Testosterone and Your Heart: What the Largest Clinical Trial Ever Tells Us

Testosterone and Your Heart: What the Largest Clinical Trial Ever Tells Us

For years, men and their doctors have been caught in a frustrating bind: low testosterone causes real symptoms — fatigue, low libido, depression, cognitive fog, loss of muscle — but the fear of heart attack or stroke has kept many from seeking treatment.

That fear is now largely resolved. Here's what the science actually says.

The Question That Needed an Answer

The controversy started with conflicting observational studies in the early 2010s. Some showed increased cardiovascular risk with testosterone therapy. Others showed decreased risk. The data was a mess — largely because these studies couldn't adequately account for the fact that healthier men were more likely to be prescribed testosterone in the first place.

In 2015, the FDA stepped in and required testosterone manufacturers to fund a definitive clinical trial. The result was the TRAVERSE trial — the largest, most rigorous study ever conducted on testosterone replacement therapy and cardiovascular safety.

What the TRAVERSE Trial Found

Published in the *New England Journal of Medicine* in 2023, TRAVERSE enrolled 5,246 men between the ages of 45 and 80. These weren't healthy low-risk men — 54% had preexisting cardiovascular disease (coronary artery disease, stroke, or peripheral arterial disease), and nearly all had hypertension, dyslipidemia, or diabetes. This was a high-risk population by design.

All participants had confirmed low testosterone (below 300 ng/dL on two separate fasting morning blood draws) and were experiencing symptoms of hypogonadism. Half received daily transdermal testosterone gel, dose-adjusted to maintain levels between 350 and 750 ng/dL. The other half received placebo.

After nearly three years of follow-up, the results were clear:

- Heart attack rate: 7.0% (testosterone) vs 7.3% (placebo) — no significant difference - Stroke: similar in both groups - Cardiovascular death: similar in both groups - The hazard ratio was 0.96 — essentially identical outcomes

The trial met its primary endpoint: testosterone-replacement therapy was noninferior to placebo for major adverse cardiac events.

What This Means for Men With Low Testosterone

If you have hypogonadism and your doctor has been hesitant to treat you because of cardiovascular concerns, this trial provides important reassurance. In the highest-risk men studied — those with established heart disease — testosterone therapy did not increase the risk of heart attack, stroke, or cardiovascular death.

This matters because the symptoms of untreated low testosterone are not trivial. Fatigue, depression, loss of sexual function, loss of muscle mass, increased body fat, and cognitive changes are well-documented consequences of hypogonadism. These symptoms affect quality of life, relationships, and long-term health outcomes. Leaving them untreated has its own risks.

What to Watch For

The TRAVERSE trial also identified some signals that deserve attention. Men on testosterone had slightly higher rates of:

- Atrial fibrillation — an irregular heart rhythm - Pulmonary embolism — blood clots in the lungs - Acute kidney injury

These are not reasons to avoid testosterone therapy if you're a good candidate — but they are reasons to be monitored appropriately. Any man on testosterone replacement should have regular follow-up including blood work (hematocrit, PSA, metabolic panel) and should report symptoms like palpitations or shortness of breath promptly.

The Bottom Line

The cardiovascular fear surrounding testosterone therapy has been based on imperfect, conflicting data. The TRAVERSE trial — FDA-mandated, rigorously designed, and published in the *New England Journal of Medicine* — provides the clearest answer we've had: testosterone replacement therapy does not increase the risk of heart attack, stroke, or cardiovascular death in men with hypogonadism.

If you're experiencing symptoms of low testosterone and haven't pursued evaluation because of concerns about your heart, this is the conversation to have with your doctor. The science has caught up. The question is whether your care has too.

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*Steven E. Nissen, MD, and colleagues; TRAVERSE Study Investigators. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine. June 2023.*

*This article is for informational purposes only and does not constitute medical advice. Please consult your physician before starting, stopping, or changing any medical treatment.*