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Eskenazi, B*; Warner, M*; Samuels, S; Needham, L L.; Patterson, D G. Jr; Olive, D O.§; Vercellini, P; Gerthoux, P M.; Mocarelli, P

Program and Abstracts: The Seventeenth Conference of the International Society for Environmental Epidemiology (ISEE): Abstracts

*School of Public Health, University of California, Berkeley, CA, USA; †School of Public Health, State University of New York at Albany, Albany, NY, USA; ‡Division of Environmental Health Laboratory Science, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA; §Department of Obstetrics and Gynecology, University of Wisconsin Medical School, Madison, WI, USA; ¶Department of Obstetrics and Gynaecology, Mangiagalli Hospital, University of Milan, Milan, Italy; ∥Department of Laboratory Medicine, University of Milano-Bicocca, School of Medicine, Hospital of Desio, Desio-Milano, Italy.


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2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD), the most toxic halogenated aromatic hydrocarbon, is a ubiquitous contaminant of various industrial and combustion processes. TCDD is a known carcinogen and endocrine disruptor. Concern about the reproductive toxicity of dioxin in humans has been growing as a number of animal studies have reported reproductive health effects following in utero or postnatal TCDD exposure, although there are few studies conducted to confirm these findings in humans.

In 1976, a chemical plant explosion in Seveso, Italy exposed the nearby residents to the highest exposure to TCDD known in humans.

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Twenty years later (1996–1998), we initiated the Seveso Women's Health Study (SWHS), a retrospective cohort study, to determine whether exposure increased risk for reproductive disease. We will present a summary of the findings of the SWHS to date.

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Women eligible for the SWHS were <40 years in 1976, had resided in one of the most highly contaminated zones (A or B) and had stored sera collected soon after the explosion. Participation included informed consent, venipuncture, personal interview, gynecologic examination and transvaginal ultrasound, medical records, and a 3-month menstrual diary. Individual serum TCDD exposure was measured by high-resolution/mass spectrometry. The primary objectives of the SWHS are to investigate the relationship of TCDD and reproductive endpoints.

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Between 1996–1998 we enrolled 981 women averaging 41 years of age. The median serum TCDD was 55.8 ppt, (range: 2.5 – 56,000), with higher levels in those younger than 10 years old. We found no association of log10 TCDD with spontaneous abortion (adjusted OR= 0.8, 95% CI = 0.6, 1.2); birthweight (adjusted beta = −4 grams, 95% CI = −68, 60); or small for gestational age births (adjusted OR = 1.2, 95% CI = 0.8, 1.8), although associations were stronger for pregnancies within the first eight years. Among women who were premenarcheal (29%) at explosion, log10 TCDD was associated with a 0.93-day increase (95% CI = −0.01, 1.86) in menstrual cycle length and a reduction in the odds of scanty flow (adjusted OR = 0.33, 95% CI = 0.10, 1.06); there were no associations among post-menarcheal women. We reported a doubled but non-significant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher and a doubled significant risk (HR=2.1, 95% CI =1.0, 4.6) for breast cancer. We also observed a non-monotonic dose response relationship for age at menopause. Overall, we found no change in risk of menarche with TCDD levels; however, among women who were <5 years at explosion, there was a somewhat greater risk for earlier menarche (HR = 1.2, 95% CI = 0.98 – 1.6).

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We will present detailed results of the reproductive endpoints described above as well as results of ongoing analyses including fibroids, serum hormones and ovarian cysts.

© 2005 Lippincott Williams & Wilkins, Inc.