Per- and Polyfluoroalkyl Substances Are Associated with Increased Vasomotor Symptom Prevalence and Incident Occurrence among Midlife Women in the United States

Abstract Vasomotor symptoms (VMS), including hot flashes and night sweats, are frequently reported by women during the menopause transition. Per- and polyfluoroalkyl substances (PFAS) are linked to elevated follicle-stimulating hormone, decreased estrogen, and earlier menopause, but their associations with VMS remain unexplored. This study assessed individual PFAS levels and their patterns in association with prevalent and incident VMS using data from 1,400 women aged 45−56 years at baseline PFAS measurement in the Study of Women’s Health Across the Nation (1999−2000), who were followed through 2016. VMS were defined as any hot flashes or night sweats reported in the previous 2 weeks at each visit. Serum concentrations of seven PFAS with high detection rates (>96%) were included. Multiple imputation was used to impute missing values in covariates and left-truncation weights. Modified Poisson regression estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) in cross-sectional analyses; weighted interval-censored accelerated failure time models with a Weibull distribution computed time ratios (TRs), which were converted to hazard ratios (HRs) and 95% CIs in longitudinal analyses. Three clusters of participants with distinct PFAS exposure profiles (low-, medium-, or high-exposure patterns across all measured PFAS) were identified using k-means clustering and evaluated in relation to VMS prevalence and incidence. Adjusting for baseline sociodemographic, behavioral, psychosocial, and clinical factors, a doubling of linear perfluorooctanoic acid (n-PFOA) and 2-(N-methyl-perfluorooctane sulfonamido)acetic acid (MeFOSAA) was associated with modestly higher VMS prevalence (n-PFOA: PR = 1.05, 95% CI: 1.01−1.09; MeFOSAA: PR = 1.03, 95% CI: 1.01−1.06) and incidence (n-PFOA: HR = 1.11, 95% CI: 1.05−1.16; MeFOSAA: HR = 1.07, 95% CI: 1.03−1.11). Results of dose−response analyses indicated an increasing hazard of VMS occurrence with higher concentrations of several PFAS. Analyses using clusters indicated that women with medium PFAS exposure patterns had higher VMS prevalence and incidence compared to the low exposure group (PR = 1.13, 95% CI: 1.06−1.22; HR = 1.27, 95% CI: 1.17−1.39). Women with high exposure patterns had modestly higher VMS incidence and prevalence (PR = 1.10, 95% CI: 1.01−1.20; HR = 1.14, 95% CI: 1.02−1.28). These findings suggest that certain PFAS may increase VMS prevalence and accelerate the onset of VMS, potentially influencing quality of life in midlife women.