearly one third (31%) of SLE patients were using prescription opioids during the study period (2014-2015), compared with 8% of persons without SLE (p<0.001). Among the SLE patients using opioids, 97 (68%) were using them for >1 year, and 31 (22%) were concomitantly on two or more opioid medications. Among SLE patients, those using the emergency department (ED) were approximately twice as likely to use prescription opioids (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3-3.6; p = 0.004). In SLE, the combined contributions of underlying disease and adverse effects of immunosuppressive and glucocorticoid therapies already put patients at higher risk for some known adverse effects attributed to long-term opioid use. Addressing the widespread and long-term use of opioid therapy in SLE will require strategies aimed at preventing opioid initiation, tapering and discontinuation of opioids among patients who are not achieving treatment goals of reduced pain and increased function, and consideration of nonopioid pain management strategies., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Afton Hassett reports personal fees from AbbVie outside the submitted work. Siobán Harlow reports personal fees from American Reagent, outside the submitted work. Chad Brummett serves on the advisory board for Recro Pharma Inc. and Heron Therapeutics, and receives grants from the Michigan Department of Health and Human Services (Sub K Michigan OPEN), NIDA (Centralized Pain Opioid Non-Responsiveness R01 DA038261-05), the University of Michigan Genomics Initiative, during the conduct of the study. In addition, Dr. Brummett has a patent for Peripheral Perineural Dexmedetomidine (no royalties) Application number 12/791,506; Issue Date 4/2/13; licensed. No other potential conflicts of interest were disclosed.

Objectives: To assess the association of living and working conditions experienced during trafficking with mental health of female and male survivors., Methods: We analyzed a cross-sectional study of 1015 survivors who received post-trafficking services in Cambodia, Thailand, and Vietnam. Modified Poisson regression models were conducted by gender to estimate prevalence ratios., Results: For females, the elevated prevalence of anxiety, depression, and post-traumatic stress disorder (PTSD) symptoms was associated with adverse living conditions, while for males the prevalence of anxiety (PR = 2.21; 95% CI 1.24-3.96) and depression (PR = 2.63; 95% CI 1.62-4.26) more than doubled and almost tripled for PTSD (PR = 2.93; 95% CI 1.65-5.19) after adjustment. For males in particular, excessive and extreme working hours per day were associated with more than a four- and threefold greater prevalence of PTSD. Being in a detention center or jail was associated with all three mental health outcomes in males., Conclusions: Providers and stakeholders need to consider the complex mental health trauma of the differential effects of living and working conditions for female and male survivors during trafficking to support treatment and recovery.

