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: To 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/m2, and serum total testosterone levels < 10 nmol/L. All patients started on 1 tablet of 2.5 mg/week, with subsequent dose escalation every month until a serum total testosterone of 20 nmol/L was reached. Endpoints: psychological function, body composition, exercise capacity, and glucose, lipid and bone metabolism. RESULTS: 39 patients completed the study according to protocol. Letrozole decreased serum estradiol from 119.1 +/- 10.1 to 59.2 +/- 6.1 pmol/L (P < 0.001), increased serum LH from 3.3 +/- 0.3 to 8.8 +/- 0.9 U/L (P < 0.0001), and raised serum total testosterone from 8.6 +/- 0.7 to 21.5 +/- 1.3 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.