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Vasomotor symptoms (VMS), the most frequently reported symptoms during the menopausal transition, have been associated with inflammation. Whether inflammation is a risk factor for or a consequence of VMS remains unclear. The objectives of these analyses were to determine if elevated proinflammatory marker levels were associated with increased incident VMS in women without VMS at baseline and whether these associations varied by menopause transition stage or race/ethnicity.We used longitudinal data on incident VMS, high-sensitivity C-reactive protein (hs-CRP; n = 1,922) and interleukin-6 (IL-6; n = 203) from 13 follow-up visits in the Study of Women's Health Across the Nation, which included five racial/ethnic groups of midlife women. We performed multivariable discrete-time survival analyses to determine adjusted hazard ratios (aHRs) for the association of these proinflammatory markers with incident VMS in women without VMS at baseline.We found no significant associations of incident VMS with dichotomized hs-CRP (3 vs ≤3 mg/L) at baseline, concurrent or prior visit (aHRs, 1.04-2.03) or IL-6 (1.44 vs ≤1.44 pg/mL) at visit 1, concurrent or prior visit (aHRs, 0.67-1.62), or continuous hs-CRP or IL-6 values over 13 follow-up visits (with nonsignificant adjusted increased hazards ranging from 0% to 2%).Our results showed no significant association of the proinflammatory biomarkers, hs-CRP or IL-6, either concurrently or with subsequent incident VMS, indicating that inflammation was unlikely to be a risk factor for VMS. Thus, clinical treatments directed at reducing inflammation would be unlikely to reduce the occurrence of VMS.

Supplementary Table 1 from Low to Moderate Alcohol Intake Is Not Associated with Increased Mortality after Breast Cancer

Objective Methods for meta-analysis of studies with individual participant data and continuous exposure variables are well described in the statistical literature but are not widely used in clinical and epidemiological research. The purpose of this case study is to make the methods more accessible. Study Design and Setting A two-stage process is demonstrated. Response curves are estimated separately for each study using fractional polynomials. The study-specific curves are then averaged pointwise over all studies at each value of the exposure. The averaging can be implemented using fixed effects or random effects methods. Results The methodology is illustrated using samples of real data with continuous outcome and exposure data and several covariates. The sample data set, segments of Stata and R code, and outputs are provided to enable replication of the results. Conclusion These methods and tools can be adapted to other situations, including for time-to-event or categorical outcomes, different ways of modelling exposure-outcome curves, and different strategies for covariate adjustment.

AlJohara AlQuaiz,1,2 Muneerah Albugami,3 Ambreen Kazi,1,2 Fahdah Alshobaili,2 Fawzia Habib,1,4 Ellen B Gold5 1Princess Nora Bent Abdullah Chair for Women’s Health Research, King Saud University Medical City, Riyadh, Saudi Arabia; 2Department of Family & Community Medicine, King Saud University Medical city, Riyadh, Saudi Arabia; 3Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 4Department of Gynecology & Obstetrics, Taibah University, Madinah al Munawara, Saudi Arabia; 5Department of Public Health Sciences, University of California Davis, Davis, CA, USACorrespondence: Ambreen Kazi, Princess Nora Bent Abdullah Research chair for Women’s Health Research, King Saud University Medical city, PO Box 231831, Riyadh, 11321, Saudi Arabia, Tel +966 1 4692714, Fax +966 1 4691127, Email akamran@ksu.edu.saPurpose: 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.Keywords: mental distress, coffee, diet, women, premenstrual symptoms

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.

