Cardiovascular safety in middle-aged and older men under testosterone replacement therapy: a systematic review and meta-analysis.

Authors

Hongzhuo Qin, Dandan Zuo, Zhan Wang, Luwei Li, Lulu Zuo, Yingying Lv, Shiqi Tu, Jiaojiao Wang, Yun Chen, Xiaosi Li, Jieyu He, Qinyu Zou, Qiong Lu, Qiyue Zheng, Zhaokai Zhou

Published in

Endocrine. Volume 91. Issue 1. Oct 06, 2026. Epub Oct 06, 2026.

Abstract

Testosterone replacement therapy (TRT) is a standard treatment for men with hypogonadism, offering potential benefits including improvements in sexual function, body composition, bone mineral density, mood, and metabolic health. However, its cardiovascular safety remains uncertain due to conflicting evidence.
To assess the cardiovascular safety of testosterone replacement therapy in middle-aged and older men.
PubMed, Web of Science, EMBASE and the Cochrane Library databases were searched for randomized-controlled trials (RCTs) published up to July 25, 2024. The Cochrane Handbook for Systematic Reviews of Interventions, version 6.0, guided our meta-analysis. PROSPERO registration number 42,023,421,479.
This meta-analysis included 31 RCTs with a total of 9,437 participants, and treatment durations ranged from 40 days to 36 months. TRT was associated with significant reductions in total cholesterol (WMD: -10.20; 95% CI: -14.52, -5.88 mg/dL; P = 0.005), triglyceride (WMD: -7.03; 95% CI: -12.25, -1.81 mg/dL; P = 0.008), and low-density lipoprotein (WMD: -6.64; 95% CI: -8.65, -4.63 mg/dL; P < 0.00001), whereas no significant change was observed in high-density lipoprotein cholesterol (WMD: -1.39; 95% CI: -3.12, 0.35 mg/dL; P = 0.12), compared with placebo. Additionally, TRT significantly prolonged the exercise time to the onset of 1-mm ST-segment depression during treadmill exercise testing (single-dose to 14 weeks; WMD: 67.37; 95% CI: 55.05, 79.69 s; P < 0.00001), and reduced carotid intima-media thickness (12-36 months; WMD: -0.03; 95% CI: -0.05, -0.02 mm; P = 0.0003). Among nonfatal cardiovascular events, a potential arrhythmia safety signal was observed (6598 participants, OR: 1.58; 95% CI: 1.21, 2.05; P = 0.0007).
TRT appears to reduce overall cardiovascular risk factors in middle-aged and older men with low or low-normal testosterone levels, but the clinical significance of the observed arrhythmia signal remains uncertain.

PMID:
42836912
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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