TRT and Heart Health: What the Latest Research Says

Few topics in men's health have generated as much confusion and fear as the relationship between testosterone replacement therapy and cardiovascular risk. For over a decade, sensationalized headlines and flawed studies created a chilling effect that kept millions of men with clinically low testosterone from seeking treatment. Physicians became hesitant to prescribe. Patients lived with debilitating symptoms. Insurance companies found convenient reasons to deny coverage.

But science is self-correcting. In 2023, the largest and most rigorous randomized controlled trial ever conducted on TRT and heart health delivered a verdict that is reshaping how the medical community thinks about testosterone therapy. If you have been hesitant about TRT because of cardiovascular concerns, this article will walk you through every major study, explain what went wrong with the early research, and give you the tools to have an informed conversation with your provider.

The Studies That Started the Scare

The testosterone-heart panic can be traced to two studies that received enormous media coverage. The first was a 2010 study often called the TOM trial (Testosterone in Older Men with Mobility Limitations). This small trial of 209 elderly men with significant comorbidities was actually stopped early because the testosterone group experienced more cardiovascular events than the placebo group. However, the men enrolled were far sicker than typical TRT candidates, with many having pre-existing heart disease, diabetes, and obesity. The trial was never designed to assess cardiovascular safety as its primary endpoint.

The second and more impactful study was a 2013 retrospective analysis published in JAMA that looked at VA medical records. This observational study of approximately 8,700 men found that those prescribed testosterone had a higher rate of heart attack, stroke, and death. The study made global headlines. What the headlines missed was devastating: the study had serious methodological problems. Independent researchers later found calculation errors so significant that over two dozen medical societies and more than 160 physicians signed a petition asking JAMA to retract the paper. JAMA issued corrections but did not retract.

A second observational study in 2014, published in PLOS ONE, also reported increased heart attack risk with TRT. However, this study compared men who had just started TRT (when dose optimization is still underway) against their own pre-treatment baseline rather than against untreated controls. The comparison was inherently biased because men typically seek TRT when they are feeling their worst.

The FDA's Response and the Black Box Warning

Despite the flawed evidence, the FDA took action. In 2015, the agency required testosterone products to carry a warning about possible increased risk of heart attacks and strokes. This was not a black box warning (the most severe type), but it was enough to significantly impact prescribing patterns. Many primary care physicians, already uncomfortable managing testosterone therapy, stopped prescribing it altogether. Endocrinologists and urologists pushed back, arguing the evidence did not support the warning, but the regulatory damage was done.

The FDA also mandated that a large, rigorous cardiovascular outcomes trial be conducted. This mandate would lead to the study that ultimately vindicated TRT.

The TRAVERSE Trial: The Definitive Answer

The Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men trial, mercifully abbreviated as TRAVERSE, was the gold standard study the field had been waiting for. Published in The New England Journal of Medicine in June 2023, TRAVERSE was a randomized, double-blind, placebo-controlled trial designed specifically to answer the cardiovascular safety question.

Study Design and Scope

TRAVERSE enrolled 5,246 men aged 45 to 80 who had either pre-existing cardiovascular disease or were at high cardiovascular risk. All participants had confirmed hypogonadism with total testosterone levels below 300 ng/dL and at least one symptom of low testosterone. This was a deliberately high-risk population, meaning if TRT were going to cause heart problems, this study would detect it. Participants were randomized to receive either 1.62% testosterone gel or a matching placebo gel, applied daily. The median follow-up was 33 months, with some participants followed for over four years.

The Results

The primary endpoint was major adverse cardiovascular events, a composite of cardiovascular death, nonfatal heart attack, and nonfatal stroke. The results were clear: testosterone therapy did not increase cardiovascular events compared to placebo. The incidence rate was 7.0% in the testosterone group versus 7.3% in the placebo group. The hazard ratio was 0.96, with confidence intervals that firmly established non-inferiority. In plain language, men on TRT had the same cardiovascular event rate as men on placebo, even in a population that was already at elevated heart risk.

The trial did find a modest increase in atrial fibrillation and acute kidney injury in the testosterone group, though these secondary findings require further study. Pulmonary embolism rates were also slightly higher, consistent with the known effect of testosterone on red blood cell production. These findings underscore the importance of proper monitoring, but they did not change the overall cardiovascular safety conclusion.

