Efficacy and safety of 3-month versus 1-month depot leuprolide acetate in children with central precocious puberty: a systematic review and meta-analysis

Abstract Objective To systematically compare the efficacy and safety of leuprolide acetate 3-month versus 1-month depot formulations in children with central precocious puberty (CPP). Methods A comprehensive literature search was conducted across CNKI, Wanfang, VIP, PubMed, Web of Science, the Cochrane Library, and Embase databases from inception to July 10, 2026. Randomized controlled trials (RCTs), prospective, and retrospective studies comparing leuprolide acetate 3-month depot (11.25 mg every 12 weeks) with 1-month depot (3.75 mg or 7.5 mg every 4 weeks) in children with CPP were included. Primary outcomes included hormonal parameters (Δbasal/peak LH, Δbasal/peak FSH, Δestradiol), pelvic ultrasound metrics (Δovarian/uterine volume, Δuterine diameter), bone age indices (ΔBA/CA ratio, ΔBA), growth parameters (Δgrowth velocity, predicted adult height (ΔPAH)), and adverse events. Random-effects or fixed-effects models were applied based on heterogeneity. Subgroup analyses stratified by study design and sensitivity analyses were performed. Results Thirteen studies (1,051 participants; 470 in 3-month, 581 in 1-month group) were included. No significant differences were observed in Δpeak LH, Δbasal FSH, pelvic metrics, bone age advancement, growth velocity, predicted adult height, or adverse events (P > 0.05). The 3-month depot showed greater Δpeak FSH reduction (MD = − 0.51, P = 0.01), confined to retrospective studies. The 1-month depot demonstrated greater Δbasal LH (MD = 0.34, P = 0.02) and Δestradiol reduction (MD = 4.65, P = 0.04), but neither reached significance in subgroup analyses, and estradiol lacked robustness in sensitivity analysis. Conclusions The 3-month depot provides comparable efficacy and safety to the 1-month formulation. Minor hormonal divergences lacked clinical robustness. The 3-month regimen offers a practical option that reduces injection burden, improves adherence, and optimizes healthcare resource utilization for children requiring prolonged CPP therapy.