BACKGROUND: Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with
alterations in ovarian function and hormones in animals, it has not been studied in humans. On
10 July 1976, an explosion exposed residents of Seveso, Italy, to the highest levels of TCDD in a
population. Twenty years later, we initiated the Seveso Women’s Health Study to study reproductive
OBJECTIVE: We related TCDD levels measured in sera collected near the time of explosion and
ovarian function (ovarian cysts, ovarian follicles, ovulation rate, serum hormones) at follow-up.
METHODS: We included 363 women who were 20–40 years of age and nonusers of oral contraceptives.
We examined the relationship of 1976 serum TCDD levels with ultrasound-detected ovarian
follicles among 96 women in the menstrual follicular phase and serum hormone levels (estradiol,
progesterone) among 129 women in the menstrual luteal phase at follow-up. Ovulation was defined
by serum progesterone levels > 3 ng/mL.
RESULTS: The median serum TCDD level was 77.3 ppt, lipid-adjusted. Serum TCDD was not
associated with number or size of ovarian follicles. Of women in the luteal phase, 87 (67%) ovulated.
Serum log10TCDD was not associated with odds of ovulation [adjusted odds ratio = 0.99;
95% confidence interval (CI), 0.5 to 1.9]. Among those who had ovulated, serum log10TCDD was
not associated with serum progesterone [adjusted beta (adj-β) = –0.70; 95% CI, –2.4 to 1.0] or
estradiol (adj-β = –1.81; 95% CI, –10.4 to 6.8).
CONCLUSIONS: We found no clear evidence that 1976 TCDD exposure was associated with ovarian
function 20 years later in women exposed to relatively high levels in Seveso, Italy.
endocrine disruptor; hormones; ovary; TCDD; 2,3,7,8-tetrachlorodibenzo-p-dioxin