For years, conflicting headlines about testosterone and heart health left patients and providers guessing. Some studies linked testosterone replacement therapy (TRT) to increased cardiovascular risk. Others suggested the opposite. The confusion was real, and it kept many men with low testosterone from pursuing treatment that could improve their quality of life. Now, after more than a decade of research, including the largest randomized trial ever conducted on the topic, the picture is much clearer.
Book a free consultation with 1st Optimal to discuss how hormone optimization fits into your cardiovascular health plan.
This article breaks down the key findings from the TRAVERSE trial, recent meta-analyses published through 2025 and 2026, and current clinical guidelines. Whether you are considering TRT or already on therapy, understanding the connection between testosterone and your heart is a conversation worth having with your medical team.
Why Testosterone and Heart Health Became a Concern
The debate around testosterone therapy and cardiovascular safety started heating up in the early 2010s. In 2010, a small National Institutes of Health trial (the TOM trial) was stopped early after older men with limited mobility who received testosterone gel experienced more cardiovascular events than those on placebo. That trial enrolled only 209 men, and the results were not statistically conclusive, but the signal raised alarms.
Two retrospective studies published in 2013 and 2014 added fuel. One study published in JAMA in 2013 reported higher rates of stroke, heart attack, and death among veterans receiving testosterone. Another published in PLOS ONE in 2014 found increased heart attack risk in men over 65 and younger men with existing heart disease who filled testosterone prescriptions. Both were observational studies with significant methodological limitations, including the inability to confirm whether patients actually used their prescriptions or maintained appropriate testosterone levels.
In March 2015, the FDA responded by requiring all testosterone products to carry updated labeling about a “possible increased risk of heart attacks and strokes.” The agency also mandated that manufacturers conduct a large-scale clinical trial to answer the question definitively. That mandate led directly to the TRAVERSE trial.
What the TRAVERSE Trial Found About TRT and Cardiovascular Safety
The TRAVERSE trial (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men) remains the most important study on this topic. Published in the New England Journal of Medicine in June 2023, it was the first randomized, placebo-controlled trial designed and powered specifically to evaluate cardiovascular outcomes in men receiving testosterone therapy.
Here is what the study involved:
- Participants: 5,246 men aged 45 to 80 with hypogonadism (two fasting testosterone levels below 300 ng/dL) and either existing cardiovascular disease or high cardiovascular risk
- Treatment: Daily transdermal testosterone gel (adjusted to maintain levels between 350 and 750 ng/dL) versus placebo gel
- Duration: Average treatment of 21.7 months; average follow-up of 33 months
- Primary endpoint: A composite of death from cardiovascular causes, nonfatal heart attack, or nonfatal stroke
The results were clear. A primary cardiovascular event occurred in 7.0% of men in the testosterone group compared with 7.3% in the placebo group. The hazard ratio was 0.96, with a 95% confidence interval of 0.78 to 1.17. Testosterone therapy met the prespecified threshold for noninferiority, meaning it was not worse than placebo for major cardiovascular outcomes.
The trial also examined secondary endpoints. Rates of heart attack, stroke, and cardiovascular death were similar between the two groups when analyzed individually. However, the testosterone group did show higher rates of atrial fibrillation, acute kidney injury, and pulmonary embolism, though these events were uncommon overall.
A 2026 follow-up analysis by Zitzmann and colleagues confirmed these findings, noting that the cardiovascular safety profile held across different subgroups, including men with diabetes, obesity, and prior heart events.
Does Low Testosterone Increase Heart Disease Risk?
While the TRAVERSE trial focused on whether TRT causes harm, a separate line of research asks a different question: does having low testosterone itself increase cardiovascular risk?
The evidence here is growing. A large individual participant data (IPD) meta-analysis published in the Annals of Internal Medicine (Yeap, Marriott, et al.) pooled data from over 24,000 men across 11 prospective cohort studies. The researchers found that men with baseline testosterone concentrations below 7.4 nmol/L (about 213 ng/dL) had significantly higher all-cause mortality. Men with testosterone below 5.3 nmol/L (about 153 ng/dL) had higher cardiovascular mortality specifically.
This is consistent with earlier epidemiological data. A 2010 meta-analysis by Araujo and colleagues, published in the Journal of Clinical Endocrinology and Metabolism, found that men in the lowest third of testosterone levels had a 35% higher risk of death from all causes compared to men in the highest third. Multiple studies since then have confirmed the association, though observational data cannot prove causation.
The clinical takeaway? Low testosterone is at minimum a marker of poor cardiovascular health, and may actively contribute to it. Men with symptoms of low testosterone, including fatigue, reduced muscle mass, increased body fat, and brain fog, should not dismiss these as normal aging. Getting tested is a reasonable first step.
Schedule your free discovery call to learn how thorough lab testing can identify hormone imbalances before they affect your health long-term.
How Does Testosterone Affect the Cardiovascular System?
Understanding why testosterone matters for heart health requires looking at its biological effects on the cardiovascular system. Testosterone influences several pathways that are directly relevant to heart disease risk:
Body composition: Testosterone helps maintain lean muscle mass and reduce visceral (abdominal) fat. Visceral fat is a known driver of insulin resistance, systemic inflammation, and cardiovascular disease. Studies consistently show that men who restore healthy testosterone levels see improvements in body composition over 3 to 12 months.
Metabolic health: Low testosterone is associated with higher rates of metabolic syndrome, insulin resistance, and type 2 diabetes. All three conditions independently raise cardiovascular risk. The TRAVERSE trial itself enrolled a large proportion of men with metabolic risk factors, and the cardiovascular safety finding held in this population.
Inflammation: Chronic low-grade inflammation contributes to atherosclerosis (the buildup of plaque in arteries). Some research suggests that testosterone has anti-inflammatory properties, though the mechanisms are still being studied.
Red blood cell production: Testosterone stimulates erythropoiesis (red blood cell production). While this can improve energy and oxygen delivery, excessive red blood cell production (polycythemia) can thicken the blood and increase clot risk. This is why monitoring hematocrit levels during TRT is standard clinical practice.
Vascular function: Testosterone may influence arterial dilation and blood flow. Animal studies and small human trials have shown that testosterone can promote vasodilation, but the clinical significance of this effect in humans needs more research.
What Do Current Guidelines Say About TRT and Heart Health?
Clinical guidelines have evolved as new evidence has emerged. Here is where the major medical organizations stand:
The Endocrine Society (2018 guideline, with post-TRAVERSE commentary): The Endocrine Society recommends testosterone therapy for men with symptomatic testosterone deficiency confirmed by lab testing. The 2018 guideline noted insufficient data on cardiovascular outcomes but recommended against TRT in men with recent (within 6 months) heart attack or stroke, uncontrolled heart failure, or thrombophilia. Following the TRAVERSE results, experts have noted that the data support cardiovascular noninferiority in appropriately screened men.
The American Urological Association (AUA): The AUA guidelines support TRT for men with documented low testosterone and symptoms, with regular monitoring. They emphasize shared decision-making around cardiovascular risk and recommend baseline and follow-up blood work including hematocrit, lipids, and PSA levels.
The FDA: While the 2015 labeling warning remains in place, the FDA acknowledged the TRAVERSE trial results. The agency has not updated the labeling specifically, but the trial satisfied the FDA mandate for a large cardiovascular outcomes trial. Clinical experts widely interpret the TRAVERSE data as reassuring for men who meet diagnostic criteria for hypogonadism.
What You Should Discuss With Your Provider Before Starting TRT
The TRAVERSE trial and supporting research provide reassurance, but testosterone therapy is not a one-size-fits-all decision. Before starting TRT, a thorough evaluation should include:
- Confirm the diagnosis: Two separate morning fasting testosterone levels below 300 ng/dL, combined with symptoms of low testosterone, is the standard diagnostic threshold. A single low reading is not sufficient.
- Assess cardiovascular baseline: Review your personal and family history of heart disease, stroke, blood clots, and metabolic conditions. Providers should evaluate blood pressure, lipids, fasting glucose, and body composition.
- Check related biomarkers: Hematocrit, estradiol, LH, PSA, and SHBG should all be part of the baseline workup. A DUTCH test can also reveal how your body metabolizes hormones, which helps guide treatment decisions and monitoring schedules.
- Discuss delivery method: Injectable testosterone (cypionate or enanthate), topical gels, and pellets each have different pharmacokinetic profiles. Your provider should explain the pros and cons of each option.
- Plan for monitoring: Follow-up labs at 6 to 8 weeks after starting therapy, then quarterly until stable, then at least twice yearly. Monitoring should include testosterone levels, hematocrit, estradiol, and liver function.
The goal of TRT is to restore testosterone to the physiologic range (350 to 750 ng/dL in the TRAVERSE protocol), not to push levels beyond what is natural. Supraphysiologic dosing carries different risks and is not supported by clinical evidence for long-term safety.
Book your free consultation with 1st Optimal to get a personalized assessment that includes full lab work and a cardiovascular risk review.
Key Takeaways From the Latest Research
If you have been following the testosterone and heart health conversation for years, here is a summary of where things stand based on the best available evidence through 2026:
- The TRAVERSE trial found that TRT does not increase major cardiovascular events in men aged 45 to 80 with hypogonadism and high cardiovascular risk. The hazard ratio of 0.96 supports noninferiority compared to placebo.
- Low testosterone itself is associated with higher cardiovascular and all-cause mortality. Meta-analyses of over 24,000 men show that testosterone levels below 213 ng/dL correlate with increased death risk.
- Updated meta-analyses (2025) of randomized controlled trials found no significant increase in cardiovascular events when TRT is prescribed at physiologic doses with proper monitoring.
- Clinical guidelines support TRT for symptomatic men with confirmed low testosterone, with appropriate screening and monitoring.
- Monitoring is non-negotiable. Hematocrit, estradiol, and cardiovascular risk factors should be checked regularly during therapy.
Frequently Asked Questions
Is testosterone replacement therapy safe for the heart?
According to the TRAVERSE trial published in the New England Journal of Medicine, testosterone replacement therapy was noninferior to placebo for major adverse cardiovascular events in men with hypogonadism. This means TRT did not increase heart attacks, strokes, or cardiovascular deaths when prescribed to appropriately screened patients with proper monitoring. However, slightly higher rates of atrial fibrillation and pulmonary embolism were observed, so regular medical follow-up remains important.
Does low testosterone cause heart disease?
Observational studies consistently show that men with low testosterone levels have higher rates of cardiovascular disease and mortality. A 2024 meta-analysis of over 24,000 men found that testosterone below 213 ng/dL was associated with increased all-cause mortality, and levels below 153 ng/dL were linked to higher cardiovascular death specifically. However, these are associations, not proof of causation. Low testosterone may be both a marker of poor health and a contributing factor to cardiovascular risk.
What testosterone level is considered low?
Most clinical guidelines define low testosterone (hypogonadism) as a total testosterone level below 300 ng/dL, confirmed on two separate morning fasting blood draws. Symptoms such as fatigue, reduced libido, loss of muscle mass, increased body fat, and difficulty concentrating should also be present. The Endocrine Society recommends against treating men based on lab values alone without corresponding symptoms.
Should I stop TRT if I have heart disease?
Not necessarily. The TRAVERSE trial specifically enrolled men with existing cardiovascular disease or high cardiovascular risk, and the results showed no increased risk from testosterone therapy. Current Endocrine Society guidelines recommend against starting TRT within 6 months of a heart attack or stroke, or in men with uncontrolled heart failure. Outside of those specific situations, the decision should be made in consultation with your medical provider based on your individual risk profile.
How often should cardiovascular health be monitored during TRT?
Standard practice calls for follow-up blood work at 6 to 8 weeks after starting TRT, then every 3 months until levels stabilize, and at least twice per year after that. Monitoring should include total and free testosterone levels, hematocrit (to watch for polycythemia), estradiol, lipid panel, fasting glucose, PSA, and liver function. Blood pressure and body composition should also be tracked at each visit.
Moving Forward With Confidence
The relationship between testosterone and heart health has been studied more rigorously in the past three years than in the previous two decades combined. The TRAVERSE trial answered the question the FDA demanded: does testosterone replacement therapy increase cardiovascular risk in men with hypogonadism? The answer, based on a randomized trial of over 5,000 men followed for nearly three years, is no.
That does not mean testosterone therapy is appropriate for everyone, and it does not eliminate the need for careful medical supervision. What it does mean is that men with confirmed low testosterone and symptoms that affect their quality of life should not let outdated fears about heart risk prevent them from having an honest conversation with a qualified provider.
Ready to find out where your hormone levels stand? Book a free discovery call with 1st Optimal and take the first step toward data-driven health optimization.