Context Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals that may affect sex hormones and accelerate reproductive aging in midlife women. Objective To examine associations between serum PFAS concentrations at baseline (1999-2000) and longitudinal serum concentrations of follicle-stimulating hormone (FSH), estradiol, testosterone, and sex hormone-binding globulin (SHBG) at baseline and through 2015-2016. Design Prospective cohort. Setting General community. Participants 1371 midlife women 45 to 56 years of age at baseline in the Study of Women’s Health Across the Nation (SWAN). Main Outcome Measure(s) FSH, estradiol, testosterone, SHBG. Results In linear mixed models fitted with log-transformed hormones and log-transformed PFAS adjusting for age, site, race/ethnicity, smoking status, menopausal status, parity, and body mass index, FSH was positively associated with linear perfluorooctanoate [n-PFOA; 3.12% (95% CI 0.37%, 5.95%) increase for a doubling in serum concentration), linear perfluorooctane sulfonate [PFOS; 2.88% (0.21%, 5.63%)], branched perfluorooctane sulfonate [2.25% (0.02%, 4.54%)], total PFOS (3.03% (0.37%, 5.76%)), and 2-(N-ethyl-perfluorooctane sulfonamido) acetate [EtFOSAA; 1.70% (0.01%, 3.42%)]. Estradiol was inversely associated with perfluorononanoate [PFNA; −2.47% (−4.82%, −0.05%)) and n-PFOA (−2.43% (−4.97%, 0.18%)]. Significant linear trends were observed in the associations between PFOS and EtFOSAA with SHBG across parity (Ps trend ≤ 0.01), with generally inverse associations among nulliparous women but positive associations among women with 3+ births. No significant associations were observed between PFAS and testosterone. Conclusions This study observed positive associations of PFOA and PFOS with FSH and inverse associations of PFNA and PFOA with estradiol in midlife women during the menopausal transition, consistent with findings that PFAS affect reproductive aging.

Objective The 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 Design SWAN, 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 Measures We measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C). Results A 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. Conclusion Fluctuations 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.

Background Physical 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. Methods We 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. Results Women 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. Conclusions The 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.

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.

The relation of premenopausal anti-Müllerian hormone (AMH) levels with breast cancer risk has been evaluated in a few studies, but primarily in non-Hispanic White women.We evaluated the association of AMH levels with breast cancer risk in Study of Women's Health Across the Nation (SWAN), a multi-ethnic cohort of women. At enrollment, participants had an intact uterus and ≥ 1 ovary, and ≥ 1 menstrual period in the last 3 months. AMH at first measurement was assessed in 1,529 pre- or perimenopausal women using a high-sensitivity ELISA assay; values were natural log transformed. Breast cancer diagnoses were assessed at enrollment and subsequent follow-up visits through 2018 (median 6.1 years).In total, 84 women reported an incident breast cancer diagnosis. In multivariable Cox regression models adjusting for age, race and ethnicity, body mass index, and other factors, higher AMH levels were associated with a non-significant increased breast cancer risk. Compared to women in the 1st quartile, the hazard ratio (95% confidence interval) for women in the 4th quartile was 1.77 (0.87-3.60).Our results did not suggest a significant association between AMH and breast cancer risk; however, estimates were consistent with prior studies that reported positive associations.

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.

Importance: Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD. Objective: To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause. Design, Setting, and Participants: Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019. Exposures: Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older. Main Outcomes and Measures: First nonfatal CVD event, including coronary heart disease and stroke events. Results: A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (

Objective: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. Design: A pooled analysis of six cohort studies. Setting: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). Population: 18 555 women from the UK, USA and Australia. Methods: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. Main outcome measures: Hot flushes and night sweats. Results: Frequency data showed that early menarche ≤11 years was associated with an increased risk of ‘often’ hot flushes (RRR 1.48, 95% CI 1.24–1.76) and night sweats (RRR 1.59, 95% CI 1.49–1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94–1.42) and 1.27 (95% CI 1.01–1.58) for ‘severe’ hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and ‘often’ VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of ‘severe’ VMS. Conclusions: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. Tweetable abstract: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

