Does everyday discrimination account for the increased risk of vasomotor symptoms in Black women?: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVES: Vasomotor symptoms (VMS), including hot flashes and night sweats, are hallmark symptoms of the menopause transition. Previous research has documented greater frequency, duration, and severity of VMS in Black women compared with women from other racial/ethnic groups, even after accounting for other factors. This analysis examined the association between discrimination and VMS and the extent to which discrimination accounts for the disproportionate burden of VMS in Black women. METHODS: Using available discrimination and VMS data from the SWAN cohort study (n = 2,377, 48% White, 32% Black, 6% Japanese, 4% Chinese, and 9% Hispanic women) followed approximately yearly in midlife from premenopause (42-52 y) through postmenopause (~20 y), we assessed concurrent associations between discrimination and VMS frequency in the past 2 weeks using weighted generalized mixed models. We also assessed associations between chronic discrimination across first four visits and VMS trajectories from premenopause to postmenopause using weighted multinomial logistic regression. Models were adjusted for known risk factors for VMS. RESULTS: Higher levels of discrimination were associated with concurrent reporting of any (odds ratio [OR], 1.57 [1.31-1.89]) and frequent (≥6 d) VMS (OR, 1.55 [1.21-1.99]). After adjustment, associations remained significant for any (OR, 1.30 [1.09-1.54]) but not frequent VMS. For any VMS trajectories, chronic discrimination was associated with "continuously high" (OR, 1.69 [1.03-2.77]) and "high pre-FMP-decline post-FMP" (OR, 1.70 [1.01-2.88]) versus "FMP-onset low" trajectories. After adjusting for discrimination, odds of reporting any, frequent, and of being in the "continuously high" any VMS trajectory remained elevated for Black versus White women. CONCLUSIONS: Discrimination is associated with greater concurrent risk of any (but not frequent) VMS, and chronic discrimination is associated with a continuously high reporting of any VMS over time, independent of known risk factors. Adjusting for discrimination attenuates but does not eliminate the increased risk of VMS for Black women.

Hypertension, Cardiovascular Risk Factors, and Uterine Fibroid Diagnosis in Midlife.

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

Race/Ethnicity and Incidence of Pelvic Organ Prolapse in Midlife Women: The Study of Women's Health Across the Nation.

Background: Pelvic organ prolapse (POP) affects a considerable proportion of women. Limited information exists regarding the incidence of POP as women transition through menopause. Using data from the Study of Women's Health Across the Nation (SWAN), this diverse community-based longitudinal cohort study assessed the incidence of symptomatic POP and risk by race/ethnicity. Methods: Self-reported POP was ascertained by questionnaire at 11 approximately annual SWAN visits over a median of 13.3 years of follow-up. We estimated probabilities for reporting POP using interval-censored Kaplan-Meier survival plots. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using interval-censored Cox proportional hazards models. Results: The estimated cumulative probability of POP increased linearly from 2.1% at age 45 to 10.1% by age 65 (4.0% per decade). At age 65, the probability was 4.2%, 4.8%, 8.9%, 9.7%, and 33.9% for Japanese, Chinese, Black, White, and Hispanic women, respectively. Compared with White women, the unadjusted HR for POP was 3.09 (95% CI = 2.18-4.39), 0.96 (0.71-1.31), 0.43 (0.22-0.85), and 0.48 (0.26-0.88) for Hispanic, Black, Chinese, and Japanese women, respectively. After adjustment for financial strain and vaginal birth, the low hazards among Chinese and Japanese women and the high hazard for Hispanic women remained significant. Conclusion: Incidence of symptomatic POP increased as women aged through midlife. Risks varied by race and ethnicity and were not accounted for by population differences in socioeconomic life contexts or the probability of having had a vaginal birth. Although not associated with menopause, health providers should incorporate screening for and information about POP when treating menopausal symptoms and health needs of midlife women. Research on pathophysiological factors associated with increasing POP in midlife is warranted.

Heavy Metals and Trajectories of Anti-Müllerian Hormone During the Menopausal Transition.

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

The association of urinary incontinence and disability among a diverse sample of midlife Study of Women's Health Across the Nation women.

