Perfluoroalkyl Substances and Incident Natural Menopause in Midlife Women: The Mediating Role of Sex Hormones

Abstract Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been associated with earlier natural menopause; however, the underlying mechanisms are not well understood, particularly the extent to which this relationship is mediated by sex hormones. We analyzed data (1999–2017) on 1,120 premeno...

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Published in:American journal of epidemiology 2022-06, Vol.191 (7), p.1212-1223
Main Authors: Ding, Ning, Harlow, Siobán D, Randolph, John F, Mukherjee, Bhramar, Batterman, Stuart, Gold, Ellen B, Park, Sung Kyun
Format: Article
Language:English
Subjects:
17β-Estradiol
Alkanesulfonic Acids
Chain branching
Environmental Pollutants
Estradiol
Female
Fluorocarbons
Follicle Stimulating Hormone
Gonadal Steroid Hormones
Hormones
Humans
Menopause
Original Contribution
Perfluoro compounds
Perfluoroalkyl & polyfluoroalkyl substances
Perfluorooctane sulfonic acid
Perfluorooctanoic acid
Sex hormones
Sulfonates
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Summary:Abstract Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been associated with earlier natural menopause; however, the underlying mechanisms are not well understood, particularly the extent to which this relationship is mediated by sex hormones. We analyzed data (1999–2017) on 1,120 premenopausal women from the Study of Women’s Health Across the Nation (SWAN). Causal mediation analysis was applied to quantify the degree to which follicle-stimulating hormone (FSH) and estradiol levels could mediate the associations between PFAS and incident natural menopause. Participants with higher PFAS concentrations had shorter times to natural menopause, with a relative survival of 0.82 (95% confidence interval (CI): 0.69, 0.96) for linear perfluorooctane sulfonate (n-PFOS), 0.84 (95% CI: 0.69, 1.00) for sum of branched-chain perfluorooctane sulfonate (Sm-PFOS), 0.79 (95% CI: 0.66, 0.93) for linear-chain perfluorooctanoate (n-PFOA), and 0.84 (95% CI: 0.71, 0.97) for perfluorononanoate (PFNA), comparing the highest tertile of PFAS concentrations with the lowest. The proportion of the effect mediated through FSH was 8.5% (95% CI: −11.7, 24.0) for n-PFOS, 13.2% (95% CI: 0.0, 24.5) for Sm-PFOS, 26.9% (95% CI: 15.6, 38.4) for n-PFOA, and 21.7% (6.8, 37.0) for PFNA. No significant mediation by estradiol was observed. The effect of PFAS on natural menopause may be partially explained by variations in FSH concentrations.
ISSN:0002-9262
1476-6256
DOI:10.1093/aje/kwac052