Estetrol: a unique steroid in human pregnancy

J Steroid Biochem Mol Biol. 2008 May;110(1-2):138-43. doi: 10.1016/j.jsbmb.2008.03.027. Epub 2008 Mar 29.


Estetrol (E(4)) is an estrogenic steroid molecule synthesized exclusively by the fetal liver during human pregnancy and reaching the maternal circulation through the placenta. Its function is presently unknown. After its discovery in the mid-1960s, E(4) research revealed rather unique properties of this steroid and spawned a large body of state-of-the art publications. Nevertheless, 20 years later experimental work was virtually abandoned. In recent years based on new data, E(4) has experienced a vita nova, a revival of preclinical and clinical research activities with the goal to elucidate its physiological function and explore its potential for therapeutic use in humans. This review is intended to offer an historical account of the discovery of E(4) and the preclinical studies conducted during the heyday of E(4) research that ended in the mid-1980s.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Estetrol / chemistry
  • Estetrol / metabolism*
  • Estetrol / therapeutic use
  • Female
  • Fetus / metabolism*
  • Humans
  • Models, Biological
  • Molecular Structure
  • Pregnancy


  • Estetrol