Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism.
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.


METHODS
Open, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>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 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 E(2) levels were stable throughout the week and during the 6-month treatment period.


CONCLUSIONS
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.
Loves
Sandra
S
Department of Internal Medicine, Ziekenhuis Rijnstate, Wagnerlaan 55, 6800 TA Arnhem, The Netherlands.
Ruinemans-Koerts
Janneke
J
de Boer
Hans
H
D000328:Adult; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D004958:Estradiol / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D000077289:Letrozole; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage*; D009765:Obesity / Q000150:complications*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D014230:Triazoles / Q000008:administration & dosage*
D047072:Aromatase Inhibitors; D009570:Nitriles; D012738:Sex Hormone-Binding Globulin; D014230:Triazoles; D013739:Testosterone; D004958:Estradiol; D000077289:Letrozole