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Hormone Replacement Therapy and Cardiovascular Risk

  • Review Article
  • Published:
Treatments in Endocrinology

Abstract

Hormone replacement therapy (HRT) is effective in suppressing postmenopausal symptoms and, in the past, many have claimed that it is cardioprotective. It was thought that the lower incidence of cardiovascular disease in premenopausal women was related to the cardioprotective effect of estrogen. Many of these studies were, however, observational studies. HRT alters many cardiovascular parameters, most beneficially. The mixed effect on these parameters make the overall result on cardiovascular risk difficult to predict.

However, recent randomized, placebo-controlled trials have shown not only that HRT does not confer cardioprotection, but that it actually increases one’s cardiovascular risk in the short term. Based on the current evidence, HRT should not be recommended in the hope that it will protect postmenopausal women against coronary heart disease.

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References

  1. Edmunds E, Lip GY. Cardiovascular risk in women: the cardiologist’s perspective. Q J Med 2000; 93(3): 135–45

    Article  CAS  Google Scholar 

  2. Bush TL.Preserving cardiovascular benefits of hormone replacement therapy. J Reprod Med 2000; 45(3 Suppl.): 259–73

    Google Scholar 

  3. Sites CK. Hormone replacement therapy: cardiovascular benefits for aging women. Coron Artery Dis 1998; 9(12): 789–93

    Article  PubMed  CAS  Google Scholar 

  4. Burkman RT, Collins JA, Greene RA. Current perspectives on benefits and risks of hormone replacement therapy. Am J Obstet Gynecol 2001; 185(2 Suppl.): S13–23

    Article  PubMed  CAS  Google Scholar 

  5. Kaplan RC, Heckbert SR, Weiss NS, et al. Postmenopausal estrogens and risk of myocardial infarction in diabetic women. Diabetes Care 1998; 21(7): 1117–21

    Article  PubMed  CAS  Google Scholar 

  6. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992; 117(12): 1016–37

    PubMed  CAS  Google Scholar 

  7. Grady D, Hulley SB. Postmenopausal hormones and heart disease. J Am Coll Cardiol 2001; 38(1): 8–10

    Article  PubMed  CAS  Google Scholar 

  8. Contreras I, Parra D. Estrogen replacement therapy and the prevention of coronary heart disease in postmenopausal women. Am J Health Syst Pharm 2000; 57(21): 1963–8

    PubMed  CAS  Google Scholar 

  9. Bush TL, Barrett-Connor E, Cowan LD, et al. Cardiovascular mortality and non-contraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation 1987; 75(6): 1102–9

    Article  PubMed  CAS  Google Scholar 

  10. Grodstein F, Stampfer MJ, Colditz GA, et al. Postmenopausal hormone therapy and mortality. N Engl J Med 1997; 336(25): 1769–75

    Article  PubMed  CAS  Google Scholar 

  11. Grodstein F, Manson JE, Colditz GA, et al. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med 2000; 133(12): 933–41

    PubMed  CAS  Google Scholar 

  12. Garcia-Moll X, Zouridakis E, Cole D, et al. C-reactive protein in patients with chronic stable angina: differences in baseline serum concentration between women and men. Eur Heart J 2000; 21(19): 1598–606

    Article  PubMed  CAS  Google Scholar 

  13. Albert MA. The role of C-reactive protein in cardiovascular disease risk. Curr Cardiol Rep 2000; 2(4): 274–9

    Article  PubMed  CAS  Google Scholar 

  14. Sattar N, Perera M, Small M, et al. Hormone replacement therapy and sensitive C-reactive protein concentrations in women with type-2 diabetes. Lancet 1999; 354(9177): 487–8

    Article  PubMed  CAS  Google Scholar 

  15. Ridker PM, Hennekens CH, Rifai N, et al. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999; 100(7): 713–6

    Article  PubMed  CAS  Google Scholar 

  16. van Baal WM, Kenemans P, van der Mooren MJ, et al. Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal women. Thromb Haemost 1999; 81(6): 925–8

    PubMed  Google Scholar 

  17. Mosca L, Collins P, Herrington DM, et al. Hormone replacement therapy and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 2001; 104(4): 499–503

