Dioxin Exposure and Quality of Ovarian Function

Abstract

SM1-PD-15 Introduction: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant and known endocrine disruptor, has been associated with alterations in ovarian function and steroid levels in animal studies. No studies have examined the potential effects of TCDD exposure on human ovarian function. On July 10, 1976, as a result of a chemical explosion, residents of Seveso, Italy experienced the highest levels of TCDD in a human population. Twenty years later, the Seveso Women's Health Study (SWHS), a retrospective cohort study of the reproductive health of the women, was initiated. We aimed to examine the relationship of TCDD levels measured in sera collected near the explosion and quality of ovarian function (ovarian follicles, ovulation rate, serum hormone levels) 20 years later. Methods: The SWHS cohort comprises 981 women who were 0 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. Individual TCDD exposure was measured in archived sera by high-resolution mass spectrometry. Eligible for the ovarian function analysis were 363 women who were 20 to 40 years old and did not currently use oral contraceptives. We examined the association of archived serum TCDD levels with serum hormone levels (estradiol, progesterone) at follow-up among 129 women who were in the luteal phase of their menstrual cycle. Women were classified as having ovulated if their serum progesterone level was >3 ng/mL. We examined the relationship of archived serum TCDD levels with ovarian follicles (number, size) among 96 women who underwent transvaginal ultrasound during the follicular phase of their menstrual cycle. Results: The median lipid-adjusted serum TCDD level for the 363 women was 77.3 ppt (range, 2.8–17,300). Of 129 women in the luteal phase, 87 (67%) were classified as having ovulated. Serum TCDD (logTCDD) was not associated with odds of ovulation (adjusted odds ratio [adj-OR] = 0.99; 95% CI, 0.5–1.9). Among those who had ovulated, logTCDD was associated with a nonsignificant decrease in progesterone (adj-beta = −0.70; 95% CI, −2.42, 1.01) and estradiol (adj-beta = −1.81; 95% CI, −10.4, 6.8). Among women in the follicular phase, serum TCDD was not associated with number or size of ovarian follicles. Discussion and Conclusions: These results suggest that TCDD may not have significant effects on human ovarian function 20 years after exposure in this highly exposed population. Detailed results will be presented and interpreted in light of study advantages and limitations.