Journal of Steroid Biochemistry & Molecular Biology 81 (2002) 95–102 The IGF-system in healthy pre- and postmenopausal women: relations to demographic variables and sex-steroids Svein I. Helle a , Dagfinn Ekse a , Jeff M.P. Holly b , Per E. Lønning a,∗ a Department of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway b Division of Surgery, Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK Received 19 July 2001; accepted 4 March 2002 Abstract Plasma insulin-like growth factor (IGF)-I, free IGF-I and -II, IGF-binding protein (IGFBP)-1, -2, and -3 together with IGFBP-3 protease activity were measured in 114 postmenopausal and 39 premenopausal healthy women. For each parameter, the mathematical distribution was characterised, and the normal range for pre- and postmenopausal women described, together with correlations to demographic variables and sex-steroids (postmenopausal women). Postmenopausal women had lower levels of plasma IGF-I (P< 0.001) and free IGF-I (P< 0.001) compared to premenopausal women, while plasma IGFBP-2 (P< 0.05) and immunoreactive IGFBP-3 (P< 0.001) were higher in postmenopausal women. Free IGF-I (but none of the other parameters) was significantly lower in postmenopausal smokers compared to non-smokers (P< 0.05). IGF-I and -II both correlated positively to height (r = 0.203, P< 0.05 and r = 0.198, P< 0.05, respectively), while IGF-II correlated positively to weight (r = 0.250, P< 0.01). Plasma IGF-I correlated positively to androstenedione (r = 0.292, P< 0.01) and dehydroepiandrosterone sulphate (DHEAS, r = 0.202, P< 0.05), while a significant positive correlation was observed between IGF-II on the one side and oestradiol (E 2 , r = 0.227), oestrone sulphate (E 1 S, r = 0.238) and androstenedione (r = 0.213) on the other side (P< 0.05 for all). Our results support a relation between sex-steroids and IGF-I and -II in healthy postmenopausal women. The lower levels of total and free IGF-I in postmenopausal compared to premenopausal women indicate lower bioavailability of this growth factor in elderly females. © 2002 Published by Elsevier Science Ltd. Keywords: Insulin-like growth factors; Oestrogens; Distribution; Normal range; Correlations 1. Introduction The insulin-like growth factor (IGF) system plays an im- portant part in physiological growth and development [1]. IGF-I acts as an effector molecule to growth hormone (GH), and influences the secretion of GH through a negative feed- back in normal humans [2]. Considerable evidence suggests plasma IGF-I levels to be related to both genetic [3,4] as well as hormonal factors. IGF-I has been reported to decline with age [5]. This has been attributed to a decrease in GH secretion, but alterations in sex-steroid production may also be involved [6]. Most plasma IGF-I and -II are bound in a ternary 150 kDa complex consisting of IGFBP-3, an acid labile subunit, and either IGF-I or -II. This complex does not cross the capillary barrier and functions as a depot for these growth factors in the circulation [1]. However, IGF-I and -II may ∗ Corresponding author. Tel.: +47-5-5-972010; fax: +47-5-5-972046. E-mail address: plon@haukeland.no (P.E. Lønning). be released from the 150 kDa complex by proteolytic cleav- age of IGFBP-3. The resulting IGFBP-3 fragments have reduced affinity for IGFs, and the released IGF-I and -II are redistributed to a 50 kDa binary complex associated with one of the other IGFBPs (1,2,4–6) [7]. This complex has a shorter half-life (20–30 min) compared to the 150 kDa complex (12–15 h) [8], and may cross the capillary barrier. Recent studies indicate that a decrease or an increase in plasma IGFBP-3 protease activity may influence plasma levels of IGF-I [9,10]. Noteworthy, there is a physiological increase in IGFBP-3 protease activity during normal pregnancy [11], but also in several different disease states like AIDS, cancer, di- abetes mellitus and critical illness in general [12–14]. The prevalence of increased IGFBP-3 protease activity in presumptively healthy individuals is not known. Thus, de- termination of IGF-binding protein profile and IGFBP-3 protease activity may provide useful information regarding potential confounding factors when assessing plasma IGF-I and -II. 0960-0760/02/$ – see front matter © 2002 Published by Elsevier Science Ltd. PII:S0960-0760(02)00052-3