Comparative Study of Subcutaneous 6-Month Versus Intramuscular 3-Month Leuprorelin Use in Central Precocious Puberty

This study in central precocious puberty girls receiving gonadotropin-releasing hormone analogues for 18 months aimed to compare leuprorelin biannual (6-mo subcutaneous leuprorelin, group 1, n=13) with the quarterly (3-mo intramuscular leuprorelin, group 2, n=10) on height, pubertal progression, and adverse events.Twenty-three girls aged 5.7-9.0 years with median bone age advancement (2.7 y and 2.3 y, respectively) underwent clinical visits every 3 months, including pelvis, breasts and injection site ultrasound and luteinizing hormone measurements 2 hours after and 1 week after gonadotropin-releasing hormone analogue administration. Bone age was determined every 6 months.Both protocols were able to stop height lost (stabilization of one age adjusted height standard deviation score: group 1=-1.1 to -1.1 and group 2=-0.2 to -0.1, respectively). The difference between bone age and chronological age was significantly reduced in group 1 (p=0.001) and showed a trend in group 2 (p=0.08). The body mass index-standard deviation score remained similar. A decreased breast diameter (p=0.04) and a reduction in uterine volume (p=0.02) were observed in patients from group 1. Local non-inflammatory nodules were identified in groups 1 and 2 (100% and 50%, respectively). Local nodules were larger in group 1 (1.3 vs. 0.1 cm; p=0.03). Luteinizing hormone levels were reduced in all groups, with random luteinizing hormone levels remaining below 0.6 IU/L. Luteinizing hormone values 2 hours after gonadotropin-releasing hormone analogue administration showed a more homogeneous suppressive effect in group 1. Mild to moderate pain was present in both groups, but higher in group 1. Scores for acceptance, easiness and satisfaction were similar between groups.Six month subcutaneous leuprorelin deaccelerated bone age, preserving the predicted final height in a manner similar to 3-month intramuscular leuprorelin. Only 6-month subcutaneous leuprorelin could reduce uterine and breast volumes. Pain was more prominent with six-month subcutaneous leuprorelin, and drug deposition in the subcutaneous tissue was identified more frequently, without an inflammatory process or a risk of therapeutic failure.