Efficacy and safety of different doses of gonadotropin-releasing hormone analogues in the treatment of precocious puberty in children: a systematic review and meta-analysis.

Abstract

Background: Precocious puberty comprises a group of disorders characterized by abnormal pubertal development that significantly impacts children's physical and mental health. Gonadotropin-releasing hormone analogue (GnRHa) is the standard treatment; however, the efficacy and safety of different dosages remain uncertain. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy and safety of various GnRHa doses for preventing and treating precocious puberty in children.

Methods: Relevant studies published up to September 2024 were searched across seven electronic databases. Literature that met the inclusion criteria was reviewed to compare the effects of low-dose versus high-dose GnRHa on bone age, predicted adult height (PAH), bone metabolism indices, sex hormone levels, and safety in children with precocious puberty. The risk of bias for the included studies was assessed in accordance with the guidelines for bias assessment provided in the Cochrane Handbook. And data were quantitatively analyzed using RevMan 5.3 software.

Results: Thirteen studies involving 686 children were included in this analysis. The overall quality of the included studies was moderate. Meta-analysis indicated no significant differences between low-dose and high-dose GnRHa regarding changes in bone age [mean difference (MD) =0.10, 95% confidence interval (CI): 0.00 to 0.16, P=0.06], predicting adult heights (PAH) (MD =-0.14, 95% CI: -1.23 to 0.96, P=0.06). However, the low-dose group showed a more significant effect on luteinizing hormone (LH) (MD =0.10, 95% CI: 0.03 to 0.18, P=0.009), while the high-dose group had a more pronounced impact on P1NP (MD =-36.03, 95% CI: -57.63 to -14.43, P=0.001). Additionally, adverse reaction rates were significantly lower in the low-dose group (odds ratio =0.21, 95% CI: 0.13 to 0.33, P<0.001) compared to the high-dose group.

Conclusions: This meta-analysis suggests that low-dose GnRHa is as effective as higher doses for treating precocious puberty in children and presents a better safety profile. These findings provide evidence-based guidance for selecting GnRHa dosages in clinical applications for managing childhood precocious puberty.