To examine physical activity (PA) patterns from pre- to post-diagnosis, and compare these changes to women without breast cancer. To determine pre-diagnosis predictors of PA change, post-diagnosis, in breast cancer survivors (BCS). Data were from 2314 Study of Women’s Health Across the Nation (SWAN) participants, average age of 46.4 ± 2.7 years at baseline (1996–1997). In Pink SWAN, 151 women who reported an incident breast cancer diagnosis over 20 years were classified as BCS; the remaining 2163 women were controls. LOESS plots and linear mixed models were used to illustrate and compare PA changes (sports/exercise [primary measure] and total PA) from pre- to post-diagnosis (or corresponding period) in BCS versus controls. Adjusted linear regression models were used to determine pre-diagnosis predictors of at-risk post-diagnosis PA change patterns (consistently low and decreased PA). No differences in pre- to post-diagnosis PA (or corresponding period) were observed in BCS versus controls. Among BCS, the odds of at-risk post-diagnosis PA change patterns was 2.50 (95% CI 0.96–6.48) times higher for those who reported sleep problems at ≥ 50% (compared to 0%) of pre-diagnosis visits and 3.49 (95% CI 1.26–9.65) times higher for those who were overweight or obese at all (compared to no) pre-diagnosis visits. No other statistically significant predictors were noted. Age-related declines in PA were not amplified by a breast cancer diagnosis. Given the beneficial role of PA across the cancer control continuum, efforts to increase or maintain adequate PA, post-diagnosis, should be continued. While age-related physical activity declines were not amplified breast cancer diagnosis, efforts to identify breast cancer survivors at increased risk for post-diagnosis physical activity declines (or maintenance of low activity) may be a high-yield strategy to improve prognosis and quality of life.

Context Previous epidemiologic studies of per- and polyfluoroalkyl substances (PFASs) and menopausal timing conducted in cross-sectional settings were limited by reverse causation because PFAS serum concentrations increase after menopause. Objectives To investigate associations between perfluoroalkyl substances and incident natural menopause. Design and Setting A prospective cohort of midlife women, the Study of Women’s Health Across the Nation, 1999-2017. Participants 1120 multiracial/ethnic premenopausal women aged 45-56 years. Methods Serum concentrations of perfluoroalkyls were quantified by high-performance liquid chromatography isotope dilution tandem mass spectrometry. Natural menopause was defined as the bleeding episode prior to at least 12 months of amenorrhea not due to surgery or hormone use. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Participants contributed 5466 person-years of follow-up, and 578 had incident natural menopause. Compared with the lowest tertile, women at the highest tertile of baseline serum concentrations had adjusted HR for natural menopause of 1.26 (95% CI: 1.02-1.57) for n-perfluorooctane sulfonic acid (n-PFOS) (Ptrend = .03), 1.27 (95% CI: 1.01-1.59) for branched-PFOS (Ptrend = .03), and 1.31 (95% CI: 1.04-1.65) for n-perfluorooctanoic acid (Ptrend = .01). Women were classified into four clusters based on their overall PFAS concentrations as mixtures: low, low–medium, medium–high, and high. Compared with the low cluster, the high cluster had a HR of 1.63 (95% CI: 1.08-2.45), which is equivalent to 2.0 years earlier median time to natural menopause. Conclusion This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life.

Context Cardiometabolic conditions increase in midlife, but early customized prevention strategies are not established for such women. Objective To characterize and identify factors longitudinally related to constellations of cardiometabolic risk components in multiracial/ethnic women in midlife. Design We conducted a prospective, longitudinal, multiethnic cohort study of 3003 midlife women undergoing menopausal transition (MT). Metabolic syndrome (MetS) was defined as having at least three of five components: high fasting triglyceride (hTG) level, low high-density lipoprotein cholesterol (lHDL-C) level, high fasting plasma glucose (hGluc) level, large waist circumference (abdominal obesity; Ob), and hypertension (HTN). We described the patterns of constellations and estimated hazard ratios (HRs) for constellations at (i) incident MetS and (ii) recovery from MetS, using multivariable-adjusted Cox regression. Setting Seven US sites. Participants In all, 1412 non-Hispanic white, 851 black, 272 Japanese, 237 Hispanic, and 231 Chinese women. Exposures Race/ethnicity, lifestyle factors, and MT stage. Main outcomes measures Cardiometabolic constellations, incident MetS, and MetS recovery. Results Central obesity was the most frequent component. Having no components was the most frequent (31%) baseline constellation. Physical activity (HR = 1.68; 95% CI: 1.06, 2.68) and lower caloric intake (HR = 0.96; 95% CI: 0.93, 0.99 per 100 cal/d) were associated with recovery from MetS. Ob/hTG/lHDL-C (18%), Ob/HTN/lHDL-C (16%), and Ob/HTN/hGluc (14%) were frequent incident constellations. Physically active women had 26% to 62% lower hazards of incident MetS than inactive women. Conclusions Modifiable lifestyle behaviors were related to recovery from MetS and decreased risk of the most frequent MetS constellations in midlife women.

