title: Metabolic Health in Short Children Born Small for Gestational Age Treated With Growth Hormone and Gonadotropin-Releasing Hormone Analog: Results of a Randomized, Dose-Response Trial.
abstract: BACKGROUND
  Previously we showed that pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment with GH 1 mg/m(2) per day (∼ 0.033 mg/kg/d) in combination with 2 years of GnRH analog (GnRHa) and even more so with a double GH dose. GnRHa treatment is thought to have negative effects on body composition and blood pressure. Long-term effects and GH-dose effects on metabolic health in children treated with combined GH/GnRHa are unknown.
  
  
  OBJECTIVE
  This study aimed to investigate body composition, blood pressure, and lipid profile during GH treatment, either with or without 2 years of additional GnRHa. To assess whether GH 2 mg/m(2) per day (∼ 0.067 mg/kg/d) results in a similar or even more favorable metabolic health at AH than GH 1 mg/m(2) per day.
  
  
  METHODS
  This was a longitudinal, randomized, dose-response GH trial involving 107 short SGA children (58 girls) treated with GH until AH (GH randomized 1 or 2 mg/m(2)/d during puberty). Sixty-four children received additional GnRHa. At AH, metabolic parameters were compared between children treated with combined GH/GnRHa and those with only GH. The GH dose effect on metabolic health was evaluated in a subgroup of 47 children who started GH treatment in early puberty (randomized 1 or 2 mg/m(2)/d) with 2 years of GnRHa.
  
  
  RESULTS
  At AH, fat mass percentage (FM%) SD score (SDS), lean body mass (LBM) SDS, blood pressure SDS, and lipid profile were similar between children treated with combined GH/GnRHa and those with only GH. In the pubertal subgroup, FM% SDS was lower during treatment with GH 2 mg/m(2) per day. There was no GH dose-dependent effect on LBM SDS, blood pressure, and lipid profile.
  
  
  CONCLUSIONS
  Combined GH/GnRHa treatment has no long-term negative effects on metabolic health compared with only GH. Started in early puberty, a GH dose of 2 mg/m(2) per day results in a similar metabolic health at AH and a more favorable FM% than GH 1 mg/m(2) per day.
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Manouk
authors.initials: M
authors.lastname: van der Steen
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Annemieke J
authors.initials: AJ
authors.lastname: Lem
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Danielle C M
authors.initials: DC
authors.lastname: van der Kaay
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Willie M
authors.initials: WM
authors.lastname: Bakker-van Waarde
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Flip J P C M
authors.initials: FJ
authors.lastname: van der Hulst
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Floor S
authors.initials: FS
authors.lastname: Neijens
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Noordam
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Roelof J
authors.initials: RJ
authors.lastname: Odink
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Wilma
authors.initials: W
authors.lastname: Oostdijk
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Eelco J
authors.initials: EJ
authors.lastname: Schroor
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Ciska
authors.initials: C
authors.lastname: Westerlaken
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.K.), Rotterdam, 3001 KB, The Netherlands; Children's Hospital Erasmus MC-Sophia (M.v.d.S., A.C.S.H.K.), 3000 CA, Rotterdam, The Netherlands; Department of Pediatrics (W.M.B.v.W.), University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Pediatrics (F.J.P.C.M.v.d.H.), Zaans Medisch Centrum, 1502 DV Zaandam, The Netherlands; Department of Pediatrics (F.S.N.), Rijnstate Hospital, 6815 AD Arnhem, The Netherlands; Department of Pediatrics (C.N.), Radboud University Medical Center, 6525 HP Nijmegen, The Netherlands; Department of Pediatrics (R.J.O.), Catharina Hospital, 5623 EJ Eindhoven, The Netherlands; Department of Pediatrics (W.O.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Amalia Department of Pediatrics (E.J.S.), Isala Clinics, 8025 AB Zwolle, The Netherlands; and Department of Pediatrics (C.W.), Canisius Hospital, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Anita C S
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000293:Adolescent; D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects*; D001827:Body Height / Q000187:drug effects*; D002648:Child; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007236:Infant, Small for Gestational Age; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D016896:Treatment Outcome
chemical_list: D019382:Human Growth Hormone; D016729:Leuprolide