| Serum Dioxin Concentrations and Age at Menarche Marcella Warner,1 Steven Samuels,1,2 Paolo Mocarelli,3 Pier Mario Gerthoux,3 Larry Needham,4 Donald G. Patterson Jr.,4 and Brenda Eskenazi1 1School of Public Health, University of California at Berkeley, Berkeley, California, USA; 2Division of Occupational/Environmental Medicine and Epidemiology, University of California at Davis, Davis, California, USA; 3Department of Laboratory Medicine, University of Milano-Bicocca, School of Medicine, Hospital of Desio, Desio-Milano, Italy; 4Division of Environmental Health Laboratory Science, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) , a widespread environmental contaminant, is associated with delays in pubertal development in animal studies. On 10 July 1976, as a result of a chemical explosion, residents of Seveso, Italy, experienced the highest levels of TCDD exposure experienced by a human population. Twenty years later, we initiated the Seveso Women's Health Study (SWHS) , a retrospective cohort study of female residents of the most contaminated areas, to determine whether the women were at higher risk for reproductive disease. We examined the association of TCDD serum levels, based on measurements in serum collected soon after the explosion, with reported age at menarche among the 282 SWHS women who were premenarcheal at the time of the explosion. We found no change in risk of onset of menarche with a 10-fold increase in TCDD (e.g., 10-100 ppt ; hazard ratio = 0.95 ; 95% confidence interval, 0.83-1.09 ; p-value for trend = 0.46) . When TCDD levels were categorized, there was also no evidence of a dose-response trend (p = 0.65) . In summary, we found that individual serum TCDD measurements are not significantly related to age at menarche among women in the SWHS cohort. The women in this study experienced substantial TCDD exposure during the postnatal but prepubertal developmental period. Given that animal evidence suggests in utero exposure has the most significant effect on onset of puberty, continued follow-up of the offspring of the SWHS cohort is important. Key words: dioxin, endocrine disruptors, environmental exposures, epidemiology, menarche, puberty, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Environ Health Perspect 112:1289-1292 (2004) . Online 10 June 2004]
Address correspondence to M. Warner, School of Public Health, University of California, 2150 Shattuck Ave., Suite 600, Berkeley, CA 94720-7380 USA. Telephone: (510) 642-9545. Fax: (510) 642-9083. E-mail: mwarner@calmail.berkeley.edu We thank S. Casalini and P. Brambilla for coordinating data collection at the Hospital of Desio and W. Turner (CDC) for serum TCDD measurements. This work was supported by the following grants: R82471 from the U.S. Environmental Protection Agency, R01 ES07171 and F06 TW0207501 from the National Institutes of Health, 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. The authors declare they have no competing financial interests. Received 5 February 2004 ; accepted 10 June 2004.
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