In a national sample of US women in their mid-40s to mid-50s, those with high serum levels of per- and polyfluoroalkyl substances (PFAS) were likely to enter menopause 2 years earlier than those with low levels of these chemicals.

That is, the median age of natural menopause was 52.8 years versus 50.8 years in women with high versus low serum levels of these chemicals in an analysis of data from more than 1100 women in the Study of Women’s Health Across the Nation (SWAN) Multi-Pollutant Study (MPS), which excluded women with premature menopause (before age 40) or early menopause (before age 45).

“This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life,” Ning Ding, PhD, MPH, University of Michigan School of Public Health in Ann Arbor, and colleagues conclude in their article published online June 3 in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

“Even menopause a few years earlier than usual could have a significant impact on cardiovascular and bone health, quality of life, and overall health in general among women,” added senior author Sung Kyun Park, ScD, MPH, from the same institution, in a statement.  

PFAS Don’t Break Down in the Body, Build Up With Time

PFAS have been widely used in many consumer and industrial products such as nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam, the authors explain.

These have been dubbed “forever chemicals” because they do not degrade. Household water for an estimated 110 million Americans (one in three) may be contaminated with these chemicals, according to an Endocrine Society press release.

“PFAS are everywhere. Once they enter the body, they don’t break down and [they] build up over time,” said Ding.

“Because of their persistence in humans and potentially detrimental effects on ovarian function, it is important to raise awareness of this issue and reduce exposure to these chemicals,” he stressed.

Environmental Exposure and Accelerated Ovarian Aging

Earlier menopause has been associated with an increased risk of cardiovascular disease, osteoporosis, and earlier cardiovascular and overall mortality, and environmental exposure may accelerate ovarian aging, the authors write.

PFAS, especially the most studied types — perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) — are plausible endocrine-disrupting chemicals, but findings so far have been inconsistent.

A study of people in Ohio exposed to contaminated water found that women with earlier natural menopause had higher serum PFOA and PFOS levels (J Clin Endocriniol Metab. 2011;96:1747-53).

But in research based on National Health and Nutrition Survey Examination (NHANES) data, higher PFOA, PFOS, or perfluorononanoic acid (PFNA) levels were not linked to earlier menopause, although higher levels of perfluorohexane sulfonic acid (PFHxS) were (Environ Health Perspect. 2014;122:145-50).

There may have been reverse causation, where postmenopausal women had higher PFAS levels because they were not excreting these chemicals in menstrual blood.  

In a third study, PFOA exposure was not linked with age at menopause onset, but this was based on recall from 10 years earlier (Environ Res. 2016;146:323-30).

The current analysis examined data from 1120 premenopausal women who were 45 to 56 years old from 1999 to 2000.

The women were seen at five sites (Boston, Massachusetts; Detroit, Michigan; Los Angeles, California; Oakland, California; and Pittsburgh, Pennsylvania) and were ethnically diverse (577 white, 235 black, 142 Chinese, and 166 Japanese).

Baseline serum PFAS levels were measured using high performance liquid chromatography-mass spectrometry.

The women were followed up to 2017 and incident menopause (12 consecutive months with no menstruation) was determined from annual interviews. 

Of the 1120 women and 5466 person-years of follow-up, 578 women had a known date of natural incident menopause and were included in the analysis.

The remaining 542 women were excluded mainly because their date of final menstruation was unknown due to hormone replacement therapy (451) or they had a hysterectomy, or did not enter menopause during the study.

Compared with women in the lowest tertile of PFOS levels, women in the highest tertile had a significant 26% to 27% greater risk of incident menopause — after adjusting for age, body mass index, and prior hormone use, race/ethnicity, study site, education, physical activity, smoking status, and parity.

Higher PFOA and PFNA levels but not higher PFHxS levels were also associated with increased risk.

Compared to women with a low overall PFAS level, those with a high level had a 63% increased risk of incident menopause (hazard ratio, 1.63; 95% CI: 1.08 – 2.45), equivalent to having menopause a median of 2 years earlier.  

Although production and use of some types of PFAS in the United States are declining, Ding and colleagues write, exposure continues, along with associated potential hazards to human reproductive health.

“Due to PFAS widespread use and environmental persistence, their potential adverse effects remain a public health concern,” they conclude.

SWAN was support by the National Institutes of Health (NIH), Department of Health & Human Services through the National Institute on Aging (NIA), National Institute of Nursing Research (NINR), NIH Office of Research on Women’s Health (ORWH), and the SWAN repository. The current article was supported by the National Center for Research Resources and National Center for Advancing Translational Sciences, NIH, National Institute of Environmental Health Sciences, and Centers for Disease Control and Prevention (CDC)/National Institute for Occupational Safety and Health. The authors have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online June 3, 2020. Abstract

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