Reproductive and Hormonal Risk Factors for Adenomyosis

子宫腺肌病，也称为子宫内膜异位症，是子宫内膜腺和间质从子宫内膜向下进入子宫肌层，即子宫内侧肌壁的进行性侵袭。在美国，每年有超过15万名女性被诊断为这种疾病，可能与严重的盆腔和月经疼痛以及大量出血有关，几乎总是需要子宫切除术才能确定治疗。临床观察提出了多胎和过量雌激素可能增加疾病风险的假说；然而，几乎没有流行病学数据来证实或否认这一假说。因此，我们建议进行一项病例对照研究，以调查子宫腺肌病与生殖和激素相关的暴露之间的关系，包括涉及类固醇激素合成和代谢的基因的多态性。这项研究将在普吉特湾的团体健康合作社(GHC)进行，这是一个为华盛顿州西部约50万人提供服务的健康维护组织。2001年3月1日至2006年2月28日期间，将有500名18-59岁的女性GHC登记患者被诊断为子宫腺肌病。将使用两个对照组：1)500名在研究期间接受子宫切除术的妇女，她们被发现患有子宫腺肌症、子宫内膜异位症或子宫肌瘤以外的疾病，频率与年龄匹配，2)从计算机化登记文件中随机选择500名妇女，频率也与年龄匹配。将通过面谈、人体测量和采集血液样本进行DNA分析，从病例和对照中获得数据；这些数据将与GHC计算机化药房数据库连接。受试者将就已知或怀疑与子宫创伤或类固醇激素水平有关的因素(包括生殖、避孕和月经史；肥胖；运动；饮食；吸烟)以及其他子宫腺肌病的潜在危险因素进行访谈。将对血液样本进行分析，以检测两种编码雌激素代谢活性酶的多态基因(CYP17，COMT)。将进行关于生殖和荷尔蒙危险因素及其与遗传多态相互作用的病例和对照的分析，以解决具体目标。

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.