Age at natural Menopause in Women exposed to DiEthylStilbestrol in Utero

DES Follow-up Study Summary

A recent analysis of data from questionnaires returned by the participants in the DES Follow-up Study suggests that exposed daughters tend to have a slightly earlier age at natural menopause than unexposed daughters (Hatch EE et al, Age at Natural Menopause in Women Exposed to Diethylstilbestrol in Utero, American Journal of Epidemiology, October 1, 2006). The researchers analyzed data on over 4210 exposed daughters and 1829 unexposed daughters, and accounted for other factors that could be related to the age at natural menopause, such as cigarette smoking, hormone use, pregnancy history, and the age of the mother’s menopause. The average age at menopause was 52.2 years in unexposed women and 51.5 years in DES-exposed women, equivalent to about a nine month earlier menopause. Women who had been exposed to higher cumulative doses of DES tended to have menopause even earlier than those who had lower doses. Although this relatively small difference in age at menopause should not be related to any major health problems among the DES daughters, it does highlight the fact that DES seems to have health effects across the lifespan, especially in the reproductive tract. In general, menopause is thought to occur when the number of ovarian follicles left in the ovaries reaches a ‘critical’ level, therefore it is possible that DES daughters may have been born with a smaller reserve of follicles than unexposed women.

2006 Study Abstract

BACKGROUND:
Age at natural menopause is related to several health outcomes, including cardiovascular disease and overall mortality. Age at menopause may be influenced by the number of follicles formed during gestation, suggesting that prenatal factors could influence menopausal age. Diethylstilbestrol (DES), a nonsteroidal estrogen widely prescribed during the 1950s and 1960s, is related to reproductive tract abnormalities, infertility, and vaginal cancer in prenatally exposed daughters but has not been studied in relation to age at menopause. The authors used survival analyses to estimate the risk of natural menopause in 4,210 DES-exposed versus 1,829 unexposed US women based on responses to questionnaires mailed in 1994, 1997, and 2001. DES-exposed women were 50% more likely to experience natural menopause at any given age (hazard ratio = 1.49, 95% confidence interval: 1.28, 1.74). Among women for whom dose information was complete, there were dose-response effects, with a greater than twofold risk for those exposed to >10,000 mg. The causal mechanism for earlier menopause may be related to a smaller follicle pool, more rapid follicle depletion, or changes in hormone synthesis and metabolism in DES-exposed daughters. Age at menopause has been related, albeit inconsistently, to several exposures, but, to the authors’ knowledge, this is the first study to suggest that a prenatal exposure may influence reproductive lifespan.

Sources

• Age at natural menopause in women exposed to diethylstilbestrol in utero,NCBI, PMID: 16887893, 2006 Oct 1;164(7):682-8. Epub 2006 Aug 3. Full text Oxford Journals Medicine & Health International Journal of Epidemiology link.
• NCI, DES Follow-up Study Published Papers.

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