Objective: Isolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E 2 ) production and E 2 -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 indexO 35.0 kg/m 2 ) 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 E 2 from 123G11 to 58G7 pmol/l (P!0.001, meanG S.E.M.), and increased serum LH from 4.4G0.6 to 11.1G1.5 U/l (P!0.001). Total testosterone rose from 5.9G0.5 to 19.6G1.4 nmol/l (P!0.001), and free testosterone from 163G13 to 604G 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 E 2 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.European Journal of Endocrinology 158 741-747

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 O35 kg/m

High-dose DZX-mediated insulin suppression, in combination with moderate caloric restriction and lifestyle advice, is associated with a clinically relevant degree of weight reduction. A more extensive exploration is warranted to optimize this mode of treatment and to further clarify its risks and benefits.

In nondiabetic obese men, insulin levels can be reduced up to 70% without major metabolic side effects. The marked intersubject variation in maximal tolerated dose indicates that DZX dose titration needs to be individualized.

Obesity-related hypogonadotrophic hypogonadism is a reversible condition in the majority of obese men. It does not reduce the efficacy of bariatric surgery. Preoperative weight-adjusted normal values are recommended to avoid an incorrect diagnosis of hypogonadism in obese men.