The Study That Scared Everyone: The 2010 TRT Trial
In November 2010, a study published in the New England Journal of Medicine — the NEJM TRT trial, also called the "Testosterone in Older Men with Mobility Limitations" study — was stopped early after researchers observed a higher rate of cardiovascular events in men receiving testosterone compared to placebo. The numbers were small (23 events vs. 5), but the signal was alarming enough to halt the trial.
The medical community, already cautious about TRT, amplified the concern. The FDA added black box warnings. Many physicians became reluctant to prescribe testosterone. Men who might benefit were told to hold off.
The problem with that response: the 2010 study enrolled very old, frail men with severe mobility limitations who were already at extremely high cardiovascular risk. The study population was not representative of the typical man seeking TRT, the sample size was too small to draw broad conclusions, and the early termination made statistical interpretation difficult. Critics pointed out these limitations immediately — but the narrative of "TRT is dangerous for the heart" had already taken hold.
The TRAVERSE Trial: The Study That Changed Everything
Published in the New England Journal of Medicine in June 2023, the TRAVERSE trial is the definitive cardiovascular safety study that TRT needed. It was a randomized, double-blind, placebo-controlled trial specifically designed to address the cardiovascular question — adequately powered, properly conducted, and with a population that actually reflects men being considered for TRT.
Who Was in the Trial?
TRAVERSE enrolled 5,246 men between the ages of 45 and 80 with confirmed hypogonadism (testosterone levels below 300 ng/dL) and either pre-existing cardiovascular disease or high cardiovascular risk based on established risk factors. This was not a healthy young population — it was the group that physicians had been most worried about treating.
What Did It Find?
Men were randomized to testosterone replacement (via daily topical gel) or placebo and followed for a median of 33 months. The primary outcome was major adverse cardiovascular events (MACE) — a composite of heart attack, stroke, and cardiovascular death.
Result: No significant difference in MACE between the testosterone and placebo groups. The hazard ratio was 0.96, meaning if anything there was a slight (non-significant) trend toward fewer events in the testosterone group.
This was a landmark finding. In the highest-risk population that could be assembled — older men with cardiovascular disease — testosterone replacement did not increase the risk of heart attack, stroke, or cardiovascular death compared to placebo.
What About the Caveats?
The TRAVERSE trial also reported a slightly higher rate of atrial fibrillation (3.5% vs. 2.4%) and pulmonary embolism (0.9% vs. 0.5%) in the testosterone group. These findings were statistically significant and deserve attention. Atrial fibrillation in particular is a meaningful finding that warrants monitoring in men on TRT, especially those with pre-existing cardiac conduction issues.
The key takeaway is not that TRT is without any cardiovascular consideration — it is that the primary fear (heart attacks and strokes) is not borne out by the best evidence available, while other signals (AFib, VTE) warrant monitoring and individualized assessment.
How Low Testosterone Is Itself a Cardiovascular Risk Factor
The conversation about TRT and the heart has often focused on potential harms while underemphasizing a critical piece of the puzzle: untreated hypogonadism carries its own cardiovascular risk.
Multiple large observational studies have found that men with low testosterone have significantly higher rates of cardiovascular disease and cardiovascular mortality compared to men with normal testosterone levels. The mechanisms are well-characterized:
- Visceral fat accumulation: Low testosterone promotes storage of metabolically dangerous abdominal fat, which drives insulin resistance and systemic inflammation
- Dyslipidemia: Low T is associated with lower HDL cholesterol and higher triglycerides
- Endothelial dysfunction: Testosterone has vasodilatory effects on coronary and peripheral arteries; its deficiency impairs vascular function
- Insulin resistance: Low testosterone is strongly associated with metabolic syndrome, which is itself a major cardiovascular risk cluster
- Inflammation: Low testosterone is associated with elevated inflammatory markers including CRP and IL-6
In other words, a physician who refuses to treat documented hypogonadism out of cardiovascular caution is not necessarily protecting the patient — they may be allowing a risk factor to persist untreated.
