Is TRT Safe for Your Heart? What the Largest Trial Actually Found

For nine years, the official position of the United States drug regulator was that testosterone might cause heart attacks. The label carried a warning. Prescriptions fell. Men who needed treatment did not get it, and men who were on it came off.

The warning was not based on a trial designed to answer the question. No such trial existed. It was based on a study that stopped early, two database analyses that were criticised almost immediately, and a reasonable regulator deciding that caution was safer than silence.

In 2023 the trial finally arrived. It answered the question it was built to answer, and then it found something nobody had been looking for.

Where the warning came from

Three things happened between 2010 and 2015, and each one sounded worse than it was.

The TOM trial, 2010. A study of testosterone gel in older men with limited mobility was stopped early because more cardiovascular events occurred in the treatment group. It sounds decisive until you look at the size: the trial had enrolled fewer than 210 men, the events numbered in single figures, and the population was frail men with a high burden of existing disease. A difference of a few events in a group that small can arise by chance, and the investigators said as much.

Two database analyses, 2013 and 2014. Both reported more cardiovascular events in men prescribed testosterone. Both were observational, meaning they compared men who happened to be prescribed testosterone with men who were not. The first was subject to a correction after an error was identified, and more than a hundred medical organisations formally requested its retraction. Men prescribed testosterone are, on average, less healthy than men who are not, which is precisely why they were prescribed it.

The FDA warning, 2015. Faced with a weak signal and no definitive evidence, the regulator required a cardiovascular warning on testosterone labels and asked manufacturers to run a proper trial.

That request produced TRAVERSE.

What TRAVERSE was built to do

The design was deliberately unforgiving. If testosterone caused cardiovascular harm, this trial was set up so the harm would show.

• 5,246 men, aged 45 to 80, randomised to transdermal testosterone gel or placebo
• Every man hypogonadal, with two fasting testosterone measurements below 10.4 nmol/L, plus symptoms
• Every man cardiovascularly vulnerable, with either established cardiovascular disease or a high risk of it
• Mean follow-up 33 months, double-blind, placebo-controlled

That third point is what makes the trial useful. Researchers did not test testosterone in healthy men where events would be rare. They tested it in the men most likely to have a heart attack, because that is where a real effect would be visible.

The headline result

The primary endpoint was a composite of cardiovascular death, non-fatal heart attack and non-fatal stroke.

182 events in the testosterone group, 7.0%. 190 events in the placebo group, 7.3%. Hazard ratio 0.96, confidence interval 0.78 to 1.17, non-inferiority met.

Read that carefully. Slightly fewer events on testosterone, in a population selected for cardiac risk, over nearly three years. The confidence interval is wide enough that the honest conclusion is not that testosterone protects the heart, but that it does not damage it in the way the label had claimed for nine years.

In 2025 the FDA removed the cardiovascular warning from testosterone labelling on the strength of this trial.

What nobody expected

Here is the part that responsible coverage includes and enthusiastic coverage skips.

Three adverse events occurred significantly more often on testosterone.

• Atrial fibrillation: 3.5% on testosterone versus 2.4% on placebo
• Acute kidney injury: 2.3% versus 1.5%
• Pulmonary embolism: 0.9% versus 0.5%

Non-fatal arrhythmias requiring intervention were also higher, at 5.2% versus 3.3%.

These are not trivial conditions. Atrial fibrillation raises stroke risk and often needs long-term treatment. A pulmonary embolism is a clot in the lung and can be fatal.

The absolute numbers deserve equal weight. The atrial fibrillation difference is roughly one additional man in ninety over nearly three years. The pulmonary embolism difference is roughly one in 250. These are real and they are small, and both halves of that sentence matter.

The clot signal was not a surprise to everyone. Testosterone raises haematocrit, thickening the blood, and existing guidance already advised caution in men with a history of clots. TRAVERSE confirmed a known concern rather than discovering a new one. Men with underlying clotting disorders were excluded from the trial entirely.

The atrial fibrillation and kidney findings were genuinely new, and the trial was not designed to explain them. One suggestion is that men who feel better become more physically active, which can unmask a rhythm problem that was already there. That is a hypothesis, not a finding.

Why this is a different question from steroids

Nothing here transfers to anabolic steroid use, and the distinction is not a technicality.

TRAVERSE dosed men to a normal physiological range, roughly 12 to 26 nmol/L, with monitoring and dose adjustment throughout. Anabolic steroid cycles run at many multiples of that, often with several compounds at once, frequently including orally active drugs that are directly toxic to the liver, and typically without any monitoring at all.

