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ObjectiveTo examine whether patterns of sexual intercourse frequency and demographic, menopausal status, genitourinary, health, and psychosocial factors are associated with developing sexual pain across the menopausal transition.MethodsThese were longitudinal analyses of questionnaire data from the multicenter, multiracial and ethnic prospective cohort SWAN (Study of Women's Health Across the Nation) (1995-2008). We used multivariable discrete-time proportional hazards models to examine whether incident sexual pain was associated with preceding long-term (up to 10 visits) or short-term (two and three visits) sexual intercourse frequency patterns or other factors (eg, menopause status, genitourinary symptoms, lifestyle factors, and mental health).ResultsOf the 2,247 women with no sexual pain at baseline, 1,087 (48.4%) developed sexual pain at least "sometimes" up to 10 follow-up visits over 13 years. We found no consistent association between prior patterns of sexual intercourse frequency and development of sexual pain. For example, neither decreases in intercourse frequency from baseline (adjusted hazard ratio [aHR] 0.93, 95% CI 0.73-1.19) nor decreases in frequency over three prior visits (aHR 1.00, 95% CI 0.72-1.41) were associated with incident pain. Reasons for interruptions in intercourse activity at the prior visit, including lack of interest (aHR 1.64, 95% CI 0.74-3.65) and relationship issues (aHR 0.36, 95% CI 0.04-2.88), were not associated with developing pain. Being postmenopausal using hormone therapy (aHR 3.16, 95% CI 1.46-6.85), and reported vaginal dryness (aHR 3.73, 95% CI 2.88-4.83) were most strongly associated with incident sexual pain.ConclusionLong-term and short-term declines in sexual intercourse frequency across the menopausal transition were not associated with increased hazard of developing pain with intercourse. This empirical evidence does not support the common belief that a reduction in women's sexual frequency is responsible for their symptoms of sexual pain.

PurposeWe compared trajectories of vasomotor symptoms (VMS) and their risk factors in women with breast cancer (BrCa) to those of cancer-free controls.MethodsData were from 15 nearly annual follow-up visits (1996-2017) of the multi-racial/ethnic cohort of midlife women enrolled in the Study of Women's Health Across the Nation (SWAN). We compared women with incident BrCa to controls for patterns of VMS, controlling for risk factors identified in bivariate analyses using multivariable longitudinal analyses.ResultsCharacteristics at study entry largely did not differ between cases (n = 151) and controls (n = 2161). Adjusted prevalence of any VMS increased significantly among cases from diagnosis to 2.75 years post diagnosis [per-year adjusted odds ratio (aOR) = 1.76, 95% confidence interval (CI) 1.39-2.24], peaking at 2.75 years post diagnosis, whereas prevalence was stable among controls in this interval [aOR = 1.04, 95% CI 0.99-1.11]. Beyond 2.75 years post diagnosis, prevalence declined significantly in cases [aOR = 0.72, 95% CI 0.61-0.84] and less in controls [aOR = 0.96, 95% CI 0.92-1.00]. Patterns were similar for frequent VMS. Adjustment for tamoxifen use slightly reduced the per-year OR for any prevalent VMS post diagnosis, partially explaining excess VMS in cases. Other treatments were unassociated with VMS.ConclusionsPatterns of prevalent VMS reporting differed significantly between cases and controls, particularly post diagnosis, the latter only partially explained by tamoxifen use among cases. Risk factors for VMS largely did not differ between cases and controls.

BackgroundExposure to metals and metal mixtures may influence ovarian aging. However, epidemiologic evidence of their potential impact is lacking.ObjectiveWe 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.MethodsThe 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.ResultsThe 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.ConclusionThis study suggests that arsenic, lead, and metal mixtures are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life.

