Anastrozole Improves Height Outcomes in Growing Children With Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency.

Abstract

Hyperandrogenemia resulting in estrogen-mediated accelerated bone maturation and early growth plate fusion contributes to short stature in children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Aromatase inhibitors block androgen conversion to estrogen and have been used off-label in children with short stature to improve adult height. There are no adequately powered studies examining the use of aromatase inhibitors in children with CAH with advanced bone age and reduced predicted adult height. Records of CAH patients treated with anastrozole were reviewed. Z-scores of bone age, predicted adult height, and height corrected for bone age were examined over an 8-year period. Outcome changes were analyzed using weighted mixed-effects models, adjusting for sex, diagnosis, age at diagnosis, and average hydrocortisone dose before and during treatment with anastrozole. In 60 patients (26 females; 52 classic, 8 nonclassic) started on anastrozole therapy, the mean bone age Z-score decreased from 4.2 to 2.0 at 4 years and 1.3 at 6 years (both P < .001); predicted adult height Z-score improved from -2.1 to -0.45 at 4 years and 0.18 at 6 years (both P < .001); corrected height Z-scores improved from -1.7 to -0.33 at 4 years and 0.18 at 6 years (P < .001). There was no significant difference in the average total daily hydrocortisone dose used before or during treatment. Anastrozole decreased the rate of bone maturation and led to improved height outcomes, indicating that anastrozole could have a role as an adjunct therapy in children with CAH and advanced bone age.