The TRAVERSE Trial
Testosterone Replacement and Vascular Events in Hypogonadal Men, The Cardiovascular Safety RCT
Evidence grade 5 of 5, Settled. Read how the Atlas grades evidence.
1 human trial, about 1 studies, 5,246 participants men (TRAVERSE). The written rationale for this grade is still being prepared.
- FDA
- Basis for Feb 2025 FDA label change
Reference only. Not medical advice.
What can go wrong
The neutrality finding applies to physiological replacement in diagnosed hypogonadism. Supraphysiological and anabolic dosing, which raise hematocrit and have documented cardiac structural effects, were not tested and remain understudied. Secondary signals (pulmonary embolism, atrial fibrillation, acute kidney injury, fractures) warrant clinical attention and were not part of the negative primary endpoint.
This is something to take to a clinician. The Atlas can tell you what is known about the traverse trial in general. It cannot tell you what is happening in your body, and the difference matters most for exactly the symptoms that bring people to this page.
TRAVERSE (Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men) is the most important testosterone safety trial ever conducted. Sponsored to satisfy an FDA post-marketing requirement, it randomized 5,246 men aged 45-80 with hypogonadism and either pre-existing cardiovascular disease or high CV risk to transdermal testosterone gel or placebo, with a mean follow-up of about 33 months (mean treatment duration ~22 months). The primary finding: testosterone did NOT increase major adverse cardiovascular events (MACE), roughly 7.0% on testosterone versus 7.3% on placebo. Published in the New England Journal of Medicine in 2023, it converted decades of observational uncertainty into randomized evidence of cardiovascular neutrality at physiological replacement doses.
The largest testosterone safety trial ever run, and the reason the cardiovascular black box is gone.
What people take it for
What it is taken for. Approval, where it exists, covers only some of these.
How it works
TRAVERSE was a randomized, double-blind, placebo-controlled non-inferiority trial. By enrolling a high-CV-risk hypogonadal population and powering for MACE, it could detect whether physiological testosterone replacement raised cardiovascular event rates, the central safety question left unresolved by prior observational studies that could not separate testosterone's effect from confounding illness.
The trial design deliberately targeted men in whom harm, if real, would be most detectable: established cardiovascular disease or multiple risk factors. Testosterone was titrated to the mid-normal physiological range using transdermal gel, keeping the intervention squarely within replacement rather than supraphysiological territory.
What TRAVERSE proved, and the asterisks the marketing drops
TRAVERSE established cardiovascular neutrality specifically for transdermal gel, titrated to physiological levels, in confirmed hypogonadal men. It did NOT bless supraphysiological dosing, injectable peak-trough swings, or testosterone for men with normal levels. It also recorded signals worth noting: numerically more pulmonary embolism, acute kidney injury, and atrial fibrillation in the testosterone group, and a higher rate of fractures (a counterintuitive finding). Telehealth marketing frequently compresses 'TRAVERSE showed testosterone is heart-safe' into a blanket endorsement that erases the dose, formulation, and population in which the result actually holds.
Safety in detail
TRAVERSE supports cardiovascular safety only for physiological replacement in confirmed hypogonadal men under medical supervision. Testosterone therapy still requires evaluation and ongoing monitoring by a qualified physician; self-administration and supraphysiological dosing carry documented health risks.
Replacement is not the same as a cycle
TRAVERSE titrated testosterone to mid-normal physiological levels (replacement). Its cardiovascular reassurance does NOT extend to supraphysiological or anabolic dosing (commonly 300-1000+ mg/week), which raises hematocrit and blood viscosity and carries documented cardiac hypertrophy and thrombotic risks the trial never evaluated.
What it does to fertility
TRAVERSE did not change the fact that exogenous testosterone suppresses LH/FSH and spermatogenesis. Its participants were older hypogonadal men for whom fertility was generally not the concern; the trial's reassurance is about cardiovascular events, not reproductive preservation.
What has to be monitored
The bloodwork this needs, and the reason it belongs with a clinician rather than a website.
