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

描述（由申请人提供）：近年来，老年男性中睾酮补充剂的使用增加，引起了对外源性睾酮给药安全性的担忧。新的配方和输送机制，增加直接面向消费者的营销，以及更广泛地认识到老年和慢性疾病中睾酮水平的自然下降，都有助于更广泛地使用睾酮治疗，但没有强有力的证据证明已经处于发病和死亡风险中的老年男性的益处或安全性保证。最近的随机试验表明，心血管事件的风险增加，但文献的主体仍然没有确凿的证据。需要对大量人群进行额外的分析，以更好地描述睾酮治疗在现实世界中的应用，并评估使用睾酮可能增加严重不良事件风险的可能性。我们提出了一个大型回顾性队列研究，使用医疗保健和实验室检测数据，从一个大的人口在美国的老年男性医疗保险或商业保险。我们还将使用英国全科医学研究数据库的临床数据创建第二个队列。我们将研究与睾酮检测相关的启动模式，以及处方如何随时间变化。我们将使用倾向评分技术比较睾酮使用者与睾酮水平相当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局。这些影响也将在脆弱亚组（如老年人，慢性疾病，不同程度的睾酮缺乏症）进行研究。我们将使用自身对照病例交叉分析研究急性事件的短暂风险。最后，将比较不同的睾酮递送机制（例如贴剂、凝胶、注射剂），以确定不同制剂之间是否存在差异风险。这项研究的结果将为不断增长的，但尚未确定的，围绕老年男性使用外源性睾酮安全性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.