Background: Per- and poly-fluoroalkyl substances (PFAS) are public health concerns because of widespread exposure through contaminated foods/drinking water. Although some determinants of PFAS exposure have been suggested, the role of geographic location and race/ethnicity in PFAS exposure has not been well characterized., Objectives: We examined potential determinants of PFAS from the Study of Women's Health Across the Nation (SWAN)., Methods: This study includes 1302 women aged 45-56 years from 5 SWAN sites where white women and women from one minority group were recruited (black from Southeast Michigan, Pittsburgh, Boston; Chinese from Oakland; Japanese from Los Angeles). We determined concentrations of 11 PFAS in serum samples collected in 1999-2000 and examined 7 PFAS detected in most women (>97%). Linear regression with backward elimination was used to identify important determinants of PFAS serum concentrations among a set of pre-specified variables (age, body mass index, site, race/ethnicity, education, financial hardship, occupation, born outside the United States (US), parity, menstrual bleeding within the past year, smoking status, alcohol consumption, and consumption of fish, dairy, pizza, salty snack, and French fries)., Results: Site and race/ethnicity were two major determinants of PFAS. White women had higher concentrations of linear perfluorooctanoic acid (PFOA) compared with the Chinese in Oakland (p < 0.0001) and blacks in Pittsburgh (p = 0.048). Black women in Southeast Michigan and Boston (vs. white women) had higher concentrations of linear (p < 0.001 for Southeast Michigan; p < 0.0001 for Boston) and total perfluorooctane sulfonic acid (PFOS) (p < 0.001 for both Southeast Michigan and Boston) and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (p = 0.02 for Southeast Michigan; p < 0.001 for Boston). Chinese (Oakland) and Japanese (Los Angeles) women had higher concentrations of perfluorononanoic acid (PFNA) compared with white women in each site (p < 0.01 for both). Within white women, those in Pittsburgh had relatively higher concentrations of PFAS. Within Chinese and Japanese women, those who were born outside the US had significantly lower concentrations of most PFAS but significantly higher PFNA concentrations. Menstrual bleeding and parity were significantly associated with lower PFAS concentrations. Higher intake of salty snacks including popcorn was significantly associated with higher concentrations of linear PFOA, PFOS and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid., Discussion: Geographic locations and race/ethnicity play an important role in differential exposure to PFAS, with racial/ethnic burdens differing between PFOS, PFOA and PFNA. Menstruation and parity were also determinants of PFAS concentrations possibly as an elimination route., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Human trafficking is a crime and a human rights violation that involves various and simultaneous traumatic events (sexual and physical violence, coercion). Yet, it is unknown how the patterning of violence and coercion affects the mental health of female and male trafficking survivors., Methods: We conducted a cross-sectional study using a sample of 1015 female and male survivors of trafficking who received post-trafficking assistance services in Cambodia, Thailand or Vietnam. We assessed symptoms of anxiety and depression with the Hopkins Symptoms Checklist and symptoms of post-traumatic stress disorder (PTSD) with the Harvard Trauma Questionnaire. Violence was measured with questions from the World Health Organization International Study on Women's Health. Latent class analysis (LCA) was used to identify distinct patterns of violence and coercion in females and males. Novel multi-step mixture modelling techniques were employed to assess the association of the emergent classes with anxiety, depression and PTSD in females and males., Results: LCA identified two distinct classes of violence and coercion experiences in females (class I: severe sexual and physical violence and coercion (20%); class II: sexual violence and coercion (80%)) and males (class I: severe physical violence and coercion (41%); class II: personal coercion (59%)). Females in class I had a two-fold increase in the odds of anxiety (OR = 2.10; 95% CI: 1.57-2.81) and PTSD (OR = 2.07; 95% CI: 1.03-4.17) compared with females in class II, but differences in the prevalence of anxiety, depression and PTSD were not significant when comparing males in class I to class II., Conclusions: Specific patterns of violence and coercion provide a more in-depth understanding of the role of gender in the experience of violence and coercion and its association with mental health in survivors of trafficking. This information could be useful to target comprehensive mental health services for female and male trafficking survivors.

Background: Human trafficking is a pervasive global crime with important public health implications that entail fundamental human rights violations in the form of severe exploitation, violence and coercion. Sex-specific associations between types of violence or coercion and mental illness in survivors of trafficking have not been established., Methods: We conducted a cross-sectional study with 1015 female and male survivors of trafficking (adults, adolescents and children) who received post-trafficking assistance services in Cambodia, Thailand or Vietnam and had been exploited in various labor sectors. We assessed anxiety and depression with the Hopkins Symptoms Checklist (HSCL-25) and post-traumatic stress disorder (PTSD) symptoms with the Harvard Trauma Questionnaire (HTQ), and used validated questions from the World Health Organization International Study on Women's Health and Domestic Violence to measure physical and sexual violence. Sex-specific modified Poisson regression models were estimated to obtain prevalence ratios (PRs) and their 95% confidence intervals (CI) for the association between violence (sexual, physical or both), coercion, and mental health conditions (anxiety, depression and PTSD)., Results: Adjusted models indicated that for females, experiencing both physical and sexual violence, compared to not being exposed to violence, was a strong predictor of symptoms of anxiety (PR = 2.08; 95% CI: 1.64-2.64), PTSD (PR = 1.55; 95% CI: 1.37-1.74), and depression (PR = 1.57; 95% CI: 1.33-1.85). Among males, experiencing physical violence with additional threats made with weapons, compared to not being exposed to violence, was associated with PTSD (PR = 1.59; 95% CI: 1.05-2.42) after adjustment. Coercion during the trafficking experience was strongly associated with anxiety, depression, and PTSD in both females and males. For females in particular, exposure to both personal and family threats was associated with a 96% elevated prevalence of PTSD (PR = 1.96; 95% CI: 1.32-2.91) and more than doubling of the prevalence of anxiety (PR = 2.11; 95% CI: 1.57-2.83)., Conclusions: The experiences of violence and coercion in female and male trafficking survivors differed and were associated with an elevated prevalence of anxiety, depression, and PTSD in both females and males. Mental health services must be an integral part of service provision, recovery and re-integration for trafficked females and males.

