Polyfluoroalkyl chemicals and menopause among women 20-65 years of age (NHANES)

Polyfluoroalkyl chemicals (PFCs) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) have been associated with early menopause. However, previous cross-sectional studies have lacked adequate data to investigate possible reverse causality (i.e., higher serum concentrations due to decreased excretion after menopause). We investigated the association between PFOS, PFOA, perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) and age at natural menopause among women 20-65 years of age in NHANES (National Health and Nutrition Examination Survey). We used proportional hazard models to estimate hazard ratios (HRs) for the onset of natural menopause as a function of age and serum PFC levels, and to investigate reverse causation by estimating associations between PFC levels and the rate of hysterectomy. We also used multivariable linear regression to determine whether time since menopause predicted serum PFC levels. After adjusting for age at survey, race/ethnicity, education, ever smoking, and parity, women with higher levels of PFCs had earlier menopause than did women with the lowest PFC levels. We observed a monotonic association with PFHxS: The HR was 1.42 (95% CI: 1.08, 1.87) for serum concentrations in tertile 2 versus tertile 1, and 1.70 (95% CI: 1.36, 2.12) for tertile 3 versus tertile 1. We also found evidence of reverse causation: PFCs were positively associated with rate of hysterectomy, and time since natural menopause was positively associated with serum PFCs. Our findings suggest a positive association between PFCs and menopause; however, at least part of the association may be due to reverse causation. Regardless of underlying cause, women appear to have higher PFC concentrations after menopause.