SERUM IGF-1 AND BINDING-PROTEIN-1 AND BINDING-PROTEIN-3 IN POSTMENOPAUSAL WOMEN AND THE EFFECTS OF ESTROGEN

Few data exist on the insulin-like growth factor (IGF) axis in postmen opausal women, particularly on the effects of estrogen on the IGF bind ing proteins (BPs). Although serum IGF-BP1 (BP1) levels are regulated primarily by pancreatic hormones (insulin and somatostatin), a role fo r estrogens has been suggested. We studied 14 postmenopausal women [me an age, 54.8 +/- 0.6 years; (BMI) body mass index 23.8 +/- 1] before a nd after oral estrogen (2 mg/day of micronized estradiol for 3 months) . Ten normal premenopausal women (mean age, 28.7 +/- 1 years; mean BMI , 23.1 +/- 1) served as controls. Serum IGF-1, IGF-BP3 (BP3, BP1, and insulin were measured before and after estrogen. The ratio of IGF-1/BP 3 was calculated, as was the ratio of IGF-1/BP1. Glucose and BP1 sensi tivity to insulin was measured after insulin administration (0.1 U/kg, with blood samples obtained at 0, 2, 5, 10, 15, and 30 min). Before t reatment, postmenopausal women had fasting insulin levels (60 +/- 3 pM ), IGF-1 (32 +/- 3 nM), BP3 (155 +/- 10 nM); and BP1 (0.12 +/- 0.02 nM ) that were similar to the values in premenopausal women. Insulin admi nistration revealed a reduced glucose disappearance (reduced insulin s ensitivity) and a blunted BP1 decrease in postmenopausal women compare d to normal women (p < 0.05). After 3 months of estrogen, serum IGF-1 levels decreased (22.3 +/- nM; p < 0.05) and serum BP1 increased (0.24 +/- 0.03 nM; p < 0.05), while BP3 and insulin levels were unchanged. The ratio of IGF1/BP3 was not significantly reduced but the ratio of I GF-1/BP1 decreased (p < 0.05). Insulin and BP1 sensitivity was improve d after estrogen, although not significantly. In conclusion, oral estr ogen increases BP1 in postmenopausal women, probably by stimulating it s hepatic secretion and without modifying insulin levels. Because BP1 reduces the biologic activity of IGF-1 on several tissues including th e ovary, estrogens may decrease IGF-1 stimulated ovarian androgen secr etion. Some metabolic effects of estrogens may be mediated by changes in the biologic activity of IGF-1.