The effects of sex steroid replacement therapy on an expanded panel of IGF-related peptides.
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.
Renehan
Andrew G
AG
Department of Surgery, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. arenehan@picr.man.ac.uk
Frystyk
Jan
J
Howell
Anthony
A
O'dwyer
Sarah T
ST
Shalet
Stephen M
SM
Flyvbjerg
Allan
A
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*
D004967:Estrogens; D012739:Gonadal Steroid Hormones; D018969:Insulin-Like Growth Factor Binding Proteins; D010455:Peptides; D011372:Progestins; D013002:Somatomedins