Introduction: Hypogonadotropic hypogonadism is frequently observed in morbidly obese men, due to aromatase-dependent conversion of androgens to estrogens in adipocytes. The clinical impact of this sex hormone imbalance is not known.
Aim: To evaluate the clinical effects of aromatase inhibition in obesity-related hypogonadotropic hypogonadism.
Methods: Double-blind, placebo-controlled trial for 6 months in severely obese men (BMI > 35 kg/m2) with obesity-related hypogonadism (serum total testosterone < 10 nmol/l). Predefined drug regimen: Starting dose 1 tablet/week, subsequent dose escalation up to a maximum of 7 tablets/week or until a serum total testosterone of 20 nmol/l.
Results: So far, 16 patients have completed the study, 8 on letrozole (mean dose: 2 tablets/week) and eight receiving placebo (mean dose: 7 tablets/week). Both groups were well matched for all study parameters. Age (mean±S.E.M.) 40.6±1.6 years, BMI 43.5±1.3 kg/m2, serum LH 3.6±0.4 U/l, total testosterone 7.2±0.4 nmol/l, free testosterone 214.5±14 pmol/l, total estradiol 127.5±11.7 pmol/l. Six months of Letrozole treatment decreased serum estradiol by 53.3±20.5 pmol/l (P<0.05) and increased serum LH by 6.4±1.6 U/l (P<0.005). Total testosterone rose by 12.8±1.2 nmol/l (P<0.0001), and free testosterone by 412±52 pmol/l (P<0.0001), whereas placebo treatment had no statistically significant effects. Placebo-subtracted changes in body weight and abdominal circumference were −7 kg (P<0.02) and −5.2 cm (P<0.005), respectively. Glucose metabolism, lipid profiles, bone density, and physical exercise capacity did not change. Psychological testing did not reveal any changes during treatment.
Conclusion: Short-term, low dose aromatase inhibition in obesity-related hypogonadotropic hypogonadism normalizes serum testosterone and has beneficial effects on body composition.