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

The fear around testosterone replacement therapy and heart attacks did not come from nowhere. It came from a string of observational studies published in the early 2010s that found higher rates of cardiovascular events in men using TRT, and those studies got picked up by the media, flagged by the FDA, and turned into a warning that stuck in the public consciousness for over a decade.

The problem is that observational studies cannot control for the most important variable: why someone started TRT in the first place.

Men who go on testosterone replacement therapy are, almost by definition, men who already have low testosterone. And low testosterone is independently associated with obesity, metabolic syndrome, insulin resistance, and poor cardiovascular health. So when you compare TRT users to non-users and find more heart attacks in the TRT group, you are not necessarily seeing a drug effect. You may just be seeing the baseline health profile of men who needed the drug to begin with. Researchers call this something called confounding by indication, which means the condition being treated is itself a risk factor for the outcome you are measuring, which makes it nearly impossible to separate the effect of the treatment from the effect of the underlying disease.

That is the fundamental flaw in most of the early research, and it is why a randomized controlled trial was the only way to actually answer this question.

In a randomized trial, you take a group of people, flip a coin, and assign half to the treatment and half to placebo. Both groups have the same baseline characteristics on average because randomization distributes them equally, which means any difference in outcomes you see later is much more likely to be caused by the treatment itself and not by some pre-existing difference between the groups.

The TRAVERSE trial, published in the New England Journal of Medicine in 2023, was the largest randomized controlled trial ever conducted on this question. Researchers enrolled 5,246 men between the ages of 45 and 80 who had documented low testosterone, defined as levels below 300 nanograms per deciliter, and who also had either established cardiovascular disease or multiple risk factors for it. This was not a healthy low-risk population. These were the men you would most worry about putting on TRT if the old studies were right.

Half were randomized to testosterone gel and half to placebo gel, and they were followed for an average of 33 months, just under three years.

The primary outcome was a composite of major adverse cardiovascular events: heart attack, stroke, and cardiovascular death. The TRT group had a 7.0 percent event rate over the trial period. The placebo group had a 7.3 percent event rate. That difference was not statistically significant, which means the trial found no evidence that TRT increases the risk of heart attack, stroke, or cardiovascular death, even in men who already had heart disease risk factors going in.

A meta-analysis published in the Journal of the American College of Cardiology in 2024 pooled TRAVERSE together with every other randomized controlled trial that had examined cardiovascular outcomes on TRT, and it confirmed the same finding across a larger combined dataset. An expert review published in Andrology in 2026 looked at the full body of evidence, including TRAVERSE and the downstream mechanistic research, and came to the same conclusion.

So where does this leave the actual biology?

Testosterone affects the cardiovascular system through several pathways, and not all of them point in the same direction. On the positive side, testosterone improves insulin sensitivity, reduces fat mass particularly visceral fat which is the metabolically active fat around the organs, and has vasodilatory effects on blood vessels, meaning it helps them relax and open rather than constrict. Men with chronically low testosterone tend to have worse lipid profiles and more arterial stiffness, and restoring testosterone toward the normal range appears to partially reverse some of those changes.

On the side that requires monitoring, testosterone drives something called erythropoiesis, which is the production of red blood cells. More red blood cells means a higher hematocrit, which is the percentage of your blood volume that is occupied by red cells. When hematocrit rises above roughly 54 percent, the blood becomes measurably more viscous, meaning thicker, and thicker blood moves more slowly through narrowed arteries and is more prone to clotting. This is not a theoretical concern. It is a real physiological consequence of elevated hematocrit, and it is the most common adverse finding in men on TRT who are not getting regular bloodwork.

This is also where the failure mode lives for men on TRT who do end up with problems.

The trial showed that TRT does not inherently raise cardiovascular risk when it is managed properly, but TRT without monitoring is a different situation entirely. Hematocrit needs to be checked regularly, at minimum every six months, and it needs to stay below 54 percent. If it climbs above that threshold the standard response is either a temporary pause in therapy, a dose reduction, or a therapeutic phlebotomy which is essentially a controlled blood draw to reduce red cell volume.

Lipids also matter. Testosterone, particularly when used at supraphysiologic doses or when converted to other hormones at higher rates, can suppress HDL cholesterol, which is the form of cholesterol that carries lipids away from arterial walls. A meaningful drop in HDL while hematocrit is also elevated is a combination that works against the cardiovascular system rather than for it, and it is exactly the kind of thing that gets missed when someone is not checking labs.

And then there is the behavior piece, which is harder to measure in a trial but impossible to ignore in practice. TRT improves energy, motivation, and recovery, and for a lot of men that translates into more time in the gym and a stronger appetite. Neither of those things is a problem unless the gym time comes at the expense of cardiovascular training in favor of only lifting, or unless the appetite increase goes toward a diet that is driving cholesterol and blood pressure upward.

The trial controlled the intervention. It did not control what men ate, how they exercised, or whether they were sleeping. The real world does not have those guardrails.

The honest read of this evidence is that testosterone replacement therapy, when prescribed to men with genuinely low testosterone and monitored appropriately, does not carry the cardiovascular risk that a decade of headlines suggested it did. The older observational studies were measuring the wrong thing and drawing the wrong conclusions from it.

But the replacement therapy itself has never been the whole protocol. Managing hematocrit, monitoring lipids, maintaining cardiovascular fitness, and keeping up with bloodwork every six months, those are not optional extras. They are what separates a managed intervention from an unmanaged one.

The injection is not the treatment. The injection plus the monitoring is the treatment. And most of the men who end up in trouble are the ones who only did half of it.

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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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