Testosterone Replacement Therapy and Heart Health: What the Latest Research Shows

For years, a cloud of cardiovascular concern hung over testosterone replacement therapy — fueled by flawed studies and a 2015 FDA warning that left millions of men undertreated. The landmark 2023 TRAVERSE trial finally delivered the definitive answer doctors and patients needed: TRT is not the cardiac villain it was made out to be. Here's what the science actually shows, and what it means for men considering treatment today.

The Origins of the TRT-Heart Controversy

The fear that testosterone could damage the heart didn't come out of nowhere — it came from a pair of early studies that ignited a firestorm in the medical community. A 2010 study published in The New England Journal of Medicine was halted early after researchers reported an increase in cardiovascular events in older men receiving testosterone gel. Then, in 2014, a retrospective analysis in PLOS ONE suggested a higher rate of heart attacks in men who filled testosterone prescriptions.

These findings prompted the FDA to require a black-box warning on all testosterone products in 2015, noting that "the safety and efficacy of testosterone products for low testosterone levels due to aging have not been established." The result? A dramatic chill in prescribing, and millions of men left to wonder whether treating their hypogonadism was worth the supposed risk.

However, scientists and clinicians quickly began raising serious questions about the methodology of those early studies. The 2014 PLOS ONE analysis had been compared against the wrong control population, and the NEJM study had enrolled men who were exceptionally frail and at high baseline cardiovascular risk — not the typical candidate for TRT. The controversy needed a definitive, well-designed randomized controlled trial. That trial was TRAVERSE.

The TRAVERSE Trial: The Definitive Answer

Published in The New England Journal of Medicine in June 2023, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men) trial was specifically designed to answer the cardiovascular safety question once and for all.

Study Design and Population

TRAVERSE enrolled 5,246 men between the ages of 45 and 80 who had confirmed hypogonadism (low testosterone) and pre-existing cardiovascular disease or a high risk of it — the very population that critics said was most endangered by TRT. This was not a healthy, low-risk cohort. These were men with conditions like obesity, diabetes, hypertension, and prior cardiovascular events. Participants were randomized to receive either testosterone gel (targeting levels of 350–750 ng/dL) or placebo and were followed for a median of 33 months — nearly three years.

The primary outcome was a composite of major adverse cardiovascular events (MACE): nonfatal heart attack, nonfatal stroke, and death from cardiovascular causes.

What the Results Showed

The headline finding: testosterone therapy was non-inferior to placebo for MACE. In other words, TRT did not increase the risk of heart attack, stroke, or cardiovascular death — even in a high-risk male population followed for nearly three years.

The study did identify two areas of elevated risk that warrant attention: atrial fibrillation (AF) occurred slightly more often in the testosterone group (3.5% vs. 2.4%), and pulmonary embolism was also modestly elevated (0.9% vs. 0.5%). These findings suggest that men with pre-existing AF or a history of blood clots should have individualized discussions with their provider before initiating TRT. But for the vast majority of hypogonadal men — including those with significant cardiovascular risk — the trial found no increase in major cardiac events.

Why Low Testosterone Itself Is a Cardiovascular Risk Factor

One of the most important — and underappreciated — aspects of the TRT debate is that untreated hypogonadism is itself associated with worse cardiovascular outcomes. A growing body of epidemiological literature links low testosterone levels to:

• Increased visceral fat accumulation — the type of fat most strongly associated with insulin resistance and coronary artery disease
• Worsening insulin sensitivity — raising the risk of type 2 diabetes
• Elevated inflammatory markers — including C-reactive protein and interleukin-6
• Unfavorable lipid profiles — lower HDL and higher triglycerides in some men
• Reduced lean muscle mass — a known independent risk factor for cardiovascular mortality
• Endothelial dysfunction — impaired blood vessel responsiveness that precedes atherosclerosis

Men with testosterone deficiency also tend to have higher rates of metabolic syndrome, which clusters risk factors for heart disease and diabetes. Seen in this light, treating hypogonadism isn't just about quality of life — it may have real cardiovascular benefit in certain populations.

