Publications by authors named "Sioban D Harlow"

161 Publications

Symptom clusters predict risk of metabolic-syndrome and diabetes in midlife: the Study of Women's Health Across the Nation.

Ann Epidemiol 2021 Feb 22;58:48-55. Epub 2021 Feb 22.

Epidemiologic Science, School of Public Health, University of Michigan, Ann Arbor, MI; Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI.

Purpose: Women's cardio-metabolic risk increases in midlife. Previous work relating menopause symptoms to diabetes/Metabolic Syndrome (MetS) does not consider the adverse impact of multiple concurrent physical and psychological symptoms in midlife.

Methods: Data are from 3097 participants in the Study of Women's Health Across the Nation, a cohort of midlife women followed for over 20 years. Baseline latent symptom classes (LSC) were derived from 58 questions assessing physical, psychological and menopausal symptoms. Six identified LSCs ranged from 1 (most symptoms present at high severity) to 6 (few symptoms present at low severity). Accelerated failure time models estimated time to onset of type 2 diabetes and MetS for each LSC.

Results: Women with multiple high/moderate severity symptoms had an earlier onset of diabetes (13.2%, 14.1% and 20.8% earlier onset in LSCs 1, 2, 3, respectively) and MetS (15.5%, 13.0% and 19.7% earlier onset in LSCs 1, 2, 3, respectively) than women with few/low severity symptoms.

Conclusions: Having multiple concurrent moderate to high intensity physical and psychological symptoms in midlife are associated with early onset of diabetes and MetS. Monitoring and subsequent intervention on a broad range of symptoms in midlife may significantly mitigate cardio-metabolic risk during this critical life stage.
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http://dx.doi.org/10.1016/j.annepidem.2021.02.011DOI Listing
February 2021

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women.

medRxiv 2020 Nov 3. Epub 2020 Nov 3.

Anti-Müllerian hormone (AMH) is expressed by antral stage ovarian follicles in women. Consequently, circulating AMH levels are detectable until menopause. Variation in age-specific AMH levels has been associated with breast cancer and polycystic ovary syndrome (PCOS), amongst other diseases. Identification of genetic variants underlying variation in AMH levels could provide clues about the physiological mechanisms that explain these AMH-disease associations. To date, only one variant in has been identified to be associated with circulating AMH levels in women. We aimed to identify additional variants for AMH through a GWAS meta-analysis including data from 7049 premenopausal women of European ancestry, which more than doubles the sample size of the largest previous GWAS. We identified four loci associated with AMH levels at p < 5×10 : the previously reported locus and three novel signals in or near , and . The strongest signal was a missense variant in the gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among SNPs for AMH levels and for age at menopause (r = 0.82, FDR=0.003). Exploratory Mendelian randomization analyses did not support a causal effect of AMH on breast cancer or PCOS risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored. In conclusion, we identified a variant in the gene and three other loci that may affect circulating AMH levels in women.
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http://dx.doi.org/10.1101/2020.10.29.20221390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654897PMC
November 2020

Urinary metal mixtures and longitudinal changes in glucose homeostasis: The Study of Women's Health Across the Nation (SWAN).

Environ Int 2020 12 12;145:106109. Epub 2020 Sep 12.

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, United States. Electronic address:

Background: Epidemiologic studies on associations between metals and insulin resistance and β-cell dysfunction have been cross-sectional and focused on individual metals.

Objective: We assessed the association of exposure to metal mixtures, based on assessment of 15 urinary metals, with both baseline levels and longitudinal changes in homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-β).

Methods: We examined 1262 women, aged 45-56 years at baseline (1999-2000), who were followed through 2015-2016, from the Study of Women's Health Across the Nation. Urinary concentrations of 15 metals (arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc) were determined at baseline. HOMA-IR and HOMA-β were repeatedly measured over 16 years of follow-up. A two-stage modeling was used to account for correlations in dependent and independent variables: In stage-1, linear mixed effects models were used to estimate the participant-specific baseline HOMA levels from random intercepts and participant-specific rates of changes from random slopes. In stage-2, adaptive elastic-net (AENET) models were fit to identify components of metal mixtures associated with participant-specific baseline levels and rates of changes in HOMA-IR and HOMA-β, respectively. An environmental risk score (ERS) was used to integrate metal mixture effects from AENET results.

Results: In multivariable adjusted AENET models, urinary zinc was associated with higher HOMA-IR at baseline, whereas molybdenum was associated with lower HOMA-IR at baseline. The estimated changes in baseline HOMA-IR for one standard deviation increase in log-transformed urinary metal concentrations were 5.76% (3.05%, 8.55%) for zinc and -3.25% (-5.45%, -1.00%) for molybdenum, respectively. Urinary zinc was also associated with lower HOMA- β at baseline. Arsenic was associated with a slightly faster rate of decline in HOMA-β in the AENET model evaluating associations between metals and rate of changes. Significant associations of ERS with both HOMA-IR and HOMA-β at baseline were observed. ERS for the rate of changes was not calculated and examined in relation to rates of changes in HOMA-IR and HOMA-β because only a single metal was selected by AENET.

Conclusion: Exposure to metal mixtures may be exerting effects on insulin resistance and β-cell dysfunction, which might be mechanisms by which metal exposures lead to elevated diabetes risks.
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http://dx.doi.org/10.1016/j.envint.2020.106109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577932PMC
December 2020

Associations between sleep and cognitive performance in a racially/ethnically diverse cohort: the Study of Women's Health Across the Nation.

Sleep 2021 Feb;44(2)

Department of Epidemiology, University of Michigan, Ann Arbor, MI.

Study Objectives: To determine whether actigraphy-assessed indices of sleep are associated with cognitive performance in women, and explore whether these associations vary by race/ethnicity.

Methods: Participants were 1,126 postmenopausal community-dwelling females (mean age 65 years) from the observational Study of Women's Health Across the Nation (SWAN); 25% were black, 46% white, 13% Chinese, 11% Japanese, and 5% Hispanic. Actigraphy-assessed sleep measures included total sleep time, wake after sleep onset (WASO), and fragmentation. Cognitive measures included immediate and delayed verbal memory, working memory, and information processing speed. All measures were assessed in conjunction with SWAN annual visit 15.

Results: Across the sample, after covariate adjustment, greater WASO and fragmentation were concurrently associated with slower information processing speed. Black participants had significantly worse sleep relative to other race/ethnic groups. Significant race/sleep interactions were observed; in black, but not white, participants, greater fragmentation was concurrently associated with worse verbal memory and slower information processing speed, and greater WASO was concurrently associated with slower information processing speed. Sleep-cognitive performance associations were not different in Chinese and Japanese participants relative to white participants.

