Blockade of oestrogen biosynthesis in peripubertal boys: effects on lipid metabolism, insulin sensitivity, and body composition.
OBJECTIVE
In males, the pubertal increase in sex hormone production has been associated with proatherogenic changes in lipid and carbohydrate metabolism. Aromatase inhibitors, a novel treatment modality for some growth disorders, may significantly influence these risk factors for cardiovascular disease by suppressing oestrogen biosynthesis and stimulating gonadal androgen production. In the current study, we explored the effects of aromatase inhibition on lipid metabolism, insulin sensitivity, body composition and serum adiponectin in peripubertal boys.


METHODS
Prospective, double-blind, randomised, placebo-controlled clinical study.


METHODS
Thirty-one boys, aged 9.0-14.5 years, with idiopathic short stature were treated with the aromatase inhibitor letrozole (2.5 mg/day) or placebo for 2 years. During the treatment, the concentrations of sex hormones, IGF-I, lipids, lipoproteins and adiponectin were followed-up. The percentage of fat mass (FM) was assessed by skinfold measurements and insulin resistance by homeostasis model assessment (HOMA) index.


RESULTS
In pubertal boys, who received letrozole, high-density lipoprotein cholesterol (HDL-C) decreased by 0.47 mmol/l (P<0.01) during the study. Simultaneously, their percentage of FM decreased from 17.0 to 10.5 (P<0.001), in an inverse relationship with serum testosterone. The concentrations of low-density lipoprotein cholesterol, triglycerides and HOMA index remained at pretreatment level in both groups. Serum adiponectin decreased similarly in letrozole- and placebo-treated pubertal boys (2.9 and 3.3 mg/l respectively).


CONCLUSIONS
In males, aromatase inhibition reduces HDL-C and decreases relative FM after the start of puberty. The treatment does not adversely affect insulin sensitivity in lean subjects.
Hero
Matti
M
Hospital for Children and Adolescents, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Ankarberg-Lindgren
Carina
C
Taskinen
Marja-Riitta
MR
Dunkel
Leo
L
D000293:Adolescent; D016632:Apolipoprotein A-I / Q000378:metabolism; D001055:Apolipoproteins B / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology; D001823:Body Composition / Q000502:physiology*; D001827:Body Height / Q000502:physiology; D015992:Body Mass Index; D050260:Carbohydrate Metabolism; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000096:biosynthesis*; D006062:Gonadotropins / Q000097:blood / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D000077289:Letrozole; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D011446:Prospective Studies; D014230:Triazoles / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D047072:Aromatase Inhibitors; D008076:Cholesterol, HDL; D004965:Estrogen Antagonists; D004967:Estrogens; D006062:Gonadotropins; D009570:Nitriles; D014230:Triazoles; D014280:Triglycerides; D000077289:Letrozole