Background: Central precocious puberty (CPP) results from the premature pubertal activation of the hypothalamic-pituitary-gonadal axis before eight years for girls or nine years for boys. A systematic review and meta-analysis was conducted to evaluate the long-term efficacy and safety of leuprolide acetate (LA) 11.25mg 3-month formulation in children with CPP.
Methods: A systematic search in PubMed and Embase was conducted for eligible studies. Primary end points include mean stimulated or peak LH, FSH (≤4 IU/L), oestradiol (<20 pg/ml) and testosterone (≤30 ng/dL) level after treatment; proportion of children with a supressed LH, FSH, oestradiol, testosterone levels; Secondary endpoints include height, weight, BMI, bone age, bone age to chronological age (BA-CA) and growth velocity before and after treatment; proportion of children with clinical suppression of breast or genitals.
Results: A total of 11 articles were included in this study and consisted of 582 patients with CPP. After treatment, the mean stimulated LH levels decreased to 1.03 IU/L (95% CI: 0.56 ̶ 1.49) at 6 months and remained low at 12 months (1.78 IU/L [95% CI: 1.19 ̶ 2.37]). The proportion of children with a suppressed LH at 6 months was 89.0% (95% CI: 82–94). The mean stimulated FSH levels were decreased to 1.65 IU/L (95% CI: 0.62 ̶ 2.68) by 6 months. The mean basal estradiol and testosterone levels were suppressed in 97% (95% CI: 81–100) and 91% (95% CI: 79–97). Compared to baseline, the mean change in BA-CA ratio decreased at 6, 12 months and 3 years to -0.04 (95% CI: -0.08 ̶ -0.00), -0.30 (95% CI: -0.46 ̶ -0.14) and -0.65 (95% CI: -1.50 ̶ 0.20) respectively. The mean growth velocity was 6.07 cm/year (95% CI: 2.27 ̶ 9.87) at 6 months and decreased to 4.45 cm/year (95% CI: 3.05 ̶ 5.85) at 12 months. LA 3-month formulation was well tolerated and most observed adverse events (AEs) were moderate.
Conclusion: LA 11.25 mg 3-month formulation is efficacious in suppressing LH, FSH peak, other gonadal hormones and in slowing the bone age and growth velocity in children with CPP.
21 Sep 2023 - 23 Sep 2023