Longevity & Aging · Metabolic & Cardiometabolic
testosterone therapy does not increase cardiovascular risk
In plain terms: Is testosterone therapy safe for your heart?
Contested Longevity & Aging 💰 Industry COI noted🔬 Includes disconfirming
Part of: 💊 Testosterone therapy (TRT)
RefutedContestedStrong support
consensus score 0.16
Mostly reassuring, not fully settled. The big 2023 TRAVERSE trial found no increase in major cardiac events (heart attack, stroke, cardiac death) — putting an old scare to rest — but it did find more atrial fibrillation and blood clots in the lungs. So: probably safe for major events in the right patients, with a real, unresolved signal for irregular heartbeat and clots.
📅 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)
MechanismIn-vitroAnimalObservationalRCTMeta-analysis
How the studies fall
7 support 7 contradict 1 tested null 5 mixed · 20 sources, 14 independent groups
What the evidence shows
TRT's cardiovascular safety is reassuring on the biggest question but not fully settled. The large TRAVERSE randomized trial (2023) found testosterone was non-inferior to placebo for major cardiac events (heart attack, stroke, CV death) — strong evidence against the earlier scare — and several meta-analyses agree.
The evidence (21)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| La Vignera S, Condorelli RA 2026 · Eur J Intern Med | RCT | supports | moderate | Narrative review, not evidence: 'This review synthesizes evidence from randomized controlled trials, prospective registries, and observational studies'; restates 'Cardiovascular safety data from large trials indicate noninferiority to placebo for major adverse cardiac events'. Review — zero weight. |
| García-Becerra CA, Arias-Gallardo MI, Juárez-García JE, Soltero-Molinar V, Parra-Camaño LF, Rivera-Rocha MI, García-Becerra N, García-Gutiérrez CM 2026 · Int J Impot Res | meta-analysis | supports | moderate | Meta-analysis of 41 RCTs (n = 11,161; PROSPERO CRD42024603054): 'TTh was not associated with a statistically significant increase in MACE (OR 0.83; 95% CI: 0.52-1.32; I² = 53.2%)'. Supports the negated claim, but only weakly: the interval still admits a 32% relative increase, heterogeneity is moderate and author-attributed to case-mix ('Comorbidities contributed to heterogeneity in MACE outcomes'), and the authors limit their own conclusion to 'the short- to mid-term safety of TTh, though long-term data remain necessary'. Silent on atrial fibrillation and venous thromboembolism — MACE is the only cardiovascular endpoint pooled. Paywalled; abstract-only, so no risk-of-bias table, event counts or follow-up durations were seen. |
| Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, Cunningham GR, Granger CB, Khera M, Thompson IM, Wang Q, Wolski K, Davey D, Kalahasti V, Khan N, Miller MG, Snabes MC, Chan A, Dubcenco E, Li X, Yi T, Huang B, Pencina KM, Travison TG, Nissen SE, TRAVERSE Study Investigators 2023 · N Engl J Med | RCT | mixed | high | TRAVERSE (n=5246): non-inferior to placebo for MACE (HR 0.96) BUT higher atrial fibrillation, acute kidney injury, and pulmonary embolism in TRT group. |
| Xu L, Freeman G, Cowling BJ, Schooling CM 2013 · BMC Med | meta-analysis | contradicts | moderate | Meta 27 RCTs: increased CV-event risk overall (OR 1.54); non-industry trials OR 2.06 vs industry OR 0.89. |
| Basaria S, Davda MN, Travison TG, Ulloor J, Singh R, Bhasin S 2012 · J Androl | RCT | contradicts | moderate | TOM trial substudy: trial halted early for excess CV events; greater free-T rise associated with events. |
| Merlino L, Rainone F, Tollitt J, Kalra MJ, Williford S, Rusconi F, Battini GG, Dunne RA, Hackett G, Kalra PA 2026 · World J Mens Health | observational | supports | low | TriNetX propensity-matched cohort of hypogonadal men with CKD stages 3-5 (1,545 per arm, median follow-up 60 months treated vs 45 months untreated). Stroke, myocardial infarction and heart failure were pre-specified 5-year outcomes: 'In the matched cohorts, under the proportional hazards assumption, there were no statistically significant differences between the TRT and non-TRT groups for any secondary outcome', and 'the risk of cardiovascular events and prostate cancer was not significantly higher among CKD TRT users'. All-cause mortality was lower on TRT (HR 0.78, 95% CI 0.63-0.98). Scope limit that matters for this claim: atrial fibrillation and venous thromboembolism/pulmonary embolism - the two signals TRAVERSE left open - were NOT among the measured outcomes, so this paper is silent on them; per-outcome hazard ratios sit in an image-only table, the design is retrospective EHR with prescription-channelling bias (only 32.2% of hypogonadal men treated) and 'the retrospective nature of our study design restricts the ability to infer causality'. [CAL read: index date is first TRT dose for treated vs diagnosis date for untreated - up to six months of immortal time favouring TRT, not named in the paper's Limitations.] |
| Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM 2013 · JAMA | observational | contradicts | moderate | Retrospective cohort (n=8709): TT associated with increased death/MI/stroke (25.7% vs 19.9% at 3y). |
| Alexander GC, Iyer G, Lucas E, Lin D, Singh S 2017 · Am J Med | meta-analysis | mixed | low | SR/meta 39 RCTs + 10 observational: no significant increase in MI/stroke/mortality, but evidence rated very low quality. |
| Munro V, Law J, Matheson K, Imran SA 2026 · The Journal of clinical endocrinology and metabolism | observational | supports | moderate | In 408 men with pituitary disease followed a median 8.1 years, multivariable analysis found no significant difference in MACE between TRT-treated secondary hypogonadism, untreated secondary hypogonadism, and no-hypogonadism groups; untreate |
| Higa S, Sakanashi M, Tsutsui M, Tasaki T, Tanimoto A, Taira Y, Shimokawa H, Kuniyoshi Y, Furukawa K 2026 · Circulation journal : official journal of the Japanese Circulation Society | animal | contradicts | low | In nitric-oxide-synthase-knockout mice with reduced NO production (modeling elderly men), long-term testosterone treatment worsened survival, increased myocardial infarction incidence, impaired arterial relaxation, and worsened cardiovascul |
| Vo TT, Roy S, Ye T, Erterfaie A, Pham Nguyen TP, Flory J, Leonard CE, Small DS, Hennessy S 2026 · American journal of epidemiology | observational | supports | moderate | Using three complementary quasi-experimental designs in a US insurance database, exogenous testosterone (vs glaucoma-treatment active comparator) showed no difference in risk of the composite endpoint of MI, ischemic stroke, and sudden card |
| Kerniss H, Curman P, Olbrich H, Kridin K, Francis R, Leistner DM, Alam U, Ludwig RJ 2026 · EBioMedicine | observational | contradicts | high | In 358,957 men, TT initiated without evidence of hypogonadism (35.4%) had higher MACE than TT initiated with evidence of hypogonadism (16.53% vs 11.83%; HR 1.51, 1.45-1.56) and higher all-cause mortality, ischaemic stroke, cardiac arrest, a |
| Cannarella R, Gusmano C, Leanza C, Garofalo V, Crafa A, Barbagallo F, Condorelli RA, Vignera S, Calogero AE 2023 · J Clin Med | meta-analysis | supports | moderate | Meta (14 RCTs + observational): no increased arterial/venous thrombosis, stroke, MI, or mortality in RCTs. |
| Morbey EJ, Day FR, Butterworth AS, Wareham NJ, Perry JRB, Ong KK 2026 · The Journal of clinical endocrinology and metabolism | observational | contradicts | moderate | Mendelian randomization in 425,097 UK Biobank men found higher genetically predicted circulating testosterone conferred higher coronary artery disease risk (OR 1.17, 1.07-1.27), likely mediated by blood pressure, while observational analysi |
| Ayele HT, Brunetti VC, Renoux C, Tagalakis V, Filion KB 2021 · Drug Saf | meta-analysis | mixed | moderate | Meta 13 RCTs (n=5050): TRT not associated with VTE (RR 1.03) but wide CIs cannot rule out risk. |
| Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF, Hoover RN 2014 · PLoS One | observational | contradicts | moderate | Self-controlled cohort (n=55,593): post-prescription MI rate ratio 1.36 overall; 2.19 in men >=65. |
| Glueck CJ, Goldenberg N, Wang P 2017 · Clin Appl Thromb Hemost | observational | mixed | low | Case-control: VTE peaks ~3 months post-initiation, concentrated in men with underlying thrombophilia (unmasks Factor V Leiden/high Lp(a)). |
| Traish AM, Haider KS, Saad F 2026 · The world journal of men's health | RCT | supports | moderate | Reviewing MEDLINE literature on TTh and atrial fibrillation in hypogonadal men, the majority of studies (including trial data) found T deficiency associated with greater AF incidence and that TTh does not increase AF incidence, though no tr |
| Sood A, Hosseinpour A, Sood A, Avula S, Durrani J, Bhatia V, Gupta R 2023 · J Urol | meta-analysis | supports | high | Meta 26 RCTs (n=10,941): no significant differences in all-cause/CV mortality, MI, stroke, CHF, AF, PE, or VTE. |
| Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Boloña ER, Sideras K, Uraga MV, Erwin PJ, Montori VM 2007 · Mayo Clin Proc | meta-analysis | tested-null | moderate | Meta 30 RCTs: any-CV-event OR 1.82 (95% CI 0.78-4.23, ns); weakly reassuring. |
| Tienforti D, Terrana G, Di Geronimo R, Perfetto E, Spagnolo L, Baroni MG, Barbonetti A 2026 · Journal of endocrinological investigation | RCT | mixed | high | Synthesizing TRAVERSE, TRT showed non-inferiority for MACE in older hypogonadal men (HR 0.96, 0.78-1.17), but non-MACE signals for atrial fibrillation (3.1% vs 2.4%), pulmonary embolism (2.0% vs 1.5%), and acute kidney injury (2.3% vs 1.5%) |
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