AndroGel Safety Signals and FDA Actions: What the Evidence Actually Shows

Which product the evidence covers

TRAVERSE, the cardiovascular outcome trial, used AndroGel 1.62% [1]. The label text on this page is the AndroGel 1% prescribing information, which says dosage and administration for AndroGel 1% differ from AndroGel 1.62% and that topical testosterone products may have different doses, strengths or application instructions that may result in different systemic exposure [3]. Where the AndroGel 1% label reports 1.62% trial data, this page says so.

What FDA has actually done

In January 2014, FDA issued a Drug Safety Communication warning about reported risks of stroke, heart attack and death in men taking FDA-approved testosterone products [2]. In September 2014 the agency convened a joint meeting of two advisory committees, which led to its recommendation for an industry-wide clinical trial to assess safety in men with age-related hypogonadism, the trial that became TRAVERSE [2]. A March 2015 Drug Safety Communication announced required labeling changes and urged caution about using testosterone products for low testosterone due to aging [2].

The largest recent step came on February 28, 2025, after FDA reviewed TRAVERSE and the ambulatory blood pressure studies it had required of every testosterone product. FDA recommended adding TRAVERSE results to testosterone labels, retaining the Limitation of Use for age-related hypogonadism, and removing boxed-warning language about an increased risk of adverse cardiovascular outcomes; it also required product-specific blood pressure information where monitoring studies were completed and a blood pressure warning for products that lacked one [2]. FDA stated that the completed studies confirmed an increase in blood pressure with all testosterone products, class-wide [2]. Whether a given label shows these changes depends on the product: the AndroGel 1% label, revised July 2025, still carries the limitation of use for age-related hypogonadism [3].

In June 2026, FDA said it had requested a further round of updates: removing that limitation of use and revising prostate cancer and benign prostatic hyperplasia safety information [1]. Those are requests to sponsors, and FDA still states that none of the approved testosterone products are approved for men with low testosterone who lack an associated medical condition [1].

What TRAVERSE found

TRAVERSE enrolled 5,246 men aged 45 to 80 who had symptoms of hypogonadism, two fasting testosterone levels below 300 ng/dL, and existing cardiovascular disease or a high risk of it. They were randomly assigned to daily transdermal 1.62% testosterone gel, dose-adjusted to keep testosterone between 350 and 750 ng/dL, or to placebo gel, in a double-blind, placebo-controlled noninferiority design [4].

The primary endpoint, a composite of cardiovascular death, nonfatal heart attack or nonfatal stroke, occurred in 182 men (7.0%) on testosterone and 190 men (7.3%) on placebo [4].

What FDA took from this was narrow: TRAVERSE did not demonstrate a new safety signal or trend in adverse cardiovascular outcomes with testosterone use [1]. FDA did not describe testosterone as free of cardiovascular effects, and its 2025 action added blood pressure information rather than removing it [2].

The 2010 TOM trial, where the concern started

TOM was a randomized trial of testosterone gel versus placebo gel in 209 men aged 65 and older with mobility limitations and a total testosterone of 100 to 350 ng/dL (or a low free testosterone). The data and safety monitoring board recommended stopping it early because of a significantly higher rate of adverse cardiovascular events in the testosterone group: 23 men in the testosterone group had cardiovascular-related adverse events compared with 5 on placebo, in a group with a high prevalence of hypertension, diabetes, hyperlipidemia and obesity [5].

The authors' own conclusion was measured: in older men with mobility limitations and a high burden of chronic disease, testosterone gel was associated with an increased risk of cardiovascular adverse events, but the small size of the trial and the unique population prevent broader inferences [5].

The 2014 insurance-claims analysis

A cohort study of 55,593 men who received an initial testosterone prescription compared the rate of nonfatal heart attack in the 90 days after that prescription with the rate in the year before it. The overall rate ratio was 1.36 (95% CI 1.03 to 1.81); in men 65 and older it was 2.19 (95% CI 1.27 to 3.77); in men under 65, excess risk was confined to those with a prior history of heart disease, with a rate ratio of 2.90 (95% CI 1.49 to 5.62) [6]. That design compares each man with himself and is not a randomized comparison.