OBJECTIVE: To evaluate factors associated with incident self-reported vaginal dryness and the consequences of this symptom across the menopausal transition in a multi-racial/ethnic cohort of community-dwelling women. METHODS: We analyzed questionnaire and biomarker data from baseline and 13 approximately annual visits over 17 years (1996–2013) from 2435 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 sexual intercourse pain and changes in sexual intercourse frequency. RESULTS: The prevalence of vaginal dryness increased from 19.4% among all women at baseline (ages 42–53 years) to 34.0% at the thirteenth 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 dihydroepiandrosterone-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. CONCLUSION: In 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.

Objective To further characterize the endocrinology of the menopause transition, we sought to determine: whether relationships between urine and serum hormones are maintained as women enter their sixth decade; whether a single luteal phase serum progesterone (P) is reflective of integrated-luteal urinary pregnanediol glucuronide (uPdg); and whether serum P, like luteal uPdg, declines as women approach their final menses (FMP). Methods The Study of Women's Health Across the Nation (SWAN) Daily Hormone Study's (DHS) is a community-based observational study. A subset of participants underwent a timed, luteal blood draw planned for cycle days 16 to 24 during the same month of DHS collection. Serum-luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and P, and urine LH, FSH, estrone conjugates (E1c), and daily and integrated luteal uPdg were measured in 268 samples from 170 women. Serum/urine hormone associations were determined using Pearson's correlation and linear regression, adjusted for concurrent age, body mass index, smoking status, and race/ethnicity. Results Pearson's r ranged from 0.573 (for LH) to 0.843 (for FSH) for serum/urine correlations. Integrated luteal uPdg weakly correlated with serum P (Pearson's r = 0.26, P = 0.004) and explained 7% of the variability in serum P in adjusted linear regression (total R 0.09, P = 0.002). Serum P demonstrated a marginally significant decline with approaching FMP in adjusted analysis (P = 0.04). Conclusions Urine and serum hormones maintain a close relationship in women into their sixth decade of life. Serum luteal P was weakly reflective of luteal Pdg excretion.

Context Menstrual cycle hormone patterns in women approaching menopause are inadequately studied. Objective To describe day-to-day menstrual cycle hormones in women as they approach menopause from the Study of Women's Health Across the Nation Daily Hormone Study (DHS). Design DHS enrollees collected daily urine for one entire menstrual cycle or up to 50 days, whichever came first, annually, up to the final menstrual period (FMP) or for up to 10 years. Setting Seven sites across the United States. Participants A total of 511 premenopausal or early perimenopausal women at enrollment, within 10 years before menopause. Intervention Time-to-FMP measurement. Main outcome measures Evidence of luteal activity (ELA), determined using objective algorithms. Menstrual cycle/segment length; whole cycle, and segment integrated urinary luteinizing hormone, follicle-stimulating hormone, estrone conjugates, and pregnanediol glucuronide (Pdg) for each year, organized around the FMP. Results Mean menstrual cycle length was remarkably preserved at 26 to 27 days in ELA cycles; non-ELA cycles had greater variability. The percentage of cycles that were ELA remained high until 5 years before the FMP (87.9%); only 22.8% of cycles within 1 year of the FMP were ELA. Whole cycle hormones remained relatively stable up to 3 years before the FMP, when gonadotropins began to increase. Pdg excretion declined slowly with progress to the FMP, but Pdg patterns of ELA cycles remained distinguishable from non-ELA. Conclusions Menstrual cycle hormone patterns in perimenopausal women resemble those of midreproductive-aged women until 5 years before menopause, and presumably ovulatory cycles retain a potentially fertile pattern up to the end of reproductive life.