Conclusions: Greater wakefulness and fragmentation during sleep are concurrently associated with slower information processing. Sleep continuity impacted concurrent cognitive performance in black, but not white, women. This effect may not have been detected in white women because their sleep was largely within the normal range. Future longitudinal studies in diverse samples are critical to further understand whether race/ethnicity moderates the influence of sleep on cognitive performance.
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http://dx.doi.org/10.1093/sleep/zsaa182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879413PMC
February 2021

Is race or ethnicity associated with under-utilization of statins among women in the United States: The study of women's health across the nation.

Clin Cardiol 2020 Dec 30;43(12):1388-1397. Epub 2020 Aug 30.

Division of Rheumatology, Division of Pharmacoepidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: Rates of statin use among minority women are unclear.

Hypothesis: We hypothesized that statin use would vary by race/ethnicity with lower rates among minority women compared with Whites.

Methods: Data from the study of women's health across the nation, a multiethnic cohort of women collected between 2009 to 2011 were used to examine reported statin use by race/ethnicity and risk profile. Multivariable logistic modeling was performed to estimate the odds ratio (OR) of statin treatment.

Results: Of the 2399 women included, 234 had a diagnosis of atherosclerotic disease (ASCVD), 254 were diabetic (without ASCVD), 163 had an LDL ≥190 mg/dL, and 151 had a 10 year ASCVD pooled risk score ≥7.5%. Statins were used by 49.6% of women with CVD; 59.8% of women with diabetes without known ASCVD; 42.3% of women with an LDL ≥190 mg/dL; and 19.9% of women with an ASCVD risk ≥7.5%. Rates of statin use were 43.8% for women with ≥ two prior ASCVD events and 69.4% for women with ≥ one prior ASCVD event plus multiple high-risk conditions. Among women eligible for statins, Black women had a significantly reduced adjusted odds of being on a statin (OR 0.53, 95% confidence interval [CI] 0.36-0.78) compared with White women.

Conclusions: In this cohort of multiethnic women, rates of statin use among women who would benefit were low, with Black women having lower odds of statin use than White women.
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http://dx.doi.org/10.1002/clc.23448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724205PMC
December 2020

Changes in kidney function during the menopausal transition: the Study of Women's Health Across the Nation (SWAN) - Michigan site.

Menopause 2020 09;27(9):1066-1069

Department of Epidemiology, University of Michigan, Ann Arbor, MI.

Objective: The aim of the study was to examine changes in kidney function during the menopausal transition (MT) and associations with levels of sex hormones (follicle stimulating hormone [FSH], sex hormone binding globulin [SHBG], estradiol, and testosterone).

Methods: We used data from the Michigan site of Study of the Women's Health Across the Nation, a longitudinal study of the MT. For this analysis, we included women who had at least one creatinine measure before the final menstrual period (FMP) and at least one creatinine measure after the FMP (n = 101 women with 440 observations). To determine whether the declines in estimated glomerular filtration rate (eGFR) remained constant during the MT, we used local weighted regression curves to fit eGFR estimates. We examined the association between sex hormones and eGFR with longitudinal mixed models adjusting for baseline age, day of menstrual cycle, and time from FMP.

Results: At baseline, women had a mean age of 45.4 ± 2.5 years; 54% were African-American and 46% were white. Although eGFR declined significantly over time, declines were linear, consistent with declines in eGFR due to age alone rather than the MT. Total testosterone, estradiol, ratio of testosterone:estradiol, and free androgen index were not significantly associated with eGFR, whereas lower FSH (-0.039, 95% confidence interval [CI] -0.067 to -0.012) and higher SHBG (0.050, 95% CI 0.004-0.096) were associated with higher eGFR.

Conclusions: Kidney function declines during the MT. Although associated with levels of FSH and SHBG, the rate of decline in eGFR is consistent with what would be expected of age alone.
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http://dx.doi.org/10.1097/GME.0000000000001579DOI Listing
September 2020

Urinary metals and incident diabetes in midlife women: Study of Women's Health Across the Nation (SWAN).

BMJ Open Diabetes Res Care 2020 07;8(1)

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA

Introduction: Environmental exposure to metals may play a role in the pathogenesis of diabetes; however, evidence from human studies is limited. We prospectively evaluated the associations of 20 urinary metal concentrations and their mixtures with incident diabetes in the Study of Women's Health Across the Nation, a multisite, multiethnic cohort study of midlife women.

Research Design And Methods: The sample included 1237 white, black, Chinese and Japanese-American women, aged 45-56 years, free of diabetes at baseline (1999-2000) who were followed through 2016. Concentrations of 20 metals (arsenic, barium, beryllium, cadmium, cobalt, chromium, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, uranium, vanadium, tungsten and zinc) were measured in urine specimens at baseline. Incident diabetes was identified annually by fasting glucose ≥126 mg/dL, self-reported doctor-diagnosed diabetes, or self-reported use of antidiabetic medications. A non-parametric clustering method, k-means clustering, was used to identify subgroups with different exposure patterns to metal mixtures.

Results: After multivariable adjustment, the HR (95% CI) for diabetes associated with each doubling increase in urinary metal concentrations was 1.19 (1.10 to 1.30) for arsenic and 1.20 (1.05 to 1.37) for lead, in Cox proportional hazards models after controlling for multiple comparisons. A doubling in urinary excretion of zinc was associated with higher risk of diabetes (adjusted HR 1.31, 95% CI 1.11 to 1.53). Two distinct exposure patterns to metal mixtures-'high' versus 'low'-were identified. Participants assigned to the 'high' pattern had higher overall concentrations of all metals compared with those classified into the 'low' pattern. Adjusted HR for diabetes associated with 'high' pattern compared with 'low' was 1.42 (1.08 to 1.87).

Conclusions: Higher urinary concentrations of arsenic and lead, increased urinary excretion of zinc, as well as higher overall exposure to metal mixtures were associated with elevated risk of diabetes. Future studies should further investigate the underlying mechanisms.
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http://dx.doi.org/10.1136/bmjdrc-2020-001233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398092PMC
July 2020

Associations of Perfluoroalkyl Substances with Incident Natural Menopause: The Study of Women's Health Across the Nation.

J Clin Endocrinol Metab 2020 09;105(9)

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan.

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.
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http://dx.doi.org/10.1210/clinem/dgaa303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418447PMC
September 2020

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary.

Hum Reprod Update 2020 09;26(5):724-752

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are found widespread in drinking water, foods, food packaging materials and other consumer products. Several PFAS have been identified as endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormonal signalling. Experimental models and epidemiologic studies suggest that PFAS exposures target the ovary and represent major risks for women's health.

