Endocrine Abstracts (2011) 26 P328

Letrozole normalizes serum testosterone but has no clinical effects in men with obesity-related hypogonadotropic hypogonadism

S Loves1, J de Jong2, A van Sorge3, D Telting4, A Hermus5 & H de Boer1

1Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands; 2Department of Psychology, Rijnstate Hospital, Arnhem, The Netherlands; 3Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem, The Netherlands; 4Department of Clinical Chemistry, Rijnstate Hospital, Arnhem, The Netherlands; 5Department of Endocrinology, Radboud University Medical Centre, Nijmegen, The Netherlands.

Introduction: Hypogonadotropic hypogonadism is frequently observed in morbidly obese men, due to aromatase-dependent conversion of androgens to estrogens. The clinical impact of this sex hormone imbalance is unknown.

Aim: Evaluate the clinical effects of aromatase inhibition in obesity-related hypogonadism.

Methods: Double-blind, placebo-controlled, 6-month trial in severely obese men (BMI>35 kg/m2) with obesity-related hypogonadism (serum total testosterone<10 nmol/l). Starting dose (Letrozole or placebo) 1 tablet/week, subsequent monthly dose escalation up to a maximum of 7 tablets/week or until a serum total testosterone of 20 nmol/l. The dose was reduced if serum estradiol decreased below 40 pmol/l.

Results: Eighteen patients on Letrozole and 21 receiving placebo completed the study. Mean age 44.6±1.1 years (mean±S.E.M.), BMI 41.1±0.8 kg/m2. At baseline, both groups were well matched for all study parameters. Placebo treatment did not affect serum hormone levels. Letrozole decreased serum estradiol from 119±10 to 59.2±6.1 pmol/l (P=0.0001, normal range (NR) 40–160 pmol/l), increased serum LH from 3.3±0.3 to 8.8±0.9 U/l (P<0.0001, NR:2–9 U/l) and free testosterone from 244±19 to 691±39 pmol/l (P<0.0001, NR:225–625 pmol/l). Both groups demonstrated a decrease in body weight of about 5 kg, and a decrease in abdominal circumference of about 4 cm. Changes in fat free mass, fat mass and bone density also did not differ between groups. Glucose metabolism, lipid profiles, physical exercise capacity and psychological characteristics did not change during treatment.

Conclusion: Despite a marked rise in serum free testosterone, low dose aromatase inhibition had no somatic or psychological effects in men with obesity-related HH. We hypothesize that, with respect to non-sexual somatic and psychological parameters, males primarily thrive on oestrogens, not testosterone.

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