IMMUNORESPONSIVENESS IN ENDOMETRIOSIS - IMPLICATIONS OF ESTROGENIC TOXICANTS

Endometriosis is a reproductive disease characterized by the growth of endometrial cells at sites outside the uterus. This disease is a seri ous disorder associated with chronic pain and infertility, which may b e present in 6 million women in this country. Traditional medical ther apy has consisted of hormonal regimens that limit the action of endoge nous estrogen. The etiology of endometriosis is unknown, but studies s uggest that soluble factors known as cytokines play a role in disease pathogenesis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is an environmental toxicant that alters the action of estrogen in reprod uctive organs and adversely affects immunocompetence. The incidence of endometriosis was determined in rhesus monkeys that were chronically exposed to dioxin for a period of approximately 4 years. Ten years aft er termination of dioxin treatment, the presence and severity of endom etriosis was assessed by surgical laparoscopy. The incidence of endome triosis correlated with dioxin exposure and disease severity was depen dent upon the dose administered. Moderate to severe endometriosis was not found in control animals but was documented in three of seven anim als exposed to 5 ppt dioxin (43%) and in five of seven animals exposed to 25 ppt dioxin (71%). The frequency of spontaneous disease in the c ontrol group was 33%, similar to an overall prevalence of 30% in 304 r hesus monkeys with no history of dioxin exposure. This study indicates that endometriosis may be associated with dioxin exposure in the rhes us. In view of overwhelming evidence that cytokines participate in the mediation of reproductive-endocrine phenomena regulation of endometri al growth, future assessment of the effects of environmental toxicants on reproductive health may depend upon our understanding of the bidir ectional cytokine network between the immune and endocrine systems.