Central precocious puberty (CPP) is defined as the reactivation of the hypothalamic–pituitary–gonadal (HPG) axis before age 8 in girls and age 9 in boys. Gonadotropin-releasing hormone analog (GnRHa) therapy is the standard of care for patients with CPP. In a Phase 3 open-label study, a 12-month histrelin subcutaneous implant (Supprelin LA) suppressed peak luteinizing hormone (LH) and sex steroid levels for 1 year; a subsequent implant suppressed the HPG axis through a second year. Herein reports on Year 3 of histrelin therapy.
The aim of this study was to report on the prospective extended-access phase of the open-label study involving a third 12-month histrelin implant.
Patients who completed the initial extension (second implant) portion of the study and for whom the decision was made to continue GnRHa therapy were offered the option for a third implant.
Thirteen children (12 females [8 treatment-naive, 4 with prior treatment] and 1 male with prior treatment; at baseline, mean age = 6.6 years [range = 4.5–9.1]) received a third implant. LH suppression, assessed by GnRHa stimulation, was maintained in all patients throughout the third year of therapy (M = 0.36 vs. 13.71 mIU/mL at baseline; p = .0132). Mean estradiol levels in the girls remained suppressed (<4.73 pg/mL). Mean bone age to chronological age ratio after 36 months of therapy was significantly lower compared with baseline (1.21 vs. 1.41; p < .002). Consequently, Bailey–Pinneau predicted that adult height (PAH) after 36 months of therapy was significantly higher compared with baseline (156.87 vs. 150.05 cm; p < .015). During 3 years, 9 (69%) patients experienced implant site reactions (mild pain, itch, and discomfort) related to the insertion procedure that lasted less than 24 hours. No patient discontinued because of a site reaction.
A third 12-month histrelin implant continued to suppress the HPG axis in all patients. In addition, bone age to chronological age ratio and PAH improved compared with baseline through 3 years of therapy.
These results suggest that 3 years of 12-month histrelin implant therapy is effective in suppressing LH and improving PAH in patients with CPP while eliminating the need for intramuscular injections associated with other GnRHa therapies.
© 2012 Published by Elsevier Inc.