A specific aromatase inhibitor and potential increase in adult height in boys with delayed puberty:: a randomised controlled trial

Background The role of oestrogens in the closure of growth plates in both sexes is unequivocal. We postulated that inhibition of oestrogen synthesis in boys with delayed puberty would delay maturation of the growth plates and ultimately result in increased adult height. Methods We did a randomised, double-blind, placebo-controlled study in which we treated boys with constitutional delay of puberty with testosterone and placebo, or testosterone and letrozole. Boys who decided to wait for the spontaneous progression of puberty without medical intervention composed the untreated group. Findings Letrozole effectively inhibited oestrogen synthesis and delayed bone maturation. Progression of bone maturation was slower in the letrozole group than in the placebo group. In 18 months, bone age had advanced 1.1 (SD 0.8) years in the untreated group and 1.7 (0.9) years in the group treated with testosterone and placebo, but only 0.9 (0.6) years in the letrozole group (p=0.03 between the treatment groups). Predicted adult height did not change significantly in the untreated group and in the placebo group, whereas in the group treated with letrozole the increase was 5.1 (3.7) cm (p=0.004). Interpretations Our findings suggest that if oestrogen action is inhibited in growing adolescents, adult height will increase. This finding provides a rationale for studies that aim to delay bone maturation in several growth disorders.