Objective And Rationale: This review summarises human population and toxicological studies on the association between PFAS exposure and ovarian function.

Search Methods: A comprehensive review was performed by searching PubMed. Search terms included an extensive list of PFAS and health terms ranging from general keywords (e.g. ovarian, reproductive, follicle, oocyte) to specific keywords (including menarche, menstrual cycle, menopause, primary ovarian insufficiency/premature ovarian failure, steroid hormones), based on the authors' knowledge of the topic and key terms.

Outcomes: Clinical evidence demonstrates the presence of PFAS in follicular fluid and their ability to pass through the blood-follicle barrier. Although some studies found no evidence associating PFAS exposure with disruption in ovarian function, numerous epidemiologic studies, mostly with cross-sectional study designs, have identified associations of higher PFAS exposure with later menarche, irregular menstrual cycles, longer cycle length, earlier age of menopause and reduced levels of oestrogens and androgens. Adverse effects of PFAS on ovarian folliculogenesis and steroidogenesis have been confirmed in experimental models. Based on laboratory research findings, PFAS could diminish ovarian reserve and reduce endogenous hormone synthesis through activating peroxisome proliferator-activated receptors, disrupting gap junction intercellular communication between oocyte and granulosa cells, inducing thyroid hormone deficiency, antagonising ovarian enzyme activities involved in ovarian steroidogenesis or inhibiting kisspeptin signalling in the hypothalamus.

Wider Implications: The published literature supports associations between PFAS exposure and adverse reproductive outcomes; however, the evidence remains insufficient to infer a causal relationship between PFAS exposure and ovarian disorders. Thus, more research is warranted. PFAS are of significant concern because these chemicals are ubiquitous and persistent in the environment and in humans. Moreover, susceptible groups, such as foetuses and pregnant women, may be exposed to harmful combinations of chemicals that include PFAS. However, the role environmental exposures play in reproductive disorders has received little attention by the medical community. To better understand the potential risk of PFAS on human ovarian function, additional experimental studies using PFAS doses equivalent to the exposure levels found in the general human population and mixtures of compounds are required. Prospective investigations in human populations are also warranted to ensure the temporality of PFAS exposure and health endpoints and to minimise the possibility of reverse causality.
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http://dx.doi.org/10.1093/humupd/dmaa018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456353PMC
September 2020

Antimullerian Hormone and Impending Menopause in Late Reproductive Age: The Study of Women's Health Across the Nation.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Obstetrics and Gynecology, University of Colorado Medical School, Aurora, Colorado.

Background: A test that helps predict the time to the final menstrual period (FMP) has been sought for many years.

Objective: To assess the ability of antimullerian hormone (AMH) measurements to predictions the time to FMP.

Design: Prospective longitudinal cohort study.

Setting: The Study of Women's Health Across the Nation.

Participants And Measurements: AMH and FSH were measured in 1537 pre- or early perimenopausal women, mean age 47.5 ± 2.6 years at baseline, then serially until 12 months of amenorrhea occurred. AMH was measured using a 2-site ELISA with a detection limit of 1.85 pg/mL.

Main Outcome Measure: Areas under the receiver operating curves (AUC) for AMH-based and FSH-based predictions of time to FMP, stratified by age. Probabilities that women would undergo their FMP in the next 12, 24, or 36 months across a range of AMH values were assessed.

Results: AUCs for predicting that the FMP will occur within the next 24 months were significantly greater for AMH-based than FSH-based models. The probability that a woman with an AMH <10 pg/mL would undergo her FMP within the next 12 months ranged from 51% at h<48 years of age to 79% at ≥51 years. The probability that a woman with an AMH >100 pg/mL would not undergo her FMP within the next 12 months ranged from 97% in women <48 years old to 90% in women ≥51 years old.

Conclusions: AMH measurement helps estimate when a woman will undergo her FMP, and, in general, does so better than FSH.
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http://dx.doi.org/10.1210/clinem/dgz283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067546PMC
April 2020

Longitudinal trends in perfluoroalkyl and polyfluoroalkyl substances among multiethnic midlife women from 1999 to 2011: The Study of Women's Health Across the Nation.

Environ Int 2020 02 13;135:105381. Epub 2019 Dec 13.

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, United States. Electronic address:

Background: Limited information exists regarding longitudinal trends in midlife women's exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS). Further, little is known about how patterns of exposure differ by race/ethnicity and reproductive characteristics including parity and menopause.

Objective: We aimed to examine temporal variations in serum PFAS concentrations among midlife women from the Study of Women's Health Across the Nation.

Methods: Serum concentrations of 11 PFAS homologues were measured in 75 White, Black and Chinese women with blood samples collected in 1999-2000, 2002-2003, 2005-2006, and 2009-2011. Rates of changes in PFAS concentrations were calculated assuming a first-order elimination model. Associations between PFAS concentrations and race/ethnicity, menstruation and parity were evaluated with linear mixed models, adjusting for age, body mass index and study site.

Results: Serum concentrations of linear-chain perfluorooctanoic acid (n-PFOA), linear- and branched-chain perfluorooctane sulfonic acid (n-PFOS and sm-PFOS) decreased significantly (-6.0%, 95% CI: -8.3%, -3.6% per year for n-PFOA; -14.8%, 95% CI: -17.3%, -12.3% per year for n-PFOS; -16.9%, 95% CI: -19.1%, -14.6% per year for sm-PFOS); whereas perfluorononanoic acid (PFNA) increased (16.0%, 95% CI: 10.6%, 21.6% per year). Detection rates of perfluorodecanoic acid (PFDeA) and perfluoroundecanoic acid (PFUA) doubled. Temporal trends varied significantly by race/ethnicity. Chinese women tended to have consistently higher PFNA concentrations at each follow-up visit, compared with White and Black women. Serum PFHxS concentrations significantly decreased in White and Black women, but not in Chinese. Menstruating women consistently had lower concentrations. Parity was associated with lower concentrations at baseline but the differences between nulliparous and parous women became smaller over time.

Conclusions: Our results suggest longitudinal declines in serum concentrations of legacy PFAS and increases in serum concentrations of emerging compounds from 1999 to 2011 in midlife women. Temporal trends in PFAS concentrations are not uniform across race/ethnicity and parity groups.
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http://dx.doi.org/10.1016/j.envint.2019.105381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374929PMC
February 2020

Does midlife aging impact women's sleep duration, continuity, and timing?: A longitudinal analysis from the Study of Women's Health Across the Nation.

Sleep 2020 04;43(4)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.