ObjectiveThe menopausal transition is characterized by progressive changes in ovarian function and increasing circulating levels of gonadotropins, with some women having irregular menstrual cycles well before their final menstrual period. These observations indicate a progressive breakdown of the hypothalamic-pituitary-ovarian axis often associated with an increase in menopausal symptoms. Relationships between vasomotor symptoms (VMS) and depressed mood and sleep as well as a bidirectional association between VMS and depressed mood in mid-life women have been reported, but the endocrine foundations and hormone profiles associated with these symptoms have not been well described. Our objective was to determine the relationship between daily urinary hormone profiles and daily logs of affect and VMS during the early perimenopausal transition.Study designSWAN, the Study of Women's Health Across the Nation, is a large, mutli-ethnic, multisite cohort study of 3302 women aged 42-52 at baseline, designed to examine predictors of health and disease in women as they traversed the menopause. Inclusion criteria were: an intact uterus and at least one ovary present, at least one menstrual period in the previous three months, no use of sex steroid hormones in the previous three months, and not pregnant or lactating. A subset (n = 849) of women aged 43-53 years from all study sites in the first Daily Hormone Study collection were evaluated for this substudy.Outcome measuresWe measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C).ResultsA variable pattern of LH and negative LH feedback were the hormone patterns most strongly associated with increased VMS. In contrast, no hormone pattern was significantly related to negative mood.ConclusionFluctuations of LH associated with low progesterone production were associated with VMS but not negative mood, suggesting different endocrine patterns may be related to increased negative mood than to the occurrence of VMS.

BackgroundPhysical activity (PA) has the potential to attenuate cardiovascular disease risk in midlife women through multiple pathways, including improving lipid profiles. Longitudinal patterns of PA and blood lipid levels have not been studied in midlife women. Our study identified trajectories of PA and blood lipids across midlife and characterized the associations between these trajectories.MethodsWe evaluated 2,789 participants from the Study of Women's Health Across the Nation (SWAN), a longitudinal cohort study with follow-up over the menopause transition. Women reported PA using the Kaiser Physical Activity Survey at seven study visits across 17 years of follow-up. Serum high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were measured at eight study visits across the same 17-year follow-up period. We used group-based trajectory models to characterize trajectories of PA and blood lipids over midlife and dual trajectory models to determine the association between PA and blood lipid trajectories adjusted for race/ethnicity, body mass index category, smoking, and lipid-lowering medication use.ResultsWomen were 46 years old, on average, at study entry. Forty-nine percent were non-Hispanic white; 32 % were Black; 10 % were Japanese; and 9 % were Chinese. We identified four PA trajectories, three HDL cholesterol trajectories, four LDL cholesterol trajectories, and two triglyceride trajectories. The most frequently occurring trajectories were the consistently low PA trajectory (69 % of women), the low HDL cholesterol trajectory (43 % of women), the consistently moderate LDL cholesterol trajectory (45 % of women), and the consistently low triglycerides trajectory (90 % of women). In dual trajectory analyses, no clear associations were observed between PA trajectories and HDL cholesterol, LDL cholesterol, or triglycerides trajectories.ConclusionsThe most frequently observed trajectories across midlife were characterized by low physical activity, low HDL cholesterol, moderate LDL cholesterol, and low triglycerides. Despite the absence of an association between long-term trajectories of PA and blood lipids in this study, a large body of evidence has established the importance of clinical and public health messaging and interventions targeted at midlife women to promote regular and sustained PA during midlife to achieve other cardiovascular and metabolic benefits.

