SERUM DIOXIN CONCENTRATIONS AND RISK OF UTERINE FIBROIDS

Abstract

ISEE-68 Introduction: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant and known endocrine disruptor. Studies in rats suggest an anti-oestrogenic response of TCDD in the uterus. Uterine fibroids, benign tumours accounting for one-third of all hysterectomies, are associated with reproductive dysfunction. The etiology of fibroids is unknown, however increased oestrogen receptor levels and enhanced expression of several oestrogen-regulated genes have been observed in fibroids. On July 10, 1976, as a result of a chemical explosion, residents of Seveso, Italy, experienced the highest levels of TCDD exposure in a human population. Twenty years later (1996-1998), we initiated the Seveso Women’s Health Study (SWHS), a retrospective cohort study, to determine whether the women were at higher risk for reproductive disease. Aim: We will examine the association between serum TCDD levels and occurrence of uterine fibroids in the SWHS cohort. Methods: The SWHS cohort comprises 981 women who were 0 to 40 years in 1976, resided in the most contaminated areas, Zones A and B, at the time of the explosion, and had archived sera collected soon after the explosion. Individual serum TCDD exposure was measured by high-resolution/mass spectrometry. Using current status modelling techniques, we will examine the relation of serum TCDD and uterine fibroids in two ways: 1) limiting to incident cases diagnosed by the study trans-vaginal ultrasound, and 2) including cases based on self-report. Results: Of 413 women who were still menstruating, ≥32 years (youngest age of cases), and had an intact uterus, 88 cases (21%) of fibroids were diagnosed by study trans-vaginal ultrasound. Cases were older, less educated, had higher body mass index, were less likely to have used oral contraceptives, and reported a longer time since last pregnancy than non-cases. Lipid-adjusted serum TCDD levels for cases (n=88, median=“44.8” ppt, range: 2.5-3,830) was lower than for non-cases (n=325, median = 46.3 ppt; range: 2.5-5,710). In multivariate analysis, a 10-fold increase in serum TCDD (log TCDD) was associated with a non-significant reduced odds of fibroids (odds ratio (OR) = 0.93; 95% confidence interval (CI): 0.58 – 1.50). When TCDD was categorized, compared to the lowest exposure group (≤20 ppt), the OR (95% CI) for the two dose groups, 20.1-100 ppt, and >100 ppt, were 0.49 (0.25-0.97) and 0.68 (0.31-1.49), respectively. We will present the results of the expanded analysis which will include the full SWHS cohort (n=981) and as cases, women who self-report disease. Discussion: These preliminary data suggest that TCDD may have anti-oestrogenic effects on the uterus, in contrast to apparently oestrogenic effects previously found in breast of SWHS.