Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy?

J Steroid Biochem Mol Biol. 2005 Apr;94(5):499-518. doi: 10.1016/j.jsbmb.2004.12.038. Epub 2005 Mar 23.


The benefits of plant extracts from soy and red clover as alternatives to conventional hormone replacement therapy (HRT) have been debated in the past. Here, an attempt has been made to summarize the biochemical and pharmacological data in the light of clinical aspects. Red clover and soy extracts contain isoflavones, which have a high affinity to estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR). The higher affinity to ERbeta compared to ERalpha has been used as an explanation why red clover extracts function as food additives to treat menopausal disorders and may reduce risk of breast cancer. Biochemical analysis shows that these representatives of phytoestrogens have multiple actions beside selective estrogen receptor modulator (SERM)-activity. They act as selective estrogen enzyme modulators (SEEMs), have antioxidant activity and interact with transcription factors such as NF-kappaB. Furthermore, it is indicated that they have protective effects on osteoporosis and the cardiovascular system. Currently 40-50mg of isoflavones (biochanin A, daidzein, formononetin and genistein) are recommended as daily dose. This recommendation is based on the daily intake of phytoestrogens in a traditional Japanese diet.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / prevention & control
  • Cardiovascular Diseases / prevention & control
  • Estrogen Replacement Therapy*
  • Female
  • Humans
  • Isoflavones / isolation & purification
  • Isoflavones / pharmacology
  • Isoflavones / therapeutic use*
  • Models, Animal
  • Molecular Structure
  • Osteoporosis / prevention & control
  • Phytoestrogens / isolation & purification
  • Phytoestrogens / pharmacology
  • Phytoestrogens / therapeutic use*
  • Receptors, Steroid / chemistry
  • Receptors, Steroid / drug effects
  • Selective Estrogen Receptor Modulators / isolation & purification
  • Selective Estrogen Receptor Modulators / pharmacology
  • Selective Estrogen Receptor Modulators / therapeutic use*
  • Trifolium / chemistry*
  • Vitamin A / metabolism


  • Isoflavones
  • Phytoestrogens
  • Receptors, Steroid
  • Selective Estrogen Receptor Modulators
  • Vitamin A