TRT and Hematocrit: The Real Variable to Watch
The most clinically important cardiovascular consideration with TRT is hematocrit elevation. Testosterone stimulates red blood cell production by increasing erythropoietin. In some men — particularly those on injectable testosterone — this can raise hematocrit to levels that increase blood viscosity and theoretically elevate thrombosis risk.
Standard TRT management includes monitoring hematocrit (and hemoglobin) at baseline and regularly during treatment — typically at 3 and 6 months initially, then annually. If hematocrit rises above approximately 54%, the standard approach is to reduce the testosterone dose, increase the interval between injections, or in some cases consider a therapeutic blood draw (phlebotomy).
This is why competent TRT management is not just about writing a prescription — it includes appropriate monitoring to catch and manage these known physiological effects before they become clinical problems.
Who Should Be Cautious?
While the TRAVERSE trial's findings are reassuring for most men with hypogonadism, certain situations warrant extra care:
- Men with uncontrolled heart failure: TRT can cause fluid retention, which may worsen decompensated heart failure. Stable heart failure is a different situation than acute or poorly controlled failure.
- Men with very high baseline hematocrit: Starting TRT in a man with hematocrit already at 50%+ requires careful dose selection and monitoring
- Men with history of pulmonary embolism or DVT: Given the TRAVERSE signal on VTE, men with prior clotting events require individualized risk-benefit discussion
- Men with atrial fibrillation: The AFib signal from TRAVERSE warrants discussion of cardiac monitoring in men with existing arrhythmias
None of these represent absolute contraindications in all cases — they represent reasons for careful physician evaluation, appropriate monitoring, and sometimes collaboration with a cardiologist.
What This Means for Men Considering TRT
The evidence landscape has changed significantly since 2010. The TRAVERSE trial provides the strongest evidence to date that TRT does not increase the risk of heart attack, stroke, or cardiovascular death in properly selected men with hypogonadism — even in a high-risk cardiovascular population.
What remains important is that TRT is managed appropriately: with baseline cardiovascular assessment, regular hematocrit and lab monitoring, dose optimization, and appropriate follow-up. TRT is not a "set it and forget it" treatment — it is a medical therapy that benefits from ongoing physician oversight.
At Truventa Medical, our licensed physicians provide comprehensive TRT management that includes the lab monitoring, dose adjustment, and follow-up care that men need to use testosterone safely and effectively — all online across all 50 states.
Frequently Asked Questions
Is TRT bad for your heart?
Current evidence does not support the idea that TRT is harmful to the heart in properly selected patients. The 2023 TRAVERSE trial — the largest cardiovascular safety study of TRT ever conducted — found no significant increase in major adverse cardiovascular events in men with hypogonadism treated with testosterone compared to placebo. Meanwhile, low testosterone itself is an independent cardiovascular risk factor.
What did the TRAVERSE trial find?
Published in the New England Journal of Medicine in 2023, the TRAVERSE trial enrolled over 5,200 men aged 45–80 with hypogonadism and pre-existing or high-risk cardiovascular disease. Men were randomized to testosterone gel or placebo and followed for a median of 33 months. The primary finding: no significant difference in major adverse cardiovascular events (MACE) between the testosterone and placebo groups. The trial also noted slightly higher rates of atrial fibrillation and pulmonary embolism in the testosterone group — findings that warrant monitoring in clinical practice.
Does testosterone raise blood pressure?
TRT can raise hematocrit (red blood cell mass), which increases blood viscosity and may elevate blood pressure in some men. Testosterone also causes some degree of fluid retention, which can temporarily affect blood pressure. In men with well-controlled TRT and appropriate monitoring, significant hypertension from testosterone is not commonly reported — but blood pressure should be tracked as part of routine follow-up.
Can men with heart disease use TRT?
The TRAVERSE trial specifically included men with pre-existing cardiovascular disease — making it the most relevant evidence set for this question. The trial did not find a significantly elevated MACE risk in this population. However, individual risk assessment is essential. Men with uncontrolled heart failure, severe coronary artery disease, or very high hematocrit require careful evaluation. TRT in these populations requires close collaboration between a cardiologist and the prescribing physician.