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

Andrew G. Renehan, Jan Frystyk, Anthony Howell, Sarah T. O'Dwyer, Stephen M. Shalet, Allan Flyvbjerg

    Research output: Contribution to journalArticlepeer-review


    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. Design: 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. © 2007 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)210-219
    Number of pages9
    JournalGrowth Hormone and IGF Research
    Issue number3
    Publication statusPublished - Jun 2007


    • Binding proteins
    • Cancer risk
    • Estrogen
    • Free IGF-I
    • Insulin-like growth factors
    • Progestin


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