title: Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age.
abstract: OBJECTIVE
  To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls.
  
  
  METHODS
  A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS).
  
  
  METHODS
  One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated).
  
  
  METHODS
  Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment.
  
  
  RESULTS
  Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries.
  
  
  CONCLUSIONS
  GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown.
  
  
  BACKGROUND
  EudraCT 2005-001507-19.
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Tinggaard
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: rikke.beck@dadlnet.dk.
authors.forename: Rikke Beck
authors.initials: RB
authors.lastname: Jensen
authors.affiliation: Department of Fetal Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karin
authors.initials: K
authors.lastname: Sundberg
authors.affiliation: Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Birkebæk
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Christiansen
authors.affiliation: Department of Pediatrics, Holbæk Hospital, Holbæk, Denmark.
authors.forename: Annie
authors.initials: A
authors.lastname: Ellermann
authors.affiliation: Department of Pediatrics, Nordsjællands Hospital, Hillerød, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Holm
authors.affiliation: Department of Pediatrics, Herlev Hospital, Herlev, Denmark.
authors.forename: Eva Mosfeldt
authors.initials: EM
authors.lastname: Jeppesen
authors.affiliation: Department of Pediatrics, Randers Hospital, Randers, Denmark.
authors.forename: Britta
authors.initials: B
authors.lastname: Kremke
authors.affiliation: Department of Pediatrics, Vendsyssel Hospital Hjørring, Hjørring, Denmark.
authors.forename: Pawel
authors.initials: P
authors.lastname: Marcinski
authors.affiliation: Department of Pediatrics, Kolding Hospital, Kolding, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Pedersen
authors.affiliation: Department of Pediatrics, Herlev Hospital, Herlev, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Saurbrey
authors.affiliation: Department of Pediatrics, Sønderborg Hospital, Sønderborg, Denmark.
authors.forename: Ebbe
authors.initials: E
authors.lastname: Thisted
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
mesh_terms: D054304:Anti-Mullerian Hormone / Q000097:blood; D001827:Body Height / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007236:Infant, Small for Gestational Age / Q000254:growth & development*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D010053:Ovary / Q000000981:diagnostic imaging* / Q000502:physiology*; D012016:Reference Values; D012741:Sexual Maturation; D014463:Ultrasonography; D014599:Uterus / Q000000981:diagnostic imaging / Q000502:physiology
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D054304:Anti-Mullerian Hormone
keywords: Growth hormone treatment; ovarian function; small for gestational age