Uterine Tumors and the Environment

Uterine adenocarcinomas of the endometrium are the eighth leading cause of cancer deaths in women affecting primarily postmenopausal women. Although uterine leiomyomas are benign, they are the most common pelvic tumor and are the leading cause for hysterectomy in women. Thus, uterine tumors have a significant impact on women's health. The uterus is exquisitely sensitive to the ovarian steroid hormones, estradiol and progesterone, and is therefore a target tissue for endocrine-disrupting chemicals (EDCs). Such chemicals occur almost ubiquitously in our environment and may have profound effects on normal uterine development and function. This chapter provides an overview of what is known about the effects of various classes of EDCs on the incidence of uterine tumors in animal models. The importance of choosing the correct animal model, particularly when using rodent models, is discussed. This chapter also summarizes the different types of uterine tumors that occur in women as well as findings from epidemiological studies that implicate EDCs in uterine tumor development. The development of various human uterine cell lines for in vitro studies has allowed the identification of the mechanisms of action of EDCs and how these chemicals interact with estrogen receptor (ER) to act as either estrogen agonists or antagonists. Discussion of the transgenerational effects of exposure to EDCs is also included. Although it has been difficult to show a direct link between environmental exposure to EDCs and an increased incidence of uterine tumors in women, the use of in vivo animal models, cell culture systems, and limited epidemiological data suggests a causal relationship between the two. Future studies will undoubtedly lead to an increased understanding of the potential clinical importance of environmental toxicants in the uterus.