Evidence question

PubMed sourcedAbstract-based analysisUpdated Sep 2026Human reviewedUpdated Aug 2026

Evidence / Men's Hormone Health

CoverageMen's Hormone Health

Does testosterone replacement increase cardiovascular risk?

Reviewed by Neal Rouzier, MD, Preventive Medicine · Aug 2026

Updated Aug 2026·11 studies analyzed·2 core studies·2 conflicting·Applies to: hypogonadal men

Bottom line

Large randomized data (including TRAVERSE) do not show a significant increase in major adverse cardiovascular events with testosterone therapy in hypogonadal men over median follow-up of roughly three years. Older observational studies conflict, and absolute risk depends on baseline cardiovascular disease, formulation, and monitoring.[1–6]

Evidence confidence

Evidence Confidence

High
LimitedModerateHigh

Multiple high-quality studies directly address this question, with generally consistent findings.

Key uncertainty. Long-term outcomes beyond trial follow-up and effects in high-risk subgroups remain less certain.

Ask RAGMD

Get the live evidence synthesis

10 complimentary queries. Full clinical intelligence — PubMed citations, conflict analysis, Evidence Confidence — with 7-day free trial.

Ask this questionStart free trialWhy physicians use RAGMD

Also asked

TRAVERSE trial testosterone MACE▼

TRAVERSE found testosterone noninferior to placebo for major adverse cardiovascular events in hypogonadal men at elevated cardiovascular risk over median follow-up of roughly three years.

Is TRT safe for the heart?▼

Large randomized data, including TRAVERSE, do not show a significant increase in MACE with indicated testosterone therapy. Older observational harm signals conflict and require careful interpretation.

Is TRT hard on your heart?▼

In men with diagnosed hypogonadism and appropriate indication, TRAVERSE and related trials do not show excess major adverse cardiovascular events over roughly three years. Baseline cardiovascular assessment and monitoring remain standard.

Does TRT cause plaque buildup in arteries?▼

Trial data do not establish that indicated testosterone therapy accelerates coronary plaque progression at the population level. Subclinical atherosclerosis signals from older observational work conflict with randomized cardiovascular outcomes.

Does TRT increase the risk of stroke?▼

TRAVERSE was not powered for stroke alone, but major adverse cardiovascular event composites did not favor harm. Individual stroke risk still depends on baseline cerebrovascular disease and blood pressure control.

Testosterone therapy cardiovascular outcomes▼

Large randomized data (including TRAVERSE) do not show a significant increase in major adverse cardiovascular events with testosterone therapy in hypogonadal men over median follow-up of roughly three years. Older observational studies conflict, and absolute risk depends on baseline cardiovascular disease, formulation, and monitoring.

Body of evidence

Clinical Evidence Brief

RAGMD analyzed 10 relevant studies.

Overall finding

2 studies address quality of life, with weighted findings showing mixed findings. 2 studies address sleep-related cognitive symptoms, with weighted findings showing a positive association. 2 studies address venous thromboembolism, with weighted findings showing no meaningful effect. 2 studies address mortality, with weighted findings showing mixed findings. 4 randomized or systematic-review reports and 6 observational studies address treatment. For men with diagnosed hypogonadism and appropriate indication, testosterone therapy should not be withheld solely because of historical cardiovascular concerns.

Evidence by outcome

Direction: ↑ Favors treatment / reassuring · ↓ Harm signal · ↔ No clear effect · ± Mixed · ↗ Observational link · ? Unclear

Mixed

Quality of life

high · 2 studies

2 studies address quality of life, with weighted findings showing mixed findings. This is a patient-reported / subjective outcome.

Patient-reported

Studies

PMID 39248210PMID 35904664
Positive link

Sleep-related cognitive symptoms

high · 2 studies

2 studies address sleep-related cognitive symptoms, with weighted findings showing a positive association.

Mixed measurement

Studies

PMID 34536053PMID 35904664
Reassuring

Venous thromboembolism

moderate · 2 studies

2 studies address venous thromboembolism, with weighted findings showing no meaningful effect. This is an objectively measured outcome. This is a hard clinical endpoint.

Objectively measured · Hard clinical endpoint

Studies

PMID 37326322PMID 26205547
Mixed

Mortality

moderate · 2 studies

2 studies address mortality, with weighted findings showing mixed findings. This is an objectively measured outcome. This is a hard clinical endpoint.

Objectively measured · Hard clinical endpoint

Studies

PMID 39248210PMID 27165609
Mixed

Mood-related cognitive symptoms

moderate · 1 study

1 study addresses mood-related cognitive symptoms, with weighted findings showing mixed findings. This is a patient-reported / subjective outcome.

Patient-reported

Studies

PMID 39248210
Mixed

Sexual activity

moderate · 1 study

1 study addresses sexual activity, with weighted findings showing mixed findings. This is a patient-reported / subjective outcome.

Patient-reported

Studies

PMID 39248210

Magnitude / clinical importance

Validated effect estimates in the analyzed set include odds ratio 1.07; HR 1. Statistical significance is not the same as clinical importance.

Interpret magnitude in absolute terms for the patient in front of you, not from relative estimates alone.

Agreement across studies

Most studies agree on quality of life (mixed findings), while venous thromboembolism findings are no meaningful effect and more consistent across domains.

