title: Comparison of the metabolic effects of raloxifene and oral estrogen in postmenopausal and growth hormone-deficient women.
abstract: BACKGROUND
  The endocrine and metabolic functions of the liver are affected by estrogen. Oral estrogen reduces IGF-I and suppresses fat oxidation despite augmenting GH secretion. The aim of this study was to determine whether selective estrogen receptor modulators display similar effects and whether these effects are magnified in GH-deficient (GHD) women because of the loss of GH feedback.
  
  
  METHODS
  This was an open-label, randomized, two-period, crossover study comparing treatment (raloxifene vs. estradiol) and group (normal vs. GHD).
  
  
  METHODS
  The setting of this study was a clinical research unit.
  
  
  METHODS
  Twelve postmenopausal women and 12 women with hypopituitarism participated in this study.
  
  
  METHODS
  Two 4-wk treatments with 17beta-estradiol (E2; 2 mg, followed by 4 mg) or raloxifene (60 mg, followed by 120 mg) were given, crossing over to the alternate treatment after a 4-wk washout period.
  
  
  METHODS
  Endocrine [GH, IGF-I, IGF-binding protein-3 (IGFBP-3), GH-binding protein, and SHBG] and metabolic (fat oxidation) end points were used as outcome measures.
  
  
  RESULTS
  E2 reduced serum IGF-I levels in a dose-dependent manner in both groups, with effects greater (P < 0.05) than raloxifene. Raloxifene reduced IGF-I levels in the GHD group (P < 0.001), but not in the postmenopausal group. E2 reduced (P < 0.05), and raloxifene increased (P < 0.05), IGFBP-3 levels in both groups. E2, but not raloxifene, increased GH (P < 0.05) in postmenopausal women. The effects of E2 and raloxifene on IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, GH-binding protein, and SHBG were significantly different (P < 0.05). E2 and raloxifene reduced (P < 0.05) fat oxidation equally in GHD, whereas the decrease in postmenopausal women was not significant.
  
  
  CONCLUSIONS
  E2 and raloxifene exert different hepatic endocrine, but not lipid oxidative, effects. The greater effects seen in GHD women may be explained by the loss of endogenous GH feedback.
authors.affiliation: Pituitary Research Unit, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales 2010, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Gibney
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Johannsson
authors.forename: Kin-Chuen
authors.initials: KC
authors.lastname: Leung
authors.forename: Ken K Y
authors.initials: KK
authors.lastname: Ho
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D050356:Lipid Metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D017698:Postmenopause / Q000378:metabolism*; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D012738:Sex Hormone-Binding Globulin; D019382:Human Growth Hormone; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D007334:Insulin-Like Growth Factor I