Medical School, University of Western Australia.
Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth.
Curr Opin Endocrinol Diabetes Obes. 2024 Dec 1;31(6):222-229. doi: 10.1097/MED.0000000000000886. Epub 2024 Sep 18.
Lower testosterone concentrations have been associated with poorer health outcomes in ageing men, but proving causality and demonstrating potential for therapeutic benefit requires randomized clinical trials (RCTs). This review discusses recent observational findings and results of major testosterone RCTs, to explore the need for another, larger trial.
Evidence of Leydig cell impairment emerges in men above the age of 70 years. Lower testosterone is associated with diabetes risk, and also risk of incident dementia. An individual participant data meta-analysis found that below thresholds of testosterone of 7.4 nmol/L and 5.3 nmol/l respectively, risks of all-cause mortality and cardiovascular deaths in men increased. Testosterone for the Prevention of Type 2 Diabetes Mellitus (T4DM), a multicentre RCT, showed that testosterone treatment prevented or reverted type 2 diabetes in men at high risk. Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE), a cardiovascular safety trial, demonstrated cardiovascular and prostate safety of testosterone treatment in men with or at risk of cardiovascular disease. T4DM confirmed findings from the Testosterone Trials (T-Trials) that testosterone improved sexual function, and bone microarchitecture and density. However, in TRAVERSE, testosterone-treated men had a higher risk of clinical bone fractures, but not major osteoporotic fractures.
Men with disorders of the hypothalamic-pituitary-testicular (HPT) axis causing androgen deficiency warrant consideration for testosterone therapy. In men with an intact HPT axis, testosterone treatment is a pharmacological intervention which requires justification from high quality RCT data. Currently, there is insufficient evidence to justify wider use of testosterone for prevention of cardiometabolic disease. However, there is scope for another large testosterone RCT to investigate whether testosterone treatment might, in older men, extend disability-free survival.
较低的睾酮浓度与老年男性健康状况较差有关，但要证明因果关系并证明潜在的治疗益处，需要进行随机临床试验（RCT）。本综述讨论了最近的观察性发现和主要睾酮 RCT 的结果，以探讨是否需要进行另一项更大规模的试验。
70 岁以上男性的睾丸间质细胞功能障碍证据逐渐显现。睾酮水平较低与糖尿病风险相关，也与痴呆症发病风险相关。一项个体参与者数据荟萃分析发现，当睾酮水平分别低于 7.4nmol/L 和 5.3nmol/L 的阈值时，男性的全因死亡率和心血管死亡率风险增加。预防 2 型糖尿病的睾酮（T4DM）多中心 RCT 表明，睾酮治疗可预防或逆转高危男性的 2 型糖尿病。评估低睾酮男性长期血管事件和疗效反应的睾酮替代治疗（TRAVERSE）心血管安全性试验表明，睾酮治疗在有或有心血管疾病风险的男性中具有心血管和前列腺安全性。T4DM 证实了睾酮试验（T-Trials）的发现，即睾酮改善了性功能以及骨微结构和密度。然而，在 TRAVERSE 中，接受睾酮治疗的男性发生临床骨折的风险较高，但主要骨质疏松性骨折的风险没有增加。
患有下丘脑-垂体-睾丸（HPT）轴功能障碍导致雄激素缺乏的男性需要考虑进行睾酮治疗。对于 HPT 轴完整的男性，睾酮治疗是一种需要高质量 RCT 数据证明合理性的药物干预措施。目前，尚无足够证据支持更广泛地使用睾酮预防心血管代谢疾病。然而，有必要进行另一项大型睾酮 RCT，以调查在老年男性中，睾酮治疗是否可以延长无残疾生存时间。