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

Objective Greater body mass index (BMI) and body fat are associated with vasomotor symptoms (VMS). Thus, weight loss may prevent VMS. We analyzed whether concurrent BMI or waist circumference and/or changes in weight or waist circumference predicted incident VMS and whether these relations differed by menopause stage or race/ethnicity. Methods Data from 10 follow-up visits for 1,546 participants in the Study of Women's Health Across the Nation who reported no VMS at baseline were modeled for time to first symptomatic visit in relation to concurrent BMI and waist circumference and change in weight and waist circumference during early and late menopause using discrete survival analyses, adjusting for covariates. Results Greater concurrent BMI and waist circumference were significantly related to greater any and frequent (≥6 d in the last 2 wk) incident VMS in early menopause and lower VMS risk in late menopause. Percentage weight change since baseline and since the prior visit was unrelated to incident any VMS in either menopause stage. Percentage weight change since baseline had a significant shallow U-shaped association with incident frequent VMS in early menopause (P = 0.02), a shallow inverse U-shape in late menopause (P = 0.02), and a significant interaction with menopause stage (P = 0.004) but not with race/ethnicity. Recent weight change was unassociated with incident VMS in either menopause stage. Results were similar for waist change. Conclusions Concurrent BMI and waist circumference were positively related to incident VMS in early menopause and negatively related in late menopause. Maintaining healthy weight in early menopause may help prevent VMS.

BACKGROUND:Frequent and severe vasomotor symptoms during menopause are linked with adverse health outcomes. Understanding modifiable lifestyle factors for the risk of vasomotor menopausal symptoms is important to guide preventive strategies. OBJECTIVE:We investigated the associations between body mass index and smoking, their joint effects with the risk of vasomotor symptoms, and whether the associations differed by menopausal stage. STUDY DESIGN:The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events pooled data on 21,460 midlife women from 8 studies (median age, 50 years; interquartile range, 49-51 years) for the cross-sectional analysis. Four studies provided data for the prospective analysis (n=11,986). Multinomial logistic regression models with 4 categories of frequency/severity for the outcome of vasomotor symptoms were used to estimate relative risk ratios and 95% confidence intervals that were adjusted for within-study correlation and covariates. RESULTS:At baseline, nearly 60% of the women experienced vasomotor symptoms. One-half of them were overweight (30%) or obese (21%), and 17% were current smokers. Cross-sectional analyses showed that a higher body mass index and smoking more cigarettes with longer duration and earlier initiation were all associated with more frequent or severe vasomotor symptoms. Never smokers who were obese had a 1.5-fold (relative risk ratio, 1.52; 95% confidence interval, 1.35-1.73) higher risk of often/severe vasomotor symptoms, compared with never smokers who were of normal-weight. Smoking strengthened the association because the risk of often/severe vasomotor symptoms was much greater among smokers who were obese (relative risk ratio, 3.02; 95% confidence interval, 2.41-3.78). However, smokers who quit at

Background: Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease. Methods: We harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40–44 years (early menopause), 45–49 years (relatively early), 50–51 years (reference category), 52–54 years (relatively late), and 55 years or older (late menopause). Findings: Overall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4·3%) had a first non-fatal cardiovascular disease event after menopause, of whom 9369 (3·1%) had coronary heart disease and 4338 (1·4%) had strokes. Compared with women who had menopause at age 50–51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age