OBJECTIVE: The aim of the study is to examine whether urinary incontinence (UI) type, frequency, and amount are associated with self-reported disability in a racially/ethnically diverse cohort of community-dwelling midlife women. METHODS: Data were from longitudinal analyses of questionnaires from the multicenter, prospective cohort Study of Women's Health Across the Nation (SWAN). We used multivariable ordinal logistic regression to examine whether urinary incontinence type, frequency, and amount at the 13th follow-up were associated with the World Health Organization Disability Assessment Schedule at the 15th follow-up controlling for other factors (menopause status, body mass index, lifestyle and psychosocial factors, and disability at follow-up 13). RESULTS: Urinary incontinence was associated with subsequent reports of disability in participants, particularly in the World Health Organization Disability Assessment Schedule domains of mobility ( P < 0.0001), communication ( P = 0.0057), and life activities ( P = 0.0407). Associations were strongest for mixed UI type compared with stress UI or urgency UI (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.26-2.17, P < 0.001), daily frequency of UI compared with monthly or less than weekly frequency of UI (OR = 1.61, 95% CI = 1.04-2.47, P < 0.001), and larger amounts of urine leakage compared with drops of leakage (OR = 2.98, 95% CI = 1.58-5.62, P < 0.0001) for mobility/getting around domain. CONCLUSIONS: Urinary incontinence seems to have a strong association with multiple domains of disability, including mobility and interacting with others, after approximately 3.7 years. Thus, UI may be an important factor limiting social engagement among women. Screening for mixed UI and UI that occurs greater than weekly and in amounts requiring pads may yield better information regarding an individual's future disability risk and may preserve social interaction.

Associations between CD70 methylation of T cell DNA and age in adults with systemic lupus erythematosus and population controls: The Michigan Lupus Epidemiology & Surveillance (MILES) Program.

BACKGROUND: Environmental factors can influence epigenetic regulation, including DNA methylation, potentially contributing to systemic lupus erythematosus (SLE) development and progression. We compared methylation of the B cell costimulatory CD70 gene, in persons with lupus and controls, and characterized associations with age. RESULTS: In 297 adults with SLE and 92 controls from the Michigan Lupus Epidemiology and Surveillance (MILES) Cohort, average CD70 methylation of CD4+ T cell DNA across 10 CpG sites based on pyrosequencing of the promoter region was higher for persons with SLE compared to controls, accounting for covariates [ß = 2.3, p = 0.011]. Using Infinium MethylationEPIC array data at 18 CD70-annoted loci (CD4+ and CD8+ T cell DNA), sites within the promoter region tended to be hypomethylated in SLE, while those within the gene region were hypermethylated. In SLE but not controls, age was significantly associated with pyrosequencing-based CD70 methylation: for every year increase in age, methylation increased by 0.14 percentage points in SLE, accounting for covariates. Also within SLE, CD70 methylation approached a significantly higher level in Black persons compared to White persons (ß = 1.8, p = 0.051). CONCLUSIONS: We describe altered CD70 methylation patterns in T lymphocyte subsets in adults with SLE relative to controls, and report associations particular to SLE between methylation of this immune-relevant gene and both age and race, possibly a consequence of "weathering" or accelerated aging which may have implications for SLE pathogenesis and potential intervention strategies.

Self-Reported Sleep Disturbances over the Menopausal Transition and Fracture Risk: The Study of Women's Health Across the Nation.

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

Operationalizing racialized exposures in historical research on anti-Asian racism and health: a comparison of two methods.

Background: Addressing contemporary anti-Asian racism and its impacts on health requires understanding its historical roots, including discriminatory restrictions on immigration, citizenship, and land ownership. Archival secondary data such as historical census records provide opportunities to quantitatively analyze structural dynamics that affect the health of Asian immigrants and Asian Americans. Census data overcome weaknesses of other data sources, such as small sample size and aggregation of Asian subgroups. This article explores the strengths and limitations of early twentieth-century census data for understanding Asian Americans and structural racism. Methods: We used California census data from three decennial census spanning 1920-1940 to compare two criteria for identifying Asian Americans: census racial categories and Asian surname lists (Chinese, Indian, Japanese, Korean, and Filipino) that have been validated in contemporary population data. This paper examines the sensitivity and specificity of surname classification compared to census-designated "color or race" at the population level. Results: Surname criteria were found to be highly specific, with each of the five surname lists having a specificity of over 99% for all three census years. The Chinese surname list had the highest sensitivity (ranging from 0.60-0.67 across census years), followed by the Indian (0.54-0.61) and Japanese (0.51-0.62) surname lists. Sensitivity was much lower for Korean (0.40-0.45) and Filipino (0.10-0.21) surnames. With the exception of Indian surnames, the sensitivity values of surname criteria were lower for the 1920-1940 census data than those reported for the 1990 census. The extent of the difference in sensitivity and trends across census years vary by subgroup. Discussion: Surname criteria may have lower sensitivity in detecting Asian subgroups in historical data as opposed to contemporary data as enumeration procedures for Asians have changed across time. We examine how the conflation of race, ethnicity, and nationality in the census could contribute to low sensitivity of surname classification compared to census-designated "color or race." These results can guide decisions when operationalizing race in the context of specific research questions, thus promoting historical quantitative study of Asian American experiences. Furthermore, these results stress the need to situate measures of race and racism in their specific historical context.

