Anastrozole Increases Predicted Adult Height of Short Adolescent Males Treated With Growth Hormone: A Randomized, Placebo-Controlled, Multicenter Trial for One to Three Years

Abstract

Estrogen is an important regulator of epiphyseal fusion in males as well as in females. The potent aromatase inhibitor anastrozole holds promise of delaying the acceleration of bone age and increasing predicted adult height in adolescent boys with growth hormone (GH) deficiency. Anastrozole blocks the conversion of A4-androstenedione to estrone and testosterone to estradiol. Studies of young males with a 50% reduction in circulating estradiol have failed to demonstrate negative effects on metabolic measures. The present double blind, randomized, placebo-controlled trial assigned 52 GH-deficient adolescent males to treatment with anastrozole in a dose of 1 mg daily or placebo for up to 3 years. Fifty of the boys completed 12 months in the study; 41, 24 months; and 28, 36 months. Linear growth was comparable in boys given anastrozole and placebo recipients, but the increase in bone age advancement from baseline was significantly slower in actively treated subjects after 2 years and also after 3 years. The resultant net increase in predicted adult height in the anastrozole group was +4.5 cm at 24 months and +6.7 cm at 36 months. Placebo recipients had a 1-cm gain at both time points. Blood levels of estradiol and estrone increased less in boys given anastrozole than in the placebo group. In no instance did active treatment alter the normal course of virilization. The treated and control groups exhibited no substantial differences in blood glucose and plasma lipid concentrations or in bone mineral density measured at the lumbar spine. Anastrozole was well tolerated and was largely free of side effects. No serious adverse events could be attributed directly to anastrozole therapy. Anastrozole therapy is an attractive alternative means of enhancing potential height in adolescent boys taking GH, but longer-term follow-up is needed to affirm the efficacy and safety of this approach.