Evidence question

PubMed sourcedAbstract-based analysisUpdated Sep 2026Human reviewedUpdated Aug 2026

Evidence / Men's Hormone Health

CoverageMen's Hormone Health

Does testosterone therapy reduce cardiovascular events?

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

Updated Aug 2026·10 studies analyzed·2 core studies·1 conflicting·Applies to: hypogonadal men

Bottom line

TRAVERSE found no significant difference in major adverse cardiovascular events between testosterone and placebo over trial follow-up. Meta-analyses of earlier trials are mixed; testosterone should not be prescribed primarily for cardiovascular protection.[1–6]

Evidence confidence

Evidence Confidence

High
LimitedModerateHigh

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

Key uncertainty. TRAVERSE was not designed to demonstrate cardiovascular benefit; longer follow-up and primary-prevention populations remain understudied.

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Also asked

TRT MACE outcomes▼

TRAVERSE found no significant difference in major adverse cardiovascular events between testosterone and placebo over trial follow-up. Meta-analyses of earlier trials are mixed; testosterone should not be prescribed primarily for cardiovascular protection.

Testosterone heart attack prevention▼

TRAVERSE found no significant difference in major adverse cardiovascular events between testosterone and placebo over trial follow-up. Meta-analyses of earlier trials are mixed; testosterone should not be prescribed primarily for cardiovascular protection.

Body of evidence

Clinical Evidence Brief

RAGMD analyzed 9 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. 1 study addresses mood-related cognitive symptoms, with weighted findings showing mixed findings. 4 randomized or systematic-review reports and 5 observational studies address treatment. Do not prescribe testosterone primarily to prevent heart attacks or strokes.

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
No clear effect

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

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
Mixed

Mortality

moderate · 1 study

1 study addresses 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 39248210

Magnitude / clinical importance

Validated effect estimates in the analyzed set include odds ratio 1.07. 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: 0

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

Conflicting findings

  • 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…
  • Testosterone therapy should be individualized with cardiovascular risk assessment and monitoring rather than categorically avoided.
  • Introduction : The use of testosterone therapy (TTh) in men with prostate cancer (PCa) is relatively new, and controversial, due to the longstanding maxim that TTh is contraindicated in men with PCa.

Risks & harms

5 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

  • TRAVERSE was not designed to demonstrate cardiovascular benefit; longer follow-up and primary-prevention populations remain understudied.
  • TRAVERSE was not designed to demonstrate cardiovascular benefit; longer follow-up and primary-prevention populations remain understudied.
  • Surrogate improvement does not prove a hard clinical outcome.

Clinical takeaway

Do not prescribe testosterone primarily to prevent heart attacks or strokes. TRAVERSE addresses safety, not cardioprotection; use testosterone for hypogonadism with appropriate indication while managing conventional cardiovascular risk factors separately.

Mixed

Quality of life?

Mixed findings

high[39248210 · 35904664]

Positive link

Sleep-related cognitive symptoms?

A positive association

high[34536053 · 35904664]

No clear effect

Venous thromboembolism?

No meaningful effect

moderate[37326322 · 26205547]

Mixed

Mood-related cognitive symptoms?

Mixed findings

moderate[39248210]

Mixed

Sexual activity?

Mixed findings

moderate[39248210]

Mixed

Mortality?

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 5 observational studies address treatment. Weighted treatment findings show mixed findings.

4 RCT / systematic review · 5 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

1 study with different findings reduces complete certainty.

9 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

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 replacement increase cardiovascular risk?

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.

11 linked studies

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

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