Longevity & Aging · Metabolic & Cardiometabolic
testosterone replacement therapy is noninferior to placebo
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
What the evidence shows
TRAVERSE, the large dedicated safety trial, found testosterone replacement non-inferior to placebo for major cardiac events over about three years, and a 30-trial meta-analysis agrees. Non-inferior is not harmless: the trial raised atrial fibrillation, ambulatory monitoring shows testosterone gel raising systolic blood pressure, and regulators added a class-wide warning in 2025.
The evidence (13)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Pencina KM, Lincoff AM, Klein EA, Nissen SE, Shang YV, Khan N, Li X, Chan A, Miller MG, Bhasin S 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, Cristiano E, Wiegmann T, Grasing K, Drees B, Sharma R, Garcia-Touza M 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 L, Maslyk M, Kaminska H, Al-Jeabory M, Pruc M, Denegri A 2026 · Pol Heart J | RCT | mixed | moderate | Narrative review, not evidence: 'This narrative review integrates randomized and real‑world evidence on TRT‑associated AF, AKI, and PE'. Re-describes TRAVERSE: 'demonstrated non‑inferiority of TRT vs. placebo for MACE, but reported higher event rates of AF, AKI, and PE in the testosterone group.' Review — zero weight. |
| Krishnan S, Aldana-Bitar J, Golub I, Ichikawa K, Shabir A, Bagheri M, Hamidi H, Benzing T, Kianoush S, Budoff MJ 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 GI 2025 · World J Mens Health | observational | supports | moderate | Hackett narrative review of TRAVERSE (5,246 hypogonadal men at CV risk, T gel vs placebo, mean 27.1 mo): 'TRAVERSE found no increase in major adverse cardiac events or prostate related events'. Re-describes the trial already counted via trt-lincoff-traverse-2023 — review, zero weight. |
| Bhasin S, Lincoff AM, Nissen SE, Wannemuehler K, McDonnell ME, Peters AL, Khan N, Snabes MC, Li X, Li G, Buhr K, Pencina KM, Travison TG 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 MA, Aslam S, Efros MD, Chan A, Khan N, Li X, Dubcenco E, Miller MG 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 V, Sawhney A, Nebuwa C, Borra V, Deb N, Halder A, Rajak K, Jha M, Wajid Z, Thachil R, Bandyopadhyay D, Mattumpuram J, Lavie CJ 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 BB, Anawalt BD 2026 · J Clin Endocrinol Metab | observational | supports | moderate | Narrative review, no new data: 'This narrative review summarizes the relationships between testosterone and cardiovascular health outcomes, based on observational and interventional studies.' Restates TRAVERSE: 'found no increased risk of major adverse cardiovascular events in men randomized to testosterone treatment vs placebo, with average follow-up of 3 years.' Review — zero weight; TRAVERSE votes on its own. |
| Zitzmann M, Rastrelli G, Murray RD, Edwards D, Reisman Y, Rao PM, Sahi A, Jones TH, Ferlin A, Armeni E, Corpas E, Cremers JF, David J, Arver S, Antonio L, Corona G 2026 · Andrology | observational | supports | moderate | European expert-panel position statement, no new data or pooling: 'This position statement synthesizes the current evidence on the cardiovascular safety of testosterone therapy, drawing from key studies including the TRAVERSE trial, other trials, and recent meta‐analyses.' It restates a cited meta-analysis: 'The meta‐analysis found no significant difference in the occurrence of MACE between the TTh and placebo groups'. Review — zero weight; TRAVERSE and the meta-analysis vote on their own. |
| Haider SH, Irfan A, Sheikh SM, Abid MT, Naz T, Abbas M, Raza A 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, Dhingra OP 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 A, Murtola TJ, Kausz J, Talala K, Taari K, Tammela TL, Auvinen A 2023 · Acta Oncol | observational | supports | moderate | Finnish cohort found TRT not associated with increased cardiovascular-specific mortality. |
Disagree, or know a study we missed?
We grade by evidence, not opinions. The way to weigh in is to point us to a study we haven't cited (check the evidence table above first), or to flag a problem with one we have. Every submission is reviewed; if it holds up, the grade updates and shows in Science Changes Its Mind.
Opens a short form. You'll sign in with Google so submissions are tied to a real account — we don't display your identity, and we only accept a link we can verify (PubMed, DOI, ClinicalTrials.gov).
Educational only, not medical advice. Grades and scores reflect published evidence weighted by study design and quality; see the methodology.