BackgroundExposure to particulate matter air pollution has been associated with cardiovascular disease (CVD) morbidity and mortality; however, most studies have focused on fine particulate matter (PM2.5) exposure and CVD. Coarse particulate matter (PM10-2.5) exposure has not been extensively studied, particularly for long-term exposure, and the biological mechanisms remain uncertain.MethodsWe examined the association between ambient concentrations of PM10-2.5 and inflammatory and hemostatic makers that have been linked to CVD. Annual questionnaire and clinical data were obtained from 1694 women (≥ 55 years old in 1999) enrolled in the longitudinal Study of Women's Health Across the Nation (SWAN) at six study sites from 1999 to 2004. Residential locations and the USEPA air monitoring network measurements were used to assign exposure to one-year PM10-2.5, as well as co-pollutants. Linear mixed-effects regression models were used to describe the association between PM10-2.5 exposure and markers, including demographic, health and other covariates.ResultsEach interquartile (4 μg/m3) increase in one-year PM10-2.5 exposure was associated with a 5.5% (95% confidence interval [CI]: 1.8, 9.4%) increase in levels of plasminogen activator inhibitor-1 (PAI-1) and 4.1% (95% CI: - 0.1, 8.6%) increase in high-sensitivity C-creative Protein (hs-CRP). Stratified analyses suggested that the association with PAI-1 was particularly strong in some subgroups, including women who were peri-menopausal, were less educated, had a body mass index lower than 25, and reported low alcohol consumption. The association between PM10-2.5 and PAI-1 remained unchanged with adjustment for PM2.5, ozone, nitrogen dioxide, and carbon monoxide.ConclusionsLong-term PM10-2.5 exposure may be associated with changes in coagulation independently from PM2.5, and thus, contribute to CVD risk in midlife women.

Fine particles (PM2.5) are known to increase risks of cardiovascular diseases, but it is unclear how they affect plasma lipid levels. In this study, we examined the associations between PM2.5 exposure and lipid/lipoprotein levels from 2289 midlife women enrolled in the longitudinal Study of Women's Health Across the Nation. The average exposure to PM2.5 and gaseous co-pollutants during the prior one year, six months, 30 days, and one day were estimated for each woman based on U.S. Environmental Protection Agency ambient monitoring data. Blood samples were collected annually from 1999 to 2005 and analyzed for lipids/lipoproteins. Mixed-effect models were used to account for repeated measures for each woman, adjusted for demographic, health and behavior covariates. PM2.5 exposures, especially the long-term exposure, were negatively associated with protective lipoproteins, and positively associated with atherogenic lipoproteins. For example, each 3 μg/m3 increase of one-year PM2.5 exposure was associated with decreases of -0.7% (-1.4%, -0.1%) in high-density lipoprotein cholesterols and -0.6% (-1.1%, -0.1%) in apolipoprotein A1 (ApoA1), as well as increases of 3.8% (1.0%, 6.6%) in lipoprotein(a) and 1.4% (0.5%, 2.3%) in the ratio of apolipoprotein B (ApoB)/ApoA1. In stratified analysis, increased atherogenic lipoproteins were mainly observed in women without dyslipidemia, and both increased atherogenic lipoproteins and reduced protective lipoproteins were observed among women in perimenopause. In summary, PM2.5 exposure was associated with adverse lipid level changes, and thus, may increase cardiovascular risks in midlife women.

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]

ObjectiveTo evaluate factors associated with incident self-reported vaginal dryness and the consequences of this symptom across the menopausal transition in a multiracial/ethnic cohort of community-dwelling women.MethodsWe analyzed questionnaire and biomarker data from baseline and 13 approximately annual visits over 17 years (1996-2013) from 2,435 participants in the Study of Women's Health Across the Nation, a prospective cohort study. We used discrete-time Cox proportional-hazards regression to identify predictors of incident vaginal dryness and to evaluate vaginal dryness as a predictor of pain during intercourse and changes in sexual intercourse frequency.ResultsThe prevalence of vaginal dryness increased from 19.4% among all women at baseline (ages 42-53 years) to 34.0% at the 13th visit (ages 57-69 years). Advancing menopausal stage, surgical menopause, anxiety, and being married were positively associated with developing vaginal dryness, regardless of partnered sexual activity. For women not using hormone therapy, higher concurrent levels of endogenous estradiol were inversely associated (multivariable-adjusted hazard ratio: 0.94 per 0.5 standard deviation increase, 95% confidence interval: 0.91-0.98). Concurrent testosterone levels, concurrent dehydroepiandrosterone sulfate levels, and longitudinal change in any reproductive hormone were not associated with developing vaginal dryness. Both vaginal dryness and lubricant use were associated with subsequent reporting of pain during intercourse, but not with a decline in intercourse frequency.ConclusionIn these longitudinal analyses, our data support many clinical observations about the relationship between vaginal dryness, menopause, and pain during intercourse, and suggest that reporting of vaginal dryness is not related to androgen level or sexual intercourse frequency.

