A retrospective cohort study of the safety of testosterone therapy in older men

描述(申请人提供)：近年来，在老年男性中越来越多地使用睾酮补充剂，这引起了人们对外源性睾丸素服用安全性的担忧。新的配方和递送机制，更多的直接面向消费者的营销，以及更广泛地认识到老年和慢性病中睾酮水平的自然下降，所有这些都有助于更广泛地使用睾酮疗法，而没有强有力的证据表明对已经面临发病率和死亡率风险的老年男子有疗效或安全性保证。最近的随机试验表明心血管事件的风险增加，但文献主体仍然没有确凿的证据。需要对大量人群进行更多的分析，以更好地描述睾酮疗法在现实世界实践中的使用情况，并评估使用睾酮可能增加严重不良事件风险的可能性。我们建议进行一项大型回溯性队列研究，使用来自美国拥有医疗保险或商业保险的大量老年男性的医疗保健和实验室测试数据。我们还将使用来自英国全科医学研究数据库的临床数据创建第二个队列。我们将研究与睾酮测试相关的启动模式，以及处方如何随着时间的推移而变化。我们将使用倾向评分技术来比较睾丸素使用者和具有相似睾酮水平的非使用者的心血管事件发生率。我们将检查骨折和前列腺癌的风险作为次要结果。这些影响也将在弱势群体(例如，老年、慢性病、不同程度的睾丸素缺乏)中进行调查。我们将使用自身对照病例交叉分析来研究急性事件的瞬时风险。最后，将比较不同的睾酮释放机制(如贴片、凝胶、注射)，以确定不同配方之间是否存在不同的风险。这项研究的结果将为围绕老年男性使用外源性睾酮安全性的越来越多但尚不确定的文献提供重要证据。

DESCRIPTION (provided by applicant): Increased use of testosterone supplementation among older men in recent years has caused concern about the safety of exogenous testosterone administration. New formulations and delivery mechanisms, increased direct-to-consumer marketing, and wider recognition of natural declines in testosterone levels in older age and chronic disease have all contributed to wider use of testosterone therapy, without strong evidence of benefit or assurance of safety in older men who are already at risk for morbidity and mortality. Recent randomized trials have suggested an increased risk of cardiovascular events, but the body of literature is still without conclusive evidence. Additional analyses of large populations are needed to better describe how testosterone therapy is used in real-world practice and assess the possibility that use of testosterone may increase risk of serious adverse events. We propose a large retrospective cohort study using healthcare and laboratory testing data from a large population of older men in the United States with Medicare or commercial insurance. We will also create a second cohort using clinical data from the United Kingdom's General Practice Research Database. We will study patterns of initiation relative to testosterone testing, and how prescribing has changed over time. We will use propensity score techniques to compare rates of cardiovascular events in testosterone users to those of non-users with comparable testosterone levels. We will examine the risk of bone fractures and prostate cancer as secondary outcomes. These effects will also be investigated in vulnerable subgroups (e.g. older age, chronic disease, varying levels of testosterone deficiency). We will study transient risk of acute events using a self-controlled case-crossover analysis. And finally, different testosterone delivery mechanisms (e.g. patch, gel, injections) will be compared to determine if there are differential risks among the different formulations. The results of this stuy will contribute important evidence to the growing, but yet inconclusive, body of literature surrounding the safety of exogenous testosterone use among older men.