The Effect of Leuprolide Acetate 11.25 mg 3-Month Formulation in Children with Central Precocious Puberty: A Systematic Review and Meta-analysis

Introduction: Compared to the well-established leuprolide acetate (LA) 1-month formulations, the LA 11.25 mg 3-month formulation could reduce the frequency of injections and potentially improve treatment adherence in children with central precocious puberty (CPP). The objective of this study was to evaluate the efficacy and safety of the LA 11.25 mg 3-month formulation in children with CPP. Methods: PubMed, Embase, WanFang, CNKI, Cochrane and clinical trial registries were searched from inception to 11 December 2023. Clinical trials reporting the efficacy and toxicity of the LA 11.25 mg 3-month formulation in children with CPP were considered. Efficacy endpoints included mean basal/stimulated or peak luteinizing hormone (LH) or follicle stimulating hormone (FSH), proportion of children with suppressed LH and FSH response, oestradiol and testosterone levels, bone age to chronological age (BA-CA) ratio, growth velocity before and after treatment and safety. Results: Twelve articles with 657 CPP patients were included. Post-treatment, the mean stimulated LH levels decreased to 1.90 IU/l and 0.70 IU/l at 3 and 6 months, respectively, from the baseline value; 94% (< 3 IU/l) showed peak LH suppression at 6 months. Compared to baseline, the mean change in bone age to chronological age ratio decreased at 6 and 12 months and 3 years to - 0.04, - 0.30 and - 1.10, respectively. Growth velocity was 6.11 cm/year at 6 months, decreased to 3.60 cm/year at 12 months and remained low at 2 (5.10 cm/year) and 3.5 years (5.30 cm/year), respectively. LA 11.25 mg 3 M formulation was well tolerated with most adverse events of local pain and erythaema being mild to moderate. Conclusion: LA 11.25 mg 3-month formulation is efficacious in suppressing LH, FSH peak and other gonadal hormones and slowing the bone age and growth velocity in children with CPP.