The effects of sex steroid replacement therapy on an expanded panel of IGF-related peptides

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.

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.

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.

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.