Traverse: The Testosterone Cardiovascular Safety Study Everyone Was Waiting For

For years, testosterone therapy (TRT) lived under a cloud of concern: does TRT increase the risk of heart attack, stroke, or cardiovascular death? The TRAVERSE trial was designed specifically to answer that question in the population that matters most—men who already have, or are at high risk for, cardiovascular disease.

What Traverse Studied (The Design, in Plain English)

TRAVERSE was a large, rigorous, randomized, double-blind, placebo-controlled noninferiority trial that enrolled 5,246 men, ages 45–80, who had:

• Symptoms consistent with hypogonadism, and
• Two fasting testosterone levels <300 ng/dL, and
• Preexisting cardiovascular disease or high CV risk.

Participants were randomized to:

• Transdermal 1.62% testosterone gel daily (dose adjusted to keep testosterone 350–750 ng/dL) vs.
• Placebo gel

Average exposure was about 22 months, and average follow-up about 33 months.

The Headline Result: Trt Did Not Increase Major Adverse Cardiac Events (Mace)

The primary endpoint was “MACE”: cardiovascular death + nonfatal heart attack + nonfatal stroke.

Results:

• MACE occurred in 7.0% of men on testosterone
  • vs. 7.3% on placebo
• Hazard ratio 0.96 (95% CI 0.78–1.17)
• Met the prespecified criteria for noninferiority (i.e., not worse than placebo).

In other words: In appropriately selected men with true hypogonadism, TRT was not associated with higher rates of heart attack, stroke, or cardiovascular death over the trial’s time horizon.

Why “Noninferior” Matters (And What It Means Clinically)

TRAVERSE wasn’t designed to prove testosterone reduces cardiac events. It was designed to answer: “Is TRT unacceptably more dangerous than placebo for major cardiovascular outcomes?”

The answer was no—TRT was noninferior to placebo for MACE.

That’s a big deal because TRAVERSE included men with real-world CV risk, not just healthy volunteers.

Important Nuance: Some Adverse Events Were Higher on Testosterone

While MACE was similar between groups, TRAVERSE reported a higher incidence of:While MACE was similar between groups, TRAVERSE reported a higher incidence of:

• Atrial fibrillation
• Acute kidney injury
• Pulmonary embolism

This doesn’t negate the MACE finding—but it does reinforce that TRT should be:

• Prescribed for the right indication (documented hypogonadism)
• Monitored appropriately
• Individualized based on a patient’s clotting risk, arrhythmia history, kidney health, and overall risk profile

FDA Response: Labeling Updated Based on Traverse

After reviewing TRAVERSE, the FDA stated the results did not demonstrate a new cardiovascular safety signal for TRT when used for indicated hypogonadism, and issued class-wide labeling changes reflecting these findings

The FDA also highlighted blood pressure considerations in labeling updates (a separate but important CV factor to monitor).

Practical Takeaways for Patients and Clinicians

TRAVERSE supports this core message:

“In men with true hypogonadism (confirmed low testosterone + symptoms), including those with high CV risk, TRT did not increase MACE over ~3 years of follow-up.”

But TRT is not “set it and forget it.” Based on TRAVERSE, smart TRT care includes monitoring:

• Blood pressure
• Hematocrit/hemoglobin (polycythemia risk; not the main TRAVERSE headline, but standard TRT safety)
• Sleep apnea symptoms
• Arrhythmia symptoms (palpitations)
• Clot risk history (DVT/PE)
• Kidney function when clinically appropriate

What Traverse Does Not Prove

To keep this evidence-based:

• TRAVERSE does not prove TRT reduces heart attacks or strokes.
• It studied one formulation strategy (dose-titrated transdermal gel) aiming for mid-normal testosterone levels—not every dosing approach.
• It applies best to men who match the enrollment criteria: symptoms + two low morning levels (<300 ng/dL) + appropriate medical indication

The Bottom Line

TRAVERSE is the strongest evidence to date that properly prescribed testosterone therapy does not increase major adverse cardiac events in men with confirmed hypogonadism—even in those with significant baseline cardiovascular risk.