Exposure to some perfluoroalkyl and polyfluoroalkyl substances (PFAS) may be associated with an earlier onset of natural menopause, suggesting that PFAS may have a significant effect on ovarian aging, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

PFAS are widely used in many industrial and consumer products, including cookware, food packaging, and outdoor apparel. These chemicals may persist in the environment and in the human body and some may have endocrine-related disruptive properties.

As there are conflicting data on the association between PFAS and natural menopause, the goal of the current study was to explore this association in women who participated in the Study of Women’s Health Across the Nation (SWAN), a multiracial and multiethnic study aimed to assess changes during the menopausal transition.

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The study cohort included 1120 premenopausal women aged 45 to 56 years (median age, 48.9 years) with 5466 person-years of follow-up through 2017. Of these women, 578 experienced incident natural menopause.

To date, the most studied PFAS are perfulorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), which were the PFAS detected at the highest concentrations in this study.

There were significant racial/ethnic differences in serum PFAS concentrations. White women had the highest n-PFOA levels, whereas black women had the highest concentrations of n-PFOS and sum of branched isomers of PFOS. Chinese and Japanese women had the lowest perflorohexane sulfonic acid (PFHxS) concentrations. Concentrations of perfluoronoonanoic acid (PFNA) were significantly higher in white, Chinese, and Japanese women compared with black women.

Although PFHxS concentrations were not associated with incidence of natural menopause, there was a significant association between higher serum concentrations of n-PFOS (hazard ratio [HR], 1.26; 95% CI, 1.02-1.57; P =.03), sum of branched isomers of PFOS (HR, 1.27; 95% CI, 1.01-1.59; P =.03), n-PFOA (HR, 1.31; 95% CI, 1.04-1.65; P =.01), and PFNA (HR, 1.12; 95% CI, 1.01-1.24; per doubling increase in serum concentrations) and earlier age at natural onset of menopause.

Race/ethnicity was found to be an important factor in the association between PFAS and incidence of natural menopause. Among white women, there was a statistically significant association between PFNA and n-PFOA and incidence of natural menopause, but no similar association was found in other racial/ethnic groups.

The women were classified into 4 clusters according to their overall PFAS concentrations profile: low, low-medium, medium-high, and high overall concentrations patterns. Compared with the low cluster, the risk for early incidence of natural menopause was significantly increased with the high cluster (HR, 1.63; 95% CI, 1.08-2.45). Taken together, the findings indicated that high PFAS concentration patterns might contribute to 2.0 years earlier median time to natural menopause.

The study had several limitations, including potential overestimation or underestimation of the age at final menstrual period and missing data on medical conditions that may have precluded assessment of the possible effects of PFAS on menopause.

“This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life,” concluded the researchers.


Ding N, Harlow SD, Randolph JF Jr, et al. Associations of perfluoroalkyl substances with incident natural menopause: the Study of Women’s Health Across the Nation [published online June 3, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa303

This article originally appeared on Endocrinology Advisor