Associations of Perfluoroalkyl Substances with Incident Natural Menopause: The Study of Women's Health Across the Nation.
Level 3 - non-randomized controlled study
Prospective cohort study evaluating baseline exposures and longitudinal incident outcomes
PubMed 32491182 · doi:10.1210/clinem/dgaa303
What was done
Researchers investigated the prospective association between serum perfluoroalkyl substance (PFAS) concentrations and incident natural menopause using data from the Study of Women's Health Across the Nation (SWAN) from 1999 to 2017. The study followed 1,120 multiracial/ethnic premenopausal women aged 45–56 years. Baseline serum PFAS concentrations were quantified via high-performance liquid chromatography isotope dilution tandem mass spectrometry. Incident natural menopause was defined as the bleeding episode preceding at least 12 consecutive months of amenorrhea not attributable to surgery or hormone use. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) over 5,466 person-years of follow-up.
What was found
During follow-up, 578 participants reached incident natural menopause. Comparing the highest to the lowest tertile of baseline serum concentrations, adjusted HRs for natural menopause were: - n-perfluorooctane sulfonic acid (n-PFOS): 1.26 (95% CI: 1.02–1.57; Ptrend = .03) - Branched-PFOS: 1.27 (95% CI: 1.01–1.59; Ptrend = .03) - n-perfluorooctanoic acid (n-PFOA): 1.31 (95% CI: 1.04–1.65; Ptrend = .01) When evaluated as mixtures across four exposure clusters (low, low-medium, medium-high, high), women in the high cluster had an adjusted HR of 1.63 (95% CI: 1.08–2.45) compared with the low cluster, representing an estimated 2.0 years earlier median time to natural menopause.
Why it matters
Serum PFAS levels rise after menopause due to the cessation of menstrual excretion, making earlier cross-sectional associations vulnerable to reverse causation. This prospective study demonstrates that exposure precedes earlier natural menopause, identifying environmental PFAS exposure as a potential contributor to accelerated ovarian aging.
Limits
Exposure assessment relied on baseline serum measurements in midlife rather than cumulative lifetime exposure. As an observational study, residual confounding remains possible. The sample was restricted to women aged 45–56 years at baseline who had not yet undergone menopause.
Cited by
- supports High exposure to PFAS chemicals is associated with women reaching menopause one to two years earlier.