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

J Clin Endocrinol Metab. 2000 May;85(5):1918-22. doi: 10.1210/jcem.85.5.6527.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Aged
  • 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
  • Human Growth Hormone / blood*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / metabolism*
  • Macromolecular Substances
  • Middle Aged


  • Estrogens, Conjugated (USP)
  • Insulin-Like Growth Factor Binding Protein 3
  • Macromolecular Substances
  • Human Growth Hormone
  • Ethinyl Estradiol
  • Estradiol
  • Insulin-Like Growth Factor I