BackgroundMenopausal vasomotor symptoms (ie, hot flashes and night sweats) have been associated with unfavorable risk factors and surrogate markers of cardiovascular disease, but their association with clinical cardiovascular disease events is unclear.ObjectiveTo examine the associations between different components of vasomotor symptoms, timing of vasomotor symptoms, and risk of cardiovascular disease.Study designWe harmonized and pooled individual-level data from 23,365 women in 6 prospective studies that contributed to the International Collaboration for a Life Course Approach to Women's Reproductive Health and Chronic Disease Events consortium. Women who experienced cardiovascular disease events before baseline were excluded. The associations between frequency (never, rarely, sometimes, and often), severity (never, mild, moderate, and severe), and timing (before or after age of menopause; ie, early or late onset) of vasomotor symptoms and incident cardiovascular disease were analyzed. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals.ResultsIn the adjusted model, no evidence of association was found between the frequency of hot flashes and incident cardiovascular disease, whereas women who reported night sweats "sometimes" (hazard ratio, 1.22; 95% confidence interval, 1.02-1.45) or "often" (hazard ratio, 1.29; 95% confidence interval, 1.05-1.58) had higher risk for cardiovascular disease. Increased severity of either hot flashes or night sweats was associated with higher risk of cardiovascular disease. The hazards ratios of cardiovascular disease in women with severe hot flashes, night sweats, and any vasomotor symptoms were 1.83 (95% confidence interval, 1.22-2.73), 1.59 (95% confidence interval, 1.07-2.37), and 2.11 (95% confidence interval, 1.62-2.76), respectively. Women who reported severity of both hot flashes and night sweats had a higher risk for cardiovascular disease (hazard ratio, 1.55; 95% confidence interval, 1.24-1.94) than those with hot flashes alone (hazard ratio, 1.33; 95% confidence interval, 0.94-1.88) and night sweats alone (hazard ratio, 1.32; 95% confidence interval, 0.84-2.07). Women with either early-onset (hazard ratio, 1.38; 95% confidence interval, 1.10-1.75) or late-onset (hazard ratio, 1.69; 95% confidence interval, 1.32-2.16) vasomotor symptoms had an increased risk for incident cardiovascular disease compared with women who did not experience vasomotor symptoms.ConclusionSeverity rather than frequency of vasomotor symptoms (hot flashes and night sweats) was associated with increased risk of cardiovascular disease. Vasomotor symptoms with onset before or after menopause were also associated with increased risk of cardiovascular disease.

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.

Context: Unfavorable lipid levels contribute to cardiovascular disease and may also harm bone health. Objective: Our objective was to investigate relationships between fasting plasma lipid levels and incident fracture in midlife women undergoing the menopausal transition. Design and Setting: This was a 13-year prospective, longitudinal study of multiethnic women in five US communities, with near-annual assessments. Participants: At baseline, 2062 premenopausal or early perimenopausal women who had no history of fracture were included. Exposures: Fasting plasma total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at baseline and follow-up visits 1 and 3–7. Main Outcome Measure(s): Incident nontraumatic fractures 1) 2 or more years after baseline, in relation to a single baseline level of lipids; and 2) 2–5 years later, in relation to time-varying lipid levels. Cox proportional hazards modelings estimated hazard ratios and 95% confidence interval (CI). Results: Among the lipids, TG levels changed the most, with median levels increased by 16% during follow-up. An increase of 50 mg/dl in baseline TG level was associated with a 1.1-fold increased hazards of fracture (adjusted hazard ratio, 1.11; 95% CI, 1.04–1.18). Women with baseline TG higher than 300 mg/dl had an adjusted 2.5-fold greater hazards for fractures (95% CI, 1.13–5.44) than women with baseline TG lower than 150 mg/dl. Time-varying analyses showed a comparable TG level-fracture risk relationship. Associations between total cholesterol, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol levels and fractures were not observed. Conclusions: Midlife women with high fasting plasma TG had an increased risk of incident nontraumatic fracture. Secondary Abstract: Midlife women with fasting plasma triglyceride (TG) of at least 300 mg/dl had 2.5-fold greater hazards of fracture in 2 years later and onward, compared to those with TG below 150 mg/dl, in a multiethnic cohort. Time-varying analyses revealed comparable results.

Background and Purpose— Emerging work has linked menopausal vasomotor symptoms (VMS) to subclinical cardiovascular disease (CVD) among women. However, VMS are dynamic over time. No studies have considered how temporal patterns of VMS may relate to subclinical CVD. We tested how temporal patterns of VMS assessed over 13 years were related to carotid intima media thickness (IMT) among midlife women. Methods— The Study of Women’s Health Across the Nation is a longitudinal cohort study of midlife women. Eight hundred and eleven white, black, Hispanic, and Chinese participants with a well-characterized final menstrual period completed measures of VMS, a blood draw, and physical measures approximately annually for 13 years. Women underwent a carotid artery ultrasound at study visit 12. Results— Four trajectories of VMS were identified by trajectory analysis (consistently high, early-onset, late-onset, persistently low VMS) and tested in relation to carotid indices in linear regression models. Results indicated that women with early-onset VMS had both greater mean IMT (beta, b [standard error, SE]=0.03 [0.01], P =0.03) and greater maximal IMT (b [SE]=0.04 [0.01], P =0.008) than women with consistently low VMS, adjusting for demographics and CVD risk factors. Conclusions— This is the first study to test trajectories of VMS in relation to subclinical CVD. Women with VMS early in the menopause transition had higher mean IMT and maximal IMT than those with consistently low VMS across the transition. Associations were not accounted for by demographic factors nor by CVD risk factors. Results can signal to women in need of early CVD risk reduction.

