Novel Treatment of Delayed Male Puberty with Aromatase Inhibitors

Abstract

Background: As the evidence for the role of oestrogens in epiphyseal closure appears unequivocal, we hypothesized that boys with constitutional delay of puberty would attain greater adult height if oestrogen action was suppressed. Methods: We conducted a randomized, double-blind, placebo-controlled study in which we treated boys with constitutional delay of puberty with testosterone plus placebo or testosterone plus a potent fourth-generation aromatase inhibitor, letrozole. Findings: Letrozole effectively inhibited oestrogen synthesis. The 17β-oestradiol concentrations increased in the untreated group and in the testosterone/placebo-treated group, but in the testosterone/letrozole-treated group no such increase was observed until letrozole treatment was discontinued. Testosterone concentrations were threefold higher in the testosterone/letrozole-treated group than in the other groups. Within 18 months, bone age had advanced by 1.1 ± 0.3 years in the untreated group and by 1.7 ± 0.3 years in the testosterone/placebo-treated group, but only by 0.9 ± 0.2 years in the testosterone/letrozole-treated group (p = 0.02 between treatment groups). Predicted adult height did not change significantly in the untreated group and in the testosterone/placebo-treated group, whereas in the testosterone/letrozole-treated group the increase was 5.1 ± 1.2 cm (p = 0.004). Conclusions: Our findings suggest that, if oestrogen action is inhibited in growing adolescents, adult height will increase. This observation provides a rationale for studies aimed at delaying bone maturation in several growth disorders.