Reproductive and Hormonal Risk Factors for Adenomyosis

子宫腺肌症，也被称为子宫内膜异位症，是子宫内膜腺体和间质从子宫内膜逐渐侵入子宫肌层，即子宫内肌壁。在美国，每年有超过15万名女性被诊断出这种疾病，可能与严重的骨盆和月经疼痛以及出血过多有关，并且几乎总是需要子宫切除术来进行最终治疗。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设；然而，很少有流行病学数据证实或否认这一假设。因此，我们建议开展一项病例对照研究，以调查子宫腺肌症与生殖和激素相关暴露之间的关系，包括参与类固醇激素合成和代谢的基因多态性。这项研究将在普吉特海湾集团健康合作社（GHC）进行，这是一家为华盛顿州西部约50万人提供服务的健康维护组织。病例将在2001年3月1日至2006年2月28日期间被诊断为子宫腺肌症的500名18-59岁的女性GHC参与者中进行。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bbb、子宫内膜异位症或平滑肌瘤以外的疾病，频率与年龄相匹配；2)500名妇女从计算机登记档案中随机选择，频率也与年龄相匹配。将通过面对面访谈、人体测量和采集血液样本进行DNA分析，从病例和对照中获取数据；这些数据将与GHC计算机药房数据库相连接。将对受试者进行访谈，了解已知或怀疑与子宫外伤或类固醇激素水平相关的因素（包括生殖、避孕和月经史、肥胖、运动、饮食、吸烟）以及其他可能导致子宫腺肌症的危险因素。血液样本将分析两种多态性基因编码酶活性雌激素代谢（CYP17， COMT）。将对生殖和激素危险因素及其与遗传多态性的相互作用方面的病例和对照进行分析比较，以实现具体目标。

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.