Longevity & Aging · Metabolic & Cardiometabolic
testosterone replacement therapy is-non-inferior-to-placebo-for major adverse cardiac events in older men with CV risk
In plain terms: Is testosterone therapy safe for the heart in older at-risk men?
Part of: 💊 Testosterone therapy (TRT)
The large TRAVERSE RCT found TRT non-inferior to placebo for major cardiac events over about 3 years, though it raised atrial fibrillation, pulmonary embolism, and acute kidney injury and does not speak to longer horizons.
📅 Last reviewed: 2026-07-14 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: All trials, pooled (Meta-analysis)
How the studies fall
The evidence (13)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Pencina 2025 · J Endocr Soc | RCT | supports | moderate | TRAVERSE analysis found no adverse interaction between TRT and COVID-19 on cardiovascular-relevant outcomes, consistent with overall CV safety. |
| Tadisina S 2026 · Andrology | observational | contradicts | low | VA propensity-matched retrospective study (n=2518/arm) found TRT associated with higher new-onset hypertension (10.48% vs 6.04%), stroke (1.43% vs 0.52%), CAD (2.26% vs 1.51%), and markedly higher all-cause mortality (10.13% vs 1. |
| Szarpak 2026 · Pol Heart J | RCT | mixed | moderate | Confirms TRAVERSE MACE non-inferiority but highlights higher rates of atrial fibrillation, acute kidney injury, and pulmonary embolism in the T arm — safety is not unqualified. |
| Krishnan 2024 · Prog Cardiovasc Dis | observational | mixed | moderate | Narrative review notes TRAVERSE showed no excess MACE but flags low-normal dosing, high dropout, short follow-up and TTrials non-calcified plaque signal as caveats. |
| Hackett 2025 · World J Mens Health | observational | supports | moderate | TRAVERSE: 5,246 hypogonadal men (T less than 10.4 nmol/L) with high CV risk, transdermal T gel vs placebo, mean 27 months — no increase in MACE (primary composite non-inferior) and no excess prostate events. |
| Bhasin 2024 · JAMA Intern Med | RCT | supports | high | TRAVERSE substudy found testosterone did not raise cardiovascular risk and did not worsen glycemia in men with prediabetes/diabetes. |
| Weber 2025 · Andrology | observational | contradicts | moderate | Ambulatory BP study found T gel raises systolic BP — the basis for FDA's 2025 class-wide blood-pressure warning; a real residual CV-relevant signal. |
| Jaiswal 2024 · Prog Cardiovasc Dis | meta-analysis | supports | moderate | Meta-analysis of 30 RCTs found no significant increase in cardiovascular events with testosterone therapy in hypogonadal men. |
| Yeap 2026 · J Clin Endocrinol Metab | observational | supports | moderate | Independent narrative synthesis: TRAVERSE (mean 3-yr follow-up) shows no MACE excess, but calls follow-up short and says long-term CV safety still needs confirmation. |
| Zitzmann 2026 · Andrology | observational | supports | moderate | European expert-panel synthesis of TRAVERSE plus other RCTs and meta-analyses concludes TRT does not increase MACE in hypogonadal men. |
| Haider SH 2024 · Future Sci OA | meta-analysis | supports | low | Systematic review/meta-analysis of RCTs and observational studies (search through June 2023) found no association between TRT and carotid intima-media thickness or other atherosclerosis markers, concluding TRT allows safe usage in |
| Bernstein JS 2024 · Ther Adv Urol | observational | tested-null | low | Single-arm phase III 6-month trial of oral testosterone undecanoate (n=155) reported no drug-related serious adverse events, only one adverse drug reaction (hypertension, in >=2% of participants), and a modest 1.7 mmHg rise in sys |
| Siltari 2023 · Acta Oncol | observational | supports | moderate | Finnish cohort found TRT not associated with increased cardiovascular-specific mortality. |
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