ObjectiveWe explored factors associated with reasons that women with urinary incontinence (UI) reported for not seeking treatment for their UI from a healthcare professional and whether reasons differed by race/ethnicity, socioeconomic status, or education.MethodsWe analyzed questionnaire data collected from 1995 to 2005 in the Study of Women's Health Across the Nation. In visits 7 to 9, we elicited reasons that women with UI reported for not seeking treatment and condensed them into: UI not bad enough, beliefs about UI causes (UI is a normal consequence of aging or childbirth), and motivational barriers (such as feeling too embarrassed). We used Generalized Estimating Equations and ordinal logistic regression to evaluate factors associated with these reported reasons and number of reasons.ResultsOf the 1,339 women reporting UI, 814 (61.0%) reported they did not seek treatment for UI. The most frequently reported reasons were as follows: "UI not bad enough" (73%), "UI is a normal part of aging" (53%), and "healthcare provider never asked" (55%). Women reporting daily UI had higher odds of reporting beliefs about UI causes (adjusted odds ratio UI 3.16, 95% CI 1.64-6.11) or motivational barriers (adjusted odds ratio UI 2.36, 95% CI 1.21-4.63) compared with women reporting less than monthly UI. We found no interactions by race/ethnicity, socioeconomic status, or education and UI characteristics in reasons that women reported for not seeking UI treatment.ConclusionsOver half of women who did not seek treatment for their UI reported reasons that could be addressed by public health and clinical efforts to make UI a discussion point during midlife well-women visits.

BackgroundExposures to ambient gaseous pollutants have been linked to cardiovascular diseases (CVDs), but the biological mechanisms remain uncertain.ObjectivesThis study examined the changes in CVD marker levels resulting from elevated exposure to ambient gaseous pollutants in midlife women.MethodsAnnual repeated measurements of several inflammatory, hemostatic and lipid makers were obtained from 2306 midlife women enrolled in the longitudinal Study of Women's Health Across the Nation (SWAN) between 1999 and 2004. Ambient carbon monoxide (CO), nitrogen dioxide (NO2), and sulfur dioxide (SO2) data were assigned to each woman based on proximity of the monitoring station to her residential address. Short- and long-term exposures were calculated, and their associations with markers were examined using linear mixed-effects regression models, adjusted for demographic, health and other factors.ResultsShort-term CO exposure was associated with increased fibrinogen, i.e., every interquartile increase of average prior one-week exposure to CO was associated with 1.3% (95% CI: 0.6%, 2.0%) increase in fibrinogen. Long-term exposures to NO2 and SO2 were associated with reduced high-density lipoproteins and apolipoprotein A1, e.g., 4.0% (1.7%, 6.3%) and 4.7% (2.8%, 6.6%) decrease per interquartile increment in prior one-year average NO2 concentration, respectively. Fine particle (PM2.5) exposure confounded associations between CO/NO2 and inflammatory/hemostatic markers, while associations with lipoproteins were generally robust to PM2.5 adjustment.ConclusionsExposures to these gas pollutants at current ambient levels may increase thrombotic potential and disrupt cholesterol metabolism, contributing to greater risk of CVDs in midlife women. Caution should be exercised in evaluating the confounding by PM2.5 exposure.

ObjectiveThe menopausal transition (MT) is a critical period associated with physiologic changes that influence women's long-term health and longevity. Information is, however, limited regarding factors that influence age at the onset of the MT and its duration (ie, time from MT onset to the final menstrual period).MethodsWe analyzed data for 1,145 women from four sites of the Study of Women's Health Across the Nation who participated in the menstrual calendar substudy, had the start of the MT identified, and had no missing covariate information. Participants included from four racial/ethnic groups: African American, white, Chinese, and Japanese. Women completed daily menstrual calendars from 1996 to 2006 and questions on hormone therapy use monthly. Baseline measures included education, economic strain, and menstrual cycle characteristics. Annual measures included height, weight, and smoking status. Cox proportional hazards models were used to analyze the data.ResultsThe adjusted median duration of the MT ranged from 4.37 years among the oldest age-at-onset quartile to 8.57 years among the youngest age-at-onset quartile (P

