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

Abstract

Background: 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).

Objectives: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Figure 1

Study population of women 20–65 years of age who had PFC serum measurements: NHANES years 1999–2000, 2003–2004, 2005–2006, 2007–2008, and 2009–2010.

Figure 2

Directed acyclic graph of association between PFC exposure and age of natural menopause.

Figure 3

Adjusted (Adj) HRs and 95% CIs for menopause in association with tertiles (T) of serum PFCs among women 20–65 years of age: NHANES 1999–2000, 2003–2004, 2005, 2006, 2007–2008, and 2009–2010. Data are based on the proportional hazards model for age at menopause, censoring at interview age if still menstruating, and eliminating all cases of hysterectomy. HRs are adjusted for age at interview, race/ethnicity, education, smoking, and parity.

Figure 4

Adjusted (Adj) HRs and 95% CIs for hysterectomy in association with tertiles (T) of serum PFCs among women: 20–65 years of age NHANES 1999–2000, 2003–2004, 2005, 2006, 2007–2008, and 2009–2010. Data are based on the proportional hazards model for age at hysterectomy, censoring at interview age if still menstruating, and eliminating all cases of menopause. HRs are adjusted for age at interview, race/ethnicity, education, smoking, and parity.