Per- and Polyfluoroalkyl Substances (PFAS) and Hormone Levels during the Menopausal Transition

By Siobán D Harlow, Michelle M Hood, Ning Ding, Bhramar Mukherjee, Antonia M Calafat, John F Randolph, Ellen B Gold, and Sung Kyun Park
J Clin Endocrinol Metab
July 6, 2021
DOI: 10.1210/clinem/dgab476


Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals that may affect sex hormones and accelerate reproductive aging in midlife women.


To examine associations between serum PFAS concentrations at baseline (1999-2000) and longitudinal serum concentrations of follicle stimulating hormone (FSH), estradiol, testosterone, and sex hormone-binding globulin (SHBG) at baseline and through 2015-2016.


Prospective cohort.


General community.


1,371 midlife women aged 45-56 years at baseline in the Study of Women's Health Across the Nation (SWAN).

Main Outcome Measure(s)

FSH, estradiol, testosterone, SHBG.


In linear mixed models fitted with log-transformed hormones and log-transformed PFAS adjusting for age, site, race/ethnicity, smoking status, menopausal status, parity and body mass index, FSH was positively associated with linear perfluorooctanoate (n-PFOA) (3.12% (95% CI: 0.37%, 5.95%) increase for a doubling in serum concentration), linear perfluorooctane sulfonate (n-PFOS) (2.88% (0.21%, 5.63%)), branched perfluorooctane sulfonate (Sm-PFOS) (2.25% (0.02%, 4.54%)), total PFOS (3.03% (0.37%, 5.76%)), and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) (1.70% (0.01%, 3.42%)). Estradiol was inversely associated with perfluorononanoate (PFNA) (-2.47% (-4.82%, -0.05%)) and n-PFOA (-2.43% (-4.97%, 0.18%)). Significant linear trends were observed in the associations between PFOS and EtFOSAA with SHBG across parity (Ps-trend≤0.01), with generally inverse associations among nulliparous women but positive associations among women with 3+ births. No significant associations were observed between PFAS and testosterone.


This study observed positive associations of PFOA and PFOS with FSH and inverse associations of PFNA and PFOA with estradiol in midlife women during the menopausal transition, consistent with findings that PFAS affect reproductive aging.

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