The role of sex steroids in the regulation of insulin sensitivity and serum lipid concentrations during male puberty: a prospective study with a P450-aromatase inhibitor.

OBJECTIVE Our purpose was to study the sex steroid-mediated changes in serum insulin and lipid concentrations in boys during puberty. DESIGN AND METHODS We treated boys with constitutional delay of puberty either with testosterone plus placebo or with testosterone plus an aromatase inhibitor, letrozole, which inhibits the conversion of androgens to oestrogens. We demonstrated previously that during treatment with testosterone plus letrozole the increase in testosterone concentration was more than 5-fold higher than during treatment with testosterone plus placebo. The concentrations of 17beta-oestradiol, IGF-I and IGF-binding protein-3 increased during testosterone-plus-placebo treatment, but during testosterone-plus-letrozole treatment the concentrations remained unchanged. These divergent changes in the two groups enabled us to study the effects of sex steroids and GH on insulin sensitivity and lipid concentrations. RESULTS The insulin concentration in the testosterone-plus-placebo-treated group did not change. In contrast, in the testosterone-plus-letrozole-treated group, the concentration decreased during letrozole treatment, indicating improved insulin sensitivity. Changes in insulin and IGF-I concentrations within 12 and 18 months were correlated. In the testosterone-plus-placebo-treated group, the high-density lipoprotein cholesterol concentration did not change but in the testosterone-plus-letrozole-treated group the concentration decreased. The concentrations of low-density lipoprotein cholesterol (LDL-cholesterol) and triglycerides did not change in either of the groups. CONCLUSIONS The findings indicate that androgens do not directly alter insulin sensitivity in boys during puberty. In contrast, the observations suggest tight regulation of glucose--insulin homeostasis by GH in boys at this stage. Furthermore, our findings indicate that sex steroids do not significantly participate in the regulation of serum concentrations of LDL-cholesterol or triglycerides in boys during early and mid-puberty.