Journal
AMERICAN JOURNAL OF EPIDEMIOLOGY
Volume 191, Issue 7, Pages 1212-1223Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwac052
Keywords
endocrine-disrupting chemicals; estrogen; follicle-stimulating hormone; hormones; mediation analysis; menopause; perfluoroalkyl substances; polyfluoroalkyl substances
Categories
Funding
- National Institute of Environmental Health Sciences [R01-ES026578, R01-ES026964, P30-ES017885]
- Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health [T42-OH008455]
- National Institutes of Health (NIH), US Department of Health and Human Services, through the National Institute on Aging
- National Institute of Nursing Research
- NIH Office of Research on Women's Health [U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, U19AG063720]
- SWAN Repository (NIH) [U01AG017719]
- National Center for Research Resources [U01AG017719]
- National Center for Advancing Translational Sciences, NIH, through University of California, San Francisco, Clinical and Translational Science Institute [UL1 RR024131]
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Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are associated with earlier natural menopause, potentially mediated by variations in follicle-stimulating hormone (FSH) concentrations.
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.
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