AndroGel Cardiovascular Impact Long-Term: What the Evidence Actually Shows

What did TRAVERSE actually test?

TRAVERSE was a randomized, double-blind, placebo-controlled noninferiority trial. It enrolled 5,246 men aged 45 to 80 who had symptoms of hypogonadism, two fasting testosterone levels below 300 ng/dL, and either existing cardiovascular disease or a high risk of it [2]. FDA describes the product tested as AndroGel 1.62% [1].

Men were assigned to daily transdermal 1.62% testosterone gel, with the dose adjusted to keep testosterone between 350 and 750 ng/dL, or to a matching placebo gel. Mean treatment duration was 21.7 months and mean follow-up was 33.0 months [2]. The primary endpoint was the first of cardiovascular death, nonfatal heart attack or nonfatal stroke.

Did the gel increase heart attacks, strokes or cardiovascular death?

The trial did not detect an increase. A primary endpoint event occurred in 182 men on testosterone (7.0%) and 190 on placebo (7.3%), a hazard ratio of 0.96 with a 95% CI of 0.78 to 1.17 [2]. Noninferiority required the upper limit of that interval to stay below 1.5, and it did. That result covers a mean follow-up of 33 months.

FDA reviewed the results and states that TRAVERSE did not demonstrate a new safety signal or trend in adverse cardiovascular outcomes with testosterone use [1]. In February 2025 the agency called for the TRAVERSE results to be added to all testosterone labels and for boxed-warning language about increased cardiovascular risk to be removed [4].

Which other events were more common with testosterone gel?

Several events were more frequent with gel than with placebo in TRAVERSE: nonfatal arrhythmias requiring intervention (5.2% versus 3.3%), atrial fibrillation (3.5% versus 2.4%), acute kidney injury (2.3% versus 1.5%) and bone fracture (3.5% versus 2.5%) [2]. The generic testosterone gel 1% label reports venous thromboembolism in TRAVERSE at 1.7% of men on testosterone versus 1.2% on placebo, including deep vein thrombosis in 0.6% versus 0.5% and pulmonary embolism in 0.9% versus 0.5% [3]. The label also says deep vein thrombosis and pulmonary embolism have been reported in patients using testosterone products [3].

These events were not the trial's primary endpoint, which was the heart attack, stroke and cardiovascular death composite [2].

Does testosterone gel raise blood pressure?

Yes. FDA says ambulatory blood pressure monitoring studies confirmed an increase in blood pressure with use of all testosterone products, class-wide, and it called for a blood pressure warning on products that did not already have one [4]. In TRAVERSE, mean systolic blood pressure rose 1.0 mm Hg from baseline to 36 months in the testosterone gel group, while it fell 0.5 mm Hg on placebo [2].

How much does testosterone gel raise hematocrit?

How much hematocrit rises depends partly on the formulation. A network meta-analysis of 29 placebo-controlled randomized trials covering 3,393 men found that every testosterone type raised mean hematocrit versus placebo: gel by 3.0% (95% CI 1.8 to 4.3) and intramuscular enanthate or cypionate by 4.0% (95% CI 2.9 to 5.1) [5]. A review of the erythrocytosis literature concluded that short-acting injectable formulations carry the highest associated incidence [6], and another review reported a 315% greater risk of erythrocytosis (hematocrit above 0.52) in men on testosterone replacement compared with controls [7]. One describes the link between erythrocytosis and thromboembolic events as unclear and the other as inconclusive [6][7].

Is there still a cardiovascular boxed warning?

The boxed warning in the generic testosterone gel 1% label is about secondary exposure: virilization reported in children exposed to unwashed or unclothed application sites [3]. For testosterone products in general, in February 2025 FDA called for cardiovascular-risk language to be removed from testosterone products' boxed warnings, for TRAVERSE results to be added to all labels, for the limitation of use in age-related hypogonadism to be kept, for a blood pressure warning to be added to products that lacked one, and for product-specific blood pressure data where monitoring studies were completed [4]. That was a request for label changes, not a statement that every label had already been rewritten.

FDA's testosterone information page, current as of June 23, 2026, records a further round of requested updates: removing the limitation of use stating that safety and efficacy in age-related hypogonadism have not been established, and revising prostate cancer and benign prostatic hyperplasia safety information [1].

What about coronary plaque in the T-Trials?

The Testosterone Trials gave 790 men aged 65 or older with testosterone below 275 ng/dL testosterone gel or placebo gel for one year. Adverse event rates were similar between groups, and the investigators wrote that the number of participants was too few to draw conclusions about the risks of treatment [8].

A coronary plaque substudy enrolled 170 of those men and analyzed 138 who completed 12 months of coronary CT angiography [9]. Median noncalcified plaque volume went from 204 mm3 to 232 mm3 on testosterone and from 317 mm3 to 325 mm3 on placebo, an estimated difference of 41 mm3 (95% CI 14 to 67; P=0.003). Total plaque volume rose by an estimated 47 mm3 more on testosterone (95% CI 13 to 80; P=0.006) [9]. The two groups started with different median plaque volumes, and the authors noted that the small size of the trial and the unique population prevent broader inferences about the safety of testosterone therapy [9].

What the long-term data do not cover

TRAVERSE followed men for a mean of 33 months, so it describes that window rather than a decade of use [2]. It tested a gel, and no cardiovascular outcome trial of comparable size exists for injectable testosterone [2]. Whether the plaque difference seen at 12 months in the substudy persists, plateaus or reverses with longer treatment was not measured [9].

Who the guidelines say should not start testosterone

The Endocrine Society's 2018 guideline recommends against starting testosterone therapy in men planning fertility in the near term, and in men with breast or prostate cancer, elevated hematocrit, untreated severe sleep apnea, uncontrolled heart failure, or a heart attack or stroke within the previous 6 months [10]. It recommends monitoring symptoms, serum testosterone, hematocrit and prostate cancer risk during the first year [10].