AndroGel in Special Populations: Transplant, HIV, Opioid-Induced, and Glucocorticoid-Induced Hypogonadism

Which gel was tested?

The large cardiovascular trial used AndroGel 1.62%, not a 1% gel. FDA's testosterone page says TRAVERSE tracked more than 5,200 men who received at least one dose of AndroGel 1.62% [5], and the published trial randomized 5,246 men aged 45 to 80 with hypogonadism and existing or high cardiovascular risk to daily 1.62% testosterone gel or placebo [6]. The AndroGel 1% label states in its Dosage and Administration section that dosing for AndroGel 1% differs from AndroGel 1.62% [9], so its starting dose, titration steps and application instructions do not describe AndroGel 1.62%.

FDA says testosterone products are approved only for men who lack or have low testosterone in conjunction with an associated medical condition, with examples including testicular failure from genetic problems or chemotherapy and problems with the hypothalamus or pituitary, and that none are approved for men with low testosterone who lack an associated medical condition [5]. Opioid therapy, glucocorticoid therapy and HIV are not among the examples FDA gives [5].

Opioid-induced hypogonadism

This is the one population on this page with a randomized trial of testosterone gel itself. Eighty-four men aged 18 to 64 who took opioid analgesics for chronic noncancer pain and had a total testosterone below 350 ng/dL were assigned to 14 weeks of daily transdermal gel containing 5 g of testosterone or placebo; 65 had follow-up data on efficacy outcomes [1]. Median baseline total testosterone was 243 ng/dL in the testosterone arm and 251 ng/dL in the placebo arm [1].

Compared with placebo, testosterone produced greater improvement in pressure and mechanical hyperalgesia, in sexual desire, and in role limitation due to emotional problems, plus an improvement in body composition [1]. There were no between-group differences in changes in self-reported pain [1].

In a retrospective cohort of 1,159 men taking a single opioid for chronic noncancer pain for at least 90 days, the odds of androgen deficiency compared with hydrocodone were higher for fentanyl (odds ratio 25.7, 95% CI 2.82 to 234.97), methadone (odds ratio 7.33, 95% CI 3.29 to 16.33), and oxycodone (odds ratio 3.15, 95% CI 1.87 to 5.33) [10]. The fentanyl confidence interval is very wide, so that estimate is imprecise.

Men taking long-term glucocorticoids: the trial used injections, not gel

The randomized trial in this group enrolled men who required long-term systemic glucocorticoid treatment, not men selected for a hypogonadism diagnosis, and it did not test a topical gel [2]. Fifty-one men on a mean daily prednisone dose of 12.6 plus or minus 2.2 mg were randomized double-blind to testosterone 200 mg mixed esters, nandrolone decanoate 200 mg, or placebo by intramuscular injection every fortnight for 12 months [2]. Muscle mass changed by +3.5% with testosterone, +5.8% with nandrolone, and -0.9% with placebo (P < 0.0001), and muscle strength improved (P < 0.05) [2]. Lumbar spine bone mineral density increased significantly only in the testosterone group, by 4.7 plus or minus 1.1% (P < 0.01), with no significant change at the hip or total body [2]. Testosterone also improved overall quality of life (P < 0.001) [2].

HIV-associated hypogonadism

The two HIV trials described here used intramuscular testosterone enanthate [3][4], and both are decades old. In one, 61 HIV-infected men aged 18 to 50 with serum testosterone below 12.1 nmol/L (349 ng/dL) and weight loss of 5% or more in the previous six months were assigned to placebo, testosterone enanthate 100 mg per week, placebo plus resistance exercise, or testosterone plus exercise for 16 weeks; 49 completed [3]. Body weight rose 2.6 kg with testosterone alone (P < 0.001) and 2.2 kg with exercise alone (P = 0.02), and did not change with placebo alone (-0.5 kg) or with testosterone plus exercise (0.7 kg) [3].

In the other, 51 HIV-positive men with AIDS wasting and a free testosterone below 42 pmol/L received testosterone enanthate 300 mg or placebo intramuscularly every three weeks for six months [4]. Fat-free mass changed by -0.6 kg with placebo and +2.0 kg with testosterone (P = 0.036), lean body mass by 0.0 and +1.9 kg (P = 0.041), and muscle mass by -0.8 and +2.4 kg (P = 0.005) [4]. Weight, fat mass and exercise capacity did not differ significantly between groups, and the testosterone group reported feeling better and improved quality of life [4].

Blood pressure, hematocrit and cardiovascular outcomes

FDA's review of ambulatory blood pressure monitoring studies confirmed a blood pressure increase with all testosterone products, class-wide [8]. In TRAVERSE, mean systolic blood pressure rose 1.0 mm Hg on 1.62% testosterone gel against a 0.5 mm Hg fall on placebo at 36 months [6].

Both gel and intramuscular enanthate or cypionate increased average hematocrit versus placebo in a network meta-analysis of 29 placebo-controlled randomized trials in 3,393 men: 3.0% with gel (95% CI 1.8 to 4.3) and 4.0% with intramuscular enanthate or cypionate (95% CI 2.9 to 5.1) [7]. A retrospective review of 178 hypogonadal men followed for three years found erythrocytosis (hematocrit above 50%) in 66.7% of those on injectable testosterone, 12.8% on gels and 35.1% on pellets; the injection group was younger (mean 42.5 versus about 54 years) with a higher baseline hematocrit, and the study was not randomized [11].

For cardiovascular outcomes, the large trial used AndroGel 1.62%. In TRAVERSE, 5,246 men aged 45 to 80 with hypogonadism and existing or high cardiovascular risk took daily 1.62% testosterone gel or placebo; a major adverse cardiovascular event occurred in 7.0% on testosterone and 7.3% on placebo, hazard ratio 0.96 (95% CI 0.78 to 1.17) [6]. In February 2025 FDA recommended removing boxed-warning language about an increased risk of adverse cardiovascular outcomes from all testosterone products and required a blood pressure warning for products that lacked one, after the ambulatory blood pressure studies confirmed a blood pressure increase with all testosterone products [8].