Letrozole Monotherapy in Pre- and Early-Pubertal Boys Does Not Increase Adult Height

Background: Aromatase inhibitors (AIs) have been used in boys with idiopathic short stature (ISS) to promote growth despite the lack of actual data regarding treatment effect on adult height. In this study, we characterized adult heights and long-term follow-up in AI-treated boys with ISS. Methods: Adult heights and long-term follow-up data, including spine MRIs, of a randomized, double-blind, placebo-controlled trial of boys who were treated with letrozole (Lz) (2.5 mg/d) or placebo (Pl) for 2 years during prepuberty and early puberty. The mean bone ages at treatment cessation were 10.2 and 10.8 years, respectively. Results: Adult heights were similar between the boys treated with Lz (n = 10) and those who received Pl (n = 10) (164.8 ± 4.0 vs. 163.7 ± 3.7 cm, p = 0.49, respectively). In either group, the adult heights did not differ from predicted adult heights at start of the study [Pl: 163.7 (3.7) cm vs. 166.9 (3.3), p = 0.06; Lz: 164.8 (4.0) cm vs. 167.6 (7.9), p = 0.20, respectively]. Long-term follow-up data showed that the frequency of subjects with a vertebral deformity was similar between the groups (Lz, 29% and Pl, 22%, p = 0.20), and no single comorbidity was clearly enriched in either group. Conclusions: The Lz-treated boys had similar adult heights with the subjects who received Pl for 2 years, which indicates that the treatment is not beneficial when given to pre- or early-pubertal boys. Previously observed vertebral deformities ameliorated during follow-up, which supports the skeletal safety of Lz therapy in children and adolescents.