Associations between temperature and cardiovascular (CVD) mortality have been reported, but the underlying biological mechanisms remain uncertain. We explored the association between apparent temperature and serum biomarkers for CVD. Using linear mixed effects models, we examined the relationships between residence-proximate apparent temperature (same day and 1, 7, and 30 days prior) and several inflammatory, hemostatic, and lipid biomarkers for midlife women from 1999 through 2004. Our study population consisted of 2,306 women with mean age of 51 years (± 3 years) enrolled in Study of Women's Health Across the Nation (SWAN) in Chicago, Illinois; Detroit, Michigan; Los Angeles and Oakland, California; Newark, New Jersey; and Pittsburgh, Pennsylvania. Mean daily apparent temperature was calculated using temperature and relative humidity data provided by the National Climatic Data Center and the US Environmental Protection Agency, while daily data for fine particles, ozone, carbon monoxide, and nitrogen dioxide from the US Environmental Protection Agency Air Quality Data Mart were considered as confounders. All analyses were stratified by warm and cold seasons. More significant (p

ObjectiveThe aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women.MethodsThe Study of Women's Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling.ResultsFour distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory.ConclusionsThese data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS.

ObjectivesThe International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE.Study designInterLACE is an individual-level pooled study of 20 observational studies (12 of which are longitudinal) from ten countries. Variables were harmonized across studies to create a new and systematic synthesis of life-course data.Main outcome measuresHarmonized data were derived in three domains: 1) socio-demographic and lifestyle factors, 2) female reproductive characteristics, and 3) chronic disease outcomes (cardiovascular disease (CVD) and diabetes).ResultsInterLACE pooled data from 229,054 mid-aged women. Overall, 76% of the women were Caucasian and 22% Japanese; other ethnicities (of 300 or more participants) included Hispanic/Latin American (0.2%), Chinese (0.2%), Middle Eastern (0.3%), African/black (0.5%), and Other (1.0%). The median age at baseline was 47 years (Inter-quartile range (IQR): 41-53), and that at the last follow-up was 56 years (IQR: 48-64). Regarding reproductive characteristics, half of the women (49.8%) had their first menstruation (menarche) at 12-13 years of age. The distribution of menopausal status and the prevalence of chronic disease varied considerably among studies. At baseline, most women (57%) were pre- or peri-menopausal, 20% reported a natural menopause (range 0.8-55.6%) and the remainder had surgery or were taking hormones. By the end of follow-up, the prevalence rates of CVD and diabetes were 7.2% (range 0.9-24.6%) and 5.1% (range 1.3-13.2%), respectively.ConclusionsThe scale and heterogeneity of InterLACE data provide an opportunity to strengthen evidence concerning the relationships between reproductive health through life and subsequent risks of chronic disease, including cross-cultural comparisons.

Practical Bayesian nonparametric methods have been developed across a wide variety of contexts. Here, we develop a novel statistical model that generalizes standard mixed models for longitudinal data that include flexible mean functions as well as combined compound symmetry (CS) and autoregressive (AR) covariance structures. AR structure is often specified through the use of a Gaussian process (GP) with covariance functions that allow longitudinal data to be more correlated if they are observed closer in time than if they are observed farther apart. We allow for AR structure by considering a broader class of models that incorporates a Dirichlet Process Mixture (DPM) over the covariance parameters of the GP. We are able to take advantage of modern Bayesian statistical methods in making full predictive inferences and about characteristics of longitudinal profiles and their differences across covariate combinations. We also take advantage of the generality of our model, which provides for estimation of a variety of covariance structures. We observe that models that fail to incorporate CS or AR structure can result in very poor estimation of a covariance or correlation matrix. In our illustration using hormone data observed on women through the menopausal transition, biology dictates the use of a generalized family of sigmoid functions as a model for time trends across subpopulation categories.

