Efficacy of letrozole combined with recombinant human growth hormone in boys aged ≥10 years with advanced bone age and impaired growth potential: a retrospective cohort study.

INTRODUCTION

In boys aged ≥10 years with advanced bone age and impaired growth potential (baseline height SDS < -1.5, BA-CA ≥1.5 years, and PAH < -2 SDS), growth hormone monotherapy, while promoting linear growth, fails to delay skeletal maturation, thus limiting therapeutic efficacy. Although letrozole combined with growth hormone may theoretically "decouple" height gain from epiphyseal closure, high-quality evidence specific to the advanced bone age population remains insufficient, and concerns regarding baseline bias and lack of long-term safety data persist. This study, based on real-world data, aims to clarify the benefits and risks of this combination regimen in promoting linear growth, delaying bone age progression, and improving adult height outcomes.

METHODS

A retrospective analysis was conducted on clinical data from 64 boys aged ≥10 years with advanced bone age and impaired growth potential treated in our hospital from June 2020 to December 2025 (baseline height SDS < -1.5, BA-CA ≥1.5 years, and PAH < -2 SDS). Patients were divided into a combination therapy group (letrozole + rhGH, n = 36) and a monotherapy group (rhGH alone, n = 28) according to treatment regimen. Changes in height, bone age, annual growth velocity, the ratio of bone age advancement to chronological age progression (ΔBA/ΔCA), and sex hormone levels were compared between the two groups before and after treatment.

RESULTS

The mean annual growth velocity in the combination group was (7.7 ± 1.2) cm/year, significantly higher than that in the monotherapy group [(6.7 ± 1.4) cm/year, P < 0.05]. The ΔBA/ΔCA ratio in the combination group was 0.85, significantly lower than that in the monotherapy group (1.12, P < 0.001), indicating better control of bone age progression. Among the 33 patients who had completed treatment, the mean final height was (171.2 ± 3.5) cm in the combination group, compared to (169.8 ± 4.1) cm in the monotherapy group (the difference was not statistically significant, P = 0.291).

DISCUSSION: In boys aged ≥10 years with advanced bone age and impaired growth potential, letrozole combined with rhGH significantly improved annual growth velocity and delayed bone age progression compared with rhGH monotherapy. However, the difference in final adult height among those who completed treatment was not statistically significant (1.4 cm, P = 0.291). The significantly better control of bone age advancement (ΔBA/ΔCA) and higher target-height attainment rate suggest a potential benefit of adding letrozole, but larger studies with more participants reaching final height are needed to confirm a meaningful effect on adult height.