Molecular and Clinical Evidence for the Unique Nature of Individual Selective Estrogen Receptor Modulators

  title={Molecular and Clinical Evidence for the Unique Nature of Individual Selective Estrogen Receptor Modulators},
  author={Michael W. Draper and William Wl Chin},
  journal={Clinical Obstetrics and Gynecology},
  • M. Draper, W. Chin
  • Published 1 June 2003
  • Biology
  • Clinical Obstetrics and Gynecology
Strong winds of controversy are swirling around the use of hormone replacement with estrogens and progestins in the treatment of postmenopausal symptoms and conditions such as osteoporosis, cardiovascular disease, and cognition based on a number of recent large, prospective clinical studies. In this climate, it is critical to reassess the roles of estrogen and nonsteroidal partial estrogen agonist/antagonists or SERMs in the therapy of the postmenopausal woman. This paper first examines the… 
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Selective Estrogen Receptor Modulators: An Update on Recent Clinical Findings

The complex function and interactions of selective estrogen receptor modulators (SERMs) are summarized to recall their suppression or initiation of target genes leading them to their actions; and explain their important roles in breast cancer treatment and possible side effects on bone, the genitourinary system, and on markers of cardiovascular risk.

Raloxifene: A Selective Estrogen-Receptor Modulator for Postmenopausal Osteoporosis – a Clinical Update on Efficacy and Safety

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A new selective estrogen receptor modulator with potent uterine antagonist activity, agonist activity in bone, and minimal ovarian stimulation.

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Estrogens, Selective Estrogen Receptor Modulators, and Dementia: What Is the Evidence?

  • K. Yaffe
  • Psychology
    Annals of the New York Academy of Sciences
  • 2001
The current state of knowledge of the role of estrogen for preventing dementia in postmenopausal women will be reviewed and the status of ongoing and recently completed trials of estrogen and SERMs on cognitive function or on Alzheimer's disease severity will be summarized.

Developing a SERM: Stringent Preclinical Selection Criteria Leading to an Acceptable Candidate (WAY‐140424) for Clinical Evaluation

  • B. KommC. Lyttle
  • Biology, Medicine
    Annals of the New York Academy of Sciences
  • 2001
In order to develop an improved SERM, a stringent screening process was designed to select compounds that did not stimulate the uterus or breast, and under these strict conditions, WAY‐140424 was developed and, to date, the preclinical pharmacology data have accurately predicted the clinical response demonstrated in phase I and II trials.

Re: The effects of tamoxifen and estrogen on brain metabolism in elderly women.

  • J. Benson
  • Biology
    Journal of the National Cancer Institute
  • 2002
Findings from the ATAC trial led the authors to conclude that further evaluation of the effects of aromatase inhibitors on bone mineral density and cognitive function is mandatory in order to fully assess the clinical risk–benefit ratio for these agents compared with that for tamoxifen.

Molecular mechanisms of selective estrogen receptor modulator (SERM) action.

This model provides a basis for understanding the molecular mechanisms of SERM action, and should help identify new SERMs with enhanced tissue or target gene selectivity.

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

This review focuses on the CNS and known neuroprotective effects of two specific SERMs, raloxifenes and arzoxifene, and suggests that ralOXifene and arZoxIfene are neuroprot protective and may preserve some elements of cognitive function.

Bazedoxifene acetate: Selective estrogen receptor modulator treatment and prevention of osteoporosis

The structural differences between bazedoxifene and raioxifene are apparently sufficient to conter differences in their pharmacology, which supports the potential for development of more refined molecules that could achieve the optimal therapeutic target profile for a SERM.

Identification of Selective Estrogen Receptor Modulators by Their Gene Expression Fingerprints*

Most compounds with similar GEFs had similar in vivo activities, thereby suggesting that GEF-based screens could be useful in predicting a compound's in vivo pharmacological profile.

Mechanism of action and preclinical profile of raloxifene, a selective estrogen receptor modulation.

  • H. Bryant
  • Biology
    Reviews in endocrine & metabolic disorders
  • 2001
Global evaluation of the similarities and parallel responses of raloxifene and estrogen in bone and the cardiovascular system strongly support a similar mechanistic basis for the agonist effects of these agents on the skeleton.