© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Estrogen replacement therapy, atherosclerosis, and vascular function
aComparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA
bDepartment of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki 00290, Finland
tclarkso{at}wfubmc.edu
* Corresponding author. Tel.: +1-336-716-1570; fax: +1-336-716-1601
There is strong evidence from both human and nonhuman primate studies supporting the conclusion that estrogen deficiency increases the progression of atherosclerosis. More controversial is the conclusion that postmenopausal estrogen replacement inhibits the progression of atherosclerosis. Estrogen treatment of older women (>65 years) with pre-existing coronary artery atherosclerosis had no beneficial effects. In contrast, estrogen treatment of younger postmenopausal women or monkeys in the early stages of atherosclerosis progression has marked beneficial effects. Whether progestogens attenuate the cardiovascular benefits of estrogen replacement therapy has been controversial for more than a decade. Current evidence from studies of both monkeys and women suggest little or no attenuation of estrogen benefits for coronary artery atherosclerosis. Lack of compliance with estrogen replacement therapy, usually because of fear of breast cancer, remains a major problem. Future regimens may overcome that fear by the co-administration of a breast cancer preventive agent (i.e., selective estrogen receptor modulators, phytoestrogens) with low dose estrogen.
KEYWORDS Atherosclerosis; Endothelial function; Hormones; Infection/inflammation; Lipid metabolism
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
M. L. S. Gass, S. S. Bassuk, and J. E. Manson Reassessing Benefits and Risks of Hormone Therapy American Journal of Lifestyle Medicine, January 1, 2009; 3(1): 29 - 43. [Abstract] [PDF] |
||||
![]() |
M. R. Sowers, J. Randolph Jr, M. Jannausch, B. Lasley, E. Jackson, and D. McConnell Levels of Sex Steroid and Cardiovascular Disease Measures in Premenopausal and Hormone-Treated Women at Midlife: Implications for the "Timing Hypothesis" Arch Intern Med, October 27, 2008; 168(19): 2146 - 2153. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Oneda, C. L. M. Forjaz, F. R. Bernardo, T. G. Araujo, J. L. Gusmao, E. Labes, S. B. Abrahao, D. Mion Jr., A. M. Fonseca, and T. Tinucci Low-dose estrogen therapy does not change postexercise hypotension, sympathetic nerve activity reduction, and vasodilation in healthy postmenopausal women Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1802 - H1808. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Vitale, G. Mercuro, E. Cerquetani, G. Marazzi, R. Patrizi, F. Pelliccia, M. Volterrani, M. Fini, P. Collins, and G. M.C. Rosano Time Since Menopause Influences the Acute and Chronic Effect of Estrogens on Endothelial Function Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 348 - 352. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Rosenberg RE: "INVITED COMMENTARY: HORMONE THERAPY AND RISK OF CORONARY HEART DISEASE WHY RENEW THE FOCUS ON THE EARLY YEARS OF MENOPAUSE?" Am. J. Epidemiol., December 15, 2007; 166(12): 1480 - 1481. [Full Text] [PDF] |
||||
![]() |
J. E. Manson and S. S. Bassuk Invited Commentary: Hormone Therapy and Risk of Coronary Heart Disease Why Renew the Focus on the Early Years of Menopause? Am. J. Epidemiol., September 1, 2007; 166(5): 511 - 517. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Barrett-Connor Hormones and Heart Disease in Women: The Timing Hypothesis Am. J. Epidemiol., September 1, 2007; 166(5): 506 - 510. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. H. Straub The Complex Role of Estrogens in Inflammation Endocr. Rev., August 1, 2007; 28(5): 521 - 574. [Abstract] [Full Text] [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] |
||||
![]() |
J. E. Manson, M. A. Allison, J. E. Rossouw, J. J. Carr, R. D. Langer, J. Hsia, L. H. Kuller, B. B. Cochrane, J. R. Hunt, S. E. Ludlam, et al. Estrogen Therapy and Coronary-Artery Calcification N. Engl. J. Med., June 21, 2007; 356(25): 2591 - 2602. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. E. Mendelsohn and R. H. Karas HRT and the Young at Heart N. Engl. J. Med., June 21, 2007; 356(25): 2639 - 2641. [Full Text] [PDF] |