The cardiovascular evidence on that practice points in a very different direction, including thickened heart muscle and impaired function in long-term users. Steroids and your heart covers it, and TRT versus steroids covers why the two conversations should never be merged.

The lead investigator made a related point about the trial itself: these results came from a setting where levels were carefully monitored and doses adjusted. How often that happens in ordinary practice, particularly at online clinics, is an open question. What over-replacement looks like covers the signs.

What this means if you are considering TRT

The old warning no longer stands. If a clinician still cites heart attack risk as a reason to refuse treatment, that position has been overtaken by the largest trial in the field.

Previous clots change the calculation. A history of deep vein thrombosis or pulmonary embolism, or a known clotting disorder, is a genuine reason for caution and specialist input, not a routine prescription.

A history of atrial fibrillation deserves a conversation. Not a prohibition, but a discussion that includes the trial data.

Haematocrit monitoring is not optional. This is the mechanism most likely to link testosterone to clotting, it is cheap to measure, and it is managed by adjusting the dose. TRT side effects covers the monitoring schedule.

Kidney function belongs on the panel. Given the acute kidney injury signal, baseline and periodic testing is reasonable.

None of this applies if you are not deficient. Every man in TRAVERSE had confirmed hypogonadism. This is evidence about correcting a deficiency, not about raising a normal man's level, and the risk column of that second decision looks entirely different.

The honest summary

Testosterone replacement, given to hypogonadal men at physiological doses with monitoring, does not increase heart attacks or strokes. That question is now as settled as clinical evidence gets.

It does appear to increase atrial fibrillation, clots in the lung and acute kidney injury, by small absolute amounts, in a population already at high cardiovascular risk.

Neither statement cancels the other. A treatment can be cardiovascularly safe in the sense that mattered for nine years, and still carry effects worth knowing about and monitoring for. That is true of most effective medicines, and it is a more useful way to think about TRT than either the old warning or the enthusiasm that replaced it.

If you are weighing this decision, TRT versus natural optimisation covers the wider comparison, the TRT guide covers what treatment involves, and the blood test guide covers confirming a deficiency properly first.

Common questions

Does TRT cause heart attacks?

No. In 5,246 men at high cardiovascular risk, major cardiac events occurred in 7.0% on testosterone and 7.3% on placebo over a mean of 33 months. The FDA removed its cardiovascular warning in 2025 on the strength of this trial.

So why was there a warning for so long?

Because a small trial stopped early in 2010 and two observational analyses in 2013 and 2014 suggested harm. All three were weak, one required correction, and none was designed to answer the question. The regulator acted cautiously and asked for a proper trial.

What are the risks that did increase?

Atrial fibrillation (3.5% versus 2.4%), acute kidney injury (2.3% versus 1.5%) and pulmonary embolism (0.9% versus 0.5%). Real, statistically significant, and small in absolute terms.

Should I avoid TRT if I have had a blood clot?

It is a genuine reason for caution and specialist assessment. Testosterone thickens the blood, guidance already advised care in men with previous clots, and TRAVERSE excluded men with clotting disorders.

Does this mean steroids are safe for the heart?

No, and the trial says nothing about them. TRAVERSE used physiological doses with monitoring. Steroid cycles use many times that amount, often several compounds at once, usually unmonitored. The evidence on that practice is separate and considerably worse.

What should I monitor if I start?

Haematocrit, blood pressure, kidney function and PSA, with a baseline before starting and repeat testing during the first year. Haematocrit matters most for the clotting question and is managed by adjusting the dose.

Sources: Lincoff AM et al., Cardiovascular safety of testosterone-replacement therapy, N Engl J Med 2023;389(2):107-17 · Basaria S et al., Adverse events associated with testosterone administration, N Engl J Med 2010;363(2):109-22 · Vigen R et al., Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels, JAMA 2013;310(17):1829-36 · Bhasin S et al., Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline, J Clin Endocrinol Metab 2018;103(5):1715-44 · Ohlander SJ, Varghese B, Pastuszak AW, Erythrocytosis following testosterone therapy, Sex Med Rev 2018;6(1):77-85 · Educational only, not medical advice. Decisions about testosterone therapy should be made with your doctor.

Keep reading: TRT side effects · Does testosterone cause prostate cancer · Steroids and your heart · TRT versus steroids · The TRT guide · Free 2-minute testosterone test