Blood pressure: what FDA found and what the AndroGel label says

The AndroGel 1% label says AndroGel 1% can increase blood pressure, which can increase cardiovascular risk over time [3]. It reports a 4-month study of AndroGel 1.62% using 24-hour ambulatory monitoring in which 169 men had acceptable recordings at both baseline and week 16: mean systolic and diastolic pressure rose 1.9 mm Hg (95% CI 0.6 to 3.1) and 1.3 mm Hg (95% CI 0.5 to 2.1). In men with hypertension already on treatment, the rises were 3.0 systolic and 2.2 diastolic mm Hg [3]. The label's blood pressure section says AndroGel 1.62% is not recommended for patients with uncontrolled hypertension [3].

In TRAVERSE, systolic pressure rose 1.0 mm Hg from baseline to 36 months, versus a 0.5 mm Hg fall on placebo, a between-group difference of 1.5 mm Hg [3].

Blood clots

The AndroGel 1% label carries a venous thromboembolism warning based on postmarketing reports of deep vein thrombosis and pulmonary embolism in patients using testosterone products such as AndroGel 1% [3]. In TRAVERSE, the label reports, VTE was numerically higher on AndroGel 1.62%, 1.7% versus 1.2% on placebo, including DVT in 0.6% versus 0.5% and PE in 0.9% versus 0.5% [3]. The label directs evaluation of pain, edema, warmth and erythema in the lower extremity for DVT and acute shortness of breath for PE, and discontinuation of AndroGel 1% with appropriate workup if a VTE is suspected [3].

Hematocrit and polycythemia

The AndroGel 1% label says to check hematocrit before starting, re-evaluate it 3 to 6 months after starting and then annually, stop therapy if hematocrit becomes elevated until it falls to an acceptable level, and notes that an increase in red blood cell mass may increase the risk of thromboembolic events [3].

How much hematocrit rises depends on the formulation. A network meta-analysis of 29 placebo-controlled trials in 3,393 men found mean hematocrit increases of 3.0% with gel (95% CI 1.8 to 4.3), 4.0% with intramuscular enanthate or cypionate (95% CI 2.9 to 5.1) and 1.4% with patch (95% CI 0.2 to 2.6) [7]. A retrospective review of 178 men found erythrocytosis (hematocrit above 50%) in 66.7% of men on injectable testosterone, 12.8% on gels and 35.1% on pellets over 3 years, though the injection group was younger (mean 42.5 versus about 54 years) with higher baseline hematocrit, and the study was not randomized [8]. One review reported a 315% greater risk of erythrocytosis, defined as hematocrit above 0.52, in men on testosterone replacement versus controls, with all formulations affected and injectables most [9]. Whether erythrocytosis translates into thromboembolic events remains unclear [10].

Secondary exposure: the boxed warning on AndroGel 1%

The AndroGel 1% label carries a boxed warning for secondary exposure. Virilization has been reported in children exposed to testosterone gel, with signs including enlargement of the penis or clitoris, pubic hair, increased erections and libido, aggressive behavior and advanced bone age. In most reported cases these signs regressed once exposure was removed, but in a few, enlarged genitalia did not fully return to age-appropriate size and bone age stayed modestly greater than chronological age [3]. The label states that children and women should avoid contact with unwashed or unclothed application sites, and that the risk of transfer was increased in some cases by not following the precautions for use [3].

Prostate and BPH

The AndroGel 1% label states that the gel is contraindicated in men with known or suspected prostate cancer, that men with BPH treated with androgens are at increased risk of worsening BPH signs and symptoms, and that patients treated with androgens may be at increased risk of prostate cancer and should be evaluated before and during treatment [3]. In a 6-month study the mean PSA rise was 0.26 ng/mL; in a 3-year extension study of 162 men, 29 (18%) met a protocol criterion of more than twice baseline PSA or any single PSA above 6 ng/mL, and prostate cancer was found on biopsy in two of the four men whose PSA exceeded 6 ng/mL [3]. In that extension study, enlarged prostate was reported in 11.7% and carcinoma of the prostate in 1.2% [3].

Other monitoring in the label

The AndroGel 1% label says to monitor serum testosterone, PSA, hemoglobin, hematocrit, liver function tests and lipid concentrations periodically [3]. It also flags interactions that change routine care: androgens may lower blood glucose and insulin requirements; the label recommends more frequent monitoring of INR and prothrombin time when androgen therapy is started or stopped in a person taking an oral anticoagulant; and testosterone with corticosteroids or ACTH may increase fluid retention [3].

The Endocrine Society guideline recommends monitoring symptoms, serum testosterone, hematocrit and prostate cancer risk in the first year, and recommends against starting testosterone therapy in men with breast or prostate cancer, elevated hematocrit, untreated severe sleep apnea, uncontrolled heart failure, or a heart attack or stroke within 6 months [11].