Selective estrogen receptor modulators: tissue actions and potential for CNS protection

CNS Drug Rev. 2002 Fall;8(3):309-30. doi: 10.1111/j.1527-3458.2002.tb00230.x.


Significant physiologic changes occur during menopause. Evidence exists to suggest that estrogen may be neuroprotective under specific conditions. However, there are limitations in the neuroprotection afforded by standard hormone therapy. Accordingly, alternative agents with selected estrogenic effects may hold even greater promise rather than conventional hormone replacement therapy for the prevention and treatment of CNS injury. Recently, a variety of selective estrogen receptor modulators (SERMs) have been developed to retain the favorable and minimize the adverse side effects of estrogens. This review focuses on the CNS and known neuroprotective effects of two specific SERMs, raloxifene and arzoxifene. Recent studies hint that raloxifene and arzoxifene are neuroprotective and may preserve some elements of cognitive function. However, the mechanism of action is not well described and it is unclear if the beneficial effects of SERMs rely on activation of estrogen receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy
  • Cardiovascular System / drug effects
  • Central Nervous System / drug effects*
  • Central Nervous System / physiology
  • Cognition / drug effects
  • Estrogen Antagonists / adverse effects
  • Estrogen Antagonists / therapeutic use
  • Estrogen Receptor Modulators / chemistry
  • Estrogen Receptor Modulators / pharmacology
  • Estrogen Receptor Modulators / therapeutic use*
  • Female
  • Hormone Replacement Therapy
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Osteoporosis, Postmenopausal / drug therapy
  • Piperidines / pharmacology
  • Piperidines / therapeutic use
  • Raloxifene Hydrochloride / pharmacology
  • Raloxifene Hydrochloride / therapeutic use
  • Receptors, Neurotransmitter / drug effects
  • Structure-Activity Relationship
  • Tamoxifen / adverse effects
  • Tamoxifen / therapeutic use
  • Thiophenes / pharmacology
  • Thiophenes / therapeutic use
  • Uterus / drug effects


  • Estrogen Antagonists
  • Estrogen Receptor Modulators
  • Neuroprotective Agents
  • Piperidines
  • Receptors, Neurotransmitter
  • Thiophenes
  • Tamoxifen
  • Raloxifene Hydrochloride
  • LY 353381