Letrozole vs Anastrozole for Height Augmentation in Short Pubertal Males: First Year Data

Context: Aromatase inhibitors are used off-label to treat short stature in peripubertal boys. Objective: To investigate short- and long-term hormonal and auxologic differences in short pubertal boys treated with letrozole (L) or anastrozole (A). Design: Patients are seen for laboratory evaluation and physical examination every 6 months, bone age yearly, DEXA and spine film every 2 years. They will be followed until they reach their final height. This is a preliminary report after 1 year of treatment. Setting: A single academic children's hospital outpatient clinic. Patients: Boys with age >10 years, bone age ≤14 years, clinical and hormonal evidence of central puberty, and either height < fifth percentile or predicted adult height (PAH) more than 10 cm below mid-parental height (MPH). Intervention: Letrozole (2.5 mg) or anastrozole (1 mg) was administered orally each day. Main Outcome Measures: Hormonal and clinical parameters, growth velocity, and change in bone age and PAH. Results: Thirty-nine boys have completed 1 year of treatment. Baseline means were age 14.1 years, PAH 166 cm, and testosterone 198 ng/dL. At 1 year, letrozole resulted in higher LH (L 6.1 ± 2.5 vs A 3.2 ± 1.7 IU/L) and testosterone (1038 ± 348 vs 536 ± 216 ng/dL) with lower estradiol (2.8 ± 2.8 vs 5.6 ± 2.9 pg/mL) and IGF-1 (237 ± 51 vs 331 ± 79 ng/mL). First year growth velocities were identical (7.2 cm/year), but an increase in PAH was greater in the anastrozole group (4.2 ± 3.5 vs 1.4 ± 4.4 cm, p = 0.03) after 1 year. Conclusions: We present first-year data from a direct comparison of anastrozole and letrozole for height augmentation in short pubertal boys. Letrozole was more potent in hormonal manipulation than anastrozole. First-year growth velocities were comparable, but improvement in PAH was greater in the anastrozole group. It remains to be seen if positive PAH trends will translate to increase in final height in either group.