TRT and Heart Health: What the Research Says About Cardiovascular Risk

Jun 17, 2026

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If you’re looking into testosterone replacement therapy in your late 40s, 50s, or 60s, the heart-risk question shows up fast. Usually right after the energy crash, the lousy recovery, and the doctor who says your labs are “normal for your age” as if that explains anything useful. Fair enough. TRT cardiovascular risk is the part that deserves a straight answer, not clinic marketing and not the old panic that treated testosterone like contraband with a copay.

The short version is more reassuring than it used to be. The biggest randomized trial ever run on testosterone therapy found no increase in heart attack, stroke, or cardiovascular death in men with documented hypogonadism who were already at elevated cardiovascular risk. A 2024 meta-analysis that pooled 30 randomized trials landed in basically the same place. Then, on February 28, 2025, the FDA removed the boxed warning about increased cardiovascular risk from testosterone products.

That doesn’t mean TRT is harmless or automatic. It means the scary headline most men heard for a decade is now behind the evidence. The real conversation has shifted from “Does TRT cause heart attacks?” to “Which risks still need monitoring, and are you actually a reasonable candidate in the first place?” That’s a much better question.

The TRAVERSE Trial: The Largest Study on TRT Cardiovascular Risk and Heart Safety

For years, this topic was a mess because the evidence was a mess. Small studies pointed in different directions, observational data got overinterpreted, and the loudest voices usually had something to sell. The TRAVERSE trial changed that by finally doing the grown-up version of the research.

Published in the New England Journal of Medicine in 2023, TRAVERSE enrolled 5,246 men ages 45 to 80 who had both symptoms of hypogonadism and testosterone levels below 300 ng/dL. These weren’t college sprinters looking for a beach-season shortcut. They were men with a real medical indication for treatment, and many already had cardiovascular disease or were considered high risk for it.

The primary endpoint was the one that actually matters: major adverse cardiovascular events, or MACE. That means cardiovascular death, nonfatal heart attack, or nonfatal stroke. Over a mean follow-up of about 33 months, those events occurred in 7.0% of the testosterone group and 7.3% of the placebo group. The hazard ratio was 0.96, with a 95% confidence interval of 0.78 to 1.17, and the trial met noninferiority.

In plain English, the biggest and best study on the subject did not show that TRT raised the rate of the worst cardiovascular outcomes. Not in a healthy-young-guy fantasy population. In older men, many with preexisting risk.

That matters because it kills off a lot of stale talking points. If someone is still speaking as though the evidence stops in 2015, they’re driving with an old map. And old maps are charming in a bookstore, less so when medication decisions are involved.

What TRAVERSE doesn’t prove is that every man should be on TRT. It proves something narrower and more useful: in men with documented hypogonadism who are properly evaluated, testosterone therapy did not increase the rate of heart attack, stroke, or cardiovascular death compared with placebo over the study period.

What the 2024 Meta-Analysis of 30 Trials Confirmed

One good trial is important. A broader pattern is better. That’s where the 2024 meta-analysis in Progress in Cardiovascular Diseases helps, because it answers the obvious follow-up question: was TRAVERSE a fluke?

Apparently not.

The meta-analysis pooled 30 randomized controlled trials involving 11,502 hypogonadal patients with a mean age of about 62. Across that larger dataset, testosterone therapy still did not show a significant increase in cardiovascular trouble compared with placebo. The pooled odds ratio for any cardiovascular event was 1.12, with a 95% confidence interval of 0.77 to 1.62. Stroke came in at 1.01. Myocardial infarction came in at 1.05. All-cause mortality came in at 0.94.

None of those numbers suggest a hidden disaster waiting to be uncovered by one more spreadsheet. They suggest consistency. Different trials, different populations, same general result: TRT doesn’t appear to increase major cardiovascular-event risk when studied in randomized settings among men who actually meet the diagnostic criteria for treatment.

This is the part where a lot of online discussion goes off the rails. Men hear “no increased cardiovascular risk” and translate it into “TRT is broadly safe for anyone who feels tired.” That’s not what the evidence says. The research applies to men with confirmed hypogonadism, not to every overworked executive running on five hours of sleep and three espressos. Plenty of people feel awful for reasons that have nothing to do with testosterone.

