Are common chemicals associated with earlier onset of menopause?

A study of a representative sample of US women shows a clinically significant association between early menopause and exposure to 15 different endocrine-disrupting chemicals (EDCs) commonly found in personal care products, plastics, and packaging. The magnitude of the effect, the researchers said, was greater than that documented for smoking on menopause but they caution that their results do not establish cause and effect. 

Researchers at the Washington University School of Medicine in St. Louis, Missouri used data on 31,575 women from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2009 to assess whether EDC exposure was associated with earlier age of menopause.  Serum levels of 111 individual dioxins, phytoestrogens, phthalates, polychlorinated biphenyls, phenolic derivatives, organophosphate pesticides, surfactants, and polycyclic aromatic hydrocarbons were evaluated. The primary outcome was age at last menstrual period (LMP) in menopausal women aged 30 and over. With the exception of phthalates, all of the EDCs chosen have half-lives of more than 1 year; phthalates were included because their effect on reproduction has been well documented.

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Eligible women were not currently pregnant, breastfeeding, using hormonal contraception and had no history of hysterectomy or bilateral oophorectomy. Exposures, defined by serum lipid and urine creatinine, were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models were adjusted for race/ethnicity, smoking, body mass index, and age. The EDCs were stratified into half-lives: long (>1 year), short, and unknown. Principle analyses were done for chemicals with long half-lives as well as phthalates. Secondary analysis was performed to determine if the odds of being menopausal increased with exposure to EDC among women aged 45 to 55 years.

Researchers found that the mean age of menopause was 1.9 to 3.8 years earlier in women who had high levels of β-hexachlorocyclohexane, mirex, p,p’-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners −70, −99, −105, −118, −138, −153, −156, −170, and −183 than in those with less exposure.  In addition, women exposed to EDC were up to 6 times more likely to be menopausal than were non-exposed women.

The authors noted that their study had some limitations. The date of LMP was self-reported by the women, the time between onset of menopause and measurement of EDC levels was considerable, data on EDC exposures were not available for all eligible menopausal women, and it was not possible to establish causality because the NHANES data are cross-sectional. The researchers also noted that they studied each EDC individually and humans may be exposed to multiple EDCs at any given time.

The investigators concluded that their study indicates an association between earlier age at the start of menopause and exposure to EDCs. The 15 such chemicals identified, they said, should be studied further because of their potential negative effects on ovarian function and their persistence in the body.

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