Estrogens and pharmacogenetic risks of venous thrombosis in postmenopausal women

绝经后妇女的雌激素和静脉血栓形成的药物遗传学风险

• 批准号: 7730104
• 负责人: NICHOLAS L SMITH
• 金额: $ 63.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-05 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7730104
• 关键词: Accounting; Address; Adverse effects; Age-Years; Benefits and Risks; Blood; Blood Vessels; Case-Control Studies; Clinical Trials; Coagulation Process; Comorbidity; Confidence Intervals; Conflict (Psychology); Conjugated Equine Estrogens; Conjugated Estrogens; Consent; Coronary; DNA; Data; Data Quality; Deep Vein Thrombosis; Epidemiologic Studies; Estradiol; Estrogen Therapy; Estrogens; European; Event; Formularies; Genetic Risk; Health; Healthcare; Hemostatic Agents; Hormones; Interview; Laboratories; Literature; Measures; Medical Records; Medroxyprogesterone 17-Acetate; Menopause; Names; Observational Study; Odds Ratio; Oral; Outcome; Pharmaceutical Preparations; Pharmacogenetics; Pharmacologic Substance; Pharmacy facility; Physicians; Placebos; Plasma; Population Study; Postmenopause; Progestins; Proteins; Public Health; Pulmonary Embolism; Randomized Clinical Trials; Research; Resistance; Resources; Risk; Risk Estimate; Risk Factors; Role; Safety; Series; Serious Adverse Event; Symptoms; Testing; Thrombosis; Variant; Vasomotor; Venous Thrombosis; Washington; Woman; Women' s Health; Work; abstracting; activated Protein C; base; design; evidence base; experience; genetic variant; genome wide association study; information gathering; member; novel; population based; public health relevance

DESCRIPTION (provided by applicant): Exogenous estrogens, a heterogeneous group of estrogenic compounds that includes conjugated equine estrogen (CEE), estradiol (E2), and esterified estrogen (EE), are a controversial and potentially harmful pharmaceutical therapy that nonetheless continues to be used by peri- and post-menopausal women. Venous thrombosis (VT) may be one of the most serious side-effect of short-term estrogen use. It has been demonstrated that CEE, historically the most commonly prescribed estrogen, and EE, have differential effects on VT risk. Estradiol is the second most commonly prescribed oral estrogen in the US and its association with VT risk is not known. This application is a competing renewal to support novel work investigating estrogens and pharmacogenetic risk factors for VT in peri- and post-menopausal women in a population-based, case-control study at Group Health. The recent change in the preferred formulary estrogen at Group Health to E2 provides us with a unique opportunity to characterize the VT risk associated with this commonly used oral estrogen. As our primary aim in this renewal, we hypothesize that VT risk is greater in users of oral E2 compared with non-users of estrogen and, moreover, VT risk is greater in oral E2 users compared with oral CEE users or compared with oral EE users. As a secondary aim, we will use laboratory-based measures to characterize the clotting propensity of oral E2, oral CEE, and non-users of estrogen among healthy subjects. An additional aim is to determine which newly identified genetic risks of thrombosis from the growing literature are modified by estrogen use. The setting for the study is Group Health, a large integrated healthcare organization in Washington State. The study population will include peri- and post-menopausal Group Health members 30 to 89 years of age who experienced an incident VT, either deep vein thrombosis or fatal or non-fatal pulmonary embolism. This application will support the identification and the abstraction of medical record data VT cases and their matched controls that occur through 2013. Blood will be collected and DNA abstracted from those who consent. Data on the safety of oral estrogen products are limited and hinder women and their physicians from making evidence-based decisions when choosing an estrogen product to treat vasomotor symptoms of menopause. This competing renewal is designed to expand research using this unique and valuable resource that has already produced important epidemiologic information and will likely provide high-quality data to begin to address important public health questions of women's health. PUBLIC HEALTH RELEVANCE: Data on the safety of oral estrogen products are limited and hinder women and their physicians from making evidence-based decisions when choosing an estrogen product to treat vasomotor symptoms of menopause. Venous thrombosis may be the most serious side-effect of short-term estrogen use yet virtually nothing is known about the risks of oral estradiol, the second most commonly used estrogen. We propose an extension of our population-based, case-control study in post-menopausal women to examine risks of venous thrombosis associated with oral estradiol and other estrogens.

说明（由申请人提供）：外源性雌激素是一组异质性雌激素化合物，包括结合马雌激素 (CEE)、雌二醇 (E2) 和酯化雌激素 (EE)，是一种有争议且可能有害的药物疗法，但仍继续受到关注。围绝经期和绝经后妇女使用。静脉血栓（VT）可能是短期使用雌激素最严重的副作用之一。事实证明，CEE（历史上最常用的雌激素）和 EE 对 VT 风险具有不同的影响。雌二醇是美国第二大最常用的口服雌激素，其与 VT 风险的关系尚不清楚。该应用程序是一项竞争性更新，旨在支持在 Group Health 进行的一项基于人群的病例对照研究中调查围绝经期和绝经后妇女 VT 的雌激素和药物遗传学危险因素的新工作。 Group Health 的首选处方雌激素最近更改为 E2，这为我们提供了一个独特的机会来描述与这种常用口服雌激素相关的 VT 风险。作为本次更新的主要目标，我们假设与非雌激素使用者相比，口服 E2 使用者的 VT 风险更大，此外，与口服 CEE 使用者或口服 EE 使用者相比，口服 E2 使用者的 VT 风险更大。作为次要目标，我们将使用基于实验室的措施来表征健康受试者中口服 E2、口服 CEE 和未使用雌激素的凝血倾向。另一个目的是确定从越来越多的文献中新发现的血栓形成遗传风险是否可以通过雌激素的使用而改变。该研究的背景是 Group Health，这是华盛顿州的一家大型综合医疗机构。研究人群将包括30至89岁的围绝经期和绝经后团体健康成员，他们经历过VT事件，无论是深静脉血栓形成还是致命或非致命性肺栓塞。该应用程序将支持识别和提取 2013 年发生的 VT 病例及其匹配对照的医疗记录数据。将从同意者身上采集血液并提取 DNA。有关口服雌激素产品安全性的数据有限，阻碍了女性及其医生在选择雌激素产品来治疗更年期血管舒缩症状时做出基于证据的决定。这项竞争性更新旨在利用这一独特而宝贵的资源扩大研究范围，该资源已经产生了重要的流行病学信息，并可能提供高质量的数据，以开始解决妇女健康的重要公共卫生问题。公共健康相关性：有关口服雌激素产品安全性的数据有限，阻碍了女性及其医生在选择雌激素产品来治疗更年期血管舒缩症状时做出基于证据的决定。静脉血栓形成可能是短期使用雌激素最严重的副作用，但实际上对第二常用雌激素口服雌二醇的风险一无所知。我们建议在绝经后妇女中扩展基于人群的病例对照研究，以检查与口服雌二醇和其他雌激素相关的静脉血栓形成的风险。