    Article  PubMed  CAS  Google Scholar 

  18. Isaacs AJ, Britton AR, McPherson K. Utilisation of hormone replacement therapy by women doctors. BMJ 1995; 311(7017): 1399–401

    Article  PubMed  CAS  Google Scholar 

  19. Isaacs AJ, Britton AR, McPherson K. Why do women doctors in the UK take hormone replacement therapy? J Epidemiol Community Health 1997; 51(4): 373–7

    Article  PubMed  CAS  Google Scholar 

  20. Chin BSP, Futaba K, Jethwa A, et al. The impact of coronary heart disease in determining use of hormone replacement therapy in a general practice population. Int J Clin Pract 2001; 55(8): 515–8

    PubMed  CAS  Google Scholar 

  21. Caine YG, Bauer KA, Barzegar S, et al. Coagulation activation following estrogen administration to postmenopausal women. Thromb Haemost 1992; 68(4): 392–5

    PubMed  CAS  Google Scholar 

  22. DeSouza CA, Stevenson ET, Davy KP, et al. Plasma fibrinogen levels in healthy postmenopausal women: physical activity and hormone replacement status. J Gerontol ABiol Sci Med Sci 1997; 52(5): M294–8

    Article  CAS  Google Scholar 

  23. Hahn L, Mattsson LA, Andersson B, et al. The effects of oestrogen replacement therapy on haemostatic variables in postmenopausal women with non-insulin-dependent diabetes mellitus. Blood Coagul Fibrinolysis 1999; 10(2): 81–6

    Article  PubMed  CAS  Google Scholar 

  24. Lip GY, Blann AD, Jones AF, et al. Effects of hormone-replacement therapy on hemostatic factors, lipid factors, and endothelial function in women undergoing surgical menopause: implications for prevention of atherosclerosis. Am Heart J 1997; 134(4): 764–71

    Article  PubMed  CAS  Google Scholar 

  25. Falco C, Tormo G, Estelles A, et al. Fibrinolysis and lipoprotein (a) in women with coronary artery disease: influence of hormone replacement therapy. Haematologica 2001; 86(1): 92–8

    PubMed  CAS  Google Scholar 

  26. Gebara OC, Mittleman MA, Sutherland P, et al. Association between increased estrogen status and increased fibrinolytic potential in the Framingham Offspring Study. Circulation 1995; 91(7): 1952–8

    Article  PubMed  CAS  Google Scholar 

  27. Lowe GD, Upton MN, Rumley A, et al. Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein: a cross-sectional population survey. Thromb Haemost 2001; 86(2): 550–6

    PubMed  CAS  Google Scholar 

  28. Lip GY, Felmeden DC. Hormone replacement therapy and cardiovascular risk: do abnormalities of coagulation and fibrinolysis matter? J Intern Med 2001; 249(3): 201–4

    Article  PubMed  CAS  Google Scholar 

  29. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Writing Group for the PEPI Trial. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1995; 273(3): 199–208

    Article  PubMed  Google Scholar 

  30. Kannel WB, Wolf PA, Castelli WP, et al. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA 1987; 258(9): 1183–6

    Article  PubMed  CAS  Google Scholar 

  31. Kannel WB, D’Agostino RB, Belanger AJ. Update on fibrinogen as a cardiovascular risk factor. Ann Epidemiol 1992; 2(4): 457–66

    Article  PubMed  CAS  Google Scholar 

  32. Manning PJ, Allum A, Jones S, et al. The effect of hormone replacement therapy on cardiovascular risk factors in type 2 diabetes: a randomized controlled trial. Arch Intern Med 2001; 161(14): 1772–6

    Article  PubMed  CAS  Google Scholar 

  33. Whiteman MK, Cui Y, Flaws JA, et al. Low fibrinogen level: apredisposing factor for venous thromboembolic events with hormone replacement therapy. Am J Hematol 1999; 61(4): 271–3

    Article  PubMed  CAS  Google Scholar 

  34. Nakano Y, Oshima T, Matsuura H, et al. Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis. Arterioscler Thromb Vasc Biol 1998; 18(6): 961–7

