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Background Experimental and epidemiological studies have linked metals with women's reproductive aging, but the mechanisms are not well understood. Disrupted ovarian folliculogenesis and diminished ovarian reserve could be a pathway through which metals impact reproductive hormones and outcomes. Objective The study aimed to evaluate the associations of heavy metals with anti-Müllerian hormone (AMH), a marker of ovarian reserve. Methods The study included 549 women from the Study of Women's Health Across the Nation with 2252 repeated AMH measurements from 10 to 0 years before the final menstrual period (FMP). Serum AMH concentrations were measured using picoAMH ELISA. Urinary concentrations of arsenic, cadmium, mercury, and lead were measured using high-resolution inductively coupled plasma mass spectrometry. Multivariable linear mixed regressions modeled AMH as a function of time before the FMP interaction terms between metals and time to the FMP were also included. Results Adjusting for confounders, compared with those in the lowest tertile, women in the highest tertile of urinary arsenic or mercury concentrations had lower AMH concentrations at the FMP (percent change: −32.1%; 95% CI, −52.9 to −2.2, P -trend =.03 for arsenic; percent change: −40.7%; 95% CI, −58.9 to −14.5, P -trend =.005 for mercury). Higher cadmium and mercury were also associated with accelerated rates of decline in AMH over time (percent change per year: −9.0%; 95% CI, −15.5 to −1.9, P -trend =.01 for cadmium; −7.3%; 95% CI, −14.0 to −0.1, P -trend =.04 for mercury). Conclusion Heavy metals including arsenic, cadmium, and mercury may act as ovarian toxicants by diminishing ovarian reserve in women approaching the FMP. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. RESEARCH DESIGN AND METHODS: We followed 2,952 participants in the Study of Women's Health Across the Nation (SWAN) who were premenopausal or early perimenopausal and diabetes-free at baseline. SHBG,T, and estradiol (E2) levels were measured at up to 13 follow-up visits (over up to 17 years). We used complementary log-log–based discrete-time survival models anchored at baseline. RESULTS: Diabetes developed in 376 women. A 5-unit increase in time-varying SHBG was associated with a 10% reduced risk of diabetes (hazard ratio [HR] 0.91, 95% CI 0.87–0.95), adjusting for covariates, and baseline SHBG,T, and E2 levels. Time-varying T was not associated with diabetes risk. Compared with the lowest quartile for annual rate of change of SHBG since baseline (quartile 1 [Q1] −92.3 to −1.5 nmol/L), all other quartiles were associated with a decreased risk of diabetes adjusting for covariates and baseline SHBG; associations persisted after adjusting for rate of change of T and E2 (Q2 [> −1.5 to −0.2 nmol/L] HR 0.33, 95% CI 0.23–0.48; Q3 [> −0.2 to 1.3 nmol/L] HR 0.37, 95% CI 0.25–0.55; Q4 [>1.3 to 82.0 nmol/L] HR 0.43, 95% CI 0.30–0.63). CONCLUSIONS: Increasing levels of SHBG over the menopause transition were associated with a decreased risk of incident diabetes. Stable to increasing rates of change in SHBG were also independently associated with a decreased risk of diabetes compared with decreasing rates of change, suggesting SHBG may affect glucose through a mechanism beyond androgenicity. [ABSTRACT FROM AUTHOR]

The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism.We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Women’s Health Across the Nation (SWAN).We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked ≥20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked ≥20 cigarettes/day was associated with 23.8% lower density, compared to having smoked ≤9 cigarettes/day (p

Abstract Introduction We examined the association between mammographic density and single-nucleotide polymorphisms (SNPs) in genes encoding CYP1A1, CYP1B1, aromatase, 17β-HSD, ESR1, and ESR2 in pre- and early perimenopausal white, African-American, Chinese, and Japanese women. Methods The Study of Women's Health Across the Nation is a longitudinal community-based cohort study. We analyzed data from 451 pre- and early perimenopausal participants of the ancillary SWAN Mammographic Density study for whom we had complete information regarding mammographic density, genotypes, and covariates. With multivariate linear regression, we examined the relation between percentage mammographic breast density (outcome) and each SNP (primary predictor), adjusting for age, race/ethnicity, parity, cigarette smoking, and body mass index (BMI). Results After multivariate adjustment, the CYP1B1 rs162555 CC genotype was associated with a 9.4% higher mammographic density than the TC/TT genotype (P = 0.04). The CYP19A1 rs936306 TT genotype was associated with 6.2% lower mammographic density than the TC/CC genotype (P = 0.02). The positive association between CYP1A1 rs2606345 and mammographic density was significantly stronger among participants with BMI greater than 30 kg/m2 than among those with BMI less than 25 kg/m2 (Pinteraction = 0.05). Among white participants, the ESR1 rs2234693 CC genotype was associated with a 7.0% higher mammographic density than the CT/TT genotype (P = 0.01). Conclusions SNPs in certain genes encoding sex steroid metabolism enzymes and ESRs were associated with mammographic density. Because the encoded enzymes and ESR1 are expressed in breast tissue, these SNPs may influence breast cancer risk by altering mammographic density.

