Does TRT Raise Heart Attack Risk? What the New Research Actually Shows

The fear has been around for decades. Go on testosterone replacement therapy, and you are raising your risk of a heart attack. That belief shaped how doctors prescribed, how patients decided, and how the entire conversation around TRT developed, and it came from somewhere real, which is why it stuck so long.

The problem is where it came from.

The early evidence was built almost entirely on observational studies, which means researchers looked at groups of men who were already on TRT and compared their heart outcomes to men who were not, and the issue with that design is that it cannot separate cause from correlation. Men who seek out TRT often have more health problems to begin with, lower energy, more metabolic dysfunction, worse baseline cardiovascular risk, and if those men have more heart attacks, you cannot know whether the testosterone caused that or whether the population seeking testosterone was simply sicker. Some of those early studies had methodological problems significant enough that their conclusions were disputed almost immediately after publication, but the fear they generated lasted much longer than the retractions.

So to actually answer the question, researchers needed a randomized controlled trial, which is a study design where you take a large group of people, randomly assign them to either the treatment or a placebo, and follow them forward in time under controlled conditions so you can actually compare what happens, instead of guessing about populations that were never matched in the first place.

That trial was called TRAVERSE, published in the New England Journal of Medicine in 2023, and it was the largest randomized controlled trial ever conducted on testosterone replacement therapy.

The researchers enrolled 5,246 men who had confirmed low testosterone and who already had either established cardiovascular disease or significant risk factors for it, which is important because this was not a low-risk group, these were the men you would most expect to see problems in if testosterone were genuinely harmful to the heart. Half were randomized to receive testosterone therapy and half received a placebo, and they were followed for an average of nearly three years while researchers tracked major cardiovascular events: heart attacks, strokes, and cardiovascular death.

The result was no increased risk in the testosterone group.

The men receiving TRT did not have more heart attacks. They did not have more strokes. They did not have higher rates of cardiovascular death. The event rates between the two groups were nearly identical, and if anything, the testosterone group came in slightly lower, though the difference was small enough that the researchers did not make claims about protection, only about the absence of harm.

A meta-analysis published in JACC in 2024 then pooled the TRAVERSE data together with every other randomized controlled trial on TRT and cardiovascular outcomes, and the conclusion held across the broader dataset. No significant increase in major cardiovascular events from testosterone replacement in men with low testosterone. An expert review published in Andrology in 2026 reviewed both TRAVERSE and the accumulated trial data and came to the same place.

This is now the strongest evidence base the field has ever had on this question, and it points in one direction.

But there is a part of this that the headline numbers do not capture, and it matters more than most people on TRT realize.

Testosterone therapy changes the internal environment of the body in ways that create risk if left unmanaged, even if the therapy itself does not independently cause cardiovascular events. The most important of those changes is what happens to hematocrit, which is the percentage of your blood volume made up of red blood cells. Testosterone stimulates red blood cell production, and as hematocrit rises, the blood becomes more viscous, meaning thicker and harder to move through vessels, which increases the mechanical load on the heart and raises the probability of a clot forming where it should not.

Once hematocrit climbs above 54 percent, clotting risk becomes clinically meaningful, and this is not a theoretical concern.

The men in the TRAVERSE trial who ended up with elevated hematocrit were the ones who showed the most concerning downstream markers, and elevated hematocrit is one of the reasons routine bloodwork is not optional for anyone on TRT, it is the monitoring mechanism that catches this before it becomes a problem you are treating in an emergency room instead of a lab result you are managing in advance.

The same logic applies to lipid panels. Testosterone can shift the balance of HDL and LDL depending on dose, route of administration, and individual response, and a man who stops tracking his lipids because he feels better on TRT is not protected by feeling better. The symptom improvement and the metabolic changes are separate systems, and one does not guarantee the other is moving in a good direction.

What the research actually shows, when you read it at the level of mechanism and not just headline outcome, is that testosterone replacement therapy does not appear to be the cardiovascular threat the early studies suggested, and that the risk profile of TRT is substantially shaped by what happens after the prescription is written.

The men who developed problems in the observational studies, and the men who develop problems now, are not a random sample of TRT users. They are disproportionately the ones who stopped treating TRT as one tool in a system and started treating it as a replacement for the system. Diet stops. Cardio stops. Labs go from every six months to never. Hematocrit climbs past 54 and nobody catches it because nobody checked.

The therapy did not fail those men. The monitoring did.

This is the reframe the research earns: testosterone replacement therapy has been studied at the highest level of evidence the field can produce, and the signal is reassuring, but the reassurance is conditional on the same discipline that protects cardiovascular health in anyone, managing blood thickness, tracking lipids, keeping cardio in the routine. The injection changes the hormonal environment. It does not change the rules of cardiovascular biology.

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References

1. Lincoff AM, et al. 2023. "Cardiovascular Safety of Testosterone-Replacement Therapy." New England Journal of Medicine. Source
2. Zitzmann M, et al. 2026. "Cardiovascular Safety of Testosterone Therapy: Insights from the TRAVERSE Trial and Beyond." Andrology. Source
3. Hudson J, et al. 2024. "Long-term Cardiovascular Safety of Testosterone-Replacement Therapy in Middle-Aged and Older Men: A Meta-Analysis of Randomized Controlled Trials." JACC. 04050-6 Source

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