Background Measures of subclinical atherosclerosis are predictors of future cardiovascular outcomes as well as of physical and cognitive functioning. The menopausal transition is associated with accelerated progression of atherosclerosis in women. The prospective association between a healthy lifestyle during the midlife and subclinical atherosclerosis is unclear. Methods and Results Self-reported data on smoking, diet, and physical activity from 1143 women in the Study of Women's Health Across the Nation were used to construct a 10-year average Healthy Lifestyle Score ( HLS ) during the midlife. Markers of subclinical atherosclerosis were measured 14 years after baseline and included common carotid artery intima-media thickness ( CCA - IMT ), adventitial diameter ( CCA - AD ), and carotid plaque. The associations of average HLS with CCA - IMT and CCA - AD were estimated using linear models; the association of average HLS with carotid plaque was estimated using cumulative logit models. Average HLS was associated with smaller CCA - IMT and CCA - AD in the fully adjusted models ( P=0.0031 and <0.001, respectively). Compared with participants in the lowest HLS level, those in the highest level had 0.024 mm smaller CCA - IMT (95% confidence interval: -0.048, 0.000), which equals 17% of the SD of CCA - IMT , and 0.16 mm smaller CCA - AD (95% confidence interval: -0.27, -0.04), which equals 24% of the SD of CCA - AD . Among the 3 components of the HLS , abstinence from smoking had the strongest association with subclinical atherosclerosis. Conclusions Healthy lifestyle during the menopausal transition is associated with less subclinical atherosclerosis, highlighting the growing recognition that the midlife is a critical window for cardiovascular prevention in women.

Objectives: To compare population-based sterilization rates between Latinas/os and non-Latinas/os sterilized under California's eugenics law., Methods: We used data from 17 362 forms recommending institutionalized patients for sterilization between 1920 and 1945. We abstracted patient gender, age, and institution of residence into a data set. We extracted data on institution populations from US Census microdata from 1920, 1930, and 1940 and interpolated between census years. We used Spanish surnames to identify Latinas/os in the absence of data on race/ethnicity. We used Poisson regression with a random effect for each patient's institution of residence to estimate incidence rate ratios (IRRs) and compare sterilization rates between Latinas/os and non-Latinas/os, stratifying on gender and adjusting for differences in age and year of sterilization., Results: Latino men were more likely to be sterilized than were non-Latino men (IRR = 1.23; 95% confidence interval [CI] = 1.15, 1.31), and Latina women experienced an even more disproportionate risk of sterilization relative to non-Latinas (IRR = 1.59; 95% CI = 1.48, 1.70)., Conclusions: Eugenic sterilization laws were disproportionately applied to Latina/o patients, particularly Latina women and girls. Understanding historical injustices in public health can inform contemporary public health practice.

Background: In women, midlife is a period of social and physiological change. Ostensibly stressful, cross-sectional studies suggest women experience decreasing stress perceptions and increasing positive outlook during this life stage. The aim of this paper was to describe the longitudinal changes in perceived stress as women transitioned through the midlife., Methods: Premenopausal women ( n = 3044) ages 42-52 years at baseline, were recruited from seven sites in the Study of Women's Health Across the Nation, and followed approximately annually over 13 visits with assessment of perceived stress and change in menopausal status. Longitudinal regression models were used to assess the effects of age, menopausal status and baseline sociodemographic variables on the trajectory of perceived stress over time., Results: At baseline, mean age was 46.4 ± 2.7 years; participants were white (47%), black (29%), Hispanic (7%), Japanese (9%), or Chinese (8%). Hispanic women, women with lesser educational attainment, and women reporting financial hardship were each more likely to report high perceived stress levels at baseline (all p < 0.0001). After adjustment for baseline sociodemographic factors, perceived stress decreased over time for most women ( p < 0.0001), but increased for both Hispanic and white participants at the New Jersey site ( p < 0.0001). Changing menopausal status was not a significant predictor of perceived stress., Conclusions: Self-reported stress decreased for most women as they transitioned across the midlife; changing menopausal status did not play a significant role after adjustment for age and sociodemographic factors. Future studies should explore the stress experience for women by racial/ethnic identity and demographics., Competing Interests: Competing interests The authors declare that they have no competing interests.

