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Context: The process of epiphyseal fusion during puberty is regulated by estrogen, even in males., Objective: Our objective was to investigate whether anastrozole, a potent aromatase inhibitor, could delay bone age acceleration and increase predicted adult height in adolescent boys with GH deficiency., Methods: Fifty-two adolescent males with GH deficiency treated with GH were randomized to cotreatment with anastrozole or placebo daily for up to 36 months., Results: Fifty subjects completed 12 months, 41 completed 24 months, and 28 completed 36 months. Linear growth was comparable between groups; however, there was a significantly slower increase in bone age advancement from baseline in the anastrozole group vs. placebo group after 2 yr (+1.8+/-0.1 vs. +2.7+/-0.1 yr, P<0.0001) and after 3 yr (+2.5+/-0.2 vs. +4.1+/-0.1 yr, P<0.0001). This resulted in a net increase in predicted adult height of +4.5+/-1.2 cm in the anastrozole group at 24 months and +6.7+/-1.4 cm at 36 months as compared with a 1-cm gain at both time points in the placebo group. Estradiol and estrone concentrations increased less in the anastrozole group compared with placebo group. All boys on the aromatase inhibitor had normal tempo of virilization. Safety data, including glucose, and plasma lipid concentrations were comparable between groups., Conclusions: Anastrozole increases adult height potential of adolescent boys on GH therapy while maintaining normal pubertal progression after 2-3 yr. This treatment offers an alternative in promoting growth in GH-deficient boys in puberty. Long-term follow up is needed to elucidate fully the safety and efficacy of this approach.