IntroductionLittle 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. AimThis post hoc analysis evaluated the influence of BMI on the pharmacokinetics of testosterone therapy in men with low testosterone. MethodsMen (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/m(2)), Tertile 2 (29.2-32.4kg/m(2)), and Tertile 3 (>32.4kg/m(2)). Main Outcome MeasuresEfficacy end points were average serum total testosterone concentrations over 24 hours and maximum serum testosterone concentrations at day 90. Adverse events were recorded. ResultsThe 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). ConclusionsIn 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. Dobs A, Norwood P, Potts S, Gould E, and Chitra S. Testosterone 2% gel can normalize testosterone concentrations in men with low testosterone regardless of body mass index. J Sex Med 2014;11:857-864.