BackgroundStudies have reported associations between long-term air pollution exposures and cardiovascular mortality. The biological mechanisms connecting them remain uncertain.MethodsWe examined associations of fine particles (PM2.5) and ozone with serum markers of cardiovascular disease risk in a cohort of midlife women. We obtained information from women enrolled at six sites in the multi-ethnic, longitudinal Study of Women's Health Across the Nation, including repeated measurements of high-sensitivity C-reactive protein, fibrinogen, tissue-type plasminogen activator antigen, plasminogen activator inhibitor type 1, and factor VIIc (factor VII coagulant activity). We obtained residence-proximate PM2.5 and ozone monitoring data for a maximum five annual visits, calculating prior year, 6-month, 1-month, and 1-day exposures and their relations to serum markers using longitudinal mixed models.ResultsFor the 2,086 women studied from 1999 to 2004, PM2.5 exposures were associated with all blood markers except factor VIIc after adjusting for age, race/ethnicity, education, site, body mass index, smoking, and recent alcohol use. Adjusted associations were strongest for prior year exposures for high-sensitivity C-reactive protein (21% increase per 10 μg/m³ PM2.5, 95% confidence interval [CI]: 6.6, 37), tissue-type plasminogen activator antigen (8.6%, 95% CI: 1.8, 16), and plasminogen activator inhibitor (35%, 95% CI: 19, 53). An association was also observed between year prior ozone exposure and factor VIIc (5.7% increase per 10 ppb ozone, 95% CI: 2.9, 8.5).ConclusionsOur findings suggest that prior year exposures to PM2.5 and ozone are associated with adverse effects on inflammatory and hemostatic pathways for cardiovascular outcomes in midlife women.

ObjectiveTo examine whether longitudinal urinary incontinence (UI) characteristics, race or ethnicity, socioeconomic status, and education were associated with UI treatment-seeking in a prospective cohort of community-dwelling midlife women.MethodsWe analyzed data from 9 years of the Study of Women's Health Across the Nation. The study asked participants reporting at least monthly UI about seeking treatment for their UI at baseline and in visit years 7, 8, and 9. Our main covariates included self-reported race or ethnicity, income, level of difficulty paying for basics, and education level. We used multiple logistic regression to examine associations between demographic, psychosocial, and longitudinal UI characteristics and whether women sought UI treatment. We explored interactions by race or ethnicity, socioeconomic status measures, and education level.ResultsA total of 1,550 women (68% of women with UI) reported seeking treatment for UI over the 9 years of this study. In multivariable analyses, women had higher odds of seeking treatment when UI in the year before seeking treatment was more frequent (adjusted odds ratio [OR] 3.16, 95% confidence interval [CI] 1.15-8.67) and more bothersome (adjusted OR 1.09, 95% CI 1.01-1.18), with longer symptom duration, and with worsening UI symptoms (adjusted OR 1.75, 95% CI 1.01-3.04). Women who saw physicians regularly, had more preventive women's health visits, or both were more likely to seek UI treatment (adjusted OR 1.18, 95% CI 1.07, 1.30). Race or ethnicity, socioeconomic measures, and education were not significantly related to seeking treatment for UI.ConclusionWe found no evidence of racial or ethnic, socioeconomic, or education level disparities in UI treatment-seeking. Rather, longitudinal UI characteristics were most strongly associated with treatment-seeking behavior in midlife women.Level of evidenceII.

