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. In animal studies, effects on ovarian function and steroid levels have been reported with both in utero and/or postnatal TCDD exposure.
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), the Seveso Women's Health Study (SWHS), a retrospective cohort study, was initiated to determine whether the women were at higher risk for reproductive disease.
The purpose of this presentation is to examine the association of serum TCDD levels and quality of ovarian function (serum hormone levels, ovarian follicles, functional ovarian cysts) in the SWHS cohort.
The SWHS cohort comprises 981 women, who were aged between one month to 40 years in 1976, resided in the most contaminated areas at the time of the explosion, and had archived sera collected soon after the explosion. We limit this analysis to SWHS women who were 20 to 40 years at follow-up, still menstruating, and not current oral contraceptive users. We examined the association of TCDD levels in bloods drawn at the time of the explosion and serum hormone levels (estradiol and progesterone), about 20 years later, among the 129 SWHS women who were in the luteal phase (last 14 days) of their menstrual cycle. Individual serum TCDD exposure was measured by high-resolution mass spectrometry. Women were classified as having ovulated if their serum progesterone level was >3 ng/ml. We determined the size of ovarian follicles and functional ovarian cysts among SWHS women who underwent transvaginal ultrasound during the pre-ovulatory window of the follicular phase of their menstrual cycle.
Of the 129 eligible women who were in the luteal phase, 87 (67%) had ovulated. Lipid-adjusted serum TCDD levels for women who had ovulated (n=87, median=“112.0” ppt, range: 5–3,140) were similar to women who had not ovulated (n=42, median = 107.1 ppt; range: 9–3,690). In univariate analysis, log10TCDD was not associated with decreased odds of ovulation (odds ratio (OR) = 1.12; 95% CI = 0.6 – 2.0). Among the 87 women who had ovulated, median serum levels of progesterone and estradiol were 9.8 ng/ml (range: 3.1–28.9), and 91.3 pg/ml (range: 30.5–184.5), respectively. In univariate regression analysis, a 10-fold increase in serum TCDD (log10TCDD) was associated with a 1.63 pg/ml increase in serum estradiol level (95% CI = −6.6 – 9.8) and a 0.40 ng/ml decrease in serum progesterone level (95% CI = −2.2 – 1.4), which were not significant.
TCDD may have estrogenic effects on human ovarian function, but further analysis controlling for other potential confounders is necessary. We will also present analyses on ovarian follicles and functional cysts.