美国克利夫兰诊所Steven E. Nissen团队研究了睾酮替代疗法对有心血管风险中老年男性的安全性。相关论文发表在2023年6月16日出版的《新英格兰医学杂志》上。

睾酮替代治疗患有性腺功能减退症的中老年男性的心血管安全性尚未确定。

在一项多中心、随机、双盲、安慰剂对照、非劣效性试验中，研究组招募了5246名45至80岁的男性，他们之前患有心血管疾病或有心血管疾病的高风险，并报告了性腺功能减退症状，两次空腹睾酮水平低于每分升300纳克。患者被随机分配接受每日经皮1.62%睾酮凝胶（校正剂量以保持睾酮水平在每分升350至750纳克之间）或安慰剂凝胶。

主要心血管安全终点是首次发生心血管原因死亡、非致命性心肌梗死或非致命性中风综合结局中的任何组成，在事件发生时间分析中进行评估。次要心血管终点是心血管原因死亡、非致命性心肌梗死、非致命中风或冠状动脉血运重建综合结局中任何组成的首次发生，在事件发生时间分析中进行评估。非劣效性要求在接受至少一剂睾酮或安慰剂的患者中，风险比的95%置信区间的上限小于1.5。

平均（±SD）治疗时间为21.7±14.1个月，平均随访时间为33.0±12.1个月。睾酮组182名患者（7.0%）和安慰剂组190名患者（7.3%）发生了原发性心血管终点事件（危险比为0.96；非劣效性P<0.001）。在敏感性分析中也观察到了类似的发现，其中在停用睾酮或安慰剂后的不同时间对事件数据进行审查。两组中次要终点事件或综合主要心血管终点的每一个事件的发生率大体相似。睾酮组的心房颤动、急性肾损伤和肺栓塞发生率较高。

研究结果表明，在患有性腺功能减退症和已有心血管疾病或有心血管疾病高风险的男性中，睾酮替代疗法在重大心脏不良事件的发生率方面并不逊于安慰剂。

附：英文原文

Title: Cardiovascular Safety of Testosterone-Replacement Therapy | NEJM

Author: A. Michael Lincoff, M.D.,, Shalender Bhasin, M.B., B.S.,, Panagiotis Flevaris, M.D., Ph.D.,, Lisa M. Mitchell, R.N., B.S.N.,, Shehzad Basaria, M.D.,, William E. Boden, M.D.,, Glenn R. Cunningham, M.D.,, Christopher B. Granger, M.D.,, Mohit Khera, M.D., M.P.H.,, Ian M. Thompson, Jr., M.D.,, Qiuqing Wang, M.S.,, Kathy Wolski, M.P.H.,, Deborah Davey, R.N.,, Vidyasagar Kalahasti, M.D.,, Nader Khan, M.D.,, Michael G. Miller, Pharm.D.,, Michael C. Snabes, M.D., Ph.D.,, Anna Chan, Pharm.D.,, Elena Dubcenco, M.D.,, Xue Li, Ph.D.,, Tingting Yi, Ph.D.,, Bidan Huang, Ph.D.,, Karol M. Pencina, Ph.D.,, Thomas G. Travison, Ph.D.,, and Steven E. Nissen, M.D.

Issue&Volume: 2023-06-16

Abstract:

Background

The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined.

Methods

In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo.

Results

The mean (±SD) duration of treatment was 21.7±14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group.

Conclusions

In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events.

DOI: 10.1056/NEJMoa2215025

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2215025