Estrogens exert route- and dose-dependent effects on insulin-like growth factor (IGF)-binding protein-3 and the acid-labile subunit of the IGF ternary complex

We have previously shown that exogenous estrogens exert route-dependent eff ects on serum GH and insulin-like growth factor I (IGF-I) levels. IGF-I cir culates as a ternary complex with IGF-binding protein-3 (IGFBP-3) and the a cid-labile subunit (ALS). It is not known whether IGFBP-3 and ALS in blood are regulated by estrogen and, if so, whether this is also route dependent. In the present study we investigate the effects on IGFBP-3 and ALS of oral and transdermal estrogens (study 1), of different oral estrogen formulatio ns (ethinyl estradiol, conjugated estrogen, and estradiol valerate; study 2 ), of different estrogen dosages (study 3) in normal postmenopausal women, and of oral estrogen in hypogonadal GH-deficient women (study 4). Administration of oral, but not transdermal, estrogen in normal postmenopau sal women significantly decreased serum levels of IGFBP-3 and ALS (P less t han or equal to 0.005). The suppressive effects were similar with different oral estrogen formulations, and the degree of suppression increased with e strogen dosage. In hypogonadal GH-deficient women, oral estrogen treatment also significantly reduced IGFBP-3 and ALS (P = 0.02). The changes in IGF-I in each of the four studies paralleled the changes in both IGFBP-3 and ALS . In conclusion, exogenous estrogens suppress serum IGFBP-3 and ALS in a rout e- and dose-dependent manner, which are in parallel with the effects on ser um IGF-I. These actions of oral estrogen are independent of endogenous GH s tatus.