SynthesisEndocrine2026
Cardiovascular safety in middle-aged and older men under testosterone replacement therapy: a systematic review and meta-analysis.
Synthesis in Endocrine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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15 authors.
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Abstract
backgroundTestosterone 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.
objectivesTo assess the cardiovascular safety of testosterone replacement therapy in middle-aged and older men.
methodsPubMed, 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.
resultsThis 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).
conclusionTRT 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.
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