Results of a Second Year of Therapy with the 12-Month Histrelin Implant for the Treatment of Central Precocious Puberty

Samar Rahhal,Gad B Kletter,Dorothy Shulman,Paul Saenger,E Kirk Neely,Erica A Eugster,Edward O Reiter,William L Clarke,Lawrence Silverman,Peter A Lee

doi:10.1155/2009/812517

Abstract

Background. Gonadotropin releasing hormone analogs (GnRHas) are standard of care for central precocious puberty (CPP). The histrelin subcutaneous implant is safe and effective in the treatment of CPP for one year. Objective. The study evaluates a second year of therapy in children with CPP who received a new implant after one year of treatment. Methods. A prospective one-year study following an initial 12-month treatment period was conducted. Results. Thirty-one patients (29 girls) aged 7.7 ± 1.5 years received a second implant. Eighteen were naïve to GnRHa therapy at first implantation. Peak LH declined from 0.92 ± 0.58 mIU/mL at 12 months to 0.51 ± 0.33 mIU/mL at 24 months (P < .0001) in naïve subjects, and from 0.74 ± 0.50 mIU/mL at 12 months to 0.45 ± 0.35 mIU/mL at 24 months (P = .0081) in previously treated subjects. Predicted adult height increased by 5.1 cm at 24 months (P = .0001). Minor implant site reactions occurred in 61%, while minor difficulties with explantation occurred in 32.2% of subjects. Conclusion. The histrelin implant demonstrates profound hypothalamic-pituitary-gonadal axis suppression when a new implant is placed for a second year of treatment. Prospective follow-up of this therapeutic modality for the treatment of CPP is needed.

Highlights

Central precocious puberty (CPP) is defined as activation of the hypothalamic-pituitary-gonadal (HPG) axis before the age of 8 years in Caucasian girls and 7.5 years in African American girls, and before the age of 9 years in boys [1]
Peak LH in response to Gonadotropin releasing hormone analogs (GnRHas) stimulation remained suppressed in all subjects throughout the study period (Figure 1)
While a three-month depot leuprolide is available, it has not been adequately studied in children and failed to demonstrate equivalent short-term HPG axis suppression when compared to monthly injections [9]

Summary

Introduction

Central precocious puberty (CPP) is defined as activation of the hypothalamic-pituitary-gonadal (HPG) axis before the age of 8 years in Caucasian girls and 7.5 years in African American girls, and before the age of 9 years in boys [1]. Gonadotropin releasing hormone analogs (GnRHa) have been the cornerstone of treatment of CPP for more than 20 years [2]. A one-year subcutaneous histrelin implant has emerged as an alternative approach for the treatment of CPP. A pilot study of 11 girls with CPP showed that the implant effectively suppressed the HPG axis [6]. This was followed by a phase III prospective trial involving 36 children which demonstrated. The histrelin subcutaneous implant is safe and effective in the treatment of CPP for one year. The study evaluates a second year of therapy in children with CPP who received a new implant after one year of treatment. The histrelin implant demonstrates profound hypothalamic-pituitary-gonadal axis suppression when a new implant is placed for a second year of treatment. Prospective follow-up of this therapeutic modality for the treatment of CPP is needed

Objectives

Results

Conclusion