help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on July 17, 2003
Endocrinology, doi:10.1210/en.2003-0269
A more recent version of this article appeared on November 1, 2003
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
144/11/4700    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Labrie, F.
Right arrow Articles by Pelletier, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Labrie, F.
Right arrow Articles by Pelletier, G.

Submitted on February 28, 2003
Accepted on July 9, 2003

THE COMBINATION OF A NOVEL SERM WITH AN ESTROGEN PROTECTS THE MAMMARY GLAND AND UTERUS IN A RODENT MODEL: THE FUTURE OF POSTMENOPAUSAL WOMEN'S HEALTH?

Fernand Labrie1*, Mohamed El-Alfy1, Louise Berger1, Claude Labrie1, Céline Martel1, Alain Bélanger1, Bernard Candas1, and Georges Pelletier1

1 Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL) and Laval University, Québec, G1V 4G2, Canada

* To whom correspondence should be addressed. E-mail: fernand.labrie{at}crchul.ulaval.ca.

The Women's Health Initiative Study and other reports have created major uncertainty among postmenopausal women and physicians concerning hormone replacement therapy (HRT). We have thus investigated the possibility of replacing the progestin in HRT by a novel selective estrogen receptor modulator (SERM) having potent and pure antiestrogenic activity in the mammary gland and uterus. As measured by changes in histology and Cdc47 labeling in the rat model, the present study shows that the stimulatory effect of estradiol in the mammary gland and uterus is efficiently blocked by simultaneous administration of the novel SERM EM-652, while bone mineral density is preserved and serum cholesterol is decreased. Following the administration of 14C-labeled EM-652, we have observed that there is no detectable radioactivity in the brain. Moreover, ER{alpha} immunoreactivity remained constant in the hypothalamus after EM-652 treatment, while ER{alpha} became almost undetectable in the mammary gland and uterus. The present data show the poor or absent access of EM-652 to the brain while the effects of estrogens are efficiently neutralized in the mammary gland and uterus. Such data support the exciting possibility of a novel approach which could meet most of the needs of women's health at menopause, namely control of hot flushes and prevention of breast, uterine and ovarian cancer, as well as osteoporosis while potentially helping brain function and preventing Alzheimer's disease with no identifiable risk or negative effect.
Key words: Menopause • antiestrogen • pure antiestrogen • selective estrogen receptor modulator (SERM) • EM-652 • SCH 57068 • estrogen • 17{beta}-estradiol • hormone replacement therapy • women's health • breast cancer • uterine cancer • ovarian cancer • osteoporosis • card qiovascular disease • hot flushes • cognition • memory • Alzheimer's disease • tissue-specific hormone replacement therapy (TSHRT)




This article has been cited by other articles:


Home page
 Endocr Relat CancerHome page
F Labrie
Future perspectives of selective estrogen receptor modulators used alone and in combination with DHEA.
Endocr. Relat. Cancer, June 1, 2006; 13(2): 335 - 355.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
V. Luu-The, P. Tremblay, and F. Labrie
Characterization of Type 12 17{beta}-Hydroxysteroid Dehydrogenase, an Isoform of Type 3 17{beta}-Hydroxysteroid Dehydrogenase Responsible for Estradiol Formation in Women
Mol. Endocrinol., February 1, 2006; 20(2): 437 - 443.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
F Labrie, V Luu-The, A Belanger, S-X Lin, J Simard, G Pelletier, and C Labrie
Is dehydroepiandrosterone a hormone?
J. Endocrinol., November 1, 2005; 187(2): 169 - 196.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
D. G. Rudmann, I. R. Cohen, M. R. Robbins, D. E. Coutant, and J. W. Henck
Androgen Dependent Mammary Gland Virilism in Rats Given the Selective Estrogen Receptor Modulator LY2066948 Hydrochloride
Toxicol Pathol, October 1, 2005; 33(6): 711 - 719.
[Abstract] [Full Text] [PDF]

Home page
 Obstet GynecolHome page
S. Ronkin, R. Northington, E. Baracat, M. G. Nunes, D. F. Archer, G. Constantine, and J. H. Pickar
Endometrial Effects of Bazedoxifene Acetate, a Novel Selective Estrogen Receptor Modulator, in Postmenopausal Women
Obstet. Gynecol., June 1, 2005; 105(6): 1397 - 1404.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
J. L. Turgeon, D. P. McDonnell, K. A. Martin, and P. M. Wise
Hormone Therapy: Physiological Complexity Belies Therapeutic Simplicity
Science, May 28, 2004; 304(5675): 1269 - 1273.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. E. Hoffman and S. L. Zup
Good Versus Evil: Changing the Approach to Hormone Replacement Therapy
Endocrinology, November 1, 2003; 144(11): 4698 - 4699.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2003 by The Endocrine Society