American Journal of Epidemiology Advance Access originally published online on August 3, 2006
American Journal of Epidemiology 2006 164(7):682-688; doi:10.1093/aje/kwj257
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Original Contribution |
Age at Natural Menopause in Women Exposed to Diethylstilbestrol in Utero
1 Department of Epidemiology, Boston University School of Public Health, Boston, MA
2 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
3 Slone Epidemiology Center, Boston University, Boston, MA
4 Information Management Services, Rockville, MD
5 Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH
6 Department of Obstetrics and Gynecology, New England Medical Center, Boston, MA
7 Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX
8 Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL
9 Department of Pathology, Duke University Medical Center, Durham, NC
10 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC
Correspondence to Dr. Elizabeth E. Hatch, Department of Epidemiology, Boston University School of Public Health, 715 Albany Street, Boston, MA 10029 (e-mail: eehatch{at}bu.edu).
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.
diethylstilbestrol; longitudinal studies; menopause; prenatal exposure delayed effects; survival analysis
Abbreviations: DES, diethylstilbestrol; DESAD, Diethylstilbestrol Adenosis Project; HRT, hormone replacement therapy; NCI, National Cancer Institute
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