title: The effects of sex steroid replacement therapy on an expanded panel of IGF-related peptides.
abstract: BACKGROUND
  Oral estrogen alone (EA) decreases concentrations of total IGF-I while increasing IGFBP-1, but data on other IGF-related peptides are inconsistent and/or sparse. Combined oral estrogen and progestin (EP) may have differential effects on IGF-related peptides dependent on its progestin-associated androgenic activity. The aim of this study was to clarify these relationships, as circulating IGF-related peptides are potential surrogates of predisposition to common chronic diseases.
  
  
  METHODS
  Using an open-labelled cross-sectional design within a bowel cancer screening trial (aged 55-64 years), we determined total IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in fasted serum from 210 healthy women and free IGF-I (by ultrafiltration), insulin, IGFBP-1 and IGFBP-1:IGF-I binary complex in a selected subset of 92 women. Unadjusted and adjusted (using generalized linear models) means were compared.
  
  
  RESULTS
  Among EA users, mean concentrations for total IGF-I (adjusted P=0.004) and free IGF-I (P<0.001) were reduced, whereas mean concentrations of IGFBP-1 (P=0.001) and binary complex (P=0.01) were increased compared with non-users. Taken as a whole group, EP use was not associated with differences in concentrations of IGF-related peptides, but on sub-group analyses, mean concentrations associated with the use of progestins with reduced androgenic activity reflected the use of EA. By contrast, mean IGFBP-2 concentrations were significantly reduced among both EA (P=0.008) and EP (P=0.002) users, irrespective of androgenic activity. Neither EA nor EP influenced mean concentrations of IGF-II, insulin and IGFBP-3.
  
  
  CONCLUSIONS
  The uses of oral sex steroid replacements are associated with significant changes in several IGF-related analytes in a preparation-specific manner, suggesting different regulatory mechanisms. However, the directions of these changes do not fit simple correlative models of predisposition to common diseases.
authors.affiliation: Department of Surgery, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. arenehan@picr.man.ac.uk
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Renehan
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.forename: Sarah T
authors.initials: ST
authors.lastname: O'dwyer
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Shalet
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
mesh_terms: D004194:Disease / Q000209:etiology*; D004198:Disease Susceptibility; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage / Q000009:adverse effects; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects*; D013002:Somatomedins / Q000032:analysis*
chemical_list: D004967:Estrogens; D012739:Gonadal Steroid Hormones; D018969:Insulin-Like Growth Factor Binding Proteins; D010455:Peptides; D011372:Progestins; D013002:Somatomedins