Anastrozole increases predicted adult height in adolescent males with idiopathic short stature

BACKGROUND: Estrogens have an essential role in the regulation of bone maturation and in epiphyseal fusion during puberty in both sexes. The inhibition of estrogen synthesis delays bone maturation and results in increased adult height. Aromatase inhibitors that block estrogen biosynthesis have therefore emerged as a new potential treatment option for children with short stature.OBJECTIVE: Our objective was to investigate whether inhibition of estrogen biosynthesis with the aromatase inhibitor, anastrozole, during adolescence, delays bone age acceleration and increase predicted adult height in boys.PATIENTS AND METHODS: Twelve boys with idiopathic short stature were randomized to treatment with aromatase inhibitor anastrozole 25 mg/day orally, or placebo for 2 years. Informed consent was obtained from the patients and their parents. The diagnosis of constitutional short stature was made by exclusion of systemic diseases, GH deficiency, psychosocial deprivation, or syndromatic causes. Pubertal stage was III according to Tanner, confirmed by testosterone plasma levels.RESULTS: Linear growth was similar between two groups; however, there was a slower increase in bone age advancement from baseline in the anastrozole group vs. placebo group after 2 yr. Estradiol concentrations in the boys treated with anastrozole remained at the pretreatment level, whereas the concentrations increased during spontaneous progression of puberty in placebo group. Testosterone concentrations increased in both groups, but during the anastrozole treatment the level was higher than in the control group. The bone maturation was delayed in the boys treated with anastrozole despite higher androgen concentrations and, an increase of 4.3 ± 1.1 cm in predicted adult height was observed in the boys who received anastrozole, but no change was seen in the untreated boys. All boys had normal virilization.CONCLUSIONS: Our findings indicate that in adolescent boys an increase in adult height can be obtained by use of aromatase blockade with anastrozole caused by a slowing of the bone age maturation, resulting in a gain in predicted adult height compared with placebo.