title: Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial.
abstract: OBJECTIVE
  The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy.
  
  
  METHODS
  This was a phase 3, prospective, open-label study.
  
  
  METHODS
  Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase.
  
  
  METHODS
  Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up.
  
  
  RESULTS
  Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from 1.417 (n = 20) at baseline to 1.18 (n = 8) at 48 months in treatment-naive children (P < .01). Predicted adult height in girls increased from 151.9 cm at baseline to 166.5 cm at month 60 (n = 6; P < .05), with a 10.7-cm height gain observed among treatment-naive children (n = 5). No adverse effect on growth or recovery of the hypothalamic-pituitary-gonadal axis was observed with hormonal suppression. The histrelin implant was generally well tolerated during long-term therapy.
  
  
  CONCLUSIONS
  Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP.
authors: Division of Pediatric Endocrinology (L.A.S.), Goryeb Children's Hospital Atlantic Health, Morristown, New Jersey 07962; Division of Pediatric Endocrinology and Diabetes (E.K.N.), Stanford University, Stanford, California 94305-5208; Redmond (G.B.K.), Washington 98052; Division of Endocrinology, Diabetes, and Medical Genetics (K.L.), Charleston, South Carolina 29425; Endo Pharmaceuticals Inc (S.C., O.T.), Malvern, Pennsylvania 19355; and Riley Hospital for Children at Indiana University Health (E.A.E.), Indianapolis, Indiana 46202.
authors: Lawrence A
authors: LA
authors: Silverman
authors: Division of Pediatric Endocrinology (L.A.S.), Goryeb Children's Hospital Atlantic Health, Morristown, New Jersey 07962; Division of Pediatric Endocrinology and Diabetes (E.K.N.), Stanford University, Stanford, California 94305-5208; Redmond (G.B.K.), Washington 98052; Division of Endocrinology, Diabetes, and Medical Genetics (K.L.), Charleston, South Carolina 29425; Endo Pharmaceuticals Inc (S.C., O.T.), Malvern, Pennsylvania 19355; and Riley Hospital for Children at Indiana University Health (E.A.E.), Indianapolis, Indiana 46202.
authors: E Kirk
authors: EK
authors: Neely
authors: Division of Pediatric Endocrinology (L.A.S.), Goryeb Children's Hospital Atlantic Health, Morristown, New Jersey 07962; Division of Pediatric Endocrinology and Diabetes (E.K.N.), Stanford University, Stanford, California 94305-5208; Redmond (G.B.K.), Washington 98052; Division of Endocrinology, Diabetes, and Medical Genetics (K.L.), Charleston, South Carolina 29425; Endo Pharmaceuticals Inc (S.C., O.T.), Malvern, Pennsylvania 19355; and Riley Hospital for Children at Indiana University Health (E.A.E.), Indianapolis, Indiana 46202.
authors: Gad B
authors: GB
authors: Kletter
authors: Division of Pediatric Endocrinology (L.A.S.), Goryeb Children's Hospital Atlantic Health, Morristown, New Jersey 07962; Division of Pediatric Endocrinology and Diabetes (E.K.N.), Stanford University, Stanford, California 94305-5208; Redmond (G.B.K.), Washington 98052; Division of Endocrinology, Diabetes, and Medical Genetics (K.L.), Charleston, South Carolina 29425; Endo Pharmaceuticals Inc (S.C., O.T.), Malvern, Pennsylvania 19355; and Riley Hospital for Children at Indiana University Health (E.A.E.), Indianapolis, Indiana 46202.
authors: Katherine
authors: K
authors: Lewis
authors: Division of Pediatric Endocrinology (L.A.S.), Goryeb Children's Hospital Atlantic Health, Morristown, New Jersey 07962; Division of Pediatric Endocrinology and Diabetes (E.K.N.), Stanford University, Stanford, California 94305-5208; Redmond (G.B.K.), Washington 98052; Division of Endocrinology, Diabetes, and Medical Genetics (K.L.), Charleston, South Carolina 29425; Endo Pharmaceuticals Inc (S.C., O.T.), Malvern, Pennsylvania 19355; and Riley Hospital for Children at Indiana University Health (E.A.E.), Indianapolis, Indiana 46202.
authors: Surya
authors: S
authors: Chitra
authors: Division of Pediatric Endocrinology (L.A.S.), Goryeb Children's Hospital Atlantic Health, Morristown, New Jersey 07962; Division of Pediatric Endocrinology and Diabetes (E.K.N.), Stanford University, Stanford, California 94305-5208; Redmond (G.B.K.), Washington 98052; Division of Endocrinology, Diabetes, and Medical Genetics (K.L.), Charleston, South Carolina 29425; Endo Pharmaceuticals Inc (S.C., O.T.), Malvern, Pennsylvania 19355; and Riley Hospital for Children at Indiana University Health (E.A.E.), Indianapolis, Indiana 46202.
authors: Oksana
authors: O
authors: Terleckyj
authors: Division of Pediatric Endocrinology (L.A.S.), Goryeb Children's Hospital Atlantic Health, Morristown, New Jersey 07962; Division of Pediatric Endocrinology and Diabetes (E.K.N.), Stanford University, Stanford, California 94305-5208; Redmond (G.B.K.), Washington 98052; Division of Endocrinology, Diabetes, and Medical Genetics (K.L.), Charleston, South Carolina 29425; Endo Pharmaceuticals Inc (S.C., O.T.), Malvern, Pennsylvania 19355; and Riley Hospital for Children at Indiana University Health (E.A.E.), Indianapolis, Indiana 46202.
authors: Erica A
authors: EA
authors: Eugster
mesh_terms: D001827:Body Height / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation / Q000187:drug effects; D004334:Drug Administration Schedule; D004343:Drug Implants; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006066:Gonads / Q000187:drug effects; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007279:Injections, Subcutaneous; D008297:Male; D011627:Puberty / Q000187:drug effects; D011629:Puberty, Precocious / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D004343:Drug Implants; D007987:Gonadotropin-Releasing Hormone; C029256:histrelin