Testosterone replacement therapy does not appear to increase heart attack risk in men who have genuinely low testosterone levels. The largest randomized trial ever conducted on this question, called TRAVERSE, found that the rate of major cardiovascular events was nearly identical between men receiving testosterone gel and those receiving a placebo over roughly three years of follow-up. That finding was a relief after more than a decade of conflicting data and regulatory warnings that left both patients and physicians uneasy. But the full picture involves more moving parts than a single trial can settle, and some findings from sub-studies still warrant attention.
Why This Became a Controversy
For years, the relationship between testosterone therapy and heart health was genuinely unclear. Observational studies in the early 2010s suggested that men starting TRT might face a higher risk of heart attacks and strokes, and meta-analyses pooling smaller trials produced inconsistent results with a lot of variation between studies.1PubMed Central. The Effect of Testosterone on Cardiovascular Disease and Cardiovascular Risk Factors in Men: A Review of Clinical and Preclinical Data The problem was that none of these studies were specifically designed to measure cardiovascular safety. They were small, short, or retrospective, and the populations studied varied wildly.
Those early signals were enough to prompt regulatory action. In September 2014, the FDA convened an advisory committee meeting on testosterone products. By March 2015, the agency required label changes on all testosterone products, adding a warning about possible increased cardiovascular risk and narrowing the approved indication to men with specific known causes of low testosterone rather than age-related decline alone.2PubMed. The state of testosterone therapy since the FDA’s 2015 labelling changes: Indications and cardiovascular risk Prescriptions dropped, and many men who had been doing well on TRT were left wondering whether they were taking a dangerous medication.
What was missing from the conversation was a large, properly designed trial whose primary purpose was to determine whether TRT caused heart attacks and strokes. Observational data can spot associations, but it struggles with confounding: men who are prescribed TRT already tend to be less healthy than average, which makes it hard to separate the effects of the hormone from the effects of the conditions that prompted its use.
What the TRAVERSE Trial Found
TRAVERSE (Testosterone Replacement therapy for Assessment of long-term Vascular Events and Efficacy ResponSE in hypogonadal men) was built specifically to fill this gap. It enrolled 5,246 men between 45 and 80 years old who had symptoms of low testosterone, two fasting testosterone readings below 300 ng/dL, and either preexisting cardiovascular disease or a high risk of it. Participants were randomly assigned to receive daily transdermal testosterone gel, dosed to keep their levels in a normal range, or a matching placebo gel.3PubMed. Cardiovascular Safety of Testosterone-Replacement Therapy The trial ran for a mean of about 33 months, making it by far the longest and largest randomized study of TRT’s cardiac safety.
The primary endpoint was a composite of cardiovascular death, nonfatal heart attack, or nonfatal stroke. In the testosterone group, the rate of these events was 7.0%. In the placebo group, it was 7.3%. There was no excess of blood clots either.4Mayo Clinic Proceedings. Testosterone Therapy and Cardiovascular Risk: Advances and Controversies That result met the statistical criteria for noninferiority, meaning TRT was confirmed not to be meaningfully worse than placebo for these outcomes. The Androgen Society subsequently issued a position statement declaring that it has been “conclusively determined” that TRT is not associated with increased risks of heart attack, stroke, or cardiovascular death.5Mayo Clinic Proceedings. Testosterone Therapy and Cardiovascular Risk: Advances and Controversies
A few caveats are worth noting. TRAVERSE studied transdermal gel specifically, not injections or oral testosterone. The men enrolled all had confirmed hypogonadism and were kept within a normal testosterone range through careful dose adjustments. And while roughly three years is long for a clinical trial, cardiovascular disease develops over decades. A review of the trial’s implications noted that the study design was rigorous but that even longer follow-up could reveal effects not yet apparent.6PubMed Central. Long Term Cardiovascular Safety of Testosterone Therapy: A Review of the TRAVERSE Study
How Testosterone Affects the Cardiovascular System
The reason the question was hard to settle for so long is that testosterone pulls the cardiovascular system in multiple directions at once. Some of its effects look protective, and some look potentially harmful. The net result depends on dose, duration, the patient’s baseline health, and probably genetics in ways we do not fully understand yet.
On the protective side, testosterone acts directly on blood vessel walls. In laboratory and animal studies, it relaxes coronary arteries by opening potassium channels in the smooth muscle cells that line the vessel walls, which causes them to widen.7PubMed. Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activated potassium channel This effect has been confirmed in both the larger coronary arteries and the smaller resistance vessels that control blood flow deep in the heart muscle.8PubMed. Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo There is also evidence from older adults that testosterone and its metabolite dihydrotestosterone reduce platelet activation, making blood platelets less sticky and less prone to forming clots.9PubMed Central. Testosterone and dihydrotestosterone reduce platelet activation and reactivity in older men and women
On the potentially harmful side, earlier research found that when testosterone is administered externally, it can temporarily increase the number of receptors on platelets that respond to thromboxane, a molecule that promotes clotting. That effect peaked at about four weeks and returned to baseline by eight weeks in healthy men.10PubMed. Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses The seeming contradiction between these platelet findings and the anti-clotting data may relate to differences in study populations, measurement timing, and whether the testosterone levels studied were physiological or supraphysiological. It is one of the areas where the science has not fully settled.