Systematic exclusion at study commencement masks earlier menopause for Black women in the Study of Women's Health Across the Nation (SWAN).

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

Cost-related prescription non-adherence and patient-reported outcomes in systemic lupus erythematosus: The Michigan Lupus Epidemiology & Surveillance program.

OBJECTIVES: Medication access and adherence play key roles in determining patient outcomes. We investigated whether cost-related non-adherence (CRNA) to prescription medications was associated with worse patient-reported outcomes in a population-based systemic lupus erythematosus (SLE) cohort. METHODS: Sociodemographic and prescription data were collected by structured interviews in 2014-2015 from patients meeting SLE criteria in the established Michigan Lupus Epidemiology & Surveillance (MILES) Cohort. We examined the associations between CRNA and potential confounders such as sociodemographics and health insurance coverage, and outcome measures of SLE activity and damage using multivariable linear regression. RESULTS: 462 SLE participants completed the study visit: 430 (93.1%) female, 208 (45%) Black, and mean age 53.3 years. 100 (21.6%) participants with SLE reported CRNA in the preceding 12 months. After adjusting for covariates, CRNA was associated with both higher levels of current SLE disease activity [SLAQ: ß coeff 2.7 (95% CI 1.3, 4.1), p < 0.001] and damage [LDIQ ß coeff 1.4 (95% CI 0.5, 2.4), p = 0.003]. Race, health insurance status, and fulfilling Fibromyalgia (FM) Survey Criteria were independently associated with both higher (worse) SLAQ and LDIQ scores; female sex was further associated with higher SLAQ scores. CONCLUSION: Patients with SLE who reported CRNA in the previous 12 months had significantly worse self-reported current disease activity and damage scores compared to those not reporting CRNA. Raising awareness and addressing barriers or concerns related to financial implications and accessibility issues in care plans may help to improve these outcomes.

The role of exposure to per- and polyfluoroalkyl substances in racial/ethnic disparities in hypertension: Results from the study of Women's health across the nation.

BACKGROUND: Racial/ethnic disparities in hypertension are a pressing public health problem. The contribution of environmental pollutants including PFAS have not been explored, even though certain PFAS are higher in Black population and have been associated with hypertension. OBJECTIVES: We examined the extent to which racial/ethnic disparities in incident hypertension are explained by racial/ethnic differences in serum PFAS concentrations. METHODS: We included 1058 hypertension-free midlife women with serum PFAS concentrations in 1999-2000 from the multi-racial/ethnic Study of Women's Health Across the Nation with approximately annual follow-up visits through 2017. Causal mediation analysis was conducted using accelerated failure time models. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures. RESULTS: During 11,722 person-years of follow-up, 470 participants developed incident hypertension (40.1 cases per 1000 person-years). Black participants had higher risks of developing hypertension (relative survival: 0.58, 95% CI: 0.45-0.76) compared with White participants, which suggests racial/ethnic disparities in the timing of hypertension onset. The percent of this difference in timing that was mediated by PFAS was 8.2% (95% CI: 0.7-15.3) for PFOS, 6.9% (95% CI: 0.2-13.8) for EtFOSAA, 12.7% (95% CI: 1.4-22.6) for MeFOSAA, and 19.1% (95% CI: 4.2, 29.0) for PFAS mixtures. The percentage of the disparities in hypertension between Black versus White women that could have been eliminated if everyone's PFAS concentrations were dropped to the 10th percentiles observed in this population was 10.2% (95% CI: 0.9-18.6) for PFOS, 7.5% (95% CI: 0.2-14.9) for EtFOSAA, and 17.5% (95% CI: 2.1-29.8) for MeFOSAA. CONCLUSIONS: These findings suggest differences in PFAS exposure may be an unrecognized modifiable risk factor that partially accounts for racial/ethnic disparities in timing of hypertension onset among midlife women. The study calls for public policies aimed at reducing PFAS exposures that could contribute to reductions in racial/ethnic disparities in hypertension.

