title: Age at natural menopause in women exposed to diethylstilbestrol in utero.
abstract: 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.
authors.affiliation: Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA. eehatch@bu.edu
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Hatch
authors.forename: Rebecca
authors.initials: R
authors.lastname: Troisi
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Wise
authors.forename: Marianne
authors.initials: M
authors.lastname: Hyer
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
authors.forename: Linda
authors.initials: L
authors.lastname: Titus-Ernstoff
authors.forename: William
authors.initials: W
authors.lastname: Strohsnitter
authors.forename: Raymond
authors.initials: R
authors.lastname: Kaufman
authors.forename: Ervin
authors.initials: E
authors.lastname: Adam
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Noller
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Herbst
authors.forename: Stanley
authors.initials: S
authors.lastname: Robboy
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
mesh_terms: D000367:Age Factors; D004054:Diethylstilbestrol / Q000009:adverse effects*; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D014481:United States
chemical_list: D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol