Testosterone and Cardiovascular Health: What the Research Actually Shows

The question of whether testosterone therapy increases cardiovascular risk has shaped clinical practice for over a decade. Media coverage has been inconsistent. Regulatory warnings have been issued. Many physicians remain cautious. And patients are left trying to reconcile conflicting headlines with their own experience of feeling better on treatment.

The evidence, when examined carefully, tells a more nuanced and ultimately reassuring story than the headlines suggest.

The Source of the Concern

Two studies published in 2010 and 2013 generated the initial alarm.

The TOM trial (Testosterone in Older Men with Mobility Limitations) was stopped early in 2010 due to an excess of cardiovascular events in the testosterone group. The study enrolled frail men over age 65 with a high burden of pre-existing cardiovascular disease. The testosterone doses were high, the gel application was aggressive, and the resulting testosterone levels in some participants exceeded the physiological range. The trial was small (209 participants) and the events were heterogeneous.

In 2013, Vigen and colleagues published a retrospective analysis of VA medical records suggesting increased cardiovascular risk with testosterone therapy. The study was subsequently criticized for significant methodological flaws, including miscounting events and inappropriate statistical comparisons. A correction was published, though the original finding had already entered clinical consciousness.

These two studies, neither of which reflected modern prescribing practices, triggered an FDA advisory in 2015 requiring cardiovascular risk warnings on testosterone products.

The TRAVERSE Trial

The question demanded a definitive answer, and the TRAVERSE trial (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) provided one.

TRAVERSE was a randomized, double-blind, placebo-controlled trial enrolling 5,246 men aged 45 to 80 with hypogonadism and pre-existing cardiovascular disease or elevated cardiovascular risk. Participants received either 1.62% testosterone gel or placebo, with a mean treatment duration of 21.7 months and a mean follow-up of 33 months.

The primary endpoint was major adverse cardiovascular events (MACE): a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

The result: testosterone therapy did not increase the incidence of MACE compared to placebo. The hazard ratio was 0.99 (95% CI, 0.81 to 1.21). The cardiovascular safety signal was neutral.

TRAVERSE was published in the New England Journal of Medicine in 2023 and represents the largest and most rigorous cardiovascular safety trial of testosterone therapy ever conducted.

What the Broader Literature Shows

Beyond TRAVERSE, the accumulated evidence provides a consistent picture.

A 2018 meta-analysis published in Expert Opinion on Drug Safety, which included over 5,000 men across multiple randomized controlled trials, found no significant increase in cardiovascular events with testosterone therapy at physiological replacement doses.

Observational studies have repeatedly demonstrated that men with low testosterone have higher rates of cardiovascular disease, metabolic syndrome, and all-cause mortality compared to men with normal levels. This association does not prove causation, but it does undermine the narrative that testosterone is inherently cardiotoxic. Men with documented low testosterone carry a secondary mortality risk that extends beyond the immediate effects of the hormonal deficit itself.

Testosterone influences cardiovascular physiology through several mechanisms. It modulates vascular tone, supports endothelial function, improves insulin sensitivity through enhanced glucose transporter expression and mitochondrial function, reduces visceral adiposity, and influences lipid metabolism. These effects, at physiological concentrations, are generally favourable. The bidirectional relationship between testosterone and metabolic health means that restoring testosterone can improve not only symptoms but also the underlying cardiometabolic parameters that drive long-term cardiovascular risk.

The Dose Distinction Matters

Much of the historical concern around testosterone and cardiovascular risk stems from supraphysiological dosing, the use of testosterone at levels far exceeding the normal physiological range. This is common in anabolic steroid misuse and was a feature of some of the earlier studies that raised safety flags.

Supraphysiological testosterone can increase hematocrit to dangerous levels, alter lipid profiles unfavourably (particularly by depressing HDL), promote left ventricular hypertrophy, and increase thrombotic risk. These effects are dose-dependent and are not characteristic of physiological replacement.

The distinction between replacing testosterone to optimal physiological levels and pushing it into supraphysiological territory is the difference between medicine and pharmacological excess. The safety data applies to the former.

Hematocrit Monitoring Remains Essential

The one cardiovascular-adjacent risk that testosterone therapy does consistently influence is erythropoiesis. Testosterone stimulates red blood cell production, and hematocrit rises as a predictable consequence. This is a dose-dependent effect that is proportional to the dose of testosterone administered.

Elevated hematocrit increases blood viscosity. The TRAVERSE trial did note a higher incidence of pulmonary embolism in the testosterone group (0.9% vs 0.5%), though the overall MACE endpoint was not affected. This finding, while worth noting, occurred in the context of a population specifically selected for elevated baseline cardiovascular risk, which is important context when interpreting its clinical significance.

Hematocrit must be measured at baseline and monitored at regular intervals during therapy. Patients whose hematocrit exceeds 52 to 54 percent require dose adjustment, therapeutic phlebotomy, or both. Many men who develop elevated hematocrit respond well to reduced dosing or to more frequent administration of smaller doses, which provides more stable testosterone levels and blunts the erythropoietic response. This is a manageable risk when the monitoring protocol is rigorous and the physician is willing to titrate responsively.

What Patients Should Understand

Testosterone replacement therapy, prescribed at physiological doses by a physician who monitors blood work regularly, has not been shown to increase cardiovascular risk in the best available evidence. The TRAVERSE trial, the largest of its kind, demonstrated cardiovascular neutrality in a population that was specifically selected for elevated cardiovascular risk.

This does not mean testosterone therapy is without considerations. Hematocrit must be tracked. Lipid profiles should be monitored. The dose must be titrated to achieve physiological levels, not exceed them. And treatment decisions must be made within the context of the patient’s full medical history.

The era of reflexive cardiovascular concern about testosterone therapy is giving way to a more evidence-informed approach. Men with symptomatic hypogonadism who are otherwise candidates for therapy should not be denied treatment on the basis of outdated or methodologically flawed studies.

How This Informs Our Practice

At Manus Solis, cardiovascular risk stratification is part of every testosterone therapy evaluation. The Pulsus domain includes fasting lipids, inflammatory markers, fasting insulin, HbA1c, and hematocrit alongside the hormonal panel. Treatment is initiated only when the risk-benefit profile is favourable, and monitoring is structured to detect any adverse trend early.

The goal is to optimize testosterone to a level where the patient feels and functions well, verified by blood work that confirms safety, and tracked over time with the same rigour applied to any chronic medical intervention.

Continue Reading

If you found this useful, these related articles may deepen your understanding:

• Signs of Low Testosterone That Men Often Ignore
• The Blood Work You Need Before Starting Testosterone
• How Insulin Resistance Is Destroying Your Testosterone

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Dr. Handsun Xiao is a McGill trained physician (MD, CCFP) practicing functional medicine and bioidentical hormone therapy in Toronto, with virtual consultations available to patients across Ontario. He holds advanced BHRT certification through WorldLink Medical and IFM AFMCP training. Manus Solis offers physician led BHRT consultations with custom compounding through a dedicated Ontario pharmacy partner. To learn more or book a virtual consultation, visit manussolis.ca.