Anastrozole vs Letrozole to Augment Height in Pubertal Males With Idiopathic Short Stature: A 3-Year Randomized Trial

Abstract

Abstract Context Insufficient efficacy and safety data for off-label use of aromatase inhibitors to augment height in boys with short stature. Objective To compare anastrozole and letrozole in treatment of idiopathic short stature in pubertal boys. Design Open-label trial with 2 treatment arms. Setting Pediatric Endocrine Clinic at Stanford. Participants A total of 79 pubertal males ≥10 years with bone age (BA) ≤ 14 years, predicted adult height (PAH) < 5th percentile or >10 cm below mid-parental height. Intervention Anastrozole 1.0 mg or letrozole 2.5 mg daily for up to 3 years. Main Outcome Measures Annual hormone levels and growth parameters during treatment and a year posttherapy; annual BA and PAH (primary outcome measure); spine x-rays and dual energy X-ray absorptiometry at baseline and 2 years. Results Compared with anastrozole (n = 35), letrozole (n = 30) resulted in higher testosterone levels, lower estradiol and IGF-1 levels, and slower growth velocity and BA advance. The PAH increase observed at year 1 in both groups did not persist at years 2 and 3. Change in PAH from baseline was not different between treatment groups. In groups combined, PAH gain over 3 years vs baseline was +1.3 cm (P = .043) in linear mixed models. Conclusion Letrozole caused greater deviations than anastrozole in hormone levels, growth velocity, and BA advancement, but no group differences in PAH or side effects were found. Change in PAH after 2 to 3 years of treatment was minimal. The efficacy of AI as monotherapy for height augmentation in pubertal boys with idiopathic short stature may be limited, and safety remains an issue.