Somatic and psychological effects of low-dose aromatase inhibition in men with obesity-related hypogonadotropic hypotestosteronemia

Introduction: Reduced testosterone levels are frequently observed in obese men. Increased aromatase activity may be an etiological factor. Objective: In this study, we evaluate the clinical effects of aromatase inhibition in obesity- related hypogonadotropic hypotestosteronemia (OrHH). Methods: Double- blind, placebo- controlled, 6-month trial in 42 obese men with a BMI > 35 kg/ m(2), and a serum total testosterone < 10 nmol/l. All patients started on one tablet of 2.5 mg/ week, with subsequent dose escalation every month until a serum total testosterone of 20nmol/l was reached. Endpoints: Psychological function, body composition, exercise capacity, and glucose, lipid, and bone metabolism. Results: Thirty- nine patients completed the study according to protocol. Letrozole decreased serum estradiol from 119.1G10.1 to 59.2G6.1 pmol/ l ( P< 0.001), and increased serum LH from 3.3G0.3 to 8.8G0.9 U l ( P<0.0001) and serum total testosterone from 8.6G0.7 to 21.5G1.3 nmol/l ( P<0.0001). Significant effects on the predefined endpoints were not observed. Conclusion: Despite a marked rise in serum testosterone, low- dose aromatase inhibition had no somatic or psychological effects in men with OrHH.