Hero M et al. (2006) Blockage of oestrogen biosynthesis in peripubertal boys: effects on lipid metabolism, insulin sensitivity, and body composition. Eur J Endocrinol 155: 453–460

Aromatase inhibitors such as letrozole are used to treat some growth disorders. Since aromatase inhibitors suppress estrogen biosynthesis and stimulate secretion of gonadal androgens, these drugs could also affect lipid metabolism and insulin sensitivity in peripubertal males with growth disorders.

In a prospective, double-blinded trial, 31 boys aged between 9.0 and 14.5 years with idiopathic short statue were randomly treated with placebo or 2.5 mg letrozole daily for 2 years. At baseline, there was no difference in BMI, percentage of fat mass, age or pubertal maturation stage between the groups. Pubertal boys who received letrozole showed a decrease in HDL cholesterol compared with those who received placebo. The decrease in HDL cholesterol correlated with the decrease in adiponectin levels, and there was an inverse correlation between the decrease in HDL cholesterol and rise in serum testosterone. Relative fat mass decreased during the 2-year study, which inversely correlated with increased testosterone levels in letrozole-treated boys, compared with placebo-treated boys. Insulin sensitivity, in addition to concentrations of LDL cholesterol, apolipoprotein B and triglycerides, did not alter in either group.

The authors conclude that in pubertal boys with idiopathic short statue who are treated with letrozole, levels of HDL cholesterol and relative fat mass decline. The authors, therefore, recommend a careful follow-up of lipid profile in pubertal boys with short statue who are treated with an aromatase inhibitor.