Per- and polyfluoroalkyl substances (PFAS) and menstrual cycle characteristics in midlife women: the Study of Women’s Health Across the Nation

Evidence suggests exposure to endocrine-disrupting chemicals, including per- and polyfluoroalkyl substances (PFAS), may disrupt ovarian function and influence menstrual bleeding. PFAS have been associated with reproductive aging; however, longitudinal data on PFAS and menstrual cycle characteristics (cycle length, bleeding patterns) are limited. We examined 952 women aged 45-55 years from the Study of Women’s Health Across the Nation, with seven PFAS concentrations measured in serum collected in 1999–2000. Menstrual cycle data were collected prospectively using monthly calendars for two years following PFAS measurement. Menstrual cycle length (MCL) was evaluated using linear quantile mixed models at the 25th, 50th, 75th, and 90th percentiles. Bleed length and binary bleeding outcomes (long and heavy) were analyzed using linear and generalized linear mixed models. Models were adjusted for race/ethnicity, education, physical activity, menopause status, smoking status, body mass index, and baseline menstrual characteristics. Higher perfluorooctane sulfonic acid concentrations were associated with shorter short cycles (MCL at the 25 th percentile) (-0.52 days; 95% CI, -1.09 to 0.05) and longer long cycles (MCL at the 90 th percentile) (2.77 days; 95% CI, 1.96 to 3.58). Perfluorononanoic acid was associated with longer short cycles (0.56 days; 95% CI, 0.06 to 1.05). No PFAS was associated with median MCL. Most PFAS, except 2-(N-methyl-perfluorooctane sulfonamido) acetic acid and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid, were associated with shorter menses and lower odds of long or heavy bleeding. PFAS exposure may be associated with increased menstrual cycle variability and reduced bleeding. Further research in younger cohorts is needed. • We examined PFAS and longitudinal menstrual cycle characteristics in midlife women • Higher PFOS was associated with shorter short cycles and longer long cycles • Higher PFNA was associated with longer short cycles • Most PFAS were associated with shorter menses and lower odds of long/heavy bleeding • PFAS may be linked with increased menstrual cycle variability and reduced bleeding