Still, the direction of the evidence matters. When the biggest trial and the best pooled analysis point the same way, the burden shifts. The old assumption that TRT is probably bad for the heart unless the evidence clears it is no longer the evidence-based default.

The FDA Black Box Warning That No Longer Exists

Regulators tend to move slower than private clinics and slower than internet arguments, which is usually a good thing. But sometimes the lag creates confusion. That’s what happened with testosterone labeling for years.

In February 2025, the U.S. Food and Drug Administration announced class-wide labeling changes for testosterone products. The headline item was the big one: the agency removed the boxed warning about increased risk of adverse cardiovascular outcomes that had been in place since 2015. The FDA pointed to the TRAVERSE trial as the main evidence supporting that change.

That isn’t a cosmetic edit. Boxed warnings are the most prominent safety warnings on prescription-drug labels. When one disappears, it means the regulator no longer believes the evidence supports keeping it there. For men who had been told for years that TRT carried a black-box heart warning, that is a meaningful shift in the risk conversation.

The FDA did not suddenly become a TRT fan club. It kept the limitation-of-use language for age-related hypogonadism, which matters because the agency is still drawing a line between diagnosed hypogonadism and the vague “I’m older and less sharp than I used to be” category. It also added warnings about blood-pressure increases based on ambulatory blood-pressure monitoring data.

That combination is worth paying attention to. The cardiovascular catastrophe warning is gone. The need for medical discipline isn’t. That’s a more nuanced message than most clinics deliver, because nuance doesn’t convert nearly as well as swagger.

The Risks That Still Require Monitoring

This is where the honest version of the story matters more than the comforting one. TRAVERSE found no increase in MACE, but it did identify higher rates of atrial fibrillation, acute kidney injury, and pulmonary embolism in the testosterone group. Harvard Health’s summary of the study highlighted that same point: the main headline was reassuring, but it wasn’t a license to stop paying attention.

That distinction matters because “safe for major cardiovascular events” and “risk-free” aren’t remotely the same sentence. Atrial fibrillation isn’t a rounding error if it happens to you. Neither is a pulmonary embolism. These weren’t huge absolute jumps, but they were enough to stay on the clinical radar.

Then there is blood pressure. The FDA’s 2025 label update added new warnings because ambulatory blood-pressure monitoring studies showed testosterone products can raise blood pressure across the class. If you already have hypertension, family history, borderline kidney function, or a tendency to wave off numbers you don’t like, this isn’t trivia. This is monitoring territory.

The practical takeaway is simple: good TRT management isn’t “start treatment, feel better, carry on.” It’s a surveillance plan. Blood pressure needs tracking. Symptoms that suggest arrhythmia or clotting need attention. Kidney function and the rest of the standard monitoring package need to happen on schedule.

That sounds less glamorous than the clinic ads. Good. The supplement-bro fog around this topic has done enough damage already.

Hematocrit: The Most Common Lab Change on TRT and Why It Matters for Your Heart

If there is one lab issue every man on TRT should understand, it’s hematocrit. This is the percentage of your blood volume made up by red blood cells, and testosterone therapy commonly pushes it up. That can be helpful up to a point. Past that point, thicker blood becomes a risk-management problem, not a performance advantage.

Depending on dose and formulation, erythrocytosis or elevated hematocrit affects somewhere between 5% and 66% of patients, according to the data summarized by Hone Health and supported by the Endocrine Society’s testosterone-therapy guidelines. That’s a wide range, but the core message is the same: this is common enough that you plan for it before it happens.

The usual intervention threshold is a hematocrit above 54%. The Endocrine Society recommends intervention at that point, and the American Urological Association advises stopping or reducing treatment when that threshold is crossed. Injectable testosterone tends to raise hematocrit more than transdermal gels, which is one reason formulation choice isn’t just a convenience issue.

Why does this matter for your heart? Because higher hematocrit can increase blood viscosity and potentially raise thrombotic risk. That doesn’t mean every elevated value becomes a medical emergency. It does mean ignoring the trend because your energy is finally back would be dumb in the expensive kind of way.

