title: Differential effects of raloxifene and estrogen on body composition in growth hormone-replaced hypopituitary women.
abstract: BACKGROUND
  GH deficiency causes reduction in muscle and bone mass and an increase in fat mass (FM), the changes reversed by GH replacement. The beneficial effects of GH on fat oxidation and protein anabolism are attenuated more markedly by raloxifene, a selective estrogen receptor modulator, compared with 17β-estradiol. Whether this translates to a long-term detrimental effect on body composition is unknown.
  
  
  OBJECTIVE
  Our objective was to compare the effects of 17β-estradiol and raloxifene on FM, lean body mass (LBM), and bone mineral density (BMD) during GH replacement.
  
  
  METHODS
  This was an open-label randomized crossover study.
  
  
  METHODS
  Sixteen hypopituitary women received GH (0.5 mg/d) replacement for 24 months. One group received 17β-estradiol (2 mg/d) for the first 6 months before crossover to raloxifene (60 mg/d) for the remaining 18 months; the other received the reversed sequence.
  
  
  METHODS
  Serum IGF-I and IGF-binding protein-3 concentrations, and FM, LBM, lumbar spine and femoral neck BMD were analyzed at baseline and at 6, 12, and 24 months within and between subjects.
  
  
  RESULTS
  GH therapy significantly increased mean IGF-I during 17β-estradiol and raloxifene cotreatments equally, but elevated IGF-binding protein-3 to a greater extent during raloxifene cotreatment. GH cotreatment with 17β-estradiol increased LBM and lumbar spine and femoral neck BMD and reduced FM to a greater extent than with raloxifene.
  
  
  CONCLUSIONS
  In hypopituitary women, raloxifene at therapeutic doses significantly attenuated the beneficial effects of GH on body composition compared with 17β-estradiol. Raloxifene has no metabolic advantage over 17β-estradiol during GH replacement.
authors.affiliation: Pituitary Research Unit, Garvan Institute of Medical Research and Department of Endocrinology, St. Vincent's Hospital, and The University of New South Wales, Sydney, New South Wales 2010, Australia.
authors.forename: Vita
authors.initials: V
authors.lastname: Birzniece
authors.forename: Udo J
authors.initials: UJ
authors.lastname: Meinhardt
authors.forename: James
authors.initials: J
authors.lastname: Gibney
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Johannsson
authors.forename: Nicola
authors.initials: N
authors.lastname: Armstrong
authors.forename: Robert C
authors.initials: RC
authors.lastname: Baxter
authors.forename: Ken K Y
authors.initials: KK
authors.lastname: Ho
mesh_terms: D000328:Adult; D001823:Body Composition / Q000187:drug effects*; D015519:Bone Density / Q000187:drug effects; D018592:Cross-Over Studies; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D020845:Selective Estrogen Receptor Modulators; D019382:Human Growth Hormone; D020849:Raloxifene Hydrochloride; D004958:Estradiol