European Journal of Endocrinology, Vol 158, Issue 5, 741-747
Copyright © 2008 by Society of the European Journal of Endocrinology
Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism
Sandra Loves1, Janneke Ruinemans-Koerts2 and Hans de Boer1
Departments of1 , Internal Medicine2 Clinical Chemistry, Ziekenhuis Rijnstate, Wagnerlaan 55, 6800 TA Arnhem, The Netherlands
(Correspondence should be addressed to H de Boer; Email: email@example.com)
Objective: Isolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E2) production and E2-mediated negative feedback on pituitary LH secretion. Aromatase inhibitors can reverse this process. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect.
Design: Open, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>35.0 kg/m2) with obesity-related IHH and free testosterone levels <225 pmol/l, treated with 2.5 mg letrozole once a week for 6 months.
Results: Six weeks of treatment reduced total E2 from 123±11 to 58±7 pmol/l (P<0.001, mean±S.E.M.), and increased serum LH from 4.4±0.6 to 11.1±1.5 U/l (P<0.001). Total testosterone rose from 5.9±0.5 to 19.6±1.4 nmol/l (P<0.001), and free testosterone from 163±13 to 604±50 pmol/l (P<0.001). Total testosterone rose to within the normal range in all subjects, whereas free testosterone rose to supraphysiological levels in 7 out of 12 men. The testosterone and E2 levels were stable throughout the week and during the 6-month treatment period.
Conclusion: Letrozole 2.5 mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH. However, free testosterone frequently rose to supraphysiological levels. Therefore, a starting dose <2.5 mg once a week is recommended.