Testosterone 2% gel can normalize testosterone concentrations in men with low testosterone regardless of body mass index

Introduction: Little is known about the effect of body mass index (BMI) on the efficacy and safety of testosterone therapy in hypogonadal men. A prior noncomparative trial demonstrated that testosterone 2% gel restored testosterone levels in hypogonadal men and was generally well tolerated. Aim: This post hoc analysis evaluated the influence of BMI on the pharmacokinetics of testosterone therapy in men with low testosterone. Methods: Men (N=149) aged 18-75 applied testosterone 2% gel to the front and inner thigh once daily for 90 days. Starting dose was 40mg/day, which could be adjusted at days 14, 35, and 60. Patients were split into categories depending on baseline BMI: Tertile 1 (≤29.1kg/m²), Tertile 2 (29.2-32.4kg/m²), and Tertile 3 (>32.4kg/m²). Main Outcome Measures: Efficacy end points were average serum total testosterone concentrations over 24 hours and maximum serum testosterone concentrations at day 90. Adverse events were recorded. Results: The efficacy analysis included 129 men with low testosterone (mean age 52.9, 54.0, and 54.2 years for Tertiles 1, 2, and 3, respectively) defined as serum testosterone <250-300ng/dL. Baseline testosterone levels were comparable across BMI tertiles. After 90 days of treatment with testosterone 2% gel (≥40mg/day), 79.1%, 79.5%, and 73.8% of patients in Tertiles 1, 2, and 3, respectively, achieved serum testosterone concentrations in the physiologic range (i.e., ≥300 to ≤1,140ng/dL). The mean average daily dose at day 90 was higher in participants in Tertiles 3 vs. 2 (P=0.039) and Tertiles 3 vs. 1 (P=0.010). The gel was generally well tolerated, with skin reactions the most commonly reported adverse event (16.1%; n=24). Conclusions: In this study, daily application of testosterone 2% gel was effective at returning serum testosterone to physiologic levels in men with low testosterone and high BMI, although required dose was affected by BMI.