Ospemifene: A first-in-class, non-hormonal selective estrogen receptor modulator approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy

Michael W. Degregorio, Robert L. Zerbe, Gregory T. Wurz

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Ospemifene is a selective estrogen receptor modulator (SERM) approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy (VVA) due to menopause. As the first non-hormonal treatment for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a triphenylethylene similar in chemical structure to tamoxifen and toremifene. Consistent with other SERMs such as tamoxifen, toremifene, and raloxifene, ospemifene possesses a distinctive mix of estrogenic and antiestrogenic tissue-specific effects in bone, breast tissue, serum lipids, and the vagina. Among the approved SERMs, ospemifene is the only agent with a nearly full estrogen agonist effect on the vaginal epithelium while having neutral to slight estrogenic effects in the endometrium, making ospemifene uniquely suited for the treatment of dyspareunia associated with VVA, also known as atrophic vaginitis, which affects up to 50% of postmenopausal women. This review begins with a brief history of the discovery of ospemifene, its mechanism of action, and its preclinical development, with an emphasis on its tissue-specific effects on bone, breast, uterus and endometrium, serum lipids and vagina. A brief discussion on the genotoxicity of ospemifene compared to tamoxifen and toremifene is included. The focus then shifts to the clinical development of ospemifene from Phase I through Phase III. We will close with the FDA approval of ospemifene and a justification of the future clinical evaluation of ospemifene as a potential breast cancer chemopreventive agent, where several preclinical studies in different rodent breast cancer models strongly suggest ospemifene is as effective as tamoxifen.

Original languageEnglish (US)
Pages (from-to)82-93
Number of pages12
JournalSteroids
Volume90
DOIs
StatePublished - Nov 15 2014

Fingerprint

Dyspareunia
Selective Estrogen Receptor Modulators
Atrophy
Toremifene
Tamoxifen
Therapeutics
Vagina
Tissue
Endometrium
Ospemifene
Atrophic Vaginitis
Bone
Estrogens
Breast
Breast Neoplasms
Lipids
Bone and Bones
Women's Health
Menopause
Serum

Keywords

  • Breast cancer
  • Dyspareunia
  • Ospemifene
  • Selective estrogen receptor modulator
  • Vulvar and vaginal atrophy

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology

Cite this

Ospemifene : A first-in-class, non-hormonal selective estrogen receptor modulator approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy. / Degregorio, Michael W.; Zerbe, Robert L.; Wurz, Gregory T.

In: Steroids, Vol. 90, 15.11.2014, p. 82-93.

Research output: Contribution to journalArticle

@article{4a291ffc7a364428abbb50d85c5b1ca4,
title = "Ospemifene: A first-in-class, non-hormonal selective estrogen receptor modulator approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy",
abstract = "Ospemifene is a selective estrogen receptor modulator (SERM) approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy (VVA) due to menopause. As the first non-hormonal treatment for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a triphenylethylene similar in chemical structure to tamoxifen and toremifene. Consistent with other SERMs such as tamoxifen, toremifene, and raloxifene, ospemifene possesses a distinctive mix of estrogenic and antiestrogenic tissue-specific effects in bone, breast tissue, serum lipids, and the vagina. Among the approved SERMs, ospemifene is the only agent with a nearly full estrogen agonist effect on the vaginal epithelium while having neutral to slight estrogenic effects in the endometrium, making ospemifene uniquely suited for the treatment of dyspareunia associated with VVA, also known as atrophic vaginitis, which affects up to 50{\%} of postmenopausal women. This review begins with a brief history of the discovery of ospemifene, its mechanism of action, and its preclinical development, with an emphasis on its tissue-specific effects on bone, breast, uterus and endometrium, serum lipids and vagina. A brief discussion on the genotoxicity of ospemifene compared to tamoxifen and toremifene is included. The focus then shifts to the clinical development of ospemifene from Phase I through Phase III. We will close with the FDA approval of ospemifene and a justification of the future clinical evaluation of ospemifene as a potential breast cancer chemopreventive agent, where several preclinical studies in different rodent breast cancer models strongly suggest ospemifene is as effective as tamoxifen.",
keywords = "Breast cancer, Dyspareunia, Ospemifene, Selective estrogen receptor modulator, Vulvar and vaginal atrophy",
author = "Degregorio, {Michael W.} and Zerbe, {Robert L.} and Wurz, {Gregory T.}",
year = "2014",
month = "11",
day = "15",
doi = "10.1016/j.steroids.2014.07.012",
language = "English (US)",
volume = "90",
pages = "82--93",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Ospemifene

T2 - A first-in-class, non-hormonal selective estrogen receptor modulator approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy

AU - Degregorio, Michael W.

