(Circulation. 1999;100:1851-1857.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Vascular Effects of Estrogen and Vitamin E Therapies in Postmenopausal Women
From the Cardiology Branch (K.K.K., A.B., L.H., R.M., J.A.P., R.O.C.) and Office of Biostatistics Research (M.A.W.), National Heart, Lung, and Blood Institute, and Clinical Pathology Department (G.C.), Clinical Center, National Institutes of Health, Bethesda, Md.
Correspondence to Dr Richard O. Cannon III, National Institutes of Health, Bldg 10, Room 7B15, 10 Center Dr, MSC-1650, Bethesda, MD 20892-1650. E-mail cannonr{at}gwgate.nhlbi.nih.gov
Background—Estrogen and vitamin E therapies have been suggested to reduce cardiovascular risk, but comparison of the vascular effects of these therapies to determine mechanisms of potential benefit has not been performed in postmenopausal women.
Methods and Results—In a double-blind, 3-period crossover study, we randomly assigned 28 healthy postmenopausal women to conjugated equine estrogens (CE) 0.625 mg/d, vitamin E 800 IU/d, and their combination, with measurements made before and after each 6-week treatment period. The ratio of LDL to HDL cholesterol and lipoprotein(a) decreased on therapies including CE but increased on vitamin E alone (P<0.001 and P=0.002, respectively, by ANOVA). Brachial artery flow–mediated dilation improved on all therapies (all P<0.001 versus pretreatment values) and to a similar degree (P=0.267 by ANOVA). No therapy improved the dilator response to nitroglycerin. CE lowered serum levels of cell adhesion molecules E-selectin, ICAM-1, and VCAM-1 (all P<0.05 versus pretreatment values). Vitamin E had no significant effect on levels of these markers of inflammation (P<0.001 by ANOVA for E-selectin). CE alone or combined with vitamin E but not vitamin E alone lowered or showed a trend for lowering plasma levels of plasminogen activator inhibitor type-1 (P=0.069 by ANOVA).
Conclusions—Estrogen and vitamin E therapies similarly improved arterial endothelium-dependent vasodilator responsiveness consistent with increased nitric oxide in healthy postmenopausal women, despite divergent effects on atherogenic lipoproteins. However, only estrogen reduced markers of vascular disease.
Key Words: atherosclerosis • endothelium • antioxidants • cell adhesion molecules • fibrinolysis
This article has been cited by other articles:
 |
|
 |
|
  K. K. Koh, P. C. Oh, and M. J. Quon Does reversal of oxidative stress and inflammation provide vascular protection? Cardiovasc Res, March 1, 2009; 81(4): 649 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. D. Sesso, J. E. Buring, W. G. Christen, T. Kurth, C. Belanger, J. MacFadyen, V. Bubes, J. E. Manson, R. J. Glynn, and J. M. Gaziano Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Controlled Trial JAMA, November 12, 2008; 300(18): 2123 - 2133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kublickiene, X.-D. Fu, E. Svedas, B.-M. Landgren, A. R. Genazzani, and T. Simoncini Effects in Postmenopausal Women of Estradiol and Medroxyprogesterone Alone and Combined on Resistance Artery Function and Endothelial Morphology and Movement J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1874 - 1883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Patel and R. R. Arora Review: Endothelial dysfunction: A potential tool in gender related cardiovascular disease Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 89 - 100. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Sherwood, J. K. Bower, J. McFetridge-Durdle, J. A. Blumenthal, L. K. Newby, and A. L. Hinderliter Age Moderates the Short-Term Effects of Transdermal 17{beta}-Estradiol on Endothelium-Dependent Vascular Function in Postmenopausal Women Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1782 - 1787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Christian, P. Y. Liu, S. Harrington, M. Ruan, V. M. Miller, and L. A. Fitzpatrick Intimal Estrogen Receptor (ER){beta}, But Not ER{alpha} Expression, Is Correlated with Coronary Calcification and Atherosclerosis in Pre- and Postmenopausal Women J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2713 - 2720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh and B.-K. Yoon Controversies regarding hormone therapy: Insights from inflammation and hemostasis Cardiovasc Res, April 1, 2006; 70(1): 22 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Speyer, N. J. Rancilio, S. D. McClintock, J. D. Crawford, H. Gao, J. V. Sarma, and P. A. Ward Regulatory effects of estrogen on acute lung inflammation in mice Am J Physiol Cell Physiol, April 1, 2005; 288(4): C881 - C890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Economides, L. Khaodhiar, A. Caselli, A. E. Caballero, H. Keenan, S.-E. Bursell, G. L. King, M. T. Johnstone, E. S. Horton, and A. Veves The Effect of Vitamin E on Endothelial Function of Micro- and Macrocirculation and Left Ventricular Function in Type 1 and Type 2 Diabetic Patients Diabetes, January 1, 2005; 54(1): 204 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Smith, S. R. Coats, H. Qin, M. S. Petrie, J. W. Covington, M. Su, M. Eren, and D. E. Vaughan Differential and Opposing Regulation of PAI-1 Promoter Activity by Estrogen Receptor {alpha} and Estrogen Receptor {beta} in Endothelial Cells Circ. Res., August 6, 2004; 95(3): 269 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Prestwood, C. Unson, M. Kulldorff, and M. Cushman The Effect of Different Doses of Micronized 17{beta}-Estradiol on C-Reactive Protein, Interleukin-6, and Lipids in Older Women J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2004; 59(8): M827 - M832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh and I. Sakuma Should Progestins Be Blamed for the Failure of Hormone Replacement Therapy to Reduce Cardiovascular Events in Randomized Controlled Trials? Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1171 - 1179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Schoppen, A. M. Perez-Granados, A. Carbajal, P. Oubina, F. J. Sanchez-Muniz, J. A. Gomez-Gerique, and M. P. Vaquero A Sodium-Rich Carbonated Mineral Water Reduces Cardiovascular Risk in Postmenopausal Women J. Nutr., May 1, 2004; 134(5): 1058 - 1063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M Steinberg, N. L Guthrie, A. C Villablanca, K. Kumar, and M. J Murray Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women Am. J. Clinical Nutrition, July 1, 2003; 78(1): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Teede, B. P. McGrath, L. DeSilva, M. Cehun, A. Fassoulakis, and P. J. Nestel Isoflavones Reduce Arterial Stiffness: A Placebo-Controlled Study in Men and Postmenopausal Women Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1066 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Gladwin, A. N. Schechter, F. P. Ognibene, W. A. Coles, C. D. Reiter, W. H. Schenke, G. Csako, M. A. Waclawiw, J. A. Panza, and R. O. Cannon III Divergent Nitric Oxide Bioavailability in Men and Women With Sickle Cell Disease Circulation, January 21, 2003; 107(2): 271 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Schwenke, L. L. Rudel, M. G. Sorci-Thomas, and M. J. Thomas {alpha}-Tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits J. Lipid Res., November 1, 2002; 43(11): 1927 - 1938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Evans, H. A. Harris, C. P. Miller, S. K. Karathanasis, and S. J. Adelman Estrogen Receptors {alpha} and {beta} Have Similar Activities in Multiple Endothelial Cell Pathways Endocrinology, October 1, 2002; 143(10): 3785 - 3795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Garnero, C. Jamin, C.-L. Benhamou, C. Pelissier, and C. Roux Effects of tibolone and combined 17{beta}-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial Hum. Reprod., October 1, 2002; 17(10): 2748 - 2753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Sorensen, P. Collins, P. J.L. Ong, C. M. Webb, C. S. Hayward, E. A. Asbury, P. D. Gatehouse, A. G. Elkington, G. Z. Yang, A. Kubba, et al. Long-Term Use of Contraceptive Depot Medroxyprogesterone Acetate in Young Women Impairs Arterial Endothelial Function Assessed by Cardiovascular Magnetic Resonance Circulation, September 24, 2002; 106(13): 1646 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh, J. Y. Ahn, D. K. Jin, B.-K. Yoon, H. S. Kim, D. S. Kim, M.-S. Shin, J. W. Son, I. S. Choi, and E. K. Shin Effects of Continuous Combined Hormone Replacement Therapy on Inflammation in Hypertensive and/or Overweight Postmenopausal Women Arterioscler Thromb Vasc Biol, September 1, 2002; 22(9): 1459 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh Effects of estrogen on the vascular wall: vasomotor function and inflammation Cardiovasc Res, September 1, 2002; 55(4): 714 - 726. [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Golden, A. Maguire, J. Ding, J. R. Crouse, J. A. Cauley, H. Zacur, and M. Szklo Endogenous Postmenopausal Hormones and Carotid Atherosclerosis: A Case-Control Study of the Atherosclerosis Risk in Communities Cohort Am. J. Epidemiol., March 1, 2002; 155(5): 437 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Sitges, M Heras, E Roig, M Duran, M Masotti, M.J Zurbano, M Roque, and G Sanz Acute and mid-term combined hormone replacement therapy improves endothelial function in post-menopausal women with angina and angiographically normal coronary arteries Eur. Heart J., November 2, 2001; 22(22): 2116 - 2124. [Abstract] [PDF]
|
|
|
|
 |
|
 K. K. Koh, M. H. Kang, D. K. Jin, S.-K. Lee, J. Y. Ahn, H. Y. Hwang, S. H. Yang, D. S. Kim, T. H. Ahn, and E. K. Shin Vascular effects of estrogen in type II diabetic postmenopausal women J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1409 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Visioli Effects of vitamin E on the endothelium: equivocal? {alpha}-tocopherol and endothelial dysfunction Cardiovasc Res, August 1, 2001; 51(2): 198 - 201. [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh, D. K. Jin, S. H. Yang, S.-K. Lee, H. Y. Hwang, M. H. Kang, W. Kim, D. S. Kim, I. S. Choi, and E. K. Shin Vascular Effects of Synthetic or Natural Progestagen Combined With Conjugated Equine Estrogen in Healthy Postmenopausal Women Circulation, April 17, 2001; 103(15): 1961 - 1966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ryysy and H. Yki-Järvinen Improvement of Glycemic Control by 1 Year of Insulin Therapy Leads to a Sustained Decrease in sE-Selectin Concentrations in Type 2 Diabetes Diabetes Care, March 1, 2001; 24(3): 549 - 554. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. K. Dubey and E. K. Jackson Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms Am J Physiol Renal Physiol, March 1, 2001; 280(3): F365 - F388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Carr, B.-Z. Zhu, and B. Frei Potential Antiatherogenic Mechanisms of Ascorbate (Vitamin C) and {alpha}-Tocopherol (Vitamin E) Circ. Res., September 1, 2000; 87(5): 349 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability Cardiovasc Res, September 1, 2000; 47(4): 648 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh and S. H. Yang Commentaries on "Estriol (E3) Replacement Improves Endothelial Function and Bone Mineral Density in Very Elderly Women" and Author Response: Hormone Replacement Therapy in Octogenarian Women: Good or Bad? J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2000; 55(4): 191B - 193. [Full Text]
|
|
|
|
 |
|
 Postmenopausal Estrogen and Vitamin E Journal Watch Women's Health, December 1, 1999; 1999(1201): 15 - 15. [Full Text]
|
|