Skip to main content
SpringerLink
Log in

Hormone Therapies and Vascular Outcomes: Who is at Risk?

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Postmenopausal hormone replacement therapy (HRT), such as estrogen with a progestin (E+P), is associated with an increased risk of myocardial infarction (MI), stroke, and venous thrombosis. Subgroups of susceptible women for these clinical outcomes have not been clearly identified, although women with a prior history of venous thrombosis and women with factor V Leiden are at higher risk of venous thrombosis on HRT than others. Effects of HRT on atherosclerosis, coagulation, and inflammation have been investigated, and might improve our understanding of the pathogenesis of this drug effect. In 2 trials E+P did not alter the progression of coronary atherosclerosis, while in a third trial unopposed estradiol retarded atherosclerosis progression in the carotid arteries. HRT is associated with an increase in high-sensitivity C-reactive protein (CRP), an inflammation marker associated with arterial disease risk, and an increase in activated protein C resistance, the biochemical defect associated with factor V Leiden. Given recent data, the only current indication for E+P is the short-term treatment of symptoms of estrogen deficiency, such as hot flashes. Testing for coagulation disorders or inflammatory factors, such as factor V Leiden or CRP, for use in decision-making about HRT use would be premature in unselected patients. Further research is needed to identify pathophysiological mechanisms of vascular harm from these hormones.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: The Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. JAMA 1995;273:199-208.

    Google Scholar 

  2. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998;280:605-613.

    Google Scholar 

  3. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-333.

    Google Scholar 

  4. Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI. A clinical trial of estrogen-replacement therapy after ischemic stroke. N Engl J Med 2001;345:1243-1249.

    Google Scholar 

  5. Cherry N, Gilmour K, Hannaford P, et al. Oestrogen therapy for prevention of reinfarction in postmenopausal women: A randomised placebo controlled trial. Lancet 2002;360:2001-2008.

    Google Scholar 

  6. Clarke SC, Kelleher J, Lloyd-Jones H, Slack M, Schofiel PM. A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: The Papworth HRT atherosclerosis study. BJOG 2002;109:1056-1062.

    Google Scholar 

  7. Herrington DM, Reboussin DM, Brosnihan KB, et al. Effects of estrogen replacement on the progression of coronary artery atherosclerosis. New Engl J Med 2000;343:522-529.

    Google Scholar 

  8. Waters DD, Alderman EL, Hsia J, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: A randomized controlled trial. JAMA 2002;288:2432-2440.

    Google Scholar 

  9. Hodis HN, Mack WJ, Lobo RA, et al. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2001;135:939-953.

    Google Scholar 

  10. Tracy RP, Lemaitre RN, Psaty BM, et al. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: Results from the cardiovascular health study and the rural health promotion project. Arterioscler Thromb Vasc Biol 1997;17:1121-1127.

    Google Scholar 

  11. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973-979.

    Google Scholar 

  12. Ridker PM, Glynn RJ, Hennekens CH. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998;97:2007-2011.

    Google Scholar 

  13. Koenig W, Sund M, Frolich M, et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: Results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg cohort study, 1984 to 1992. Circulation 1999;99:237-242.

    Google Scholar 

  14. Ridker PM. High-sensitivity C-reactive protein: Potential adjunct to global risk assessment in primary prevention of cardiovascular disease. Circulation 2001;103:1813-1818.

    Google Scholar 

  15. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New Engl J Med 2000;342:836-843.

    Google Scholar 

  16. Cermak J, Key N, Bach R, Balla J, Jacob H, Vercellotti G. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993;82:513-520.

    Google Scholar 

  17. Torzewski J, Torzewski M, Bowyer DE, et al. C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. Arterioscler Thromb Vasc Biol 1998;18:1386-1392.

    Google Scholar 

  18. Bhakdi S, Torzewski M, Klouche M, Hemmes M. Complement and atherogenesis: Binding of CRP to degraded, nonoxidized LDL enhances complement activation. Arterioscler Thromb Vasc Biol 1999;19:2348-2354.

    Google Scholar 

  19. Torzewski M, Rist C, Mortensen RF, et al. C-reactive protein in the arterial intima: Role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler Thromb Vasc Biol 2000;20:2094-2099.

    Google Scholar 

  20. Pasceri V, Willerson JT, Yeh ETH. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000;102:2165-2168.

    Google Scholar 

  21. Burke AP, Tracy RP, Kolodgie F, et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: Association with different pathologies. Circulation 2002;105:2019-2023.

    Google Scholar 

  22. Ridker PM, Rifai N, Clearfield M, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. New Engl J Med 2001;344:1959-1965.

    Google Scholar 

  23. Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels: The pravastatin inflammation/CRP evaluation (PRINCE): A randomized trial and cohort study. JAMA 2001;286:64-70.

    Google Scholar 

  24. Cushman M, Meilahn EN, Psaty BM, Kuller LH, Dobs AS, Tracy RP. Hormone replacement therapy, inflammation, and hemostasis in elderly women. Arterioscler Thromb Vasc Biol 1999;19:893-899.

    Google Scholar 

  25. Cushman M, Legault C, Barrett-Connor E, et al. Effect of postmenopausal hormones on inflammation-sensitive proteins: The Postmenopausal Estrogen/Progestin Interventions (PEPI) study. Circulation 1999;100:717-722.

    Google Scholar 

  26. van Baal WM, Kenemans P, van der Mooren MJ, Kessel H, Emeis JJ, Stehouwer CDA. Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal women. Thromb Haemost 1999;81:925-928.

    Google Scholar 

  27. Vehkavaara S, Silveira A, Hakala-Ala-Pietila T, et al. Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women. Thromb Haemost 2001;85:619-625.

    Google Scholar 

  28. Decensi A, Omodei U, Robertson C, et al. Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy women. Circulation 2002;106:1224-1228.

    Google Scholar 

  29. Hoibraaten E, Qvigstad E, Arnesen H, Larsen S, Wickstrom E, Sandset PM. Increased risk of recurrent venous thromboembolism during hormone replacement therapy–results of the randomized, double-blind, placebocontrolled estrogen in venous thromboembolism trial (EVTET). Thromb Haemost 2000;84:961-967.

    Google Scholar 

  30. Rosendaal FR, Vessey M, Rumley A, et al. Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis. Br J Haematol 2002;116:851-854.

    Google Scholar 

  31. Herrington DM, Vittinghoff E, Howard TD, et al. Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease. Arterioscler Thromb Vasc Biol 2002;22:1012-1017.

    Google Scholar 

  32. Post MS, Rosing J, Van Der Mooren MJ, et al. Increased resistance to activated protein C after short-term oral hormone replacement therapy in healthy post-menopausal women. Br J Haematol 2002;119:1017-1023.

    Google Scholar 

  33. Cushman M, Psaty BM, Meilahn EN, Dobs A, Kuller LH. Postmenopausal hormone therapy and concentrations of protein C and protein S in elderly women. Br J Haematol 2001;114:162-168.

    Google Scholar 

  34. Abdollahi M, Cushman M, Rosendaal FR. Obesity: Risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost 2003;89:493-498.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine and Pathology, University of Vermont, College of Medicine, Burlington, VT, 05401, USA

    Mary Cushman

Authors
  1. Mary Cushman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cushman, M. Hormone Therapies and Vascular Outcomes: Who is at Risk?. J Thromb Thrombolysis 16, 87–90 (2003). https://doi.org/10.1023/B:THRO.0000014601.57424.b8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:THRO.0000014601.57424.b8

Search

Navigation