AU - Zerbe, Robert L.

AU - Wurz, Gregory T.

PY - 2014/11/15

Y1 - 2014/11/15

N2 - Ospemifene is a selective estrogen receptor modulator (SERM) approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy (VVA) due to menopause. As the first non-hormonal treatment for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a triphenylethylene similar in chemical structure to tamoxifen and toremifene. Consistent with other SERMs such as tamoxifen, toremifene, and raloxifene, ospemifene possesses a distinctive mix of estrogenic and antiestrogenic tissue-specific effects in bone, breast tissue, serum lipids, and the vagina. Among the approved SERMs, ospemifene is the only agent with a nearly full estrogen agonist effect on the vaginal epithelium while having neutral to slight estrogenic effects in the endometrium, making ospemifene uniquely suited for the treatment of dyspareunia associated with VVA, also known as atrophic vaginitis, which affects up to 50% of postmenopausal women. This review begins with a brief history of the discovery of ospemifene, its mechanism of action, and its preclinical development, with an emphasis on its tissue-specific effects on bone, breast, uterus and endometrium, serum lipids and vagina. A brief discussion on the genotoxicity of ospemifene compared to tamoxifen and toremifene is included. The focus then shifts to the clinical development of ospemifene from Phase I through Phase III. We will close with the FDA approval of ospemifene and a justification of the future clinical evaluation of ospemifene as a potential breast cancer chemopreventive agent, where several preclinical studies in different rodent breast cancer models strongly suggest ospemifene is as effective as tamoxifen.

AB - Ospemifene is a selective estrogen receptor modulator (SERM) approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy (VVA) due to menopause. As the first non-hormonal treatment for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a triphenylethylene similar in chemical structure to tamoxifen and toremifene. Consistent with other SERMs such as tamoxifen, toremifene, and raloxifene, ospemifene possesses a distinctive mix of estrogenic and antiestrogenic tissue-specific effects in bone, breast tissue, serum lipids, and the vagina. Among the approved SERMs, ospemifene is the only agent with a nearly full estrogen agonist effect on the vaginal epithelium while having neutral to slight estrogenic effects in the endometrium, making ospemifene uniquely suited for the treatment of dyspareunia associated with VVA, also known as atrophic vaginitis, which affects up to 50% of postmenopausal women. This review begins with a brief history of the discovery of ospemifene, its mechanism of action, and its preclinical development, with an emphasis on its tissue-specific effects on bone, breast, uterus and endometrium, serum lipids and vagina. A brief discussion on the genotoxicity of ospemifene compared to tamoxifen and toremifene is included. The focus then shifts to the clinical development of ospemifene from Phase I through Phase III. We will close with the FDA approval of ospemifene and a justification of the future clinical evaluation of ospemifene as a potential breast cancer chemopreventive agent, where several preclinical studies in different rodent breast cancer models strongly suggest ospemifene is as effective as tamoxifen.

KW - Breast cancer

KW - Dyspareunia

KW - Ospemifene

KW - Selective estrogen receptor modulator

KW - Vulvar and vaginal atrophy

UR - http://www.scopus.com/inward/record.url?scp=84908697914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908697914&partnerID=8YFLogxK

U2 - 10.1016/j.steroids.2014.07.012

DO - 10.1016/j.steroids.2014.07.012

M3 - Article

C2 - 25087944

AN - SCOPUS:84908697914

VL - 90

SP - 82

EP - 93

JO - Steroids

JF - Steroids

SN - 0039-128X

ER -