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 wave of observational studies published in the early 2010s that suggested men on TRT had meaningfully higher rates of cardiovascular events, and those studies got a lot of attention because the concern made biological sense on the surface. Testosterone raises red blood cell production, it can affect lipids, and the heart is a muscle that responds to hormonal signals. So the worry was not irrational.

What was wrong was the evidence behind it.

Observational studies track what happens to people in the real world, which sounds rigorous, but the problem is that the men who go on TRT are different from the men who do not, and those differences matter enormously when you are trying to figure out whether a treatment causes harm. Sicker men get prescribed more medications. Men with more symptoms seek more treatment. When you compare treated versus untreated groups without accounting for that, you end up measuring the disease, not the drug. That is called confounding, and the early TRT studies were full of it.

To actually answer the question, you need a randomized controlled trial, which is a study design where participants are randomly assigned to the treatment or a placebo, so that both groups are equivalent at the start and any difference you see at the end can reasonably be attributed to the treatment itself.

The largest such trial ever conducted on TRT is called TRAVERSE, published in the New England Journal of Medicine in 2023. It enrolled 5,246 men who had confirmed low testosterone, defined as a level below 300 nanograms per deciliter, and who also had existing cardiovascular disease or a high risk of developing it. That last detail matters. This was not a study of healthy young men. These were middle-aged and older men who already had elevated risk, which means if TRT was going to cause problems, this was the population where you would expect to see them.

Half the men received testosterone replacement and half received a placebo, and researchers followed them for an average of nearly three years, tracking what they called MACE, which stands for major adverse cardiovascular events, meaning heart attacks, strokes, and cardiovascular death.

The result was no statistically significant difference between groups. The TRT group had a MACE rate of 7.0% and the placebo group had a rate of 7.3%, and that small numerical advantage for TRT was not statistically meaningful, but the key finding is that TRT did not increase risk even in a population that already had cardiovascular vulnerability.

A meta-analysis published in JACC in 2024 then pooled TRAVERSE with every other randomized controlled trial on TRT and cardiovascular outcomes. Meta-analyses are useful because they combine the statistical power of multiple studies and smooth out the noise from any single trial. That analysis confirmed the same conclusion: no elevated cardiovascular risk from testosterone replacement in men with low testosterone.

An expert review published in the journal Andrology in 2026, which drew on TRAVERSE and the subsequent meta-analysis literature, reached the same finding and went further in characterizing where the actual monitoring gaps tend to be.

So the science, at the level of the best available evidence, does not support the idea that TRT raises heart attack risk in men who actually need it.

But there is a mechanism worth understanding that does create real risk when it goes unmanaged, and that mechanism is called erythrocytosis, which is when testosterone signals the body to produce more red blood cells than it should.

Here is why that matters. Red blood cells carry oxygen, and testosterone is a potent driver of their production. On TRT, especially with injections that push testosterone into higher ranges, the body can overproduce red blood cells to the point where the blood becomes thicker and harder to move through narrow vessels. The measure of this is hematocrit, which is the percentage of your blood volume made up of red blood cells. In a healthy man, that number sits around 45 to 48 percent. Once it climbs above 54 percent, the viscosity of the blood increases in ways that meaningfully raise the risk of clotting events like deep vein thrombosis and pulmonary embolism.

TRAVERSE did see an increased rate of pulmonary embolism in the TRT group, which is not a headline that gets cited as often as the overall MACE finding, and it is a signal worth taking seriously. The difference was small but present, and it is almost certainly mediated by erythrocytosis in men whose hematocrit was not being monitored and managed.

This is why the protocol matters as much as the prescription.

The practical picture looks like this. A man starts TRT, his energy improves, his symptoms resolve, and he feels better in a way that can produce a false sense of complete health management. What is actually happening biologically is that his red blood cell count is slowly climbing, his lipids may be shifting, and if he has stopped doing the cardio and dietary work he was doing before, the underlying cardiovascular risk factors that were there before TRT are now progressing unchecked, while he assumes the therapy is handling everything.

It is not. TRT addresses hypogonadism. It does not address atherosclerosis, it does not manage blood pressure, and it does not replace the cardiovascular benefit of aerobic exercise.

The monitoring baseline is straightforward. Labs at minimum every six months, with hematocrit being the number that requires the most consistent attention. If it crosses 54 percent, that warrants a conversation with your prescribing physician about dose adjustment, injection frequency, or in some cases therapeutic phlebotomy, which is the process of removing blood to reduce red blood cell concentration. Lipid panels matter too because testosterone can lower HDL in some men, and if that change goes unnoticed against a background of worsening diet and reduced exercise, the net cardiovascular picture deteriorates quietly.

The men who run into serious problems on TRT are almost never the men who were at highest risk at the start. They are the men who interpreted feeling better as a signal that they could stop doing the other things.

The real insight from this body of research is that TRT is not a cardiovascular risk in a well-monitored patient, but it is not a cardiovascular free pass either. The trial evidence clears the therapy. The monitoring data explains how people still end up in trouble anyway. Those two things are not contradictory. They are just different parts of the same system, and understanding both is what actually keeps you safe.

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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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