FDA Removes the Cardiovascular Warning

Based on the TRAVERSE results and subsequent analyses, the FDA announced in early 2025 that it would be updating testosterone product labeling to remove the cardiovascular risk warning that had been in place since 2015. This was a landmark regulatory reversal, effectively acknowledging that the original warning was not supported by the highest quality evidence. For patients and clinicians, this was validation of what the endocrinology community had argued for a decade.

The updated labeling now reflects that in men with hypogonadism, TRT at physiologic doses does not appear to increase cardiovascular risk. This does not mean TRT is risk-free, but the specific heart attack and stroke fears that dominated the conversation for years have been addressed by rigorous evidence.

Who Should Still Be Cautious

While TRAVERSE was reassuring for the broad population of men with hypogonadism, certain individuals should approach TRT with additional caution and closer monitoring. Medicine is always about individual risk-benefit analysis, and no study eliminates the need for personalized care.

• Men with a history of blood clotting disorders or deep vein thrombosis should be closely monitored, as testosterone can increase red blood cell production and potentially raise clotting risk.
• Patients with severe, uncontrolled heart failure may not be ideal candidates for TRT until their cardiac condition is stabilized.
• Men with untreated severe obstructive sleep apnea should address this condition before or concurrently with starting TRT, as testosterone can worsen apnea in some cases.
• Individuals with polycythemia (abnormally high red blood cell counts) at baseline need careful hematocrit monitoring, as TRT can further elevate these levels.
• Men over 65 with multiple cardiovascular risk factors should have more frequent monitoring during the first year of therapy.

The Monitoring That Matters

The TRAVERSE trial reinforced something responsible TRT providers have always known: monitoring is essential. Testosterone therapy is not something you start and forget. Regular blood work ensures that treatment remains safe and effective. The two most important cardiovascular-related markers to track are hematocrit and blood pressure.

Hematocrit and Red Blood Cell Production

Testosterone stimulates erythropoiesis, the production of red blood cells. While this can improve energy and oxygen delivery, excessively high hematocrit levels (above 54%) can thicken the blood and increase clotting risk. This is the most common reason TRT doses need adjustment. Regular complete blood count testing, typically every 3 to 6 months, catches elevations early. If hematocrit rises too high, the solution is usually a dose reduction, a switch in delivery method, or therapeutic phlebotomy (blood donation).

Blood Pressure Monitoring

Some men experience mild blood pressure increases on TRT, often related to fluid retention or increased hematocrit. Monitoring blood pressure at home and during clinic visits allows for early intervention. In most cases, blood pressure changes are modest and manageable through lifestyle modifications or, if necessary, antihypertensive medication.

How PrimeHealth Approaches Cardiovascular Safety

At PrimeHealth, cardiovascular safety is built into every step of our TRT protocol. Before initiating therapy, every patient undergoes comprehensive lab work that includes a complete blood count, lipid panel, metabolic panel, and cardiovascular risk assessment. We do not prescribe TRT to men who are not appropriate candidates, and we do not cut corners on monitoring.

Our follow-up schedule includes lab work at 6 weeks, 3 months, 6 months, and then every 6 months thereafter. Hematocrit, PSA, lipids, liver function, and hormone levels are tracked at every visit. If any marker moves outside the optimal range, our clinical team adjusts the protocol immediately. This is what evidence-based TRT looks like, and it is why monitoring through a qualified medical team matters far more than the testosterone itself.

The Bottom Line

The question of whether TRT is safe for your heart has been answered with the best evidence medicine can produce. The TRAVERSE trial, the largest cardiovascular outcomes trial of testosterone therapy ever conducted, found no increased risk of heart attack, stroke, or cardiovascular death. The FDA has updated its labeling accordingly. The decade of fear driven by flawed observational studies is giving way to evidence-based confidence.

This does not mean TRT is without any risks. All medical therapies involve tradeoffs, and proper monitoring remains essential. But the specific cardiovascular panic that kept so many men from treating their hypogonadism was not supported by the evidence then, and it has been definitively refuted now. If low testosterone is affecting your quality of life, the heart risk should no longer be the reason you avoid treatment. Talk to a qualified provider, get your labs, and make a decision based on science rather than headlines.