TRT also tends to lower HDL cholesterol, the so-called good cholesterol. A review of this effect noted that while exogenous testosterone does reduce HDL, it often lowers total cholesterol and LDL at the same time, making the net lipid impact less straightforward than one number alone suggests.11PubMed Central. An update on testosterone, HDL and cardiovascular risk in men Additionally, testosterone therapy can activate the body’s sodium- and water-retention pathways and modestly raise blood pressure through renin-angiotensin system stimulation and increased sympathetic nervous activity.
The Coronary Plaque Question
One finding from a sub-study within an earlier testosterone trial gave cardiologists pause. When researchers used CT scans to measure coronary artery plaque in older men with low testosterone, the men receiving testosterone gel had a significantly greater increase in noncalcified plaque volume over 12 months compared to those on placebo.12PubMed Central. Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone Noncalcified plaque is the softer kind that is more likely to rupture and trigger a heart attack, so this was a genuinely concerning signal.
However, the study was small, and a follow-up analysis looking at what predicted plaque growth found that the effect was concentrated among men with a higher waist-to-hip ratio at baseline. For every 0.1 increase in waist-to-hip ratio, the testosterone-driven increase in noncalcified plaque volume grew by about 27 cubic millimeters.13The Journal of Clinical Endocrinology & Metabolism. Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone In other words, men carrying more abdominal fat seemed to be more susceptible to testosterone-related plaque changes. This hints that body composition at the time TRT is started may matter, though the data is too thin to draw firm clinical guidelines from.
Importantly, this plaque finding did not translate into more heart attacks or strokes in TRAVERSE’s much larger and longer dataset. The gap between plaque imaging and actual clinical events is a recurring theme in cardiology: not every scan finding predicts disaster, and not every clean scan guarantees safety. Still, the plaque data is a reminder that “no increased heart attack risk on average” does not mean “no effects on the cardiovascular system at all.”
Does the Type of TRT Matter
Not all testosterone formulations are created equal when it comes to heart risk. A systematic review and meta-analysis that separated studies by how testosterone was given found that oral testosterone replacement produced significant cardiovascular risk, while injectable and transdermal (gel or patch) forms did not show a clear signal in either direction.14PubMed Central. Cardiovascular risks and elevation of serum DHT vary by route of testosterone administration: a systematic review and meta-analysis The researchers suggested that differences in how much each route raises dihydrotestosterone, a potent testosterone metabolite, may explain the variation. Oral formulations pass through the liver first and can produce more extreme hormonal peaks and metabolic disturbances.
This distinction matters because TRAVERSE used transdermal gel exclusively. Its reassuring results cannot be automatically extended to oral testosterone pills or high-dose injectable testosterone cypionate, which is a common form prescribed in the United States. That said, many of the older observational studies that raised cardiovascular alarms included men on injections, and the overall signal from TRAVERSE was reassuring enough to shift expert consensus broadly. The bottom line for patients is that the delivery method is worth discussing with a prescriber, and that maintaining stable, physiological testosterone levels rather than riding peaks and troughs is probably safer.
Low Testosterone as a Heart Risk on Its Own
Part of what makes this topic so confusing is that low testosterone is itself associated with a higher risk of dying from heart disease. A large individual-participant-data meta-analysis found that men with baseline testosterone concentrations below roughly 213 ng/dL had higher all-cause mortality, and those below about 153 ng/dL had higher cardiovascular mortality specifically.15PubMed Central. Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men: Individual Participant Data Meta-analyses Low testosterone is also linked to diabetes, metabolic syndrome, chronic inflammation, and unfavorable cholesterol profiles, all of which are established cardiovascular risk factors.16PubMed Central. Welcoming low testosterone as a cardiovascular risk factor
This means men with very low testosterone face a double bind: their untreated hormone deficiency raises their cardiovascular risk, but for over a decade they were also warned that treating it might raise the same risk. TRAVERSE went a long way toward resolving that bind by showing that correcting low testosterone to a normal range did not add cardiovascular danger. But the data is clearest for the specific profile of men in that trial: middle-aged and older men with confirmed hypogonadism and existing cardiovascular risk factors. Whether the same applies to younger men, men with borderline testosterone, or men using TRT mainly for gym performance remains less certain.
