What the TRAVERSE Trial Actually Showed

For roughly a decade, the biggest reason men hesitated to start TRT was a 2015 FDA warning about cardiovascular risk. The warning was based on a handful of observational studies with methodological issues, and endocrinology societies were skeptical of it at the time. But once the warning was on the label, it shaped the conversation. Every man researching TRT ran into the same question: does this increase my risk of heart attack or stroke?

In 2023, the TRAVERSE trial published its primary results in the New England Journal of Medicine. TRAVERSE was the largest, longest, and most rigorous test of the cardiovascular safety of TRT ever run. It is the study that finally answered the question the observational studies had left open. This article is what TRAVERSE actually showed, what it did not show, and what it means for men considering TRT in 2026.

For the broader context on TRT decisions, see What TRT Actually Is. For how the cardiovascular warning reshaped clinical practice and what changed after TRAVERSE, see The Testosterone Cardiovascular Warning Is Gone. Now What?.

The background

The 2015 FDA warning came out of a cluster of observational studies in the early 2010s that suggested TRT might increase cardiovascular events. The most influential was a 2013 JAMA paper by Vigen and colleagues looking at Veterans Affairs data, and a 2014 PLOS ONE paper by Finkle and colleagues looking at insurance claims data. Both reported elevated event rates in men on TRT compared to men not on TRT.

Both studies had real methodological problems. The Vigen paper was criticized for data errors and confounding. The Finkle paper was a comparison of pre-TRT and post-TRT event rates in the same men, which did not control for the natural increase in cardiovascular events as men age. The endocrinology and men’s health communities pointed out these issues at the time, and the Endocrine Society and the American Association of Clinical Endocrinologists opposed the FDA warning when it was issued.

None of that mattered to the labels or the public conversation. The warning was on the package insert. Physicians who were already reluctant to prescribe TRT had a new reason to be reluctant. Men who were researching TRT ran into the warning in every search result. The overall effect was a decade of chilled prescribing and elevated patient hesitation.

The problem was that nobody had run a real randomized controlled trial large enough to settle the question. Observational data is vulnerable to confounding in both directions, and the question of whether TRT affects cardiovascular events could only be answered by randomization. TRAVERSE was designed to do exactly that.

The TRAVERSE design

TRAVERSE enrolled 5,246 men, ages 45 to 80, with symptomatic hypogonadism (low testosterone plus symptoms) and either pre-existing cardiovascular disease or high cardiovascular risk factors. The trial ran at 316 sites in the United States. Men were randomly assigned to receive either testosterone gel or placebo gel, applied daily. The trial was double-blind: neither patients nor investigators knew who was getting which.

The primary endpoint was MACE (major adverse cardiovascular events), defined as the first occurrence of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. Secondary endpoints included other cardiovascular outcomes, prostate events, and symptom measures.

The trial was funded by a consortium of testosterone manufacturers under an FDA mandate. This is worth noting: drug companies sponsored a trial that could have ended TRT as a commercially viable category if it had shown the cardiovascular signal. The incentive structure was such that the sponsors had reason to hope the result would be negative (no increased risk), but the trial design was constrained by the FDA and the analysis was pre-specified.

Men were followed for a median of 22 months, with some followed longer. The trial was powered to detect a 35% increase in MACE between groups, which is a modest bar, but the sample size and duration made it the most robust test of the question that has ever been run.

The primary finding

MACE occurred in 7.0% of men in the testosterone group and 7.3% of men in the placebo group over the trial period. The hazard ratio was 0.96, with a 95% confidence interval that included 1.0 and crossed the pre-specified non-inferiority margin. In plain language: TRT did not increase cardiovascular events compared to placebo in this high-risk population.

This is the headline finding and it is the most important one. The 2015 FDA warning had been based on weaker data, and the strongest available data now contradicted the warning’s core claim. TRAVERSE did not prove TRT was safe in every sense, but it did rule out the specific concern that had been driving a decade of caution.

Lincoff AM, Bhasin S, Flevaris P, et al. “Cardiovascular Safety of Testosterone-Replacement Therapy.” New England Journal of Medicine. 2023;389:107-117. The full paper is worth reading if you want the details.

The secondary findings

TRAVERSE was not a clean safety story across all outcomes. A few secondary findings warrant attention.

Atrial fibrillation. The testosterone group had more new-onset atrial fibrillation than the placebo group (3.5% vs. 2.4%). This is a real signal and it is new information relative to what was known before TRAVERSE. Men with existing atrial fibrillation or risk factors for it should factor this into the TRT decision.

