Serum Dioxin Concentrations and Endometriosis: A Cohort Study in Seveso, Italy Brenda Eskenazi,1 Paolo Mocarelli,2 Marcella Warner,1 Steven Samuels,1,3 Paolo Vercellini,4 David Olive,5 Larry L. Needham,6 Donald G. Patterson, Jr.,6 Paolo Brambilla,2 Nicoletta Gavoni,4 Stefania Casalini,2 Stefania Panazza,4 Wayman Turner,6 and Pier Mario Gerthoux2 1Center for Children's Environmental Health, School of Public Health, University of California at Berkeley, Berkeley, California, USA; 2Department of Laboratory Medicine, University of Milano-Bicocca, School of Medicine, Hospital of Desio, Desio-Milano, Italy; 3Department of Epidemiology and Preventive Medicine, University of California at Davis, Davis, California, USA; 4Department of Obstetrics and Gynecology, University of Milan School of Medicine, Milan, Italy; 5Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA; 6Division of Environmental Health Laboratory Science, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Abstract Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) . Participants were 601 female residents of the Seveso area who were 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain) . "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0) , respectively, relative to women with TCDD levels 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis. Key words: dioxin, endometriosis, environmental exposures, epidemiology. Environ Health Perspect 110:629-634 (2002) . [Online 15 May 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110p629-634eskenazi/ abstract.html Address correspondence to B. Eskenazi, School of Public Health, University of California, 140 Warren Hall, Berkeley, CA 94720-7360, USA. Telephone: (510) 642-3496. Fax: (510) 642-9083. E-mail: eskenazi@uclink4.berkeley.edu We gratefully acknowledge L. Bonsignore (Desio Hospital) for examining women at the Hospital of Desio, and members of the Scientific Advisory Board: D. Baird, L. Birnbaum, and D. Cramer. We would especially like to thank the women who participated in this study. This study was supported by grants R01 ES07171 and F06 TW02075-01 from the National Institutes of Health, R82471 from the U.S. Environmental Protection Agency, EA-M1977 from the Endometriosis Association, 2P30-ESO01896-17 from the National Institute of Environmental Health Sciences, and 2896 from Regione Lombardia and Fondazione Lombardia Ambiente, Milan, Italy. Received 13 April 2001 ; accepted 27 December 2001. Table 1 was corrected on 19 September 2002. The full version of this article is available for free in HTML or PDF formats. |