Reproductive and Hormonal Risk Factors for Adenomyosis

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Adenomyosis, also known as internal endometriosis, is the progressive invasion of endometrial glands and stroma from the uterine endometrial lining down into the myometrium, the inner muscle wall of the uterus. This condition is diagnosed in over 150,000 women in the U.S. annually, can be associated with severe pelvic and menstrual pain and excessive bleeding, and almost always requires hysterectomy for definitive treatment. Clinical observations have raised the hypothesis that multiparity and excessive estrogen may increase disease risk; however, there is little epidemiologic data to confirm or deny this hypothesis. Consequently, we propose to conduct a case-control study to investigate the relationships between adenomyosis and reproductive and hormonally-related exposures, including polymorphisms in genes involved in steroid hormone synthesis and metabolism. The study will be conducted at Group Health Cooperative of Puget Sound (GHC), a health maintenance organization serving approximately 500,000 people in western Washington State. Cases will be 500 female GHC enrollees 18-59 years of age diagnosed with adenomyosis between March 1, 2001 and Feb. 28, 2006. Two control groups will be used: 1) 500 women undergoing hysterectomy during the study period who are found to have a condition other than adenomyosis, endometriosis, or leiomyoma, frequency matched to cases on age, and 2) 500 women randomly selected from computerized enrollment files, also frequency matched to cases on age. Data will be obtained from cases and controls by in-person interview, anthropometric measurement and collection of a blood sample for DNA analysis; and these data will be linked with the GHC computerized pharmacy database. Subjects will be interviewed regarding factors known or suspected to be associated with uterine trauma or steroid hormone levels (including reproductive, contraceptive, and menstrual histories; obesity; exercise; diet; cigarette smoking) as well as other potential risk factors for adenomyosis. Blood samples will be analyzed for two polymorphic genes coding enzymes active in estrogen metabolism (CYP17, COMT). Analyses comparing cases and controls with respect to reproductive and hormonal risk factors and their interactions with genetic polymorphisms will be conducted to address the specific aims.