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

• Published in: The journal of clinical endocrinology and metabolism 2000-05, Vol.85 (5), p.1918-1922
• Main Authors: KAM, G. Y. W, LEUNG, K.-C, BAXTER, R. C, HO, K. K. Y
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Administration, Oral; Aged; Biological and medical sciences; Cross-Over Studies; Estradiol - administration & dosage; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrogen Replacement Therapy; Estrogens, Conjugated (USP) - pharmacology; Ethinyl Estradiol - administration & dosage; Ethinyl Estradiol - pharmacology; Female; Genital system. Reproduction; Human Growth Hormone - blood; Humans; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor I - metabolism; Macromolecular Substances; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Tropical medicine
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.5.1918

We have previously shown that exogenous estrogens exert route-dependent effects on serum GH and insulin-like growth factor I (IGF-I) levels. IGF-I circulates as a ternary complex with IGF-binding protein-3 (IGFBP-3) and the acid-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 formulations (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 postmenopausal women significantly decreased serum levels of IGFBP-3 and ALS (P < or = 0.005). The suppressive effects were similar with different oral estrogen formulations, and the degree of suppression increased with estrogen 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 route- and dose-dependent manner, which are in parallel with the effects on serum IGF-I. These actions of oral estrogen are independent of endogenous GH status.