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Journal Article 
Serum dioxin concentrations and age at menopause 
Eskenazi, B; Warner, M; Marks, AR; Samuels, S; Gerthoux, PM; Vercellini, P; Olive, DL; Needham, L; Patterson, D, Jr; Mocarelli, P 
Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 
2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), a halogenated compound that binds the aryl hydrocarbon receptor, is a by-product of numerous industrial processes including waste incineration. Studies in rats and monkeys suggest that TCDD may affect ovarian function. We examined the relationship of TCDD and age at menopause in a population of women residing near Seveso, Italy, in 1976, at the time of a chemical plant explosion. We included 616 of the women who participated 20 years later in the Seveso Women's Health Study. All women were premenopausal at the time of the explosion, had TCDD levels measured in serum collected soon after the explosion, and were > or = 35 years of age at interview. Using proportional hazards modeling, we found a 6% nonsignificant increase in risk of early menopause with a 10-fold increase in serum TCDD. When TCDD levels were categorized, compared with women in the lowest quintile (< 20.4 ppt), women in quintile 2 (20.4-34.2 ppt) had a hazard ratio (HR) of 1.1 (p = 0.77), quintile 3 (34.3-54.1 ppt) had an HR of 1.4 (p = 0.14), quintile 4 (54.2-118 ppt) had an HR of 1.6 (p = 0.10), and quintile 5 (> 118 ppt) had an HR of 1.1 (p = 0.82) for risk of earlier menopause. The trend toward earlier menopause across the first four quintiles is statistically significant (p = 0.04). These results suggest a nonmonotonic dose-related association with increasing risk of earlier menopause up to about 100 ppt TCDD, but not above. 
Adolescent; Adult; Age Factors; Chemical Industry; Child; Child, Preschool; Dose-Response Relationship, Drug; Environmental Pollutants/*blood; Explosions; Female; Humans; Infant; Italy/epidemiology; Menopause, Premature/*blood; Middle Aged; Retrospective Studies; Tetrachlorodibenzodioxin/*blood 
Age Factors 
Chemical Industry 
Child, Preschool 
Dose-Response Relationship, Drug 
Environmental Pollutants 
Menopause, Premature 
Middle Aged 
Retrospective Studies 
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