BackgroundMany women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions.MethodsA pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49−51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.ResultsAt baseline, the prevalence of VMS (40%, range 13–62%) and depressed mood (26%, 8–41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27–1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47–2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90–1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38–2.34).ConclusionsDifficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.

Fine particles (PM2.5) are known to increase risks of cardiovascular diseases, but very few studies have examined impact of long-term PM2.5 exposure on plasma lipid. In this study, we examined the ...

Fine particles (PM(2.5)) 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 PM(2.5) exposure and lipid/lipoprotein levels from 2,289 midlife women enrolled in the longitudinal Study of Women’s Health Across the Nation. The average exposure to PM(2.5) and gaseous co-pollutants during the prior one year, six months, 30 days, and one day were estimated for each woman based on US 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. PM(2.5) exposures, especially the long-term exposure, were negatively associated with protective lipoproteins, and positively associated with atherogenic lipoproteins. For example, each 3 μg/m(3) increase of one-year PM(2.5) 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, PM(2.5) exposure was associated with adverse lipid level changes, and thus, may increase cardiovascular risks in midlife women.

Objective To evaluate patterns in actigraphy-defined sleep measures across the menstrual cycle, testing the hypothesis that sleep would be more disrupted in the premenstrual period, i.e. in the 14 days prior to menses.

Current evidence on the association between body mass index (BMI) and age at menopause remains unclear. We investigated the relationship between BMI and age at menopause using data from 11 prospective studies. A total of 24,196 women who experienced menopause after recruitment was included. Baseline BMI was categorised according to the WHO criteria. Age at menopause, confirmed by natural cessation of menses for ≥ 12 months, was categorised as

Objective We 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. Methods We 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. Results Of 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. Conclusions Over 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.

Background: Exposures to ambient gaseous pollutants have been linked to cardiovascular diseases (CVDs), but the biological mechanisms remain uncertain. Objectives: This study examined the changes in CVD marker levels resulting from elevated exposure to ambient gaseous pollutants in midlife women. Methods: Annual 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. Results: Short-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. Conclusions: Exposures 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. Keywords: Cardiovascular, Coagulation, Fibrinolysis, Carbon monoxide, Nitrogen dioxide, Sulfur dioxide, Lipoprotein

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&nbsp

Early age at the natural final menstrual period (FMP) or menopause has been associated with numerous health outcomes and might be a marker of future ill health. However, potentially modifiable factors affecting age at menopause have not been examined longitudinally in large, diverse populations. The Study of Women's Health Across the Nation (SWAN) followed 3,302 initially premenopausal and early perimenopausal women from 7 US sites and 5 racial/ethnic groups, using annual data (1996-2007) and Cox proportional hazards models to assess the relation of time-invariant and time-varying sociodemographic, lifestyle, and health factors to age at natural FMP. Median age at the FMP was 52.54 years (n = 1,483 observed natural FMPs). Controlling for sociodemographic, lifestyle, and health factors, we found that racial/ethnic groups did not differ in age at the FMP. Higher educational level, prior oral contraceptive use, and higher weight at baseline, as well as being employed, not smoking, consuming alcohol, having less physical activity, and having better self-rated health over follow-up, were significantly associated with later age at the FMP. These results suggest that age at the natural FMP reflects a complex interrelation of health and socioeconomic factors, which could partially explain the relation of late age at FMP to reduced morbidity and mortality.