- Hematocrit (erythrocytosis remains the primary physiological risk)
- Blood pressure (per 2025 label)
- PSA / prostate monitoring per guideline
- Total testosterone to confirm physiological range
- Symptom review for PE, AFib, and edema given secondary signals
What people get wrong
Often saidTRAVERSE proved testosterone is good for your heart
ActuallyTRAVERSE proved physiological replacement did not increase major cardiac events in hypogonadal men, neutrality, not benefit, and not for supraphysiological doses or normal-T men.
Often saidThe result applies to any testosterone dose or product
ActuallyIt applies to transdermal gel titrated to physiological levels; it says nothing about injectable peaks or anabolic dosing.
Who profits, and who pushes back
Secondary-signal reviewers
Non-inferiority for MACE does not dismiss the numerically higher rates of pulmonary embolism, atrial fibrillation, and fractures that deserve continued scrutiny.
Set against the alternatives
For the man and clinician actually deciding about TRT, TRAVERSE reframes the conversation rather than ending it. The headline, cardiovascular noninferiority, means the dominant fear of the prior decade, heart attacks and strokes, is no longer the gatekeeper it was; this is the trial's central contribution to TRT decision-making. But it does not make testosterone uniformly benign: the same trial flagged more atrial fibrillation, more pulmonary embolism, and, in its bone substudy, more fractures, so the decision shifts from one big worry (MACE) to a set of smaller, monitorable ones. Practically, TRAVERSE supports treating genuinely hypogonadal, symptomatic men, particularly with transdermal gel at replacement doses, while arguing against casual use in men without biochemical hypogonadism, since the population that benefited was defined by low testosterone plus high CV risk. The findings apply most cleanly to gel; they say less about injectable or supraphysiological dosing common in optimization and telehealth contexts.
| Outcome domain | Testosterone arm | Placebo arm | Interpretation for TRT |
|---|---|---|---|
| Primary MACE | ~7.0% | ~7.3% | Noninferior; reassures on CV safety |
| Atrial fibrillation | 91 men | 63 men | Counsel and monitor for AFib |
| Pulmonary embolism | 0.9% | 0.5% | Watch thromboembolic risk |
| Clinical fractures | Higher (HR ~1.43) | Reference | Do not assume bone benefit |
| Acute kidney injury | Higher | Reference | Secondary signal, monitor |
What we do not know
- Do the AFib and pulmonary-embolism signals reflect a true causal effect, and which men are most susceptible?
- Why did testosterone raise fracture risk despite expected bone-density benefits?
- Do injectable or oral formulations carry the same CV-neutral profile as the gel tested?
- Does cardiovascular neutrality hold beyond the ~33-month follow-up over many years of use?
- How well do results generalize to younger men or those treated via telehealth without the trial's monitoring?
What could change
Secondary-outcome publicationsContinued analyses of TRAVERSE data on cognition, sexual function, diabetes, and anemiaGuideline integrationProfessional societies translating TRAVERSE into updated TRT eligibility and monitoring algorithmsSubgroup modelingIdentifying which hypogonadal phenotypes gain most benefit versus most thromboembolic riskComparative-formulation trialsCalls for outcomes data on injectable and oral testosterone not directly tested in TRAVERSE
At a glance
- Participants
- 5,246 men
- Age range
- 45-80
- Mean follow-up
- ~33 months (mean treatment ~22 mo)
- Formulation
- Transdermal gel (AndroGel 1.62%)
- MACE, TRT
- 7.0%
- MACE, placebo
- 7.3%
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about The TRAVERSE Trial. A short entry is not a safe entry.
- Cost and market. We have not documented what it sells for or who sells it.
- Supply chain. We have not mapped where it is made.
- Who uses it. We have not documented the user groups.
- Children and teenagers. We have not checked what is known about younger people.
Sources
The studies below are named and described, but not linked. You cannot open them from here and check our reading against them, which means this page is our summary of the literature rather than a document you can verify. Weigh it accordingly until the links exist.
The studies that matter
TRAVERSE (Lincoff et al., NEJM)2023
5,246 high-CV-risk hypogonadal men; testosterone gel non-inferior to placebo for MACE (7.0% vs 7.3%)
TRAVERSE secondary analyses2023-2024
Numerically higher pulmonary embolism, atrial fibrillation, acute kidney injury, and fractures in the testosterone arm