IMPE Abstracts

Background: Hyperandrogenemia resulting in estrogen-mediated accelerated bone maturation and early growth plate fusion largely 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 have been no adequately powered studies supporting the use of aromatase inhibitors in children with CAH who have advanced bone age and reduced predicted adult height.

Methods: Health records of CAH patients who were treated with anastrozole, a 3^rd generation aromatase inhibitor, were reviewed to examine anastrozole's effect on bone age z-scores, predicted adult height z-scores and height z-scores corrected for bone age. These measures were examined over an 8-year period starting 2 years before anastrozole treatment. Changes in these outcomes were analyzed using weighted mixed effects models, adjusting for sex, diagnosis, age at diagnosis, and average hydrocortisone dose before and during treatment with anastrozole.

Results: 57 patients were treated with anastrozole (26 females; 31 salt wasting, 19 simple virilizing, 7 non classic). Average age at diagnosis was 2 (SD 3) years and average age starting anastrozole was 7.7 (SD 2.5) years. After beginning anastrozole therapy, the mean bone age z-score decreased from 4.2 to 1.9 at 4 years and 1.4 at 6 years (both P< 0.001); predicted adult height z-score improved from -2.1 to -0.41 at 4 years and 0.15 at 6 years (both P< 0.001); corrected height z-scores improved from -1.7 to -0.31 at 4 years and 0.16 at 6 years (P< 0.001). There was no significant difference in the average total daily hydrocortisone dose used before or during treatment. No abnormal liver function or ovarian abnormalities were noted.

Conclusion: In our cohort of children with CAH, anastrozole decreased the rate of bone maturation, delayed epiphyseal closure and led to improved height outcomes, indicating that anastrozole could have a role as an adjunct therapy.