Our study objectives were to evaluate the age-related changes in actigraphy measures of sleep duration, continuity, and timing across 12 years in midlife women as they traversed the menopause, and to take into account factors affecting women's sleep that also change with age. Black, white, and Chinese women were recruited from the Study of Women's Health Across the Nation (SWAN) to participate in an ancillary sleep study on two occasions over 3 years apart and a third assessment 12 years after the first (N = 300, mean ages, 52, 55, and 64 at the three assessments). Women had at least four consecutive nights of actigraphy (95% with 7 nights) and sleep diaries, and self-reported sleep complaints measured at each time point. Partial correlations adjusted for time between assessments across the 12 years were significant and moderate in size (r's = .33-.58). PROC MIXED/GLIMMIX multivariate models showed that sleep duration increased over time; wake after sleep onset (WASO) declined, midpoint of sleep interval increased, and sleep latency and number of sleep complaints did not change between the first and third assessments. Blacks and whites had a greater increase in sleep duration than Chinese. Taken together, the results of this longitudinal study suggest that sleep may not worsen, in general, in midlife women. Perhaps, the expected negative effect of aging in midlife into early old age on sleep is overstated.
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http://dx.doi.org/10.1093/sleep/zsz259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157190PMC
April 2020

Monthly variation of hot flashes, night sweats, and trouble sleeping: effect of season and proximity to the final menstrual period (FMP) in the SWAN Menstrual Calendar substudy.

Menopause 2020 01;27(1):5-13

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.

Objective: Although reproductive function is influenced by season, few studies have evaluated seasonal effects on menopausal symptoms. We assessed the impact of season and proximity to the final menstrual period (FMP) on frequency of symptom reporting.

Methods: In all, 955 participants in the Study of Women's Health Across the Nation recorded whether or not they had experienced menopausal symptoms on a monthly menstrual calendar over a 10-year period. We modeled the log-odds of presence of a given symptom each month using a logistic mixed-effects model, assuming a third-order polynomial before the FMP and a different third-order polynomial after the FMP. We assumed sine and cosine functions for month of the year.

Results: Five to 10 years before the FMP, ∼20% of women reported hot flashes and night sweats, whereas ∼40% reported trouble sleeping. Prevalence rose ∼4 years before the FMP with a sharp jump in hot flash (∼60%) and night sweats (∼40%) prevalence coincident with the FMP. Peaks in hot flashes and trouble sleeping were observed in July with troughs in January. The peak and trough in night sweats occurred about 1 month earlier. Odds of hot flashes, night sweats, and trouble sleeping were 66%, 50%, and 24% greater, respectively, at the seasonal peak versus the seasonal minimum.

Conclusion: Menopausal symptoms exhibit seasonal variation associated with the summer and winter equinoxes. Seasonal increases in night sweats precede increases in hot flashes. Prospectively recorded monthly symptom data demonstrate that hot flashes and night sweats increase notably coincident with the FMP. : Video Summary:http://links.lww.com/MENO/A476.
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http://dx.doi.org/10.1097/GME.0000000000001420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934911PMC
January 2020

Prescription Opioid Use in Patients With and Without Systemic Lupus Erythematosus - Michigan Lupus Epidemiology and Surveillance Program, 2014-2015.

MMWR Morb Mortal Wkly Rep 2019 Sep 27;68(38):819-824. Epub 2019 Sep 27.

Rheumatic diseases are a leading cause of chronic, noncancer pain. Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease characterized by periodic flares that can result in irreversible target organ damage, including end-stage renal disease. Both intermittent and chronic musculoskeletal pain, as well as fibromyalgia (considered a centralized pain disorder due to dysregulation of pain processing in the central nervous system), are common in SLE. Opioids are generally not indicated for long-term management of musculoskeletal pain or centralized pain (fibromyalgia) because of lack of efficacy, safety issues ranging from adverse medical effects to overdose, and risk for addiction (1,2). In this study of 462 patients with SLE from the population-based Michigan Lupus Epidemiology and Surveillance (MILES) Cohort and 192 frequency-matched persons without SLE, nearly one third (31%) of SLE patients were using prescription opioids during the study period (2014-2015), compared with 8% of persons without SLE (p<0.001). Among the SLE patients using opioids, 97 (68%) were using them for >1 year, and 31 (22%) were concomitantly on two or more opioid medications. Among SLE patients, those using the emergency department (ED) were approximately twice as likely to use prescription opioids (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3-3.6; p = 0.004). In SLE, the combined contributions of underlying disease and adverse effects of immunosuppressive and glucocorticoid therapies already put patients at higher risk for some known adverse effects attributed to long-term opioid use. Addressing the widespread and long-term use of opioid therapy in SLE will require strategies aimed at preventing opioid initiation, tapering and discontinuation of opioids among patients who are not achieving treatment goals of reduced pain and increased function, and consideration of nonopioid pain management strategies.
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http://dx.doi.org/10.15585/mmwr.mm6838a2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762189PMC
September 2019

The association between perceived discrimination in midlife and peripheral neuropathy in a population-based cohort of women: the Study of Women's Health Across the Nation.

Ann Epidemiol 2019 09 27;37:10-16. Epub 2019 Jul 27.

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor. Electronic address:

Purpose: Peripheral neuropathy (PN) is a highly prevalent condition with serious sequelae. Many studies of the condition have been restricted to populations with diabetes, limiting evidence of potential contributing risk factors including salient psychosocial risk factors such as discrimination.

Methods: The longitudinal Study of Women's Health Across the Nation was used to assess the relationship between perceived discrimination and prevalent PN in 1718 ethnically diverse midlife women. We used multivariable logistic regression to determine the association between perceived discrimination (Detroit Area Study Everyday Discrimination Scale) and PN (symptom questionnaire and monofilament testing) and conducted an assessment of the mediating effects of body mass index (BMI).

Results: The prevalence of PN was 26.1% in the total sample and 40.9% among women with diabetes. Women who reported perceived discrimination had 29% higher odds of PN compared with women who did not report perceived discrimination (95% confidence interval, 1.01-1.66). Approximately 30% of the total effect of discrimination on PN was mediated indirectly by BMI.

Conclusions: More research is needed to determine the contributing factors to nondiabetic PN. Our findings reaffirm the impact of financial strain, BMI, and diabetes as significant correlates of PN and highlight discrimination as an important risk factor.
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http://dx.doi.org/10.1016/j.annepidem.2019.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755046PMC
September 2019

Gender differences in the association of living and working conditions and the mental health of trafficking survivors.

Int J Public Health 2019 Sep 26;64(7):1015-1024. Epub 2019 Jun 26.

