Long-Acting Gonadotropin-Releasing Hormone Analogues for Central Precocious Puberty, Including 45-mg 6-month Subcutaneous Leuprolide Acetate: Use for Treatment and Treatment Monitoring.

Abstract

Studies of gonadotropin-releasing hormone analogues [intramuscular (IM) leuprolide acetate (LA) and triptorelin] for treatment monitoring of central precocious puberty (CPP) demonstrate this approach is effective for confirming pubertal hormone suppression. Herein, we provide new data using subcutaneous LA (SC LA) suggesting similar efficacy for treatment monitoring. PubMed, Embase, and CINAHL were searched for studies of GnRHa use to monitor treatment of CPP. The titles and the abstracts were reviewed; five studies were selected. Additionally, new unpublished data for SC LA from the original phase 3 trial (primary data published by Klein et al.) were evaluated. Serum LH and leuprolide levels at screening, 1, 4, and 6 hours after the first dose SC LA were analyzed and plotted. Data from 162 children (155 girls) were evaluated. SC and IM LA produced overlapping median LH concentration curves and peak LH concentrations after the first dose. For IM LA, subsequent doses yielded suppressed peak LH levels (2.7 IU/L [mean]). For SC LA, subsequent doses also resulted in significant suppressed peak LH levels (0.2±0.02 IU/L) and achieved sex-steroid hormone suppression in >98%. Compared to IM LA and triptorelin, long-acting SC LA shows similar burst kinetics and rapid LH rise after the first dose, followed by similar suppression of LH and sex steroids after subsequent doses. Since IM LA and triptorelin have demonstrated usefulness that is comparable to that of traditional GnRH stimulation testing for monitoring CPP, we presume that SC LA may be similarly employed.