Treatment of Endometrial Hyperplasia

Endometrial hyperplasia (EH) is characterized by hyperproliferation of the endometrium. Women with EH are at increased risk for developing endometrial carcinoma, the most common malignant neoplasm of the urogenital tract in women. Unopposed estrogen or hyperestrogenism, which can arise from hormonal imbalances that occur during menopause, obesity, estrogen-secreting ovarian tumors, or estrogen replacement therapy, are the predominant causes of EH. Most women at some point in their life experience abnormal uterine bleeding that results from EH. These women often undergo hysterectomy which is the most over-prescribed surgical procedure in the United States. The estrogen receptor, a DNA-binding transcriptional activator that is a member of the steroid/thyroid receptor superfamily, mediates the ability of the endometrial cells to respond to estrogen. In the presence of estrogen, the ligand-bound activated estrogen receptor induces changes in gene expression and proliferation of the endometrium results. This proposal describes a novel pharmaceutical agent that can be used to prevent and treat endometrial hyperplasia, especially in conjunction with estrogen replacement therapy. We will inhibit the function of the estrogen receptor locally within the uterus, but in no other tissues.