Program and Abstracts: The Seventeenth Conference of the International Society for Environmental Epidemiology (ISEE): Abstracts
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.
We will examine the association between serum TCDD levels and occurrence of uterine fibroids in the SWHS cohort.
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.
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.
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.