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 real studies, published in real journals, that showed real associations between testosterone use and cardiovascular events. The problem is that observational studies, which track what people already choose to do rather than randomly assigning treatments, are almost impossible to interpret cleanly when the people choosing testosterone are already different from the people not choosing it. Sicker men get prescribed testosterone. Men already managing heart disease get prescribed testosterone. When those men have cardiac events, the studies attributed it to the testosterone, and that attribution stuck in medical culture for over a decade.

So to actually answer the question, researchers needed something different. They needed a randomized controlled trial, which is a study design where participants are randomly assigned to either the treatment or a placebo, so the two groups start out comparable and any difference in outcomes can be traced back to the treatment itself.

What they built was called the TRAVERSE trial, published in the New England Journal of Medicine in 2023, and it was the largest randomized controlled trial ever conducted specifically on testosterone replacement therapy and cardiovascular outcomes.

Here is what the trial looked like. 5,246 men with confirmed low testosterone, meaning levels below 300 nanograms per deciliter, and who also had either existing cardiovascular disease or a meaningful cluster of cardiovascular risk factors, were randomly assigned to either testosterone gel or placebo gel. They were followed for an average of 33 months, nearly three years, which is long enough for cardiovascular events to emerge if the therapy was genuinely dangerous. The primary outcome they tracked was something called MACE, which stands for major adverse cardiovascular events and includes heart attack, stroke, and cardiovascular death.

The result was that the two groups were statistically indistinguishable on that primary endpoint. The TRT group had a MACE event rate of 7 percent. The placebo group came in at 7.3 percent. That difference is not meaningful, and the trial was designed with enough statistical power to detect a meaningful difference if one existed.

That last part matters. One of the ways a trial can technically show "no difference" is by being too small to detect a real one. TRAVERSE was built to avoid exactly that problem, which is why the result carries weight that earlier smaller trials could not.

After TRAVERSE published, researchers pooled its data with every other randomized controlled trial done on testosterone and cardiovascular outcomes through a process called a meta-analysis, which combines results across multiple studies to get a cleaner and more statistically stable picture. That analysis, published in the Journal of the American College of Cardiology in 2024, confirmed the same conclusion. Testosterone replacement therapy, when delivered under a real clinical protocol to men with low testosterone, does not increase the risk of heart attack, stroke, or cardiovascular death compared to placebo.

An expert review published in Andrology in 2026 examined the TRAVERSE data alongside the accumulated body of trial evidence and landed in the same place, while also mapping out the specific mechanisms that make testosterone's cardiovascular effects more nuanced than a simple "good" or "bad" framing.

Here is where the nuance lives. Testosterone does several things to the cardiovascular system simultaneously, and some of those things move in opposite directions.

On the favorable side, testosterone tends to improve insulin sensitivity, reduce visceral fat, support lean muscle mass, and in many men with low baseline levels, improve lipid profiles. These are all things that reduce long-term cardiovascular load.

On the less favorable side, testosterone stimulates the production of red blood cells by signaling the kidneys to release something called erythropoietin, which is a hormone that drives the bone marrow to produce more red blood cells. More red blood cells means more oxygen-carrying capacity, which is one reason men on TRT often feel more energetic. But more red blood cells also means thicker blood, and thicker blood clots more easily.

The specific number to track here is hematocrit, which is the percentage of your blood volume made up of red blood cells. Normal range for men runs roughly 38 to 50 percent. Once hematocrit climbs above 54 percent, the viscosity of the blood increases enough that clotting risk becomes a real concern, not a theoretical one. In the TRAVERSE trial, elevated hematocrit and a corresponding increase in pulmonary embolism events was one of the few areas where the TRT group diverged from placebo in a way worth noting, with pulmonary embolism occurring at a rate of 0.9 percent versus 0.5 percent in the placebo group.

That signal is not large enough to reverse the overall cardiovascular safety conclusion, but it is large enough that it should change how someone manages their protocol.

This is where the clinical reality separates from the clinical study. A randomized controlled trial controls almost everything. Participants get monitored. Labs get pulled. Doses get adjusted when numbers drift. The trial is measuring testosterone under ideal management conditions, not the conditions most men actually experience when they get a prescription filled at a men's health clinic and show up for a five-minute follow-up every few months.

In the real world, hematocrit drifts upward and nobody catches it until it is at 58 percent. Lipids shift and nobody adjusts the diet. The man who was borderline sedentary before TRT feels better now, takes that energy and puts it into work instead of cardio, and his metabolic health quietly declines while his testosterone numbers look great on paper.

The therapy does not protect you from the decisions you make around the therapy. That is the part the trial cannot capture.

So the practical framework looks like this: bloodwork at minimum every six months, with hematocrit being the number to watch most closely and the target ceiling being below 54 percent. If hematocrit climbs, the two tools that reliably bring it back down are reducing dose and therapeutic phlebotomy, which is just controlled blood donation. Lipids deserve the same attention they would get without TRT, because testosterone can shift the HDL to LDL ratio in ways that vary by individual and delivery method. And cardiovascular exercise is not optional, because the metabolic benefits that make testosterone cardioprotective in the long run are partly dependent on the lifestyle context it sits inside.

The injection was never the whole answer. It was always the tool inside the system, and the system still has to work.

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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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