||||
![]() |
M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System Endocr. Rev., June 1, 2007; 28(4): 387 - 439. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Moriarty, K. H. Kim, and J. R. Bender Estrogen Receptor-Mediated Rapid Signaling Endocrinology, December 1, 2006; 147(12): 5557 - 5563. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H. Morrison, R. D. Brinton, P. J. Schmidt, and A. C. Gore Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women J. Neurosci., October 11, 2006; 26(41): 10332 - 10348. [Full Text] [PDF] |
||||
![]() |
J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Collins, M. Flather, B. Lees, R. Mister, A. J. Proudler, J. C. Stevenson, and on behalf of the WHISP (Women's Hormone Interventi Randomized trial of effects of continuous combined HRT on markers of lipids and coagulation in women with acute coronary syndromes: WHISP Pilot Study Eur. Heart J., September 1, 2006; 27(17): 2046 - 2053. [Abstract] [Full Text] [PDF] |
||||
![]() |
Abstracts Heart, February 1, 2006; 92(2): e1 - e1. [Full Text] [PDF] |
||||
![]() |
V. L. Ballard and J. M. Edelberg Harnessing Hormonal Signaling for Cardioprotection Sci. Aging Knowl. Environ., December 21, 2005; 2005(51): re6 - re6. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. M. Miller, T. B. Clarkson, S. M. Harman, E. A. Brinton, M. Cedars, R. Lobo, J. E. Manson, G. R. Merriam, F. Naftolin, and N. Santoro Women, hormones, and clinical trials: a beginning, not an end J Appl Physiol, August 1, 2005; 99(2): 381 - 383. [Full Text] [PDF] |
||||
![]() |
K. H. Kim and J. R. Bender Rapid, Estrogen Receptor-Mediated Signaling: Why Is the Endothelium So Special? Sci. Signal., June 14, 2005; 2005(288): pe28 - pe28. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y.-M. Fan, P. Dastidar, H. Jokela, R. Punnonen, and T. Lehtimaki Hepatic Lipase C-480T Genotype-Dependent Benefit from Long-Term Hormone Replacement Therapy for Atherosclerosis Progression in Postmenopausal Women J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3786 - 3792. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. K. Dubey, B. Imthurn, M. Barton, and E. K. Jackson Vascular consequences of menopause and hormone therapy: Importance of timing of treatment and type of estrogen Cardiovasc Res, May 1, 2005; 66(2): 295 - 306. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Ropponen, K. Aittomaki, M. J. Tikkanen, and O. Ylikorkala Levels of Serum C-Reactive Protein during Oral and Transdermal Estradiol in Postmenopausal Women with and without a History of Intrahepatic Cholestasis of Pregnancy J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 142 - 146. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Nakamura, K. Igarashi, T. Suzuki, J. Kanno, T. Inoue, C. Tazawa, M. Saruta, T. Ando, N. Moriyama, T. Furukawa, et al. E4F1, a Novel Estrogen-Responsive Gene in Possible Atheroprotection, Revealed by Microarray Analysis Am. J. Pathol., December 1, 2004; 165(6): 2019 - 2031. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. K. Dubey, B. Imthurn, L. C. Zacharia, and E. K. Jackson Hormone Replacement Therapy and Cardiovascular Disease: What Went Wrong and Where Do We Go From Here? Hypertension, December 1, 2004; 44(6): 789 - 795. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Helle, V. Lummaa, and J. Jokela Accelerated immunosenescence in preindustrial twin mothers PNAS, August 17, 2004; 101(33): 12391 - 12396. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Stampfer Commentary: Hormones and heart disease: do trials and observational studies address different questions? Int. J. Epidemiol., June 1, 2004; 33(3): 454 - 455. [Full Text] [PDF] |
||||
![]() |
E. Barrett-Connor Commentary: Observation versus intervention--what's different? Int. J. Epidemiol., June 1, 2004; 33(3): 457 - 459. [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
N. F. Col and S. G. Pauker The Discrepancy between Observational Studies and Randomized Trials of Menopausal Hormone Therapy Ann Intern Med, May 4, 2004; 140(9): 765 - 766. [Full Text] [PDF] |
