Perfluorooctanoic acid exposure and natural menopause: A longitudinal study in a community cohort

Perfluorooctanoic acid (PFOA), a suspected endocrine disruptor, is a bio-persistent chemical found at low levels in the serum of nearly all U.S. residents. Early menopause has been positively associated with serum PFOA in prior cross-sectional studies.

We conducted a longitudinal analysis of age at menopause among women, aged ≥40 years, (N=8759) in a Mid-Ohio Valley community cohort, exposed to high PFOA levels via contaminated drinking water. Using estimated retrospective year-specific serum PFOA concentrations (1951-2011), we examined the associations between PFOA, as cumulative exposure or year-specific serum estimates, and natural menopause using a Cox proportional hazards models. As participants were initially recruited in 2005-2006, we also analyzed the cohort prospectively (i.e., from the time of enrollment), using both modeled cumulative PFOA, and PFOA serum levels measured in 2005-2006. Women with hysterectomy (a competing risk) were either censored or excluded from the analysis.

Neither in the retrospective nor the prospective cohort did we find a significant (at α=0.05) trend between PFOA exposure and natural menopause. The non-significant, hazard ratios by quintile of increasing cumulative serum PFOA were 1.00 (referent), 1.00, 1.09, 1.05 and 1.06 (trend test for log cumulative exposure: p=0.37) with hysterectomies censored, and 1.00 (referent), 1.06, 1.13, 1.09 and 1.11 (trend test for log cumulative exposure: p=0.85) with hysterectomies excluded. Year-specific serum estimates were also not associated with early menopause.

Our data suggest that earlier age at menopause is not associated with PFOA exposure.