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. DESIGN: 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.

Nyckelord

Adolescent

Apolipoprotein A-I/metabolism

Apolipoproteins B/metabolism

Aromatase Inhibitors/pharmacology

Body Composition/*physiology

Body Height/physiology

Body Mass Index

Carbohydrate Metabolism

Child

Cholesterol

HDL/blood

Cohort Studies

Double-Blind Method

Estrogen Antagonists/*pharmacology

Estrogens/*biosynthesis

Gonadotropins/blood/metabolism

Humans

Insulin Resistance/*physiology

Lipid Metabolism/*physiology

Male

Nitriles/pharmacology

Prospective Studies

Triazoles/pharmacology

Triglycerides/blood

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)