AndroGel History and Development: From FDA Approval to Modern Testosterone Therapy

When was AndroGel approved?

FDA's Drugs@FDA record lists AndroGel under two applications: the 1% gel (NDA 021015), originally approved on February 28, 2000, and the 1.62% gel (NDA 022309), originally approved on April 29, 2011 [9]. The two strengths have different dosing instructions [5].

What did the TRAVERSE trial test?

TRAVERSE was a randomized, double-blind, placebo-controlled noninferiority trial of daily transdermal 1.62% testosterone gel versus placebo gel [2]. FDA describes the trial as following more than 5,200 men receiving at least one dose of AndroGel 1.62% [1]. It enrolled 5,246 men aged 45 to 80 with hypogonadism symptoms and two fasting testosterone levels below 300 ng/dL who had existing cardiovascular disease or high cardiovascular risk; doses were adjusted to keep testosterone between 350 and 750 ng/dL [2]. Mean treatment lasted 21.7 months and mean follow-up 33 months [2].

The primary endpoint, a composite of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke, occurred in 182 men (7.0%) on testosterone and 190 men (7.3%) on placebo, hazard ratio 0.96 (95% CI 0.78 to 1.17) [2]. Noninferiority required the upper limit of the 95% CI to fall below 1.5, and it was met [2]. Mean systolic blood pressure rose 1.0 mm Hg on testosterone gel versus a 0.5 mm Hg fall on placebo at 36 months [2][5].

Venous thromboembolism occurred in 1.7% of the testosterone group and 1.2% of the placebo group, including deep vein thrombosis in 0.6% versus 0.5% and pulmonary embolism in 0.9% versus 0.5% [5].

What did the T-Trials show?

The T-Trials assigned 790 men aged 65 or older with serum testosterone below 275 ng/dL and symptoms suggesting hypogonadism to testosterone gel or placebo gel for 1 year [4]. Each man took part in one or more of three trials: Sexual Function, Physical Function and Vitality [4]. Testosterone raised levels to the mid-normal range for men aged 19 to 40 and significantly increased sexual activity (P<0.001), sexual desire and erectile function [4]. The share of men who added at least 50 m to their 6-minute walk did not differ significantly within the Physical Function Trial but did when all three trials were pooled, 20.5% versus 12.6% (P=0.003) [4]. Vitality did not improve significantly; mood improved slightly [4]. Adverse event rates were similar, and the trial was too small to draw conclusions about risks [4].

What did FDA change in 2025 and 2026?

On February 28, 2025, FDA told sponsors to add TRAVERSE results to all testosterone labels, retain the Limitation of Use for age-related hypogonadism, and remove from the Boxed Warning the language about increased risk of adverse cardiovascular outcomes [3]. From the ambulatory blood pressure studies, FDA required product-specific blood pressure information where studies were completed and a new blood pressure warning for products that lacked one; the completed studies confirmed a blood pressure increase with all testosterone products, class-wide [3].

FDA's testosterone page, current as of June 23, 2026, says FDA requested further updates in June 2026: 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]. FDA also said TRAVERSE did not demonstrate a new safety signal or trend in adverse cardiovascular outcomes [1]. These remain requests: the generic testosterone gel 1% label (effective September 2025) still carries the age-related hypogonadism limitation [5], and FDA's page frames the June 2026 changes as requested updates [1].

What did earlier formulation studies document?

• In 11 hypogonadal men, 200 mg of intramuscular testosterone cypionate caused a threefold rise in serum testosterone peaking on days 2 to 5, with values back to baseline by days 13 to 14 [6].
• In a 24-week randomized study of 66 men, a testosterone patch produced normal-range morning hormone levels in 77% to 100% of patients versus 19% to 84% with biweekly enanthate injections; transient skin irritation was reported by 60% of patch users and 3 of them (9%) stopped treatment [7].
• In a study of 227 hypogonadal men, a 1% hydroalcoholic testosterone gel dried within a few minutes, about 9% to 14% of the applied testosterone was bioavailable, and serum testosterone rose into the normal range on day 1 [8].