Background: Adverse pregnancy outcomes, such as preterm birth (PTB), have been associated with elevated risk of maternal cardiovascular disease, but their effect on late midlife blood pressure (BP) and subclinical vascular measures remains understudied., Methods and Results: We conducted a cross-sectional analysis with 1220 multiethnic parous women enrolled in SWAN (Study of Women's Health Across the Nation) to evaluate the impact of self-reported history of adverse pregnancy outcomes (PTB, small-for-gestational-age, stillbirth), on maternal BP, mean arterial pressure, and subclinical vascular measures (carotid intima-media thickness, plaque, and pulse wave velocity) in late midlife. We also examined whether these associations were modified by race/ethnicity. Associations were tested in linear and logistic regression models adjusting for sociodemographics, reproductive factors, cardiovascular risk factors, and medications. Women were on average aged 60 years and 255 women reported a history of an adverse pregnancy outcome. In fully adjusted models, history of PTB was associated with higher BP (systolic: β=6.40; SE, 1.62 [ P <0.0001] and diastolic: β=3.18; SE, 0.98 [ P =0.001]) and mean arterial pressure (β=4.55; SE 1.13 [ P <0.0001]). PTB was associated with lower intima-media thickness, but not after excluding women with prevalent hypertension. There were no significant associations with other subclinical vascular measures., Conclusions: Findings suggest that history of PTB is associated with higher BP and mean arterial pressure in late midlife. Adverse pregnancy outcomes were not significantly related to subclinical cardiovascular disease when excluding women with prevalent hypertension. Future studies across the menopause transition may be important to assess the impact of adverse pregnancy outcomes on midlife progression of BP., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