Blood Pressure on TRT
Blood pressure is one area where TRT does produce a measurable, if modest, effect. A study using 24-hour ambulatory blood pressure monitoring in men starting an oral testosterone formulation found an average systolic blood pressure increase of about 1.7 mmHg.17PubMed Central. Effects of the oral testosterone undecanoate Kyzatrexâ„¢ on ambulatory blood pressure in hypogonadal men Previous studies using different testosterone formulations reported larger increases of around 3.7 to 5.5 mmHg for systolic pressure. For men already on blood pressure medication, the bump tended to be larger.
A few millimeters of mercury might not sound like much, but at a population level, even small sustained increases in blood pressure contribute to long-term cardiovascular risk. For an individual man, this probably means that regular blood pressure monitoring after starting TRT is sensible, and that men who already have poorly controlled hypertension should get that sorted before adding testosterone to the mix.
Body Composition and Metabolic Effects
One pathway through which TRT may indirectly benefit cardiovascular health is by improving body composition. In men with congenital hypogonadism, 36 weeks of testosterone replacement significantly reduced waist circumference, truncal fat, and insulin resistance while increasing lean body mass.18PubMed Central. Effect of testosterone replacement therapy on insulin sensitivity and body composition in congenital hypogonadism: A prospective longitudinal follow-up study In older men with type 2 diabetes, TRT increased lean mass and reduced total fat mass, including fat in the trunk, arms, and legs, compared to placebo. That said, the same study did not find improvements in insulin-stimulated glucose disposal or blood sugar control as measured by HbA1c.19PubMed. Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy
The implication is nuanced. TRT can shift body composition in a direction that is generally associated with lower cardiovascular risk: less visceral fat, more muscle. But whether those compositional changes actually translate to fewer heart attacks remains an open question that TRAVERSE was not designed to resolve. The trial showed no harm, not a benefit.
TRT Versus Anabolic Steroid Abuse
A persistent source of confusion in public discussions of testosterone and heart risk is the conflation of medically supervised TRT with anabolic steroid misuse. The two bear almost no resemblance in terms of cardiovascular impact. Synthetic anabolic steroid preparations used for bodybuilding can be up to 15 times more potent than prescribed TRT doses, and they are often stacked with multiple compounds.20PubMed Central. Anabolic steroid misuse is an important reversible cause of cardiomyopathy: a case report At those supraphysiological levels, testosterone and its synthetic relatives produce direct toxic effects on heart muscle cells, accelerate coronary artery plaque buildup, cause dangerous cholesterol distortions, and can trigger cardiomyopathy, arrhythmias, and sudden death.
When someone says “testosterone causes heart attacks,” they may be drawing on case reports and studies of steroid abusers whose hormone levels are many times higher than anything a responsible TRT protocol would produce. The TRAVERSE data applies to men kept within a normal testosterone range of roughly 350 to 750 ng/dL. Extrapolating that safety data to men running underground steroid cycles would be seriously misguided, and the reverse extrapolation, assuming steroid dangers apply to TRT patients, is equally wrong.
Testosterone and Heart Failure
A separate question from whether TRT causes heart attacks is whether it helps or hurts men who already have heart failure. The evidence here is preliminary but interesting. In a double-blind trial of men with moderate heart failure, testosterone therapy improved exercise capacity by a mean of 25 meters on a six-minute walk test, corresponding to a roughly 15% improvement from baseline, and about a third of men on testosterone improved by at least one functional class.21European Heart Journal. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial No excess of adverse events was seen, though the testosterone patch used in that trial was poorly tolerated by many participants.
Broader reviews of testosterone in heart failure have found that while some small studies report improvements in peak oxygen consumption, muscle strength, and even cardiac output, others show no functional benefit despite raising testosterone levels successfully.22Current Problems in Cardiology. Testosterone therapy in patients with heart failure and protein-calorie malnutrition: Insights from a propensity-matched cohort study Without exercise, testosterone-driven gains in body composition did not translate into better aerobic fitness in several studies. This is not the kind of evidence that would justify prescribing TRT for heart failure, but it does suggest that having heart failure is not an automatic disqualification from TRT if a man also has confirmed low testosterone and symptoms that warrant treatment.
What About Transgender Men
Transgender men who take testosterone as part of gender-affirming hormone therapy face a related but distinct version of this question. A narrative review of recent literature, including meta-analyses and large cohort studies, concluded that it remains inconclusive whether androgen administration increases cardiovascular event risk in transgender men.23PubMed Central. Cardiovascular Risk in Transgender People With Gender-Affirming Hormone Treatment The populations studied are younger on average, the treatment duration is often lifelong, and the baseline cardiovascular risk profile differs from the older hypogonadal men enrolled in TRAVERSE. Drawing direct comparisons between TRT for cisgender hypogonadal men and hormone therapy for transgender men is tempting but premature. Dedicated long-term studies in transgender populations are still needed, and the reassuring TRAVERSE data cannot be assumed to apply outside the group it studied.