Yeap Bu B, Tran Cammie, Douglass Catherine M, McNeil John J
Medical School, University of Western Australia, Perth, Australia.
Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.
Drugs Aging. 2025 Apr 27. doi: 10.1007/s40266-025-01209-1.
Testosterone is the classical male anabolic hormone, involved in sexual development, virilisation and regulation of body composition in adult men. Organic disease involving the hypothalamus, pituitary or testes may interfere with endogenous testosterone production. In such men, testosterone treatment effectively ameliorates symptoms and signs of androgen deficiency. However, non-gonadal factors including age, body mass index and medical comorbidities influence circulating testosterone, and older men have on average lower testosterone concentrations compared with younger men. In these men, testosterone treatment would be a pharmacological intervention requiring stringent justification via high-quality evidence from randomised controlled trials (RCTs). Recent RCTs show benefits of testosterone treatment to improve sexual function, anaemia and bone mineral density in older men, and to prevent or revert type 2 diabetes mellitus in men at high risk. Results from a large cardiovascular safety trial in men with or at risk of cardiovascular disease provide important reassurance as to cardiovascular and prostate safety of testosterone treatment. Key questions remain as to whether testosterone's anabolic and other effects can be used safely to counter reductions in lean mass associated with incretin-based weight loss medications in men with obesity, and whether it might prevent disabilities including frailty, osteoporotic fractures and dementia in older men generally. This last question could be answered by a new testosterone RCT, targeting men in the 65-80 years age bracket, which would necessarily be large and of extended duration. A composite endpoint could be used which integrates potential benefits and risks, such as disability-free survival.
睾酮是典型的男性合成代谢激素，参与成年男性的性发育、男性化过程以及身体成分的调节。涉及下丘脑、垂体或睾丸的器质性疾病可能会干扰内源性睾酮的产生。对于这类男性，睾酮治疗可有效改善雄激素缺乏的症状和体征。然而，包括年龄、体重指数和合并症在内的非性腺因素会影响循环睾酮水平，与年轻男性相比，老年男性的睾酮浓度平均较低。对于这些男性，睾酮治疗将是一种药物干预，需要通过随机对照试验（RCT）的高质量证据进行严格论证。最近的RCT表明，睾酮治疗对改善老年男性的性功能、贫血和骨密度，以及预防或逆转高危男性的2型糖尿病有益。一项针对患有心血管疾病或有心血管疾病风险男性的大型心血管安全性试验结果，为睾酮治疗的心血管和前列腺安全性提供了重要的保证。关于睾酮的合成代谢及其他作用能否安全用于对抗肥胖男性使用基于肠促胰岛素的减肥药物导致的瘦体重减少，以及它是否能普遍预防老年男性的残疾，包括虚弱、骨质疏松性骨折和痴呆，关键问题依然存在。最后一个问题可以通过一项新的睾酮RCT来回答，该试验针对65至80岁年龄段的男性，试验规模必然要大且持续时间要长。可以使用一个综合终点指标，将潜在的益处和风险整合在一起，如无残疾生存期。
