Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial.

CONTEXT: GnRH analog (GnRHa) therapy for central precocious puberty (CPP) typically involves im injections. The histrelin implant is a new treatment that provides a continuous slow release of the GnRHa histrelin.

OBJECTIVE

The objective of the study was to investigate the safety and efficacy of the subdermal histrelin implant for the treatment of CPP in treatment naive and previously treated children.

DESIGN

This was a phase III, open-label, prospective study of 1-yr duration.

SETTING

The study was conducted at nine U.S. medical centers.

PATIENTS: Girls ages 2-8 yr (naive) or 2-10 yr (previously treated) and boys 2-9 yr (naive) or 2-11 yr (previously treated) with clinical evidence of CPP and a pretreatment pubertal response to leuprolide stimulation were eligible.

INTERVENTION: A 50-mg histrelin implant was inserted sc in the inner upper arm.

MAIN OUTCOME MEASURES: Peak LH after GnRHa stimulation testing and estradiol (girls) and testosterone (boys) were the main outcome measures.

RESULTS

Thirty-six subjects (20 naive) were enrolled. By 1 month, peak LH fell from 28.2 +/- 19.97 (naive) to 0.8 +/- 0.39 mIU/ml (P < 0.0001) and from 2.1 +/- 2.15 (previously treated) to 0.5 +/- 0.32 mIU/ml (P < 0.0056). Estradiol suppressed from 24.5 +/- 22.27 (naive) to 5.9 +/- 2.37 pg/ml (P = 0.0016) and remained suppressed in previously treated subjects, as did testosterone. Suppression was maintained throughout the study. No significant adverse events occurred.

CONCLUSIONS

The subdermal histrelin implant achieves and maintains excellent suppression of peak LH and sex steroid levels for 1 yr in children with CPP. The treatment is well tolerated. Long-term studies are needed to confirm these results.