Molecular basis for the antiandrogen withdrawal syndrome

J Cell Biochem. 2004 Jan 1;91(1):3-12. doi: 10.1002/jcb.10757.


In patients with prostate cancer who manifest disease progression during combined androgen blockade therapy, discontinuation of antiandrogen treatment might result in prostate-specific antigen decline, often associated with clinical improvement. The response called antiandrogen withdrawal syndrome is thus acknowledged as a general phenomenon. However, molecular mechanisms responsible for this syndrome are not completely understood. This article outlines the proposed mechanisms, including alterations of androgen receptor gene and its coregulatory proteins and activation of the signal transduction pathway, and the potential therapeutic approaches based on the specific mechanisms.

Publication types

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

MeSH terms

  • Androgen Antagonists / therapeutic use*
  • Humans
  • MAP Kinase Signaling System*
  • Male
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Receptors, Androgen / metabolism
  • Substance Withdrawal Syndrome*
  • Treatment Outcome


  • Androgen Antagonists
  • Receptors, Androgen
  • Prostate-Specific Antigen