© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Cardiovascular Effects of Droloxifene, a New Selective Estrogen Receptor Modulator, in Healthy Postmenopausal Women
From the Departments of Internal Medicine/Cardiology (D.M.H., B.E.P.), Neurology (W.A.R.), Endocrinology (T.Y.T.), and Surgical Sciences-General (Hypertension Center) (K.B.B.), Wake Forest University School of Medicine, Winston-Salem, NC; the University of Arizona/Phoenix VA Medical Center (E.A.B.); and Pfizer, Inc (D.B.M.), Groton, Conn.
Abstract—Selective estrogen receptor modulators, like tamoxifen and related compounds, have mixed estrogen agonistic/antagonistic effects. Tamoxifen may confer significant cardiovascular benefits without the estrogen-associated risks of endometrial and breast cancer. Droloxifene, a structural analogue of tamoxifen, has estrogen agonistic effects on bone and antagonistic effects on endometrial and breast tissue. Its cardiovascular effects in women are unknown. We enrolled 24 healthy postmenopausal women in a randomized, double-blind, 2-period crossover trial comparing the effects of droloxifene (60 mg/d) with conjugated estrogen (0.625 mg/d). Plasma lipids, coagulation and fibrinolytic factors, and brachial flow-mediated vasodilator responses were measured at the beginning and end of each treatment period. Droloxifene and estrogen resulted in 16.6% and 12.0% reductions, respectively, in low density lipoprotein cholesterol (P<0.001) and 13.2% and 9.5% reductions, respectively, in lipoprotein(a) (P<0.05). In contrast, estrogen, but not droloxifene, increased high density lipoprotein (18.5%, P<0.001). Droloxifene also reduced fibrinogen by 17.8% versus a 7.3% reduction with estrogen (P=0.004) but produced no estrogen-like changes in plasminogen, plasminogen activator inhibitor-1, or tissue plasminogen activator. Droloxifene and estrogen produced 36.4% and 27.3% increases, respectively, in flow-mediated vasodilation (percent change from baseline, P<0.05 for both). Droloxifene has estrogen agonistic properties regarding low density lipoprotein and lipoprotein(a) metabolism, certain coagulation factors, and endothelium-dependent vasodilation but, unlike estrogen, has no effect on high density lipoprotein/triglyceride metabolism and the fibrinolytic cascade. It remains unknown whether droloxifene can confer a true cardiovascular benefit.
Key Words: droloxifene • hormone replacement therapy • women • estrogen • cardiovascular disease
This article has been cited by other articles:
 |
|
 |
|
  H.-L. Noh, K. Okajima, J. D. Molkentin, S. Homma, and I. J. Goldberg Acute lipoprotein lipase deletion in adult mice leads to dyslipidemia and cardiac dysfunction Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E755 - E760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pelzer, V. Jazbutyte, K. Hu, S. Segerer, M. Nahrendorf, P. Nordbeck, A. W. Bonz, J. Muck, K.-H. Fritzemeier, C. Hegele-Hartung, et al. The estrogen receptor-{alpha} agonist 16{alpha}-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats Cardiovasc Res, September 1, 2005; 67(4): 604 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response Eur. Heart J., February 2, 2005; 26(4): 363 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Widder, T. Pelzer, C. von Poser-Klein, K. Hu, V. Jazbutyte, K.-H. Fritzemeier, C. Hegele-Hartung, L. Neyses, and J. Bauersachs Improvement of Endothelial Dysfunction by Selective Estrogen Receptor-{alpha} Stimulation in Ovariectomized SHR Hypertension, November 1, 2003; 42(5): 991 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Colacurci, D. Manzella, F. Fornaro, M. Carbonella, and G. Paolisso Endothelial Function and Menopause: Effects of Raloxifene Administration J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2135 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Simon, P. Boutouyrie, J.M. Simon, B. Laloux, C. Tournigand, A.I. Tropeano, S. Laurent, and P. Jaillon Influence of Tamoxifen on Carotid Intima-Media Thickness in Postmenopausal Women Circulation, December 3, 2002; 106(23): 2925 - 2929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Herrington, E. Vittinghoff, F. Lin, J. Fong, F. Harris, D. Hunninghake, V. Bittner, H. G. Schrott, R. S. Blumenthal, R. Levy, et al. Statin Therapy, Cardiovascular Events, and Total Mortality in the Heart and Estrogen/Progestin Replacement Study (HERS) Circulation, June 25, 2002; 105(25): 2962 - 2967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brown, A. Abbas, D. Byrne, J. A. Schoenhard, and D. E. Vaughan Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women Circulation, January 22, 2002; 105(3): 304 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Andersson, G. Johannsson, G. Holm, B.-A. Bengtsson, A. Sashegyi, I. Pavo, T. Mason, and P. W. Anderson Raloxifene Does Not Affect Insulin Sensitivity or Glycemic Control in Postmenopausal Women with Type 2 Diabetes Mellitus: A Randomized Clinical Trial J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 122 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Herrington, M. A. Espeland, J. R. Crouse III, J. Robertson, W. A. Riley, M. A. McBurnie, and G. L. Burke Estrogen Replacement and Brachial Artery Flow-Mediated Vasodilation in Older Women Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 1955 - 1961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cushman, J. P. Costantino, R. P. Tracy, K. Song, L. Buckley, J. D. Roberts, and D. N. Krag Tamoxifen and Cardiac Risk Factors in Healthy Women : Suggestion of an Anti-inflammatory Effect Arterioscler Thromb Vasc Biol, February 1, 2001; 21(2): 255 - 261. [Abstract] [Full Text] [PDF]
|
|