Management usually involves one of four moves: reduce the dose, switch formulations, use therapeutic phlebotomy, or pause treatment temporarily. Which option makes sense depends on the number, the trend, symptoms, and the rest of the clinical picture. But the big point is non-negotiable: if you’re on TRT and nobody is checking hematocrit, that isn’t optimized medicine. That’s optimism in a lab coat.

What This Means for Men Over 45 Considering or Currently on TRT

Put the last few years together and the picture is clearer than it used to be. The New England Journal of Medicine TRAVERSE trial, the 2024 meta-analysis in Progress in Cardiovascular Diseases, and the FDA’s February 28, 2025 label update all push in the same direction: for men with confirmed hypogonadism, TRT doesn’t increase the risk of major cardiovascular events when prescribed and monitored appropriately.

That should lower the temperature for the right candidate. If you have symptoms, two low morning testosterone readings under 300 ng/dL, and a clinician who treats this like medicine instead of a subscription funnel, the cardiovascular case against TRT is much weaker than it was a decade ago.

It shouldn’t lower your standards.

Cleveland Clinic quoted Steven Nissen, the trial’s senior author, making exactly that point. The findings shouldn’t be used to justify widespread prescribing without clear medical indication. That warning is worth keeping. A good result in the right population isn’t permission to blur the population.

So what does a sane decision process look like? First, confirm the diagnosis properly. Symptoms alone are too fuzzy, and one lab draw isn’t enough. Second, look at the whole risk picture: blood pressure, hematocrit, PSA, lipid panel, sleep, body composition, and whether there are obvious non-testosterone reasons you feel worse than you used to. Third, decide whether the likely benefit is worth the monitoring burden and the possibility of dose adjustments, phlebotomy, or stopping if the numbers drift the wrong way.

For men over 45, that is the real frame. Not “Is TRT inherently dangerous?” and not “Why wait to feel amazing?” Those are both lazy versions of the question. The better frame is whether TRT fits into a long-game plan to preserve performance without pretending biology stopped mattering.

The evidence now says the heart-risk story is more reassuring than alarming for appropriate candidates. The discipline part is still your job.

Frequently Asked Questions

Does TRT increase your risk of having a heart attack?

Based on the best current evidence, TRT doesn’t appear to increase the risk of major cardiovascular events such as heart attack, stroke, or cardiovascular death in men with confirmed hypogonadism who are properly monitored. The TRAVERSE trial and a 2024 meta-analysis both support that conclusion.

Can you take TRT if you already have heart disease or high blood pressure?

Possibly, but this is where medical supervision matters most. TRAVERSE included men with preexisting cardiovascular disease or high cardiovascular risk, which is one reason its findings carry weight. But TRT can still affect blood pressure and may require closer monitoring if you already have heart disease or hypertension.

How often should blood work be checked while you’re on TRT?

That depends on the protocol, but regular follow-up is part of responsible treatment. Hematocrit, testosterone levels, PSA, and often lipids should be checked on a recurring schedule set by your clinician. If nobody has a monitoring plan, that is a red flag.

Does the delivery method affect cardiovascular risk differently?

The major cardiovascular-event data are most reassuring for TRT as a category when used appropriately, but delivery method still matters for side effects. Injectable formulations are more likely than transdermal gels to raise hematocrit, which can change the risk-management plan even if the big-picture cardiovascular data are reassuring.

If your labs are called normal for your age but you feel worse, should you push for more testing?

Yes, if symptoms are real and persistent. “Normal for your age” isn’t always a useful answer, especially if it shuts down the discussion before a proper workup. The better move is to ask for repeat morning testosterone testing, symptom review, and a broader look at sleep, stress, body composition, thyroid function, and other possible causes.

The Bottom Line

The best current research doesn’t show that TRT raises the risk of heart attack, stroke, or cardiovascular death in men with true hypogonadism. What it does show is that TRT still requires adult supervision: blood pressure, hematocrit, and the rest of the monitoring plan matter just as much as the prescription itself.

This article is for informational purposes only and is not financial advice. Consult a qualified professional for personalized guidance.

Durable Resilience