Testosterone and Heart Health: What Men Need to Know

Why the Testosterone–Heart Debate Matters

Heart disease is the leading cause of death in men, and low testosterone (hypogonadism) affects an estimated 2–5 million American men. These two facts intersect in a critically important way: low testosterone is associated with higher rates of cardiovascular disease, metabolic syndrome, obesity, and diabetes — all established heart disease risk factors. Yet for decades, clinicians were cautious about prescribing testosterone therapy partly due to concerns about cardiovascular safety.

The good news is that the science has substantially matured. We now have a large, well-designed randomized controlled trial specifically designed to answer the cardiovascular safety question — and the evidence is largely reassuring for appropriately screened men.

The Relationship Between Low Testosterone and Cardiovascular Risk

Multiple large observational studies have found that men with low testosterone have significantly higher risks of:

• Coronary artery disease and myocardial infarction
• Heart failure
• Stroke
• Atrial fibrillation
• All-cause mortality

A 2006 study in the Journal of Clinical Endocrinology & Metabolism found that men with the lowest testosterone levels had a 41% higher risk of mortality compared to those with higher levels. Low testosterone promotes visceral fat accumulation, insulin resistance, endothelial dysfunction, inflammation, and dyslipidemia — all of which damage arteries and drive cardiovascular disease.

The mechanistic picture is compelling: testosterone promotes nitric oxide production (which dilates blood vessels), supports healthy red blood cell function, helps regulate blood sugar, and maintains lean muscle mass. Deficiency in testosterone creates the opposite of these beneficial effects.

Early Concerns About TRT and Heart Risk

The cardiovascular concerns about testosterone therapy peaked after two controversial studies in 2010 and 2014 suggested increased cardiac events in men using TRT. These studies had significant methodological limitations — they were retrospective, used inadequate controls, and included populations of men with pre-existing severe cardiovascular disease. Nevertheless, the FDA required a label warning in 2015 about potential cardiovascular risks.

This created significant clinical uncertainty and caused many physicians to under-treat hypogonadism in men who would have benefited from therapy. Fortunately, that uncertainty was finally addressed directly by the TRAVERSE trial.

The TRAVERSE Trial: The Definitive Cardiovascular Safety Study

The Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE (TRAVERSE) trial, published in the New England Journal of Medicine in 2023, was specifically designed to assess the cardiovascular safety of testosterone therapy in men with hypogonadism and elevated cardiovascular risk or established cardiovascular disease.

Key details:

• Participants: 5,246 men aged 45–80 with hypogonadism (testosterone <300 ng/dL) and pre-existing cardiovascular disease or elevated cardiovascular risk
• Treatment: Daily testosterone gel (1.62%) vs. placebo
• Duration: Approximately 33 months (median)
• Primary endpoint: Major adverse cardiovascular events (MACE): non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death

The result: MACE occurred in 7.0% of the testosterone group versus 7.3% of the placebo group — a non-significant difference, confirming that testosterone therapy was non-inferior to placebo for cardiovascular events. This provides strong evidence that TRT does not increase heart attack or stroke risk in men with hypogonadism, even those at elevated cardiovascular risk.

What the TRAVERSE Trial Also Found

While the primary cardiovascular finding was reassuring, the TRAVERSE trial did identify some signals worth noting:

• Atrial fibrillation: Higher rates in the testosterone group (3.5% vs. 2.4%). This was a secondary endpoint and requires further investigation, but men with existing arrhythmia risk should discuss this with their physician.
• Pulmonary embolism: Slightly higher in the testosterone group (0.9% vs. 0.5%). This may be related to erythrocytosis (elevated red blood cell count).
• Acute kidney injury: Also slightly higher in the testosterone group.

These findings underscore the importance of appropriate patient selection, monitoring hematocrit levels during TRT, and ongoing clinical oversight. Read more about managing hematocrit on testosterone therapy.

How Testosterone Affects Cardiovascular Risk Factors

Cholesterol and Lipids

The effects of testosterone on lipids are nuanced. TRT can modestly lower HDL cholesterol — particularly with injectable testosterone formulations — while also reducing triglycerides and LDL. The net effect on cardiovascular risk appears to be neutral to slightly favorable in most men, but lipid monitoring is important.

Blood Pressure

Some studies show modest increases in blood pressure with TRT, while others show neutral or slightly beneficial effects. The data are inconsistent, and the clinical significance appears minimal in most men. Regular blood pressure monitoring during TRT is standard practice.

Insulin Sensitivity and Metabolic Health

One of testosterone's clearest cardiovascular benefits is its positive effect on metabolic health. TRT consistently improves insulin sensitivity, reduces fasting glucose, and helps reduce visceral fat — all of which are significant cardiovascular risk factors in men with metabolic syndrome or prediabetes. Men with the lowest testosterone often have the greatest metabolic benefit from TRT.

Body Composition

TRT reliably increases lean muscle mass and reduces fat mass, particularly visceral fat. Since visceral adiposity is one of the strongest drivers of cardiovascular disease, this body composition improvement represents a meaningful indirect cardiovascular benefit.

Inflammation

Low testosterone is associated with elevated inflammatory markers like C-reactive protein (CRP) and interleukin-6. TRT has been shown to reduce these markers in some studies, suggesting an anti-inflammatory effect that could benefit the cardiovascular system.

Heart Failure and Testosterone

Interestingly, testosterone may have a specific role in heart failure. The heart has testosterone receptors, and low testosterone is common in men with heart failure. Several trials have investigated TRT in men with heart failure and found improvements in exercise capacity, muscle strength, and quality of life — though large mortality trials are still needed. Current guidelines suggest TRT is not contraindicated in stable, compensated heart failure in hypogonadal men, but it should be approached with caution and specialist input.

Who Should Consider TRT for Cardiovascular Reasons?

The evidence does not currently support testosterone therapy as a standalone cardiovascular treatment. However, hypogonadal men who are experiencing symptoms (fatigue, low libido, erectile dysfunction, mood changes, muscle loss) and have cardiovascular risk factors may find that treating their testosterone deficiency offers meaningful metabolic and quality-of-life benefits without increasing cardiovascular risk.

Candidates for TRT should have:

• Confirmed hypogonadism on at least two morning testosterone measurements
• Symptoms consistent with testosterone deficiency
• No absolute contraindications (untreated prostate cancer, severe urinary symptoms, hematocrit >50%, recent cardiac event without stabilization)

Our guide to TRT delivery methods covers the differences between gels, injections, and pellets.

Monitoring During TRT

Men on testosterone therapy should have regular monitoring including:

• Hematocrit (every 3–6 months) — target below 52–54%
• PSA (prostate-specific antigen)
• Testosterone levels
• Lipid panel
• Blood pressure

According to the American Urological Association (AUA) and the Endocrine Society's clinical practice guidelines, careful monitoring is the standard of care for men on TRT.

The Bottom Line

The weight of evidence suggests that appropriately prescribed testosterone therapy for genuinely hypogonadal men is not associated with increased heart attack or stroke risk. Low testosterone itself appears to be the greater cardiovascular threat. The key is proper diagnosis, individualized patient selection, appropriate monitoring, and ongoing clinical supervision. For most men with confirmed hypogonadism and bothersome symptoms, the benefits of TRT — including metabolic improvements — likely outweigh the risks when managed correctly.