Childhood Sexual Abuse and Pelvic Floor Dysfunction in Midlife Women in the Study of Women's Health Across the Nation.

Objectives: Research has shown a link between childhood sexual abuse (CSA) and lower urinary tract and sexual disorders in clinical settings. We examined whether CSA was associated with two specific aspects of high tone, elevated resting tension pelvic floor dysfunction (PFD) in community-dwelling women. Materials and Methods: Data were from 2068 participants (25.5% Black, 9.6% Chinese, 10.8% Japanese, 5.0% Hispanic, and 49.1% Non-Hispanic White) in the Study of Women's Health Across the Nation (SWAN), a multirace/multiethnic longitudinal observational study of women's midlife health. At baseline, enrolled women were 42-52 years old and premenopausal or early perimenopausal. Annual or biennial assessments conducted over 20 years (1996 through 2017) included single-item queries about urgency urinary incontinence and pain with sexual activity used to assess PFD outcomes. The 12th follow-up visit conducted in 2009-2011 assessed the primary exposure, history of CSA, using a single-item response. Multivariate logistic regression models tested study objectives. Results: The prevalence of CSA was 15%, self-reported in 313/2068 women. CSA and PFD, both pain with sexual activity (odds ratio [OR] = 1.56 confidence interval [95% CI = 1.12-2.18]) and urgency urinary incontinence (OR = 1.87 [95% CI = 1.29-2.71]), were significantly associated in unadjusted models. The final adjusted model that included sociodemographic variables and physical and behavioral risk factors was significant for pain with sexual activity (OR = 1.48 [95% CI = 1.08-2.02]), but not for urgency urinary incontinence (OR = 1.38 [95% CI = 0.96-1.98]). Conclusions: In midlife women, pain with sex, but not urgency urinary incontinence, was associated with a history of CSA. A multidisciplinary diagnostic and therapeutic approach to PFD is key, inclusive of CSA screening.

Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause.

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

The Association of Inflammatory Factors With Peripheral Neuropathy: The Study of Women's Health Across the Nation.

PURPOSE: Previous work has focused on the role of diabetes in peripheral neuropathy (PN), but PN often occurs before, and independently from, diabetes. This study measures the association of cardiometabolic and inflammatory factor with PN, independent of diabetes. METHODS: Study of Women's Health Across the Nation participants (n = 1910), ages 60 to 73 (mean 65.6) were assessed for PN by symptom questionnaire and monofilament testing at the 15th follow-up visit (V15). Anthropometric measures and biomarkers were measured at study baseline approximately 20 years prior, and C-reactive protein (CRP) and fibrinogen were measured longitudinally. Log-binomial regression was used to model the association between metabolic syndrome (MetS), obesity (≥35 body mass index), CRP, and fibrinogen with PN, adjusting for sociodemographic and health behavior measures. RESULTS: Baseline MetS [prevalence ratio (PR) 1.79, 95% CI (1.45, 2.20)], obesity [PR 2.08 (1.65, 2.61)], median CRP [PR 1.32 per log(mg/dL), (1.20, 1.45)], and mean fibrinogen (PR 1.28 per 100 mg/dL, (1.09, 1.50)] were associated with PN symptoms at V15. After excluding participants with baseline diabetes or obesity, MetS [PR 1.59 (1.17, 2.14)] and CRP [PR 1.19 per log(mg/dL), (1.06, 1.35)] remained statistically significantly associated with PN. There was a negative interaction between MetS and obesity, and the association between these conditions and PN was mediated by CRP. CONCLUSIONS: Cardiometabolic factors and inflammation are significantly associated with PN, independent of diabetes and obesity. CRP mediates the relationship of both obesity and MetS with PN, suggesting an etiological role of inflammation in PN in this sample.

Identifying latent classes of Relative Energy Deficiency in Sport (RED-S) consequences in a sample of collegiate female cross country runners.

