The TRAVERSE trial found heart attacks, strokes and cardiovascular deaths at similar rates on testosterone gel and placebo, but it also found more atrial fibrillation, acute kidney injury and pulmonary embolism with testosterone. The TRAVERSE results tested a daily gel, not cypionate injection, and labels still warn about blood pressure and blood clots.
How FDA's position changed from 2015 to 2025
On March 3, 2015, FDA required labeling about a possible increased risk of heart attacks and strokes, and required makers to run a clinical trial on that question.
On February 28, 2025, after TRAVERSE, FDA announced class-wide changes: adding TRAVERSE results to all labels and removing Boxed Warning language on increased cardiovascular risk. The same announcement said ambulatory blood pressure studies confirmed a blood pressure increase with all testosterone products, and it required a blood pressure warning for products that lacked one.
The current Depo-Testosterone (cypionate) label says studies have been inconclusive on major adverse cardiovascular events, some but not all reported increased risk, and patients should be told of this possible risk.
What TRAVERSE tested and found
TRAVERSE was a randomized, double-blind, placebo-controlled noninferiority trial of 5,246 men aged 45 to 80. All had symptoms of hypogonadism, two fasting testosterone levels below 300 ng/dL, and existing or high risk of cardiovascular disease. They used daily 1.62% testosterone gel or placebo gel.
The main outcome, cardiovascular death, nonfatal heart attack or nonfatal stroke, occurred in 7.0% on testosterone and 7.3% on placebo (hazard ratio 0.96, 95% CI 0.78 to 1.17), meeting noninferiority. Mean treatment was 21.7 months and mean follow-up 33.0 months.
The prescribing information for Aveed, a long-acting testosterone injection, summarizes TRAVERSE as showing more nonfatal arrhythmias warranting intervention (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%) and bone fracture (3.5% vs 2.5%) with the gel than with placebo. It also notes that about 61% of all patients stopped gel or placebo.
Blood pressure
The cypionate label says testosterone can raise blood pressure, which can increase cardiovascular risk over time. It says to monitor blood pressure and does not recommend use with uncontrolled hypertension.
The AndroGel 1.62% label reports that in TRAVERSE, mean systolic blood pressure rose 1.0 mm Hg on testosterone and fell 0.5 mm Hg on placebo at 36 months, a 1.5 mm Hg difference.
Blood clots
The cypionate label reports postmarketing cases of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, and says to stop treatment if a clot is suspected. The Aveed prescribing information reports TRAVERSE had a numerically higher rate of venous thromboembolism on gel than placebo (1.7% vs 1.2%), including pulmonary embolism (0.9% vs 0.5%) and DVT (0.6% vs 0.5%).
The 2018 Endocrine Society guideline recommends against starting testosterone in men with uncontrolled heart failure, a heart attack or stroke within the last 6 months, or thrombophilia. The cypionate label lists serious cardiac disease as a contraindication.
| Question | What the source says |
|---|---|
| Heart attack, stroke or cardiovascular death | 7.0% on testosterone gel vs 7.3% on placebo in TRAVERSE. |
| Atrial fibrillation | 3.5% vs 2.4% (Aveed prescribing information summary of TRAVERSE). |
| Venous thromboembolism | 1.7% vs 1.2% (same summary). |
| Systolic blood pressure at 36 months | A 1.5 mm Hg difference (gel label). |
What this does not tell you
TRAVERSE used a daily gel in men aged 45 to 80 with heart risk, so it does not show how cypionate injections, compounded cream or younger men compare. About 61% of patients stopped gel or placebo, which limits what the results can show. An earlier ACP evidence review found no trials powered to assess cardiovascular events and judged long-term safety unknown. These results do not say what risk any one man faces. A licensed provider weighs a person's heart history, blood pressure and clot risk.