The impact of adult bone traits on changes in bone structure and mass during aging is not well understood. Having shown that intracortical remodeling correlates with external size of adult long bones led us to hypothesize that age-related changes in bone traits also depend on external bone size. We analyzed hip dual-energy X-ray absorptiometry images acquired longitudinally over 14 years for 198 midlife women transitioning through menopause. The 14-year change in bone mineral content (BMC, R 2  = 0.03, p = 0.015) and bone area (R 2  = 0.13, p = 0.001), but not areal bone mineral density (aBMD, R 2  = 0.00, p = 0.931) correlated negatively with baseline femoral neck external size, adjusted for body size using the residuals from a linear regression between baseline bone area and height. The dependence of the 14-year changes in BMC and bone area on baseline bone area remained significant after adjusting for race/ethnicity, postmenopausal hormone use, the 14-year change in weight, and baseline aBMD, weight, height, and age. Women were sorted into tertiles using the baseline bone area-height residuals. The 14-year change in BMC (p = 0.009) and bone area (p = 0.001) but not aBMD (p = 0.788) differed across the tertiles. This suggested that women showed similar changes in aBMD for different structural and biological reasons: women with narrow femoral necks showed smaller changes in BMC but greater increases in bone area compared to women with wide femoral necks who showed greater losses in BMC but without large compensatory increases in bone area. This finding is opposite to expectations that periosteal expansion acts to mechanically offset bone loss. Thus, changes in femoral neck structure and mass during menopause vary widely among women and are predicted by baseline external bone size but not aBMD. How these different structural and mass changes affect individual strength-decline trajectories remains to be determined. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Background: Antihypertensive medication use may vary by race and ethnicity. Longitudinal antihypertensive medication use patterns are not well described in women., Methods and Results: Participants from the Study of Women's Health Across the Nation (SWAN), a prospective cohort of women (n=3302, aged 42-52), who reported a diagnosis of hypertension or antihypertensive medication use at any annual visit were included. Antihypertensive medications were grouped by class and examined by race/ethnicity adjusting for potential confounders in logistic regression models. A total of 1707 (51.7%) women, mean age 50.6 years, reported hypertension or used antihypertensive medications at baseline or during follow-up (mean 9.1 years). Compared with whites, blacks were almost 3 times as likely to receive a calcium channel blocker (odds ratio, 2.92; 95% CI, 2.24-3.82) and twice as likely to receive a thiazide diuretic (odds ratio, 2.38; 95% CI, 1.93-2.94). Blacks also had a higher probability of reporting use of ≥2 antihypertensive medications (odds ratio, 1.95; 95% CI, 1.55-2.45) compared with whites. Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and thiazide diuretics increased over time for all racial/ethnic groups. Contrary to our hypothesis, rates of β-blocker usage did not decrease over time., Conclusions: Among this large cohort of multiethnic midlife women, use of antihypertensive medications increased over time, with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers becoming the most commonly used antihypertensive medication, even for blacks. Thiazide diuretic utilization increased over time for all race/ethnic groups as did use of calcium channel blockers among blacks; both patterns are in line with guideline recommendations for the management of hypertension., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Although women with vulvodynia typically have increased vulvar sensitivity, data on characteristics associated with the degree of vulvar sensitivity are lacking. We measured vulvar sensitivity using cotton swab test and vulvodolorimeter among a subset of 335 women, aged younger than 70 years, in the longitudinal Woman to Woman Health Study. Comparing the vulvodynia screening results from their online/paper survey to that at the time of the examination, 42 women had ongoing vulvodynia, 66 had a recent remission, 22 control participants had a recent onset of vulvodynia, and 205 control participants remained asymptomatic. Vulvar sensitivity was greater in each vulvodynia group compared with the control group (P < .001), and was associated with younger age at first onset of pain (P = .025), pain after intercourse (P = .008), describing the pain as a "pressure," "burning," or "irritating" (P = .015, P = .005, and P = .006, respectively), with increased severity of pain ever (P = .012), and with subsequent persistent or relapsing vulvodynia (P < .001 for each). A score of >1 for the cotton swab summary score best differentiated case from control participants (sensitivity 71.9%; specificity 72.0%). Although 13.8% of women with vulvodynia had no increased sensitivity on cotton swab testing, they did not differ in most clinical characteristics or clinical course from those with increased vulvar sensitivity., Perspective: This study showed that women with vulvodynia have more vulvar sensitivity than control women, but the spectrum of sensitivity is broad. Furthermore, those with and without vulvar sensitivity did not differ in most vulvar pain characteristics or in prognosis, suggesting a positive swab test is not required to substantiate the diagnosis., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

The development of pain is common in midlife, resulting in increased health care utilization and costs. The aim of this study was to determine the longitudinal trajectory of overall bodily pain among women during the transition between the reproductive years and menopause. We conducted analyses on a community-based, longitudinal cohort of women enrolled in the Study of Women's Health Across the Nation. One thousand four hundred ninety-five women met inclusion criteria, including: 1) defined date of the final menstrual period (FMP), and 2) complete data on Short Form-36 bodily pain. The primary exposure was time to/from the FMP. The primary outcome was the rate of change in Short Form-36 bodily pain, measured on a scale of 0 to 100 with 100 being the most severe pain. We performed within-person trajectory analyses using piecewise regression following nonparametric modeling of functional forms. Mean bodily pain score at the time of the FMP was 29. Mean bodily pain increased at a rate of .26 per year during the transmenopause (the interval spanning 4.5 years before the FMP through .5 years after the FMP), and decreased at a rate of .23 per year after that. Depression and sleep problems were associated with greater increases in pain during the late reproductive years, whereas abdominal cramps at baseline predicted greater decreases in pain during the late reproductive years., Perspective: This article shows that bodily pain increases during the transmenopause and then diminishes during postmenopause. These differences may reflect differences in underlying mechanisms of pain in the 2 periods. Although mean changes were small and unlikely to be clinically meaningful, the magnitude of change varied across subgroups of women., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)