title: Effects of oral and transdermal oestrogen replacement therapy on plasma levels of insulin-like growth factors and IGF binding proteins 1 and 3: a cross-over study.
abstract: OBJECTIVE
  Conflicting results have been reported on the effects of oral and transdermal oestrogen replacement therapy on IGF-I, while little information exists regarding the effects on IGFBP -1 and -3. In this study we evaluated the effects of oral and transdermal oestrogens on these parameters in post-menopausal women in a randomized cross-over study.
  
  
  METHODS
  A group of 14 post-menopausal women were randomized to receive progestin-opposed oestrogen replacement therapy administered orally (Trisekvens Novo: 17 beta-oestradiol 2 mg daily on days 1-22 and 1 mg daily on days 23-28, norethisterone 1 mg days 13-22) or transdermally (Estracomb CIBA: oestradiol 50 micrograms/24 h on days 1-28, norethisterone 250 micrograms/24 h on days 15-28) for 6 months after which they were crossed over to the alternative treatment option. Fasting blood samples were obtained before treatment, and after 3, 6, 9 and 12 months on treatment.
  
  
  METHODS
  IGF-I, IGF-II, IGFBP-1, IGFBP-3, oestradiol and norethisterone were analysed by radioimmuno-assays. In addition, IGFBPs were evaluated with Western ligand blots (WLB) in a subgroup of 12 patients.
  
  
  RESULTS
  Plasma levels of oestradiol were not significantly different during oral and transdermal treatment. Norethisterone levels were below the detection limit in all situations in 8 patients, while 6 patients had detectable levels in one or several samples during treatment. Oral treatment caused a significant decrease (16%, P < 0.005) in IGF-I and a non-significant decrease in IGFBP-3. A similar effect was observed when samples containing detectable levels of norethisterone were excluded from the analysis. No significant effect on IGFBP-1 was observed when all samples were included in the analysis. However, when samples with detectable norethisterone were excluded IGFBP-1 increased by 46% (P < 0.01) during oral therapy. Contrary, transdermal treatment with oestrogens did not influence any of the parameters measured. None of the treatments had any effect on plasma IGF-II levels or IGFBP profile evaluated by WLB.
  
  
  CONCLUSIONS
  Treatment with oral hormone replacement therapy significantly suppresses plasma IGF-1 levels and increases plasma IGFBP-1 while transdermal treatment had no influence. This may be due to the route of administration, as plasma oestradiol levels showed little difference between the groups. The effect of oral oestrogens on IGFBP-1 seems to be attenuated by progestins.
authors.affiliation: Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: S I
authors.initials: SI
authors.lastname: Helle
authors.forename: I H
authors.initials: IH
authors.lastname: Omsjø
authors.forename: S C
authors.initials: SC
authors.lastname: Hughes
authors.forename: L
authors.initials: L
authors.lastname: Botta
authors.forename: G
authors.initials: G
authors.lastname: Hüls
authors.forename: J M
authors.initials: JM
authors.lastname: Holly
authors.forename: P E
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D004964:Estriol / Q000008:administration & dosage* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017698:Postmenopause / Q000097:blood*; D013002:Somatomedins / Q000032:analysis*
chemical_list: D004338:Drug Combinations; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D004958:Estradiol; C032040:Trisequens; D007334:Insulin-Like Growth Factor I; D004964:Estriol; D009640:Norethindrone