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

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.