Purpose: To compare sexual functioning from diagnosis to 5 years post diagnosis among breast cancer survivors (BCS) and women without cancer (controls). Patients and Methods: Analyses included 118 BCS and 1765 controls from 20 years of the longitudinal Study of Women's Health Across the Nation (SWAN), a multiracial/ethnic cohort of mid‐life women assessed approximately annually from 1995 to 2015. Pink SWAN participants reported no cancer at SWAN enrollment and developed (BCS) or did not develop (controls) incident breast cancer after enrollment. Outcomes included: being sexually active or not, intercourse frequency, sexual desire, vaginal dryness, and pain with intercourse. Using longitudinal logistic regression, we compared BCS and controls on prevalence of sexual functioning outcomes with respect to years since diagnosis. In addition, we examined whether menopause transition stage, depressive symptoms, relationship satisfaction, vaginal dryness, or pain with intercourse modified the relation between breast cancer and sexual functioning outcomes. Results: Adjusting for partner status, both BCS and controls reported similar declines over time in being sexually active, sexual intercourse frequency, and sexual desire. Among sexually active women, more BCS than controls consistently reported vaginal dryness with significant differences between 2 and 4 years post‐diagnosis, and pain with intercourse, with statistically significant differences between 0.5 years post‐diagnosis to 2 years post‐diagnosis. Being post‐menopausal and reporting depressive symptoms were significant effect modifiers for pain with intercourse with both variables having positive and stronger associations with pain among the controls than among BCS. Conclusion: Except for more reporting of vaginal dryness and pain with intercourse among BCS, negative changes in sexual function during mid‐life were similar in those with and without breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: To measure the associations of diet, psycological distress, and lifestyle factors with premenstrual symptoms (PMSx) in women in Riyadh, Saudi Arabia. Patients and Methods: An interview-based, cross-sectional study was conducted on 1831 women aged 18– 50 years seen in primary healthcare centers and teaching institutes in Riyadh from December 2015 to June 2016. Question topics included sociodemographics, physical activity, smoking, and dietary habits information. PMSx were assessed using a symptom checklist with 6 domains: anxiety/mood changes; abdominal/back/joint pain; increased appetite/weight gain, breast pain/tenderness, severe headache, and ≥ 3 PMS symptoms (any). Multivariable logistic regression analyses were conducted to provide adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with each PMSx domain. Results: Except for breast pain, drinking > 5 cups of Arabic coffee was associated with increased odds of anxiety/mood [aOR 2.44 (95% CI 1.44, 4.12)], pain [1.83 (1.13, 2.98)], appetite/weight gain [1.66 (1.10, 2.50)], headache [1.57 (1.00, 2.56)] and ≥ 3 symptoms [1.50 (1.07, 2.11)]. A significant association was noted between sugar intake and anxiety/mood symptoms [1.53 (1.07, 2.19)] and abdominal/back pain symptoms [1.84 (1.17, 2.88)]. Increased severity of psychological distress was associated with all symptom domains: anxiety/mood [2.75 (1.92, 3.94)]; pain [1.45 (0.92, 2.28)]; appetite/weight gain [2.01 (1.53, 2.65)]; breast pain [2.19 (1.68, 2.88)]; headache [1.86 (1.37, 2.54)] and ≥ 3 symptoms [3.52 (2.49, 4.95)]. Low physical activity was significantly associated with odds of breast pain symptoms [1.29 (1.04, 1.59)]. Smokers were 3.41 (1.19, 9.77) times as likely to report any ≥ 3 symptoms compared to nonsmokers. Conclusion: Several potentially modifiable factors, such as diet and stress, were positively associated with PMSx. Thus, we suggest that increasing women's awareness of healthy lifestyles, particularly diet and stress reduction, may help to reduce the occurrence of premenstrual symptoms. [ABSTRACT FROM AUTHOR]

Background Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause. Methods and findings A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause ( Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73-2.44) (p < 0.001) and early menopause (1.80; 1.66-1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04-1.23; p = 0.006) and 1.15 (1.05-1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45-49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15-20 years, the risk was markedly higher for premature (15.58; 11.29-19.86; p < 0.001) and early (6.55; 5.04-8.52; p < 0.001) menopause. Also, current smokers with 11-15 pack-years had over 4-fold (4.35; 2.78-5.92; p < 0.001) and 3-fold (3.01; 2.15-4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98-1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias. Conclusions The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause., Author(s): Dongshan Zhu 1, Hsin-Fang Chung 1, Nirmala Pandeya 1,2, Annette J. Dobson 1, Janet E. Cade 3, Darren C. Greenwood 3, Sybil L. Crawford 4, Nancy E. Avis 5, [...]

Objective: We examined longitudinal associations of air pollution exposure, including fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), with weight, BMI, waist circumference, fat mass, lean mass, and proportion fat mass in midlife women.Research Design and Methods: The study population included 1,654 White, Black, Chinese, and Japanese women from the Study of Women's Health Across the Nation, with the baseline median age of 49.6 years, followed from 2000 to 2008. Annual air pollution exposures were assigned by linking residential addresses with hybrid estimates of air pollutant concentrations at 1-km2 resolution. Body size was measured, and body composition was measured using DXA at approximately annual visits. Linear mixed effects models were used to examine the associations between air pollution and body size and composition measures and whether these associations differed by physical activity.Results: After adjusting for potential confounders, an interquartile range increase in PM2.5 concentration (4.5 μg/m3) was associated with 4.53% (95% CI 3.85%, 5.22%) higher fat mass, 1.10% (95% CI 0.95%, 1.25%) higher proportion fat mass, and 0.39% (95% CI -0.77%, -0.01%) lower lean mass. Similar associations were also observed for NO2 and O3. Weaker associations of PM2.5 and NO2 with body composition were observed in participants who engaged in more physical activity.Conclusions: Our analyses provide evidence that exposure to PM2.5, NO2, and O3, is adversely associated with body composition, including higher fat mass, higher proportional fat mass, and lower lean mass, highlighting their potential contribution to obesity. [ABSTRACT FROM AUTHOR]