OBJECTIVE: The purpose of this study was to identify patterns of clustering of the 10 health consequences identified in the Relative Energy Deficiency in Sport (RED-S) framework among collegiate female Cross-Country runners. We also assessed risk characteristics associated with each cluster. METHODS: This randomly sampled population included 211 current National Collegiate Athletics Association (NCAA) Division I (DI) female cross country runners who completed a quantitative survey. We used latent class analysis (LCA) to group athletes into mutually exclusive classes based on shared response patterns of RED-S consequences. We computed descriptive statistics to identify demographics, personal characteristics, disordered eating and emotional health characteristics associated with each class. RESULTS: The average age of the sample was 21 years with mean body mass index 20.4 kg/m2. The LCA identified three unique classes of potential RED-S presentations: (1) low probability of RED-S consequences; (2) complex physical and psychological concerns with a higher burden of cardiovascular concern and (3) very high probability of anxiety with high burden of menstrual disturbance, bone injury and gastrointestinal concern. All classes were characterised by high levels of menstrual disturbance and distinguished by the number and burden of other potential RED-S consequences and in reported abuse history, emotional regulation and perfectionism. CONCLUSION: This study identified a high burden of menstrual disturbance in NCAA D1 cross country runners, and three unique presentations of RED-S consequences. Future research is warranted to better understand how early prevention and intervention strategies may mitigate RED-S consequences in distance runners.

Exposure to heavy metals and hormone levels in midlife women: The Study of Women's Health Across the Nation (SWAN).

Exposure to heavy metals may alter the circulating levels of sex hormones. However, epidemiologic studies on heavy metals and sex hormones have been limited, and results have been inconsistent. We assessed the associations of heavy metals assayed in urine, including arsenic, cadmium, lead, and mercury, with repeated measures of serum estradiol (E2), follicle-stimulating hormone (FSH), testosterone, and sex hormone-binding globulin (SHBG) levels in the Study of Women's Health Across the Nation Multi-Pollutant Study. The sample included 1355 White, Black, Chinese, and Japanese women, aged 45-56 years at baseline (1999-2000), whose serum hormone levels were repeatedly measured through 2017. Urinary metal concentrations were measured at baseline. Linear mixed effect models were used to calculate percent changes in serum hormone levels per doubling of urinary metal concentrations, adjusting for demographics, socioeconomic status, lifestyle, health-related factors, and urinary creatinine. After multivariable adjustment, a doubling of urinary metal concentration was associated with lower E2 levels by 2.2% (95% CI: 4.0%, -0.3%) for mercury and 3.6% (95% CI: 5.7%, -1.6%) for lead; higher FSH levels by 3.4% (95% CI: 0.9%, 5.9%) for lead; and higher SHBG levels by 3.6% (95% CI: 1.3%, 5.9%) for cadmium. The overall joint effect using the Bayesian kernel machine regression showed that metal mixtures were inversely associated with E2 and positively associated with FSH levels. No association was found between metals and testosterone levels. Results from this prospective cohort study demonstrate that environmental heavy metal exposures, including cadmium, mercury, and lead, may disturb circulating levels of E2, FSH, and SHBG in midlife women.

Sleep timing, sleep regularity, and psychological health in early late life women: Findings from the Study of Women's Health Across the Nation (SWAN).

OBJECTIVES: To examine the associations of actigraphy-assessed sleep timing and regularity with psychological health in early late life women, whose circadian rhythms may be impacted by aging. DESIGN: Cross-sectional. PARTICIPANTS: A racially/ethnically diverse sample of 1197 community-dwelling women (mean age 65 years) enrolled in the Study of Women's Health Across the Nation. MEASURES: Actigraphy-assessed sleep measures included timing (mean midpoint from sleep onset to wake-up) and regularity (standard deviation of midpoint in hours). Psychological health measures included a composite well-being score, the Center for Epidemiological Studies Depression Scale, and the Generalized Anxiety Disorder-7 Scale. Linear and logistic regression models, adjusted for covariates (including sleep duration), tested associations between sleep and psychological health measures. RESULTS: After covariate adjustment, a sleep midpoint outside of 2:00-4: 00 AM was significantly associated with depressive symptoms (ß = 0.88, 95% CI = 0.06, 1.70) and scoring above the cut-point for clinically significant depressive symptoms (OR = 1.72, 95% CI = 1.15, 2.57). Sleep irregularity was significantly associated with lower psychological well-being (ß = -0.18, 95% CI = -0.33, -0.03), depressive (ß = 1.36, 95% CI = 0.29, 2.44) and anxiety (ß = 0.93, 95% CI = 0.40, 1.46) symptoms, and scoring above the cut-point for clinically significant depressive (OR = 1.68, 95% CI = 1.01, 2.79) and anxiety (OR = 1.62, 95% CI = 1.07, 2.43) symptoms. CONCLUSION: Above and beyond sleep duration, a sleep midpoint outside of 2:00-4:00 AM was associated with depressive symptoms while sleep irregularity was associated with multiple psychological health domains in late life women.

Study Selection Bias and Racial or Ethnic Disparities in Estimated Age at Onset of Cardiometabolic Disease Among Midlife Women in the US.

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