Department of Global Health and Development, Gender Violence and Health Centre, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, WC1H 9SH, London, UK.

Objectives: To assess the association of living and working conditions experienced during trafficking with mental health of female and male survivors.

Methods: We analyzed a cross-sectional study of 1015 survivors who received post-trafficking services in Cambodia, Thailand, and Vietnam. Modified Poisson regression models were conducted by gender to estimate prevalence ratios.

Results: For females, the elevated prevalence of anxiety, depression, and post-traumatic stress disorder (PTSD) symptoms was associated with adverse living conditions, while for males the prevalence of anxiety (PR = 2.21; 95% CI 1.24-3.96) and depression (PR = 2.63; 95% CI 1.62-4.26) more than doubled and almost tripled for PTSD (PR = 2.93; 95% CI 1.65-5.19) after adjustment. For males in particular, excessive and extreme working hours per day were associated with more than a four- and threefold greater prevalence of PTSD. Being in a detention center or jail was associated with all three mental health outcomes in males.

Conclusions: Providers and stakeholders need to consider the complex mental health trauma of the differential effects of living and working conditions for female and male survivors during trafficking to support treatment and recovery.
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http://dx.doi.org/10.1007/s00038-019-01269-2DOI Listing
September 2019

Determinants of per- and polyfluoroalkyl substances (PFAS) in midlife women: Evidence of racial/ethnic and geographic differences in PFAS exposure.

Environ Res 2019 08 18;175:186-199. Epub 2019 May 18.

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States.

Background: Per- and poly-fluoroalkyl substances (PFAS) are public health concerns because of widespread exposure through contaminated foods/drinking water. Although some determinants of PFAS exposure have been suggested, the role of geographic location and race/ethnicity in PFAS exposure has not been well characterized.

Objectives: We examined potential determinants of PFAS from the Study of Women's Health Across the Nation (SWAN).

Methods: This study includes 1302 women aged 45-56 years from 5 SWAN sites where white women and women from one minority group were recruited (black from Southeast Michigan, Pittsburgh, Boston; Chinese from Oakland; Japanese from Los Angeles). We determined concentrations of 11 PFAS in serum samples collected in 1999-2000 and examined 7 PFAS detected in most women (>97%). Linear regression with backward elimination was used to identify important determinants of PFAS serum concentrations among a set of pre-specified variables (age, body mass index, site, race/ethnicity, education, financial hardship, occupation, born outside the United States (US), parity, menstrual bleeding within the past year, smoking status, alcohol consumption, and consumption of fish, dairy, pizza, salty snack, and French fries).

Results: Site and race/ethnicity were two major determinants of PFAS. White women had higher concentrations of linear perfluorooctanoic acid (PFOA) compared with the Chinese in Oakland (p < 0.0001) and blacks in Pittsburgh (p = 0.048). Black women in Southeast Michigan and Boston (vs. white women) had higher concentrations of linear (p < 0.001 for Southeast Michigan; p < 0.0001 for Boston) and total perfluorooctane sulfonic acid (PFOS) (p < 0.001 for both Southeast Michigan and Boston) and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (p = 0.02 for Southeast Michigan; p < 0.001 for Boston). Chinese (Oakland) and Japanese (Los Angeles) women had higher concentrations of perfluorononanoic acid (PFNA) compared with white women in each site (p < 0.01 for both). Within white women, those in Pittsburgh had relatively higher concentrations of PFAS. Within Chinese and Japanese women, those who were born outside the US had significantly lower concentrations of most PFAS but significantly higher PFNA concentrations. Menstrual bleeding and parity were significantly associated with lower PFAS concentrations. Higher intake of salty snacks including popcorn was significantly associated with higher concentrations of linear PFOA, PFOS and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid.

Discussion: Geographic locations and race/ethnicity play an important role in differential exposure to PFAS, with racial/ethnic burdens differing between PFOS, PFOA and PFNA. Menstruation and parity were also determinants of PFAS concentrations possibly as an elimination route.
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http://dx.doi.org/10.1016/j.envres.2019.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579633PMC
August 2019

Urinary metals and metal mixtures in midlife women: The Study of Women's Health Across the Nation (SWAN).

Int J Hyg Environ Health 2019 06 15;222(5):778-789. Epub 2019 May 15.

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Background: Little is known about the extent of exposure to metals and metal mixtures among midlife women.

Objectives: We assessed exposure to multiple metals in the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-racial/ethnic cohort of women at midlife.

Methods: We measured urinary concentrations of 21 metals (arsenic, barium, beryllium, cadmium, cobalt, chromium, cesium, copper, mercury, manganese, molybdenum, nickel, lead, platinum, antimony, tin, thallium, uranium, vanadium, tungsten and zinc) using high-resolution inductively coupled plasma-mass spectrometry among 1335 white, black, Chinese and Japanese women aged 45-56 years at the third SWAN annual visit (1999-2000). Least squared geometric mean concentrations were compared across race/ethnicity, education, financial hardship, smoking, secondhand smoking, seafood intake and rice intake groups. Overall exposure patterns of multiple metals were derived using k-means clustering method.

Results: The percentage of women with detectable concentrations of metals ranged from 100% for arsenic, cesium, molybdenum and zinc, to less than 5% for platinum; 15 metals had detection rates of 70% or more. Asian women, both Chinese and Japanese, had higher urinary concentrations of arsenic, cadmium, copper, mercury, molybdenum, lead and thallium, compared with other race/ethnic groups, independent of sociodemographic, lifestyle, dietary, and geographic characteristics. Seafood and rice intake were important determinants of urinary arsenic, cesium, mercury, molybdenum and lead levels. Two distinct overall exposure patterns- "high" vs. "low" -- were identified. Women in the "high" overall exposure pattern were more likely to be Asians, current smokers, and to report high consumption of seafood and rice. Black women were less likely to have the high exposure pattern.

Conclusions: Metal exposure of midlife women differs by racial/ethnic, sociodemographic, lifestyle, dietary, and geographic characteristics. Asian women may be experiencing the highest exposures to multiple metals compared with other racial/ethnic groups in the United States.
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http://dx.doi.org/10.1016/j.ijheh.2019.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583796PMC
June 2019

Dietary Omega Polyunsaturated Fatty Acid Intake and Patient-Reported Outcomes in Systemic Lupus Erythematosus: The Michigan Lupus Epidemiology and Surveillance Program.

Arthritis Care Res (Hoboken) 2020 07;72(7):874-881

University of Michigan, Ann Arbor.

Objective: To examine associations between dietary intake of omega-3 (n-3; generally antiinflammatory) and omega-6 (n-6; generally proinflammatory) fatty acids and patient-reported outcomes in systemic lupus erythematosus (SLE).

