Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Rev Cardiol. 2019 Sep;16(9):555-574. doi: 10.1038/s41569-019-0211-4.
Testosterone is the main male sex hormone and is essential for the maintenance of male secondary sexual characteristics and fertility. Androgen deficiency in young men owing to organic disease of the hypothalamus, pituitary gland or testes has been treated with testosterone replacement for decades without reports of increased cardiovascular events. In the past decade, the number of testosterone prescriptions issued for middle-aged or older men with either age-related or obesity-related decline in serum testosterone levels has increased exponentially even though these conditions are not approved indications for testosterone therapy. Some retrospective studies and randomized trials have suggested that testosterone replacement therapy increases the risk of cardiovascular disease, which has led the FDA to release a warning statement about the potential cardiovascular risks of testosterone replacement therapy. However, no trials of testosterone replacement therapy published to date were designed or adequately powered to assess cardiovascular events; therefore, the cardiovascular safety of this therapy remains unclear. In this Review, we provide an overview of epidemiological data on the association between serum levels of endogenous testosterone and cardiovascular disease, prescription database studies on the risk of cardiovascular disease in men receiving testosterone therapy, randomized trials and meta-analyses evaluating testosterone replacement therapy and its association with cardiovascular events and mechanistic studies on the effects of testosterone on the cardiovascular system. Our aim is to help clinicians to make informed decisions when considering testosterone replacement therapy in their patients.
睾丸激素是主要的男性性激素，对于维持男性第二性征和生育能力至关重要。由于下丘脑、垂体或睾丸的器质性疾病导致年轻男性雄激素缺乏，几十年来一直使用睾丸激素替代疗法治疗，而没有心血管事件增加的报告。在过去十年中，由于血清睾丸激素水平下降与年龄相关或与肥胖相关，为中年或老年男性开具的睾丸激素处方数量呈指数级增长，尽管这些情况不是睾丸激素治疗的批准适应症。一些回顾性研究和随机试验表明，睾丸激素替代疗法会增加心血管疾病的风险，这导致 FDA 发布了关于睾丸激素替代疗法潜在心血管风险的警告声明。然而，迄今为止，没有发表的睾丸激素替代疗法试验旨在或有足够的能力评估心血管事件；因此，这种治疗的心血管安全性仍不清楚。在这篇综述中，我们概述了内源性睾丸激素水平与心血管疾病之间的关联的流行病学数据、接受睾丸激素治疗的男性心血管疾病风险的处方数据库研究、评估睾丸激素替代疗法及其与心血管事件关联的随机试验和荟萃分析，以及关于睾丸激素对心血管系统影响的机制研究。我们的目的是帮助临床医生在考虑为患者使用睾丸激素替代疗法时做出明智的决策。