ObjectiveThis study aims to examine cross-sectional and longitudinal relations between dietary intake of isoflavones and bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in black, white, Chinese, and Japanese women during the menopausal transition.MethodsWe tested whether tertiles of isoflavone intake were associated with baseline BMD when all women were premenopausal or early perimenopausal. To analyze whether isoflavone intake was associated with longitudinal BMD, we fitted piecewise linear models to repeated measurements of baseline-normalized LS or FN BMD as functions of time before or after the final menstrual period (FMP) date.ResultsMultiply adjusted mean FN BMD values of premenopausal Japanese women were monotonically positively related to isoflavone consumption (P for trend = 0.0003). Otherwise, no statistically significant baseline associations were observed. During the period of 1 year before the FMP through 5 years after the FMP, all participants lost LS and FN BMD. Loss was unrelated to isoflavone intake, except for Japanese women during the period of 1 year before the FMP to 2 years after the FMP: higher tertiles of isoflavone intake were associated with greater annual LS BMD loss rates (P for trend = 0.01) and FN loss rates (P for trend = 0.04).ConclusionsIn Japanese women, higher isoflavone intake is associated with higher peak FN BMD but also with greater rates of LS and FN BMD loss during the menopausal transition. Results for the other racial/ethnic groups did not support a relation between dietary intake of isoflavones and either peak BMD or BMD loss during the menopausal transition.

ObjectiveFew studies have evaluated factors that influence menstrual cycle length (MCL) during the menopausal transition (MT), a life stage during which very long cycles become more likely to occur. The objective of this article was to assess how body mass index and race/ethnicity--factors associated with MCL in young women--influence MCL during the MT.MethodsStudy of Women's Health Across the Nation menstrual calendar substudy data of African-American, white, Chinese, and Japanese women were available for three sites (southeastern Michigan, Los Angeles, and northern California). Self-recorded monthly menstrual calendars with end-of-the-month questions on hormone therapy use and smoking were collected from 1996 to 2006. Height and weight were measured at annual study visits. We used quantile regression to model MCL at the 25th, 50th, 75th, and 90th percentiles with bootstrap sampling to construct 95% CIs. Models evaluated MCL with time indexed to the start of the MT (n = 963) and to the final menstrual period (n = 431).ResultsDuring the MT, increases in MCL occurred mostly at the right tail of the distribution, reflecting a lengthening of long menstrual cycles, not of the median MCL. After adjustment for smoking, education, physical activity, and time, Chinese and Japanese women had 1 day to 6 days longer MCLs compared with white women. Obese women had 1 day to 5 days longer MCLs compared with nonobese women.ConclusionsAs occurs in younger women, menstrual characteristics during the MT are influenced by race/ethnicity and obesity. The long menstrual cycles characteristic of the MT are longer in obese women and in Chinese and Japanese women.

BackgroundSeveral cohort studies report associations between chronic exposure to ambient fine particles (PM2.5) and cardiovascular mortality. Uncertainty exists about biological mechanisms responsible for this observation, but systemic inflammation has been postulated. In addition, the subgroups susceptible to inflammation have not been fully elucidated.MethodsWe investigated whether certain subgroups are susceptible to the effects of long-term exposure to PM2.5 on C-reactive protein (CRP), a marker of inflammation directly linked to subsequent cardiovascular disease. We used data from the SWAN cohort of 1923 mid-life women with up to five annual repeated measures of CRP. Linear mixed and GEE models accounting for repeated measurements within an individual were used to estimate the effects of prior-year PM2.5 exposure on CRP. We examined CRP as a continuous and as binary outcome for CRP greater than 3mg/l, a level of clinical significance.ResultsWe found strong associations between PM2.5 and CRP among several subgroups. For example a 10 µg/m(3) increase in annual PM2.5 more than doubled the risk of CRP greater than 3mg/l in older diabetics, smokers and the unmarried. Larger effects were also observed among those with low income, high blood pressure, or who were using hormone therapy, with indications of a protective effects for those using statins or consuming moderate amounts of alcohol.ConclusionsIn this study, we observed significant associations between long-term exposure to PM2.5 and CRP in several susceptible subgroups. This suggests a plausible pathway by which exposure to particulate matter may be associated with increased risk of cardiovascular disease.

