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 20 nmol/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 119.1±10.1 to 59.2±6.1 pmol/l (P<0.001), and increased serum LH from 3.3±0.3 to 8.8±0.9 U/l (P<0.0001) and 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.