Per- and Polyfluoroalkyl Substances (PFAS) and Hormone Levels during the Menopausal Transition: Study of Women’s Health Across the Nation (SWAN)

Abstract

Background: PFAS are endocrine disrupting chemicals that have been associated with an earlier age at menopause. However, information on their association with serum hormone concentrations is limited and inconsistent. We examined longitudinal associations between serum PFAS concentrations at baseline and serial serum concentrations of follicle stimulating hormone (FSH), estradiol (E2), testosterone (T) and sex hormone-binding globulin (SHBG) in the Study of Women’s Health Across the Nation (SWAN), a multi-racial/ethnic, community-based cohort of women transitioning through menopause. Methods: We assayed serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), 2-(N-ethyl-perfluorooctane sulfonamide) acetate (EtFOSAA), 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) in 1,398 women eligible for the SWAN Multi-Pollutant Study in 1999-2000 who were followed approximately annually to 2016. Serum PFAS concentrations were quantified by online solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry. Hormone and PFAS concentrations were log-transformed. Linear mixed regression with random intercepts was used to analyze longitudinal associations, adjusting for menopausal status, smoking, parity, race/ethnicity, site and body mass index (BMI). Results: At baseline, women had a mean age of 49.5 years, a mean BMI of 28.0 and included white (50.5%), black (22.0%), Chinese (12.7%) and Japanese (14.8%) women. PFAS were not associated with E2. In adjusted models including BMI, FSH was positively associated with total PFOS (β=0.041, 95% CI=0.000, 0.0092), branched-PFOS, (β=0.044, 95% CI=0.006, 0.0083), and n-PFOA (β=0.055, 95% CI=0.008, 0.0103) but not with EtFOSAA, MeFOSAA, PFHxS, or PFNA. T and SHBG were negatively associated with PFOS, n-PFOA and EtFOSAA, but these associations were greatly attenuated and not significant after adjustment for BMI. Conclusions: The results of this prospective study suggest that PFAS, especially PFOS and its precursors (MeFOSAA and EtFOSAA), and PFOA are associated with higher FSH concentrations in women during the menopausal transition, consistent with findings that PFAS affects reproductive aging.