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


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


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


METHODS
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.


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


METHODS
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.
Eugster
Erica A
EA
Pediatric Endocrinology, Riley Hospital for Children, Indiana Uniuversity School of Medicine, 702 Barnhill Drive, Indianapolis, IN 46202, USA. eeugster@iupui.edu
Clarke
William
W
Kletter
Gad B
GB
Lee
Peter A
PA
Neely
E Kirk
EK
Reiter
Edward O
EO
Saenger
Paul
P
Shulman
Dorothy
D
Silverman
Lawrence
L
Flood
Lisa
L
Gray
William
W
Tierney
David
D
D000365:Age Determination by Skeleton; D015992:Body Mass Index; D001842:Bone and Bones / Q000000981:diagnostic imaging; D001940:Breast / Q000254:growth & development; D002648:Child; D002675:Child, Preschool; D004343:Drug Implants; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006128:Growth / Q000187:drug effects; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011446:Prospective Studies; D011629:Puberty, Precocious / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood
D004343:Drug Implants; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C029256:histrelin