Acute kidney injury. Higher rates in the testosterone group (2.3% vs. 1.5%). The mechanism is not obvious and the absolute numbers are small, but it is a signal worth noting.

Pulmonary embolism. Higher rates in the testosterone group (0.9% vs. 0.5%). Small absolute numbers but a real difference. Consistent with the known effect of testosterone on hematocrit and clotting.

Prostate outcomes. No increased rate of prostate cancer in the testosterone group. This is a secondary finding that also addresses a long-standing concern about TRT.

Fractures. The testosterone group had higher rates of fractures than the placebo group, which was unexpected and has not been fully explained. Subsequent analyses have explored whether the testosterone gel formulation specifically affected bone in a way that injection-based TRT would not, but the finding remains a question mark.

The overall picture: TRAVERSE ruled out the cardiovascular MACE concern but surfaced other safety signals that were not on the radar before. Any honest reading of TRAVERSE has to include both the reassuring primary finding and the cautionary secondary findings.

The limits of the trial

TRAVERSE was rigorous but not unlimited. A few things it did not do.

It did not test injection TRT. TRAVERSE used testosterone gel. Most TRT in clinical practice is injection. The cardiovascular safety signal should generalize across delivery methods because the underlying hormone is the same, but TRAVERSE did not directly test injection TRT. The fracture signal may be gel-specific.

It did not test men with mildly low testosterone. TRAVERSE enrolled men with total testosterone below 300 ng/dL. Most of the modern optimization conversation is about men in the 300-500 range who are symptomatic but not “clinically hypogonadal” by the strictest definition. TRAVERSE does not directly address the safety of TRT in that group, though it is hard to imagine why the safety signal would differ meaningfully.

It did not test long-term TRT. Median follow-up was 22 months. The cardiovascular effects of TRT over 10 or 20 years are still not directly tested in a randomized trial. TRAVERSE is the best available evidence for the first two years of therapy in a high-risk population.

It did not test younger men. Minimum age was 45. Younger men on TRT for fertility-sparing or early-onset hypogonadism reasons are not directly addressed by TRAVERSE, though the safety signal again should generalize.

None of these limits invalidate the primary finding. They just define the scope of what TRAVERSE actually tested, which is worth being clear about.

What it means for you

If you were hesitating to start TRT because of the cardiovascular warning, TRAVERSE is the reason you can revisit that decision. The single most commonly cited concern about TRT, the one that has kept men off the therapy for a decade, is not supported by the best available randomized evidence.

That does not mean TRT is safe for everyone or that the decision is automatic. It means the cardiovascular concern specifically is not the reason to hesitate, and the real decision should be based on:

Your baseline labs and symptoms. Does the evidence support that you need TRT in the first place? See You’re in Range. You’re Not Fine. for how to think about this.

Your specific risk factors. Atrial fibrillation, kidney disease, and clotting history are now on the list of things to discuss with your provider before starting. Heart attack and stroke, in isolation, are meaningfully less of a concern than the 2015 warning suggested.

Your hematocrit. Monitoring hematocrit is standard practice on TRT and TRAVERSE reinforces why. The clotting-related signals in TRAVERSE are consistent with the known effect of testosterone on red blood cell production.

Your provider’s read on your specific case. A thoughtful provider looks at the full picture rather than treating TRAVERSE as either a green light or a red light. The trial is a data point, not a decision.

The shift in the conversation

TRAVERSE did not end the conversation about TRT safety. It shifted it. Before TRAVERSE, the conversation was dominated by the question of whether TRT causes heart attacks. After TRAVERSE, the conversation is about the more nuanced set of things TRT actually affects: hematocrit, atrial fibrillation, prostate markers, and the individual response profile that matters for decision-making in any one patient.

This is a better conversation. The old conversation was a binary that kept men off a therapy they might have benefited from, based on data that was weaker than the conversation implied. The new conversation is about specific risks in specific contexts, which is closer to how medicine should work.

If you have been sitting on the fence because of the cardiovascular warning, TRAVERSE is the reason to revisit. If you are on TRT and were worried about the warning, TRAVERSE is the reason to stop worrying about that specific thing and to keep paying attention to the things that actually matter: hematocrit, symptoms, the rest of your lab panel, and how you feel over time.

The 2015 warning was never the right framework. TRAVERSE made that clear in the only way that could have been convincing: with a trial large enough and rigorous enough that the answer stopped being debatable.