Testosterone Therapy After TRAVERSE: What the Heart-Safety Data Does and Doesn't Say

Testosterone therapy after TRAVERSE

Educational content, not medical advice. Talk to your physician before starting, stopping or changing any hormone treatment.

The FDA dropped the cardiovascular boxed warning in 2025 but added a blood pressure warning. Here is how to read both changes together.

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Key takeaways

  • Heart events: In the largest randomized trial to date (TRAVERSE, 5,246 men), testosterone gel was not worse than placebo for heart attack, stroke or cardiovascular death over about three years.
  • Not a free pass: The same trial saw more atrial fibrillation, acute kidney injury and pulmonary embolism with testosterone, and a higher fracture rate. The FDA also found that all testosterone products raise blood pressure.
  • Who it applies to: The evidence is for men with confirmed low testosterone and symptoms. It is not a reason to treat tiredness or normal aging.

01. Why this matters now

For about a decade, testosterone products carried a warning about cardiovascular risk, based on mixed observational data. TRAVERSE was designed to settle the question. In February 2025 the FDA acted on it, which is why patients and physicians are hearing conflicting messages: the heart warning is gone, but the label is not “all clear.”

02. What TRAVERSE found

TRAVERSE enrolled men aged 45-80 with symptoms of hypogonadism, two fasting testosterone readings below 300 ng/dL, and existing cardiovascular disease or high cardiovascular risk. They used daily 1.62% testosterone gel or placebo. Major adverse cardiac events (cardiovascular death, non-fatal heart attack or non-fatal stroke) occurred in 7.0% on testosterone and 7.3% on placebo (hazard ratio 0.96, 95% CI 0.78-1.17), meeting the pre-specified non-inferiority bar.

That is reassuring on its primary question. It does not mean “no risks”:

  • Non-fatal arrhythmias needing intervention: 5.2% vs 3.3%. Atrial fibrillation: 3.5% vs 2.4%.
  • Acute kidney injury: 2.3% vs 1.5%. Pulmonary embolism: 0.9% vs 0.5%.
  • In the fracture sub-study, clinical fractures were more common with testosterone (3.5% vs 2.5%; HR 1.43, 95% CI 1.04-1.97).

03. What’s new in regulation

FDA, 28 February 2025: The FDA announced class-wide labeling changes for testosterone products. It added TRAVERSE results to labels and removed boxed-warning language about increased risk of adverse cardiovascular outcomes. It also added blood pressure information or a new blood pressure warning, because the ambulatory blood pressure monitoring (ABPM) studies it required in 2018 “confirmed an increase in blood pressure with use of all testosterone products.” The limitation of use for age-related hypogonadism was retained.

FDA, 6 January 2026 (wearables): The FDA updated its General Wellness guidance. Wearables that non-invasively estimate physiologic parameters, including heart rate variability, may qualify as general wellness products if presented in wellness contexts such as sleep, stress or recovery, and if values are validated. They should not name diseases, label readings abnormal or diagnostic, or issue condition-management alerts (per law-firm summaries; confirm against the FDA text).

EU: No CE/MDR/IVDR change specific to this topic was verified, so none is claimed here.

04. For clinicians

  • TRAVERSE (Lincoff et al., NEJM 2023): Randomized, double-blind, placebo-controlled, non-inferiority, 316 US sites, n=5,246; mean treatment 21.7 months, mean follow-up 33 months. Gel dose-adjusted to 350-750 ng/dL. Primary MACE HR 0.96 (0.78-1.17), non-inferiority margin 1.5 (upper bound). Median baseline testosterone 227 ng/dL.
  • Fractures (Snyder et al., NEJM 2024): n=5,204 analyzed; clinical fracture 3.50% vs 2.46%; HR 1.43 (1.04-1.97). Testosterone did not reduce fractures.
  • Limitations: Industry-funded (AbbVie-led consortium); men with very low testosterone were not enrolled; a MACE margin of 1.5 is wide; one formulation (gel); about three years of follow-up; not powered to show symptom benefit. Do not extrapolate to men without confirmed hypogonadism.
  • Recent review (Boeri et al., Eur Urol 2026): Non-systematic review concluding therapy is safe and effective for symptomatic deficiency; recommends monitoring hematocrit, PSA and metabolic parameters at 3 months then every 6-12 months, mid-normal targets (450-600 ng/dL). Expert opinion, not new trial evidence.
  • Practice points: Confirm low total testosterone on two morning fasting samples; monitor BP, hematocrit, PSA; consider AF and VTE history; weigh the fracture signal when counseling.

05. What this means for patients

If you have been diagnosed with low testosterone and symptoms, the heart-attack-and-stroke fear is better answered than before. But “safe on the heart” is not “risk-free.” Ask your doctor about blood pressure checks, blood counts, prostate monitoring and your history of irregular heartbeat or clots. If your testosterone is in the normal range for your age, current labeling does not support treating fatigue alone. Testing should be repeated, in the morning, before any decision.

06. A note from 6Letters

Hormone decisions depend on good measurement over time. At 6Letters we are building wearable, PPG/HRV-based hormone monitoring (MOJO KING / MOJO QUEEN); it is a wellness tool, not a diagnostic or a substitute for laboratory testing or medical care. More at 6letters.co.kr.

References

  1. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy (TRAVERSE). N Engl J Med. 2023;389(2):107-117. DOI 10.1056/NEJMoa2215025. PMID 37326322.
  2. Snyder PJ, et al. Testosterone Treatment and Fractures in Men with Hypogonadism. N Engl J Med. 2024. DOI 10.1056/NEJMoa2308836. PMID 38598805.
  3. U.S. FDA. FDA issues class-wide labeling changes for testosterone products. 28 Feb 2025. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-issues-class-wide-labeling-changes-testosterone-products
  4. Boeri L, Masterson T, Antonio L, et al. Testosterone Therapy in Adult Males with Hypogonadism. Eur Urol. 2026;90(1):32-43. DOI 10.1016/j.eururo.2025.12.015. PMID 41448986.
  5. Greenberg Traurig. FDA Updates Two Digital Health Final Guidance Documents (General Wellness; CDS). Jan 2026. https://www.gtlaw.com/en/insights/2026/1/fda-updates-two-digital-health-final-guidance-documents
  6. TCTMD. Testosterone doesn’t cause CV events in high-risk men with hypogonadism. https://www.tctmd.com/news/testosterone-doesnt-cause-cv-events-high-risk-men-hypogonadism