Methods: This study was based on the population-based Michigan Lupus Epidemiology and Surveillance cohort. Estimates of n-3 and n-6 intake were derived from Diet History Questionnaire II items (past year with portion size version). Patient-reported outcomes included self-reported lupus activity (Systemic Lupus Activity Questionnaire [SLAQ]). Multivariable regression, adjusted for age, sex, race, and body mass index, was used to assess associations between absolute intake of n-3 and n-6, as well as the n-6:n-3 ratio, and patient-reported outcomes.

Results: Among 456 SLE cases, 425 (93.2%) were female, 207 (45.4%) were African American, and the mean ± SD age was 52.9 ± 12.3 years. Controlling for potential confounders, the average SLAQ score was significantly higher by 0.3 points (95% confidence interval [95% CI] 0.1, 0.6; P = 0.013) with each unit increase of the n-6:n-3 ratio. Both lupus activity and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance scores were lower with each 1-gram/1,000 kcal increase of n-3 fatty acids (SLAQ regression coefficient β = -0.8 [95% CI -1.6, 0.0]; P = 0.055; PROMIS sleep β = -1.1 [95% CI -2.0, -0.2]; P = 0.017). Higher n-3 intakes were nonsignificantly associated with lower levels of depressive symptoms and comorbid fibromyalgia, and with higher quality of life, whereas results for the n6:n3 ratio trended in the opposite direction.

Conclusion: This population-based study suggests that higher dietary intake of n-3 fatty acids and lower n-6:n-3 ratios are favorably associated with patient-reported outcomes in SLE, particularly self-reported lupus activity and sleep quality.
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http://dx.doi.org/10.1002/acr.23925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842394PMC
July 2020

Serum Sex Hormones and the Risk of Fracture Across the Menopausal Transition: Study of Women's Health Across the Nation.

J Clin Endocrinol Metab 2019 06;104(6):2412-2418

University of California, Los Angeles, Los Angeles, California.

Context: Sex steroid hormones have been linked to fractures in older women.

Objective: To test the hypothesis that hormones measured over the menopausal transition predict fractures.

Setting: Seven US clinical centers.

Subjects And Measurements: Two thousand nine hundred sixty women (average age, 46.4 ± 2.7 years) who had at least two repeat hormone measures and prospective information on fractures. Fasting serum was collected annually for hormone assays. Estradiol (E2) was measured with a modified direct immunoassay. FSH and SHBG were measured with two-site chemiluminescence immunoassays. Hormones were lagged (visit year -1) and transformed using log base 2. Incident fractures were ascertained at each annual visit. All medications including hormone therapy were time varying covariates. Discrete survival methods were used.

Results: Five hundred eight (17.2%) women experienced an incident fracture over an average follow up of 8.8 ± 4.4 years. Women who experienced an incident fracture were more likely to be white, report high alcohol intake and diabetes, and less likely to report premenopausal status at baseline. A woman whose log E2 was twice that of another had a 10% lower risk of fracture independent of covariates, relative risk (95% CI) = 0.90 (0.82, 0.98). Neither FSH nor SHBG were associated with fractures.

Conclusions: Serum E2 levels may help to identify women at higher risk of fractures over the menopausal transition. However, hormone assays must be standardized across laboratories for clinical implementation and further work is needed to define E2 thresholds.
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http://dx.doi.org/10.1210/jc.2018-02047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505454PMC
June 2019

Mental health, violence and psychological coercion among female and male trafficking survivors in the greater Mekong sub-region: a cross-sectional study.

BMC Psychol 2018 Dec 12;6(1):56. Epub 2018 Dec 12.

Gender Violence and Health Centre, Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK.

Background: Human trafficking is a pervasive global crime with important public health implications that entail fundamental human rights violations in the form of severe exploitation, violence and coercion. Sex-specific associations between types of violence or coercion and mental illness in survivors of trafficking have not been established.

Methods: We conducted a cross-sectional study with 1015 female and male survivors of trafficking (adults, adolescents and children) who received post-trafficking assistance services in Cambodia, Thailand or Vietnam and had been exploited in various labor sectors. We assessed anxiety and depression with the Hopkins Symptoms Checklist (HSCL-25) and post-traumatic stress disorder (PTSD) symptoms with the Harvard Trauma Questionnaire (HTQ), and used validated questions from the World Health Organization International Study on Women's Health and Domestic Violence to measure physical and sexual violence. Sex-specific modified Poisson regression models were estimated to obtain prevalence ratios (PRs) and their 95% confidence intervals (CI) for the association between violence (sexual, physical or both), coercion, and mental health conditions (anxiety, depression and PTSD).

Results: Adjusted models indicated that for females, experiencing both physical and sexual violence, compared to not being exposed to violence, was a strong predictor of symptoms of anxiety (PR = 2.08; 95% CI: 1.64-2.64), PTSD (PR = 1.55; 95% CI: 1.37-1.74), and depression (PR = 1.57; 95% CI: 1.33-1.85). Among males, experiencing physical violence with additional threats made with weapons, compared to not being exposed to violence, was associated with PTSD (PR = 1.59; 95% CI: 1.05-2.42) after adjustment. Coercion during the trafficking experience was strongly associated with anxiety, depression, and PTSD in both females and males. For females in particular, exposure to both personal and family threats was associated with a 96% elevated prevalence of PTSD (PR = 1.96; 95% CI: 1.32-2.91) and more than doubling of the prevalence of anxiety (PR = 2.11; 95% CI: 1.57-2.83).

Conclusions: The experiences of violence and coercion in female and male trafficking survivors differed and were associated with an elevated prevalence of anxiety, depression, and PTSD in both females and males. Mental health services must be an integral part of service provision, recovery and re-integration for trafficked females and males.
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http://dx.doi.org/10.1186/s40359-018-0269-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292017PMC
December 2018

Age at Onset of Metabolic Syndrome Among Women With and Without Polycystic Ovary Syndrome-Like Status.

J Clin Endocrinol Metab 2019 05;104(5):1429-1439

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan.

Context: Women with polycystic ovary syndrome (PCOS) have a higher prevalence of metabolic syndrome (MetS), but whether they develop MetS earlier than women without PCOS is unknown. Understanding the impact of PCOS on the timing of MetS onset is important for screening and clinical care in this population.

Design: Women with PCOS-like status (PCOSp) were identified from participants of the Michigan Bone Health and Metabolism Study based upon history of irregular menstrual cycles, high free-androgen index, and high levels of antimüllerian hormone. MetS was defined according to the Adult Treatment Panel III criteria. Age at MetS onset was compared between women with and without PCOSp using an accelerated failure time model adjusted for baseline education, lifestyle factors, and midlife body weight.

