Estrogen and related compounds: biphasic dose responses

Crit Rev Toxicol. 2001 Jul;31(4-5):503-15. doi: 10.1080/20014091111785.


This article documents and quantitatively assesses the capacity of estrogen, phytoestrogens, and antiestrogens to affect biphasic dose-response relationships in animal/human models and across a broad range of cell types, affecting multiple endpoints. The range of endpoints displaying such biphasic dose responses includes plasminogen activation, oxytocin secretion, angiogenesis, cell proliferation, bone growth, monocyte chemotaxis, secretion of various cytokines, and other effects. The quantitative features of the dose response relationships revealed that the magnitude of the stimulatory responses was typically less than twofold, whereas the stimulatory responses were markedly variable ranging from about 5- to 10(6)-fold. Mechanistic explanations of the biphasic responses are addressed.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Development / drug effects
  • Cell Division / drug effects
  • Chemotaxis
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Estrogen Receptor Modulators / pharmacology*
  • Estrogens / pharmacology*
  • Estrogens, Non-Steroidal / pharmacology*
  • Homeostasis / drug effects*
  • Humans
  • Isoflavones*
  • Monocytes / physiology
  • Neovascularization, Physiologic
  • Oxytocin / metabolism
  • Phytoestrogens
  • Plant Preparations
  • Plasminogen Activators / drug effects
  • Plasminogen Activators / physiology


  • Cytokines
  • Estrogen Receptor Modulators
  • Estrogens
  • Estrogens, Non-Steroidal
  • Isoflavones
  • Phytoestrogens
  • Plant Preparations
  • Oxytocin
  • Plasminogen Activators