This article investigates the associations of violence and traumatic stress with changes in weight and waist circumference, hypothesizing that violence in midlife would be associated with increases or decreases in weight and waist circumference. The longitudinal cohort of the Study of Women's Health Across the Nation comprised the study sample, which included an ethnically/racially and socially diverse group of 2,870 women between the ages of 42 and 52 years at baseline. Women were followed annually for 10 years, and assessments included weight and waist circumference measures and data on violence, health outcomes, and confounders. At baseline, 8.6% Caucasian, 10.8% African American, 9.2% Chinese, and 5.0% Japanese women reported violence and traumatic stress. Reporting violence and traumatic stress during follow-up was significantly associated with weight gain (odds ratio [OR] = 2.39, 95% confidence interval [CI] = [1.28-4.47]), weight loss (OR = 3.54, 95% CI = [1.73-7.22]), and gain (OR = 2.44, 95% CI = [1.37-4.37]) or loss (OR = 2.66, 95% CI = [1.23-5.77]) in waist circumference, adjusting for age, race/ethnicity, education, marital status, and smoking. Violence and traumatic stress against midlife women were associated with gains or losses in weight and waist circumference.

BackgroundGermline mutations in BRCA1 and BRCA2 (BRCA1/2) are related to an increased lifetime risk of developing breast and ovarian cancer. Although risk-reducing salpingo-oophorectomy reduces the risk of both cancers, loss of fertility is a major concern. A recent study suggested an association between BRCA1 mutation and occult primary ovarian insufficiency. The objective of the current study was to determine whether BRCA1/2 mutation carriers have an earlier onset of natural menopause compared with unaffected women.MethodsWhite carriers of the BRCA1/2 gene (n = 382) were identified within the Breast Cancer Risk Program Registry at the University of California at San Francisco and compared with non-clinic-based white women in northern California (n = 765). The 2 groups were compared with regard to median age at the time of natural menopause before and after adjustment for known risk factors, and the role of smoking within each group was examined using the Kaplan-Meier approach for unadjusted analyses and Cox proportional hazards regression analyses for adjusted analyses.ResultsThe median age at the time of natural menopause in the BRCA1/2 carriers was significantly younger than among the unaffected sample (50 years vs 53 years; P < .001). The unadjusted hazard ratio for natural menopause when comparing BRCA1/2 carriers with unaffected women was 4.06 (95% confidence interval, 3.03-5.45) and was 3.98 (95% confidence interval, 2.87-5.53) after adjusting for smoking, parity, and oral contraceptive use. For BRCA1/2 carriers who were current heavy smokers (smoking ≥ 20 cigarettes/day), the median age at natural menopause was 46 years versus 49 years for nonsmokers (P = .027).ConclusionsThe BRCA1/2 mutation was associated with a significantly earlier age at natural menopause, and heavy smoking compounded this risk. Because the relationship between menopause and the end of natural fertility is considered to be fixed, these findings suggest the risk of earlier infertility among BRCA1/2 carriers.

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.

OBJECTIVES: We investigated whether vasomotor symptom reporting or patterns of change in symptom reporting over the perimenopausal transition among women enrolled in a national study differed according to race/ethnicity. We also sought to determine whether racial/ethnic differences were explained by sociodemographic, health, or lifestyle factors. METHODS: We followed 3198 women enrolled in the Study of Women's Health Across the Nation during 1996 through 2002. We analyzed frequency of vasomotor symptom reporting using longitudinal multiple logistic regressions. RESULTS: Rates of vasomotor symptom reporting were highest among African Americans (adjusted odds ratio [OR]=1.63; 95% confidence interval [CI]=1.21, 2.20). The transition to late perimenopause exhibited the strongest association with vasomotor symptoms (adjusted OR = 6.64; 95% CI = 4.80, 9.20). Other risk factors were age (adjusted OR=1.17; 95% CI=1.13, 1.21), having less than a college education (adjusted OR = 1.91; 95% CI = 1.40, 2.61), increasing body mass index (adjusted OR=1.03 per unit of increase; 95% CI=1.01, 1.04), smoking (adjusted OR=1.63; 95% CI=1.25, 2.12), and anxiety symptoms at baseline (adjusted OR=3.10; 95% CI=2.33, 4.12). CONCLUSIONS: Among the risk factors assessed, vasomotor symptoms were most strongly associated with menopausal status. After adjustment for covariates, symptoms were reported most often in all racial/ethnic groups in late perimenopause and nearly as often in postmenopause.