What TRT Actually Does to Cardiovascular Markers

Body Composition and Metabolic Effects

Restoring testosterone to normal physiological levels consistently produces favorable metabolic changes in clinical studies. A 2016 systematic review and meta-analysis in The Journal of Clinical Endocrinology & Metabolism found that TRT significantly reduced total body fat, improved insulin sensitivity, and reduced fasting glucose in men with hypogonadism and type 2 diabetes. These are precisely the risk factors most tightly linked to cardiovascular disease.

In the Testosterone Trials (TTrials) — a coordinated set of seven trials conducted at 12 academic medical centers — testosterone treatment in older men with low levels produced improvements in bone density, sexual function, mood, and energy without increasing cardiovascular risk in the short term. The TTrials did show a modest increase in coronary artery non-calcified plaque volume on CT angiography in a subset of men, which underscored the need for the larger, longer TRAVERSE trial to definitively assess outcomes.

Effects on Red Blood Cell Production

Testosterone stimulates erythropoiesis — the production of red blood cells. This raises hematocrit (the percentage of blood volume made up of red cells), which is why providers monitor hematocrit periodically during TRT. Elevated hematocrit can theoretically increase blood viscosity and clotting risk. In practice, clinicians manage this by dose adjustment, phlebotomy if necessary, or switching delivery method. Injectable testosterone tends to produce larger hematocrit swings than gels or pellets; daily or every-other-day low-dose injections can minimize these peaks.

Who Should Use Caution

While TRAVERSE established TRT's general cardiovascular safety, certain men should approach treatment with careful provider guidance:

• Men with active atrial fibrillation — given the modest AF signal in TRAVERSE, cardiologist co-management is advisable
• Men with prior pulmonary embolism or deep vein thrombosis — elevated clotting risk warrants careful risk-benefit discussion
• Men with severe uncontrolled heart failure — limited data in this population; benefits should be weighed individually
• Men with polycythemia vera — TRT's erythropoietic effect is contraindicated in this blood disorder
• Men with known prostate cancer — an absolute contraindication given testosterone's role in prostate cancer stimulation

For the vast majority of otherwise healthy or moderately at-risk men with confirmed hypogonadism, TRAVERSE represents strong reassurance that TRT can be pursued safely under appropriate medical supervision.

Practical Monitoring: What Your Provider Should Check

Responsible TRT isn't just a prescription — it includes ongoing monitoring to ensure both efficacy and safety. A well-managed TRT program should include:

• Baseline labs: Total testosterone, free testosterone, SHBG, LH, FSH, PSA, complete blood count (CBC), comprehensive metabolic panel, lipid panel
• At 3 months: Total and free testosterone (to confirm therapeutic range), hematocrit, PSA
• Every 6–12 months thereafter: Full panel repeat; blood pressure check; symptom review
• Estradiol (E2): Especially if using injectable testosterone, which can aromatize more aggressively — elevated estradiol causes water retention, mood changes, and breast tissue sensitivity

The Bottom Line: What Should Men Do?

The era of reflexive fear around TRT and heart health is over — or should be. The TRAVERSE trial was the largest and most rigorous cardiovascular safety study ever conducted in TRT, and its message is clear: for hypogonadal men, testosterone therapy does not increase the risk of heart attack, stroke, or cardiovascular death. The modest signals for atrial fibrillation and pulmonary embolism are real and deserve attention, but they do not overturn the overall picture of safety in the broader population.

What remains true is that TRT is a medical treatment that requires appropriate diagnosis, individualized dosing, and ongoing monitoring — not a supplement you pick up at a pharmacy. Men who have symptoms of low testosterone (low energy, reduced libido, loss of muscle, mood changes, brain fog) and confirmed low levels on labs deserve to have an informed conversation about treatment without outdated fear-mongering getting in the way.

The heart of the matter — pun intended — is that leaving hypogonadism untreated carries its own risks, and those risks deserve just as much attention as the speculative concerns that have dominated the conversation for too long.