Cardiovascular and Prostatic Safety of Testosterone Therapy in Aging Males

老年男性睾酮治疗的心血管和前列腺安全性

• 批准号: 8625435
• 负责人: Craig T Cheetham
• 金额: $ 3.34万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8625435
• 关键词: Accounting; Adverse effects; Affect; Aftercare; Age; Aging; Ambulatory Care; Androgens; Benefits and Risks; Benign; Benign Prostatic Hypertrophy; Cardiovascular Diseases; Cardiovascular system; Clinical; Clinical Data; Cohort Analysis; Cohort Studies; Comorbidity; Complex; Data; Databases; Decreased Libido; Diagnosis; Diagnostic tests; Disease; Drug Formulations; Elderly; Electronic Health Record; Electronics; Epidemiologic Studies; Erectile dysfunction; Ethnic Origin; Evaluation; Event; Exposure to; Fatigue; Health Planning; Health system plans; Healthcare; Healthcare Systems; Inpatients; Laboratories; Malignant - descriptor; Malignant neoplasm of prostate; Mental Depression; Metabolic; Methods; Multivariate Analysis; Myocardial Ischemia; Newly Diagnosed; Outcome; Patients; Peripheral Vascular Diseases; Pharmaceutical Preparations; Pharmacy facility; Physical Function; Population; Prevalence; Procedures; Proportional Hazards Models; Prostate; Prostatic; Prostatic Diseases; Race; Randomized Controlled Trials; Research; Resources; Risk; Safety; Serum; Side; Stroke; Survival Analysis; Symptoms; System; Techniques; Test Result; Testing; Testosterone; Thinking; Time; United States; arm; cardiovascular risk factor; cohort; experience; health care delivery; insight; interest; male; man; member; men; muscle form; older men; population based; randomized placebo controlled trial; testosterone replacement therapy; therapy duration; treatment as usual; trend

DESCRIPTION (provided by applicant): Androgen deficiency affects approximately 9% of elderly males in the United States and the prevalence is projected to increase with the overall aging of the population. The diagnosis of androgen deficiency is made when clinical symptoms such as decreased libido, erectile dysfunction, fatigue and depression are found in conjunction with low levels of serum testosterone. Testosterone replacement therapy is a widespread and growing practice for treating androgen deficiency. Known or suspected risks of testosterone therapy include cardiovascular diseases and adverse prostate outcomes. The proposed study is a retrospective cohort analysis of testosterone users in a large integrated healthcare delivery system (health-plan) that has extensive electronic health record and clinical data so that complete utilization and exposure data can be captured. The specific aims are to: 1) to determine the risk of cardiovascular events associated with the use of testosterone replacement therapy, and 2) to test the hypothesis that the risk of benign and malignant prostate disease associated with the use of testosterone replacement therapy is greater than expected for men with similar underlying risk. The unique and comprehensive data resources available from the health-plan will allow linkage of all inpatient and outpatient care with prescriptions, laboratory testing results, procedures and diagnostic tests. The cohort will be created by inclusion of any man with a diagnosed indication (androgen deficiency) for exogenous testosterone therapy as well as those with low serum testosterone levels. Exposure to exogenously administered testosterone will be directly ascertained from electronic pharmacy data that exists within the health-plan. Comparisons will be made between androgen deficient males treated and not treated with exogenous testosterone. Standard survival analysis techniques will be used to examine testosterone replacement therapy in relation to each event of interest (cardiovascular diseases and prostate outcomes). Comorbidities that are potentially related to exogenous testosterone exposure, cardiovascular and prostate-related disease will be determined, categorized and controlled for in the multivariate analysis. In addition to conventional proportional hazards models a Propensity Score Analysis and/or an Instrumental Variable Analysis will be used to identify and control for unobserved confounding. These additional approaches will allow for a more robust and fuller understanding of the risks associated with testosterone replacement therapy. Completion of the aims will provided important information about the potential adverse effects of testosterone therapy in men, adding insight into the risk side of the risk-benefit evaluation to help guide current thinking about the appropriate use of thi therapy.

描述（由申请人提供）：雄激素缺乏影响美国约9％的老年男性，并且预计患病率会随着人口的整体老龄而增加。当临床症状降低，勃起功能障碍，疲劳和抑郁症与血清睾丸激素水平较低时，可以诊断出雄激素缺乏症。睾丸激素替代疗法是治疗雄激素缺乏症的一种广泛而增长的实践。睾丸激素治疗的已知或怀疑风险包括心血管疾病和前列腺不良结局。拟议的研究是对大型综合医疗保健输送系统（健康计划）中睾丸激素使用者进行的回顾性队列分析，该分析具有广泛的电子健康记录和临床数据，因此可以捕获完整的利用和暴露数据。具体目的是：1）确定与使用睾丸激素替代疗法相关的心血管事件的风险，以及2）测试假说，即良性和恶性前列腺疾病的风险与使用睾丸激素替代疗法相关的良性和恶性前列腺疾病的风险比具有相似风险的男性的预期更大。健康计划中可用的独特而全面的数据资源将允许将所有住院和门诊护理与处方，实验室测试结果，程序和诊断测试联系起来。该队列将通过包括任何具有诊断适应症（雄激素缺乏症）的男子对外源睾丸激素疗法以及血清睾丸激素水平较低的人创建。从健康计划中存在的电子药房数据中，将直接确定外源给予睾丸激素的暴露。将进行比较，与未用外源睾丸激素治疗的雄激素缺乏的雄性雄性。标准生存分析技术将用于检查与每种事件有关的睾丸激素替代疗法（心血管疾病和前列腺结局）。在多变量分析中，将确定，分类和控制与外源性睾丸激素，心血管和前列腺相关疾病的合并症。除了常规的比例危害模型外，倾向得分分析和/或仪器变量分析还将用于识别和控制未观察的混杂。这些额外的方法将使人们对与睾丸激素替代疗法相关的风险有更加强大，更充分的了解。目标的完成将提供有关男性睾丸激素治疗潜在不利影响的重要信息，从而深入了解风险效益评估的风险方面，以帮助指导当前有关适当使用Thi治疗的思考。