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American Journal of Epidemiology Advance Access published online on April 18, 2007

American Journal of Epidemiology, doi:10.1093/aje/kwm048
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American Journal of Epidemiology Copyright © 2007 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Original Contribution

Serum Dioxin Concentrations and Risk of Uterine Leiomyoma in the Seveso Women's Health Study

Brenda Eskenazi1, Marcella Warner1, Steven Samuels1,2, Jessica Young1, Pier Mario Gerthoux3, Larry Needham4, Donald Patterson4, David Olive5, Nicoletta Gavoni6, Paolo Vercellini6 and Paolo Mocarelli3

1 Department of Epidemiology, School of Public Health, University of California, Berkeley, CA
2 Department of Epidemiology, School of Public Health, State University of New York at Albany, Albany, NY
3 Department of Laboratory Medicine, University of Milano-Bicocca, School of Medicine, Hospital of Desio, Desio-Milano, Italy
4 Division of Laboratory Science, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA
5 Department of Obstetrics and Gynecology, University of Wisconsin Medical School, Madison, WI
6 Department of Obstetrics and Gynecology, Mangiagalli Hospital, University of Milan, Milan, Italy

Correspondence to Dr. Brenda Eskenazi, School of Public Health, University of California, 2150 Shattuck Avenue, Suite 600, Berkeley, CA 94720-7380 (e-mail: eskenazi{at}berkeley.edu).

Received for publication August 17, 2006. Accepted for publication January 5, 2007.

Uterine leiomyomata (fibroids), benign neoplasms of the smooth muscle, are a major cause of hysterectomy. Exposure to hormonally active chemicals may play an etiologic role. The authors investigated the risk of uterine leiomyoma associated with exposure to 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) for women who resided near Seveso, Italy, in 1976 at the time of a chemical explosion. Twenty years later, women enrolled in the Seveso Women's Health Study were asked about history of fibroids, medical records were obtained, and vaginal ultrasonography was performed for a subset. Serum collected soon after the explosion was analyzed for TCDD. A likelihood-based method that combines both historical and current status (ultrasound) data was adapted to estimate the hazard ratio. Of 956 eligible women, 251 (26.3%) had fibroids. Compared with that for women with TCDD levels of ≤20 parts per trillion, the age-adjusted hazard ratios were 0.58 (95% confidence interval: 0.41, 0.81) for women with levels of 20.1–75.0 parts per trillion and 0.62 (95% confidence interval: 0.44, 0.89) for women with levels of >75.0 parts per trillion. This finding suggests that TCDD may have antiestrogenic effects in the uterine myometrium, in contrast to apparently estrogenic effects previously found in the breast of Seveso Women's Health Study women.

endocrine disruptors; leiomyoma; tetrachlorodibenzodioxin; uterus

Abbreviations: CI, confidence interval; ppt, parts per trillion; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin


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