title: Neuroendocrine regulation of growth hormone and androgen axes by selective estrogen receptor modulators in healthy men.
abstract: BACKGROUND
  In men, the stimulation of GH and inhibition of LH secretion by testosterone requires aromatization to estradiol. Tamoxifen, a selective estrogen receptor modulator (SERM), possesses central estrogen antagonistic effect but peripheral hepatic agonist effect, lowering IGF-I. Thus, tamoxifen is likely to perturb the neuroendocrine regulation of GH and gonadal axes. Raloxifene, a SERM, is used for therapy of osteoporosis in both sexes. Its neuroendocrine effects in men are poorly understood.
  
  
  OBJECTIVE
  The aim was to compare the impact of raloxifene and tamoxifen on GH-IGF-I and gonadal axes in healthy men.
  
  
  METHODS
  We conducted a randomized, open-label crossover study.
  
  
  METHODS
  Ten healthy men were randomized to 2-wk sequential treatment with tamoxifen (10 and 20 mg/d) and raloxifene (60 and 120 mg/d), with a 2-wk intervening washout period.
  
  
  METHODS
  We measured the GH response to arginine and circulating levels of IGF-I, LH, FSH, testosterone, and SHBG.
  
  
  RESULTS
  Tamoxifen, but not raloxifene, significantly reduced IGF-I levels by 25±6% (P<0.01) and increased SHBG levels by 20±7% (P<0.05) at the higher therapeutic dose. There was a nonstatistically significant trend toward a reduction in the GH response to arginine with both SERMs. Both drugs significantly increased LH, FSH, and testosterone concentrations. The mean increase in testosterone (40 vs. 25%; P<0.05) and LH (70 vs. 30%; P<0.01) was significantly greater with tamoxifen than with raloxifene treatment.
  
  
  CONCLUSIONS
  Tamoxifen, but not raloxifene, reduces IGF-I levels. Both SERMs stimulate the gonadal axis, with tamoxifen imparting a greater effect. We conclude that in therapeutic doses, raloxifene perturbs the GH and gonadal axes to a lesser degree than tamoxifen.
authors.affiliation: Garvan Institute of Medical Research, 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: Akira
authors.initials: A
authors.lastname: Sata
authors.forename: Surya
authors.initials: S
authors.lastname: Sutanto
authors.forename: Ken K Y
authors.initials: KK
authors.lastname: Ho
mesh_terms: D000368:Aged; D000728:Androgens / Q000502:physiology*; D001120:Arginine / Q000494:pharmacology; D018592:Cross-Over Studies; D005640:Follicle Stimulating Hormone / Q000097:blood; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D012016:Reference Values; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D020845:Selective Estrogen Receptor Modulators; D012738:Sex Hormone-Binding Globulin; D013629:Tamoxifen; D013739:Testosterone; D020849:Raloxifene Hydrochloride; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D001120:Arginine