Results: Among the 496 women in the analysis, 11.7% (n = 58) were determined to have PCOSp. Over a mean follow-up of 11 years, 20 women with PCOSp and 136 women without PCOSp developed MetS. After adjusting for smoking, education, and physical activity, women with PCOSp developed MetS at an age 14.4% (95% CI -22.7, -5.2) younger than women without PCOSp. The magnitude of the association was attenuated to 5.4% in models additionally adjusted for body mass index (95% CI -12.4, 2.1). Because a typical study participant without PCOSp developed MetS at 51.5 years old, 5.4% translates to almost 3 years earlier onset of MetS for a comparable woman with PCOSp.

Conclusions: Women with PCOSp develop MetS at a younger age. Earlier screening for MetS in women with PCOS may be warranted.
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http://dx.doi.org/10.1210/jc.2018-01428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435100PMC
May 2019

Healthy Lifestyle During the Midlife Is Prospectively Associated With Less Subclinical Carotid Atherosclerosis: The Study of Women's Health Across the Nation.

J Am Heart Assoc 2018 12;7(23):e010405

1 Department of Epidemiology University of Michigan Ann Arbor MI.

Background Measures of subclinical atherosclerosis are predictors of future cardiovascular outcomes as well as of physical and cognitive functioning. The menopausal transition is associated with accelerated progression of atherosclerosis in women. The prospective association between a healthy lifestyle during the midlife and subclinical atherosclerosis is unclear. Methods and Results Self-reported data on smoking, diet, and physical activity from 1143 women in the Study of Women's Health Across the Nation were used to construct a 10-year average Healthy Lifestyle Score ( HLS ) during the midlife. Markers of subclinical atherosclerosis were measured 14 years after baseline and included common carotid artery intima-media thickness ( CCA - IMT ), adventitial diameter ( CCA - AD ), and carotid plaque. The associations of average HLS with CCA - IMT and CCA - AD were estimated using linear models; the association of average HLS with carotid plaque was estimated using cumulative logit models. Average HLS was associated with smaller CCA - IMT and CCA - AD in the fully adjusted models ( P=0.0031 and <0.001, respectively). Compared with participants in the lowest HLS level, those in the highest level had 0.024 mm smaller CCA - IMT (95% confidence interval: -0.048, 0.000), which equals 17% of the SD of CCA - IMT , and 0.16 mm smaller CCA - AD (95% confidence interval: -0.27, -0.04), which equals 24% of the SD of CCA - AD . Among the 3 components of the HLS , abstinence from smoking had the strongest association with subclinical atherosclerosis. Conclusions Healthy lifestyle during the menopausal transition is associated with less subclinical atherosclerosis, highlighting the growing recognition that the midlife is a critical window for cardiovascular prevention in women.
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http://dx.doi.org/10.1161/JAHA.118.010405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405552PMC
December 2018

Menstrual Cycle Changes as Women Approach the Final Menses: What Matters?

Authors:
Siobán D Harlow

Obstet Gynecol Clin North Am 2018 Dec 25;45(4):599-611. Epub 2018 Oct 25.

Department of Epidemiology, School of Public Health of the University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA. Electronic address:

Increased variability in menstrual cycle length marks the onset of the menopausal transition, with the likelihood of long cycles increasing as women approach menopause. This article describes the STRAW+10 bleeding criteria for recognizing onset of the early and late menopausal transition, as well as the specific bleeding changes a woman may experience during this life stage, including how women's bleeding experiences differ. The high probability of episodes of excessive and prolonged bleeding as women approach their final menstrual period is documented, as is the continuing probability of ovulation as women reach their final menstrual period.
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http://dx.doi.org/10.1016/j.ogc.2018.07.003DOI Listing
December 2018

Environmental Exposure History and Vulvodynia Risk: A Population-Based Study.

J Womens Health (Larchmt) 2019 01 10;28(1):69-76. Epub 2018 Oct 10.

3 Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan.

Background: Risk factors for vulvodynia continue to be elusive. We evaluated the association between past environmental exposures and the presence of vulvodynia.

Materials And Methods: The history of 28 lifetime environmental exposures was queried in the longitudinal population-based Woman-to-Woman Health Study on the 24-month follow-up survey. Relationships between these and vulvodynia case status were assessed using multinomial logistic regression.

Results: Overall, 1585 women completed the 24-month survey, the required covariate responses, and questions required for case status assessment. Screening positive as a vulvodynia case was associated with history of exposures to home-sprayed chemicals (insecticides, fungicides, herbicides-odds ratio [OR] 2.47, 95% confidence interval [CI] 1.71-3.58, p < 0.0001), home rodent poison and mothballs (OR 1.62, 95% CI 1.25-2.09, p < 0.001), working with solvents and paints (OR 2.49, 95% CI 1.68-3.70, p < 0.0001), working as a housekeeper/maid (OR 2.07, 95% CI 1.42-3.00, p < 0.0001), working as a manicurist/hairdresser (OR 2.00, 95% CI 1.14-3.53, p < 0.05), and working at a dry cleaning facility (OR 2.13, 95% CI 1.08-4.19, p < 0.05). When classified into nine individual environmental exposure categories and all included in the same model, significant associations remained for four categories (home-sprayed chemicals, home rodent poison or mothballs, paints and solvents, and working as a housekeeper).

Conclusions: This preliminary evaluation suggests a positive association between vulvodynia and the reported history of exposures to a number of household and work-related environmental toxins. Further investigation of timing and dose of environmental exposures, relationship to clinical course, and treatment outcomes is warranted.
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http://dx.doi.org/10.1089/jwh.2018.7188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343193PMC
January 2019

Perceived stress across the midlife: longitudinal changes among a diverse sample of women, the Study of Women's health Across the Nation (SWAN).

Womens Midlife Health 2018 16;4. Epub 2018 Mar 16.

Department of Epidemiology, School of Public Health, University of Michigan, 6610B SPH I, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA.

Background: In women, midlife is a period of social and physiological change. Ostensibly stressful, cross-sectional studies suggest women experience decreasing stress perceptions and increasing positive outlook during this life stage. The aim of this paper was to describe the longitudinal changes in perceived stress as women transitioned through the midlife.

Methods: Premenopausal women ( = 3044) ages 42-52 years at baseline, were recruited from seven sites in the Study of Women's Health Across the Nation, and followed approximately annually over 13 visits with assessment of perceived stress and change in menopausal status. Longitudinal regression models were used to assess the effects of age, menopausal status and baseline sociodemographic variables on the trajectory of perceived stress over time.

