The combination of Aromatase inhibitors and growth hormone treatment for idiopathic short stature in male adolescents

To evaluate the efficacy and safety in adolescent boys with idiopathic short stature (ISS) when treated with third-generation aromatase inhibitors (AIs), the combination of letrozole or anastrozole with recombinant human growth hormone (rhGH), and compare adult height (AHt) augmentation following the treatment with rhGH combined with AIs or gonadotrophin releasing hormone analogue (GnRHa) in male adolescents with ISS.

We collected data from adolescent boys with idiopathic short stature (ISS) and a bone age ≥ 13 years who received treatment at Tongji Hospital, Huazhong University of Science and Technology, from May 2017 to June 2023. Patients were allocated into the combined letrozole and rhGH group, the combined anastrozole and rhGH group and combined GnRHa and rhGH group based on their treatment. Three groups were matched by propensity score matching. There were 32 cases in each group. Follow-up was conducted every three months until adult height (AHt). Adverse events were monitored throughout.

The standard deviation score of AHt adjusted for target height (AHtSDS_THt) in the letrozole, anastrozole, and GnRHa group were 0.60 ± 0.28, 0.81 ± 0.34, and 0.48 ± 0.17, respectively. Compared with the letrozole and GnRHa groups, the anastrazole and rhGH combination group showed the most significant increase in adult height (P<0.01); The abnormal monitoring indicators of AIs group gradually returned to normal following the termination of treatment.

For adolescent males with ISS and a bone age ≥ 13 years, the combination of AI and rhGH significantly increased the adult height (AHt). Finally, our analyses showed that anastrozole exerts more significant effects with regards to augment AHt with fewer adverse reactions.