Community pharmacies serve as key locations for public health services including interventions to enhance the availability of syringes sold over-the-counter (OTC), an important strategy to prevent injection-mediated HIV transmission. Little is known about the community characteristics associated with the availability of pharmacies and pharmacies that sell syringes OTC. We conducted multivariable regression analyses to determine whether the sociodemographic characteristics of census tract residents were associated with pharmacy presence in Los Angeles (LA) County during 2008. Using a geographic information system, we conducted hot-spot analyses to identify clusters of pharmacies, OTC syringe-selling pharmacies, sociodemographic variables, and their relationships. For LA County census tracts (N = 2,054), population size (adjusted odds ratio [AOR], 1.22; 95 % confidence interval [CI], 1.16, 1.28), median age of residents (AOR, 1.03; 95 % CI, 1.01, 1.05), and the percent of households receiving public assistance (AOR, 0.97; 95 % CI, 0.94, 0.99) were independently associated with the presence of all pharmacies. Only 12 % of census tracts had at least one OTC syringe-selling pharmacy and sociodemographic variables were not independently associated with the presence of OTC syringe-selling pharmacies. Clusters of pharmacies (p

BACKGROUND: Germline 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. METHODS: White 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. RESULTS: The 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). CONCLUSIONS: The 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. Cancer 2013. © 2012 American Cancer Society.

Objective: Short sleep duration has been associated with higher current BMI and subsequent weight gain. However, most prior longitudinal studies are limited by reliance on self-reported sleep duration, and none accounted for the potential confounding effect of sleep-disordered breathing. The associations of sleep duration with current BMI and BMI change were examined among 310 midlife women in the Study of Women's Health Across the Nation (SWAN) Sleep Study (2003-2005). Methods: Sleep duration was assessed for approximately one month with concurrent wrist actigraphy and sleep diaries. The presence and severity of sleep-disordered breathing was quantified using the apnea-hypopnea index (AHI) based on in-home polysomnography. BMI was assessed annually through core SWAN visit 10 (2006 and 2008). Results: Mean BMI increased from 29.6 (SD = 7.8) kg/m2 to 30.0 (SD = 8.0) kg/m2 over an average of 4.6 years (SD = 1.0) of follow-up. In cross-sectional analyses controlling for AHI, demographic variables, and several potential confounding variables, actigraphy (estimate = -1.22, 95% confidence interval (CI): -2.03, -0.42) and diary (estimate = -0.86, 95% CI -1.62, -0.09) measures of sleep duration were inversely associated with BMI. Each hour of less sleep was associated with 1.22 kg/m2 greater BMI for actigraphy sleep duration, and a 0.86 kg/m2 greater BMI for diary sleep duration. Longitudinal associations between sleep duration and annual BMI change were nonsignificant in unadjusted and fully adjusted models. Conclusion: In this cohort of midlife women, cross-sectional associations between sleep duration and current BMI were independent of sleep-disordered breathing, but sleep duration was not prospectively associated with weight change.

Short sleep duration has been associated with higher current BMI and subsequent weight gain. However, most prior longitudinal studies are limited by reliance on self-reported sleep duration, and none accounted for the potential confounding effect of sleep-disordered breathing. The associations of sleep duration with current BMI and BMI change were examined among 310 midlife women in the Study of Women's Health Across the Nation (SWAN) Sleep Study (2003-2005).Sleep duration was assessed for approximately one month with concurrent wrist actigraphy and sleep diaries. The presence and severity of sleep-disordered breathing was quantified using the apnea-hypopnea index (AHI) based on in-home polysomnography. BMI was assessed annually through core SWAN visit 10 (2006 and 2008).Mean BMI increased from 29.6 (SD = 7.8) kg/m(2) to 30.0 (SD = 8.0) kg/m(2) over an average of 4.6 years (SD = 1.0) of follow-up. In cross-sectional analyses controlling for AHI, demographic variables, and several potential confounding variables, actigraphy (estimate = -1.22, 95% confidence interval (CI): -2.03, -0.42) and diary (estimate = -0.86, 95% CI -1.62, -0.09) measures of sleep duration were inversely associated with BMI. Each hour of less sleep was associated with 1.22 kg/m(2) greater BMI for actigraphy sleep duration, and a 0.86 kg/m(2) greater BMI for diary sleep duration. Longitudinal associations between sleep duration and annual BMI change were nonsignificant in unadjusted and fully adjusted models.In this cohort of midlife women, cross-sectional associations between sleep duration and current BMI were independent of sleep-disordered breathing, but sleep duration was not prospectively associated with weight change.

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.