Does body mass index predict changes in body composition and metabolic markers in response to testosterone therapy?

• Men with a BMI less than 35 have the greatest improvement in terms of their fat free and lean mass with testosterone • Men with a BMI greater than 35 have the least benefit in fat free and lean mass with testosterone • Leptin levels decreased the most after testosterone use in those with a BMI less than 30 Despite reported improvements in body composition, metabolic profile, skeletal outcomes and symptoms from testosterone (T) therapy in men with hypogonadism, it remains unclear whether baseline body mass index (BMI) affects response. The objective of this study is to determine if baseline BMI influences response to T therapy. This is a secondary analysis of data from a clinical trial on pharmacogenetics of response to T therapy in men with average morning T < 300 ng/dl, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Participants were divided into BMI categories: BMI 1 (< 30 kg/m 2 ), BMI 2 (30-34.99 kg/m 2 ), and BMI 3 (≥35 kg/m 2 ). T, estradiol, adipokines, metabolic markers, body composition, bone mineral density, bone turnover markers and total symptom score were assessed at baseline, 6, 12 and 18 months. All 3 groups had improvement in body composition, though BMI 1 and 2 had greater increases in truncal fat-free and truncal lean mass than BMI 3. Appendicular fat mass declined the most in BMI 1 and the least in BMI 3.. Leptin declined in all 3 groups with the most in BMI 1, while adiponectin significantly decreased only BMI 2. All groups showed increase in lumbar spine BMD. BMI 1 and 2 had improvement in symptoms but not BMI 3. Our study shows that men with a BMI <35 derived the greatest benefit from T therapy in terms of changes in body composition and symptoms, while those with higher BMI benefited the least.