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.
Loves, S., de Jong, J., van Sorge, A., Telting, D., Tack, C. J., Hermus, A., Westerterp, K., & de Boer, H. (2013). Somatic and psychological effects of low-dose aromatase inhibition in men with obesity-related hypogonadotropic hypotestosteronemia. European Journal of Endocrinology, 169(5), 705-714. https://doi.org/10.1530/EJE-13-0190