||||
![]() |
F. Grodstein, J. E. Manson, M. J. Stampfer, and W. C. Willett The Discrepancy between Observational Studies and Randomized Trials of Menopausal Hormone Therapy Ann Intern Med, May 4, 2004; 140(9): 764 - 765. [Full Text] [PDF] |
||||
![]() |
F. Akhrass, A. T. Evans, Y. Wang, S. Rich, C. R. Kannan, L. Fogelfeld, and T. Mazzone Hormone Replacement Therapy Is Associated with Less Coronary Atherosclerosis in Postmenopausal Women J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5611 - 5614. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Lokkegaard, Z. Jovanovic, B. L. Heitmann, N. Keiding, B. Ottesen, Y. A. Hundrup, E. B. Obel, and A. T. Pedersen Increased Risk of Stroke in Hypertensive Women Using Hormone Therapy: Analyses Based on the Danish Nurse Study Arch Neurol, October 1, 2003; 60(10): 1379 - 1384. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. C. Chappell, P. E. Gallagher, D. B. Averill, C. M. Ferrario, and K. B. Brosnihan Estrogen or the AT1 Antagonist Olmesartan Reverses the Development of Profound Hypertension in the Congenic mRen2.Lewis Rat Hypertension, October 1, 2003; 42(4): 781 - 786. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Barrett-Connor An Epidemiologist Looks at Hormones and Heart Disease in Women J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4031 - 4042. [Full Text] [PDF] |
||||
![]() |
R. Makela, P. Dastidar, H. Jokela, M. Saarela, R. Punnonen, and T. Lehtimaki Effect of Long-Term Hormone Replacement Therapy on Atherosclerosis Progression in Postmenopausal Women Relates to Myeloperoxidase Promoter Polymorphism J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3823 - 3828. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. van Eickels, R. D. Patten, M. J. Aronovitz, A. Alsheikh-Ali, K. Gostyla, F. Celestin, C. Grohe, M. E. Mendelsohn, and R. H. Karas 17-Beta-Estradiol increases cardiac remodeling and mortality in mice with myocardial infarction J. Am. Coll. Cardiol., June 4, 2003; 41(11): 2084 - 2092. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Grodstein, J. E. Manson, and M. J. Stampfer Postmenopausal Hormone Replacement Therapy Ann Intern Med, April 15, 2003; 138(8): 688 - 688. [Full Text] [PDF] |
||||
![]() |
K. B. Michels and J. E. Manson Postmenopausal Hormone Therapy: A Reversal of Fortune Circulation, April 15, 2003; 107(14): 1830 - 1833. [Full Text] [PDF] |
||||
![]() |
G. Colditz Review: observational studies adjusting for socioeconomic status and lifestyle show no association between HRT and CAD Evid. Based Med., March 1, 2003; 8(2): 46 - 46. [Full Text] [PDF] |
||||
![]() |
G. Colditz Review: risks and benefits of HRT comparing various sources of evidence Evid. Based Med., March 1, 2003; 8(2): 47 - 47. [Full Text] [PDF] |
||||
![]() |
K. L Moreau, A. J Donato, H. Tanaka, P. P. Jones, P. E Gates, and D. R Seals Basal leg blood flow in healthy women is related to age and hormone replacement therapy status J. Physiol., February 15, 2003; 547(1): 309 - 316. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Grodstein, T. B. Clarkson, and J. E. Manson Understanding the Divergent Data on Postmenopausal Hormone Therapy N. Engl. J. Med., February 13, 2003; 348(7): 645 - 650. [Full Text] [PDF] |
||||
![]() |
D. H. Barlow Time to reflect on the Women's Health Initiative (WHI) Study Hum. Reprod., January 1, 2003; 18(1): 1 - 3. [Full Text] [PDF] |
||||
![]() |
F. Grodstein and J. E. Manson Relationship Between Hormone Replacement Therapy, Socioeconomic Status, and Coronary Heart Disease JAMA, January 1, 2003; 289(1): 44 - 44. [Full Text] [PDF] |
||||
![]() |
N. Radford, T. Church, F. E. Speizer, B. E. Pearson Murphy, S. R. Davis, H. G. Burger, W. H. Goodson III, H. R. Franke, I. Lev, A. Lahad, et al. Risks of Postmenopausal Hormone Replacement JAMA, December 11, 2002; 288(22): 2819 - 2824. [Full Text] [PDF] |
||||
![]() |
L. Speroff The Impact of the Women's Health Initiative on Clinical Practice Reproductive Sciences, September 1, 2002; 9(5): 251 - 253. [PDF] |
||||





