Supports main conclusion: 1 · Neutral / mixed: 8 · Credible conflicting: 1

Study counts describe the landscape; RAGMD weights studies according to design, quality, and directness.

Conflicting findings

  • Conflicting evidence exists for the association between testosterone replacement therapy and mortality and cardiovascular events.
  • The results indicated that OSA is significantly correlated with the decrease in serum testosterone levels in men.
  • In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac e…

Risks & harms

6 studies report safety-relevant findings. Design mix: Randomized controlled trial, Systematic review / meta-analysis, Study design not clearly classified, Narrative review. Rare-event inference should not rest on underpowered trials alone.

Who this applies to

Most studies included hypogonadal men.

What remains uncertain

  • Long-term outcomes beyond trial follow-up and effects in high-risk subgroups remain less certain.
  • Long-term outcomes beyond trial follow-up and effects in high-risk subgroups remain less certain.
  • Surrogate improvement does not prove a hard clinical outcome.

Clinical takeaway

For men with diagnosed hypogonadism and appropriate indication, testosterone therapy should not be withheld solely because of historical cardiovascular concerns. TRAVERSE supports noninferiority for major adverse cardiovascular events over median follow-up of roughly three years in men with preexisting or high cardiovascular risk. Older observational harm signals conflict with trial data and require careful interpretation of confounding and patient selection. Baseline cardiovascular assessment, formulation choice, blood pressure and hematocrit monitoring, and shared decision-making remain standard.

Mixed

Quality of life?

Mixed findings

high[39248210 · 35904664]

Positive link

Sleep-related cognitive symptoms?

A positive association

high[34536053 · 35904664]

Reassuring

Venous thromboembolism?

No meaningful effect

moderate[37326322 · 26205547]

Mixed

Mortality?

Mixed findings

moderate[39248210 · 27165609]

Mixed

Mood-related cognitive symptoms?

Mixed findings

moderate[39248210]

Mixed

Sexual activity?

Mixed findings

moderate[39248210]

Mixed

Blood pressure?

Mixed findings

moderate[39248210]

Unclear

Weight / body composition?

Unclear findings

moderate[35904664]

4 randomized or systematic-review reports and 6 observational studies address treatment. Weighted treatment findings show mixed findings.

4 RCT / systematic review · 6 observational

Large randomized trials strongly influence the conclusion

2 landmark studies with randomized or systematic-review designs strongly inform this conclusion.

Supporting studies provide additional context

7 supporting studies add context beyond the core evidence base.

Regimen & duration

Observational and supporting studies provide context and do not outrank higher-appropriateness designs.

Long-term uncertainty

2 studies with different findings reduces complete certainty.

10 analyzed studies

Strongest evidence

The New England journal of medicine2023

Landmark studyPMID 37326322

Cardiovascular Safety of Testosterone-Replacement Therapy.

In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).

RCT
Evidence
Relevance

Important conflicting evidence

The lancet. Diabetes & endocrinology2016

Conflicting evidencePMID 27165609

Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study.

Conflicting evidence exists for the association between testosterone replacement therapy and mortality and cardiovascular events. The US Food and Drug Administration recently cautioned that testosterone replacement therapy might increase risk of heart attack and stroke, based on

Study
Evidence
Relevance
Diabetes care2014

Conflicting evidencePMID 24041679

Highly sensitive diagnosis of 43 monogenic forms of diabetes or obesity through one-step PCR-based enrichment in combination with next-generation sequencing.

Our NGS approach provides an efficient means of highly sensitive screening for mutations in genes associated with monogenic forms of diabetes and obesity. As cost and time to deliver results have been key barriers to uncovering a molecular cause in the many undiagnosed cases likely to exist, the present methodology sh…

Study
Evidence
Relevance

Supporting literature

The effects and safety of testosterone replacement therapy for men with hypogonadism: the TestES evidence synthesis and economic evaluation.

Association between obstructive sleep apnea and male serum testosterone: A systematic review and meta-analysis.

Obstructive sleep apnea and serum total testosterone: a system review and meta-analysis.

+4 more

More in this focus area

Related evidence analyses

Other structured clinical questions in Men's Hormone Health.

Does testosterone therapy increase prostate cancer risk?

Current systematic reviews and trial secondary analyses do not show a convincing increase in prostate cancer incidence among hypogonadal men treated with testosterone, though surveillance remains standard practice.

14 linked studies

Does testosterone therapy increase hematocrit and polycythemia risk?

Testosterone therapy commonly raises hematocrit; polycythemia is a recognized adverse effect requiring dose adjustment, formulation changes, or phlebotomy when thresholds are exceeded.

14 linked studies

Does testosterone therapy suppress fertility in men?

Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis and reliably reduces spermatogenesis. Recovery after discontinuation is variable and may be incomplete in some men.

14 linked studies

Does testosterone therapy increase venous thromboembolism risk?

Large observational cohorts suggest a modest increase in venous thromboembolism risk with testosterone therapy, particularly early after initiation. Absolute risk remains low in most populations but warrants attention in predisposed patients.

14 linked studies

Go deeper on Men's Hormone Health

Full evidence synthesis, study comparisons, conflicting evidence, and expert commentary are available with RAGMD. Ask follow-up questions, explore related topics, and see how the evidence has evolved.

Ask RAGMDExplore Men's Hormone HealthView pricing