36-Month Treatment Experience of Two Doses of Leuprolide Acetate 3-Month Depot for Children With Central Precocious Puberty

Context: We have recently demonstrated short-term (6-month) efficacy and safety of leuprolide acetate 3-month depot 11.25 and 30 mg in children with central precocious puberty (CPP). Objective: To assess long-term (36-month) hypothalamic-pituitary-gonadal axis suppression and safety of leuprolide acetate 3-month depot 11.25 and 30 mg in children with CPP. Design: Open-label, 36-month extension. Setting: Twenty pediatric endocrine centers. Patients: Seventy-two children (mean age, 8.5 +/- 1.6 y; 65 females) with CPP completed and showed maintenance of LH suppression after a 6-month lead-in study. Intervention: Leuprolide acetate depot (11.25 or 30 mg) administered im every 3 months. Main Outcome Measures: Peak-stimulated LH, estradiol, T, growth rate, pubertal progression, and adverse events (AEs). Results: Twenty-nine of 34 subjects in the 11.25-mg group and 36 of 38 subjects in the 30-mg group had LH values < 4 mIU/mL after day 1 at all time points. All seven subjects who escaped LH suppression at any time still maintained sex steroid concentrations at prepubertal levels and showed no signs of pubertal progression. AEs were comparable between groups, with injection site pain being the most common (26.4% overall). No AE led to discontinuation of study drug. The safety profile over 36 months was comparable to that observed during the 6-month pivotal study. Conclusions: The two doses of leuprolide acetate 3-month depot were associated with an acceptable safety profile and provided maintenance of LH suppression in the majority of children with CPP during the 36 months of the study or until readiness for puberty.