Results: At baseline, mean age was 46.4 ± 2.7 years; participants were white (47%), black (29%), Hispanic (7%), Japanese (9%), or Chinese (8%). Hispanic women, women with lesser educational attainment, and women reporting financial hardship were each more likely to report high perceived stress levels at baseline (all < 0.0001). After adjustment for baseline sociodemographic factors, perceived stress decreased over time for most women ( < 0.0001), but increased for both Hispanic and white participants at the New Jersey site ( < 0.0001). Changing menopausal status was not a significant predictor of perceived stress.

Conclusions: Self-reported stress decreased for most women as they transitioned across the midlife; changing menopausal status did not play a significant role after adjustment for age and sociodemographic factors. Future studies should explore the stress experience for women by racial/ethnic identity and demographics.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027744PMC
http://dx.doi.org/10.1186/s40695-018-0032-3DOI Listing
March 2018

Factors associated with developing vaginal dryness symptoms in women transitioning through menopause: a longitudinal study.

Menopause 2018 10;25(10):1094-1104

School of Medicine, University of California Davis, Sacramento, CA.

Objective: To 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.

Methods: We 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.

Results: The 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.

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.
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http://dx.doi.org/10.1097/GME.0000000000001130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136974PMC
October 2018

Psychosocial and health-related risk factors for depressive symptom trajectories among midlife women over 15 years: Study of Women's Health Across the Nation (SWAN).

Psychol Med 2019 01 6;49(2):250-259. Epub 2018 Apr 6.

Department of Epidemiology, Graduate School of Public Health,University of Pittsburgh, Pittsburgh, PA,USA.

Background: Psychosocial and health-related risk factors for depressive symptoms are known. It is unclear if these are associated with depressive symptom patterns over time. We identified trajectories of depressive symptoms and their risk factors among midlife women followed over 15 years.

Methods: Participants were 3300 multiracial/ethnic women enrolled in a multisite longitudinal menopause and aging study, Study of Women's Health Across the Nation. Biological, psychosocial, and depressive symptom data were collected approximately annually. Group-based trajectory modeling identified women with similar longitudinal patterns of depressive symptoms. Trajectory groups were compared on time-invariant and varying characteristics using multivariable multinomial analyses and pairwise comparisons.

Results: Five symptom trajectories were compared (50% very low; 29% low; 5% increasing; 11% decreasing; 5% high). Relative to whites, blacks were less likely to be in the increasing trajectory and more likely to be in the decreasing symptom trajectory and Hispanics were more likely to have a high symptom trajectory than an increasing trajectory. Psychosocial/health factors varied between groups. A rise in sleep problems was associated with higher odds of having an increasing trajectory and a rise in social support was associated with lower odds. Women with low role functioning for 50% or more visits had three times the odds of being in the increasing symptom group.

Conclusions: Changes in psychosocial and health characteristics were related to changing depressive symptom trajectories. Health care providers need to evaluate women's sleep quality, social support, life events, and role functioning repeatedly during midlife to monitor changes in these and depressive symptoms.
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http://dx.doi.org/10.1017/S0033291718000703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545593PMC
January 2019

Disproportionate Sterilization of Latinos Under California's Eugenic Sterilization Program, 1920-1945.

Am J Public Health 2018 05 22;108(5):611-613. Epub 2018 Mar 22.

Nicole L. Novak is with the Population Studies Center, Institute for Social Research, University of Michigan, Ann Arbor. Natalie Lira is with the Department of Latina/Latino Studies, University of Illinois at Urbana-Champaign. Kate E. O'Connor and Alexandra Minna Stern are with the Department of American Culture, University of Michigan. Siobán D. Harlow and Sharon L. R. Kardia are with the Department of Epidemiology, School of Public Health, University of Michigan.

Objectives: To compare population-based sterilization rates between Latinas/os and non-Latinas/os sterilized under California's eugenics law.

Methods: We used data from 17 362 forms recommending institutionalized patients for sterilization between 1920 and 1945. We abstracted patient gender, age, and institution of residence into a data set. We extracted data on institution populations from US Census microdata from 1920, 1930, and 1940 and interpolated between census years. We used Spanish surnames to identify Latinas/os in the absence of data on race/ethnicity. We used Poisson regression with a random effect for each patient's institution of residence to estimate incidence rate ratios (IRRs) and compare sterilization rates between Latinas/os and non-Latinas/os, stratifying on gender and adjusting for differences in age and year of sterilization.

Results: Latino men were more likely to be sterilized than were non-Latino men (IRR = 1.23; 95% confidence interval [CI] = 1.15, 1.31), and Latina women experienced an even more disproportionate risk of sterilization relative to non-Latinas (IRR = 1.59; 95% CI = 1.48, 1.70).

Conclusions: Eugenic sterilization laws were disproportionately applied to Latina/o patients, particularly Latina women and girls. Understanding historical injustices in public health can inform contemporary public health practice.
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http://dx.doi.org/10.2105/AJPH.2018.304369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888070PMC
May 2018

Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition.

Womens Midlife Health 2017 17;3. Epub 2017 Oct 17.

Department of Obstetrics & Gynecology, University of Michigan, Ann Arbor, MI, USA.

Background: Previous reports have noted that dehydroepiandrosterone-sulfate (DHEAS) increases prior to the final menstrual period (FMP) and remains stable beyond the FMP. How DHEAS concentrations correspond with other sex hormones across the menopausal transition (MT) including androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) is not known. Our objective was to examine how DHEAS, A4, T, E1, and E2 changed across the MT by White vs. African-American (AA) race/ethnicity.

Methods: We conducted a longitudinal observational analysis of a subgroup of women from the Study of Women's Health Across the Nation observed over 4 visits prior to and 4 visits after the FMP ( = 110 women over 9 years for 990 observations). The main outcome measures were DHEAS, A4, T, E1, and E2.

Results: Compared to the decline in E2 concentrations, androgen concentrations declined minimally over the MT. T (β 9.180, p < 0.0001) and E1 (β 11.365, p < 0.0001) were higher in Whites than in AAs, while elevations in DHEAS (β 28.80, = 0.061) and A4 (β 0.2556, = 0.052) were borderline. Log-transformed E2 was similar between Whites and AAs (β 0.0764, = 0.272). Body mass index (BMI) was not significantly associated with concentrations of androgens or E1 over time.

Conclusion: This report suggests that the declines in E2 during the 4 years before and after the FMP are accompanied by minimal changes in DHEAS, A4, T, and E1. There are modest differences between Whites and AAs and minimal differences by BMI.
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http://dx.doi.org/10.1186/s40695-017-0028-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761074PMC
October 2017