    Article  PubMed  CAS  Google Scholar 

  35. Mikkola T, Viinikka L, Ylikorkala O. Estrogen and postmenopausal estrogen/progestin therapy: effect on endothelium-dependent prostacyclin, nitric oxide and endothelin-1 production. Eur J Obstet Gynecol Reprod Biol 1998; 79(1): 75–82

    Article  PubMed  CAS  Google Scholar 

  36. Kinlay S, Libby P, Ganz P. Endothelial function and coronary artery disease. Curr Opin Lipidol 2001; 12(4): 383–9

    Article  PubMed  CAS  Google Scholar 

  37. Konukoglu D, Serin O, Yelke HK. Effects of hormone replacement therapy on plasma nitric oxide and total thiol levels in postmenopausal women. J Toxicol Environ Health A 2000; 60(2): 81–7

    Article  PubMed  CAS  Google Scholar 

  38. McCrohon JA, Adams MR, McCredie RJ, et al. Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women. Clin Endocrinol (Oxf) 1996; 45(4): 435–41

    Article  CAS  Google Scholar 

  39. Enderle MD, Sayer R, Balletshofer B, et al. Acute improvement of peripheral endothelial function in postmenopausal women with coronary artery disease after single oral intake of 17beta-estradiol valerate. Exp Clin Endocrinol Diabetes 2000; 108(5): 382–5

    Article  PubMed  CAS  Google Scholar 

  40. Chae CU, Ridker PM, Manson JE. Postmenopausal hormone replacement therapy and cardiovascular disease. Thromb Haemost 1997; 78(1): 770–80

    PubMed  CAS  Google Scholar 

  41. Boden WE. High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease: assessing the data from Framingham to the Veterans Affairs High—Density Lipoprotein Intervention Trial. Am J Cardiol 2000; 86(12 Suppl. A): LI 9–22

    Google Scholar 

  42. Bass KM, Newschaffer CJ, Klag MJ, et al. Plasma lipoprotein levels as predictors of cardiovascular death in women. Arch Intern Med 1993; 153(19): 2209–16

    Article  PubMed  CAS  Google Scholar 

  43. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280(7): 605–13

    Article  PubMed  CAS  Google Scholar 

  44. Herrington DM, Reboussin DM, Brosnihan KB, et al. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med 2000; 343(8): 522–9

    Article  PubMed  CAS  Google Scholar 

  45. Binder EF, Williams DB, Schechtman KB, et al. Effects of hormone replacement therapy on serum lipids in elderly women: a randomized, placebo-controlled trial. Ann Intern Med 2001; 134 (9 Pt 1): 754–60

    PubMed  CAS  Google Scholar 

  46. Sbarouni E, Kyriakides ZS, Kremastinos DT. The effect of hormone replacement therapy alone and in combination with simvastatin on plasma lipids of hyper-cholesterolemic postmenopausal women with coronary artery disease. J Am Coll Cardiol 1998; 32(5): 1244–50

    Article  PubMed  CAS  Google Scholar 

  47. Herrington DM, Reboussin DM, Klein KP, et al. The estrogen replacement and atherosclerosis (ERA) study: study design and baseline characteristics of the cohort. Control Clin Trials 2000; 21(3): 257–85

    Article  PubMed  CAS  Google Scholar 

  48. Espeland MA, Marcovina SM, Miller V, et al. Effect of postmenopausal hormone therapy on lipoprotein (a) concentration. PEPI Investigators: postmenopausal estrogen/progestin interventions. Circulation 1998; 97(10): 979–86

    Article  PubMed  CAS  Google Scholar 

  49. Rossouw JE. Hormone replacement therapy and cardiovascular disease. Curr Opin Lipidol l999; 10(5): 429–34

    Article  Google Scholar 

  50. Futterman LG, Lemberg L. Lp (a) lipoprotein: an independent risk factor for coronary heart disease after menopause. Am J Crit Care 2001; 10(1): 63–7

    PubMed  CAS  Google Scholar 

  51. Rodriguez CR, Seman LJ, Ordovas JM, et al. Lipoprotein (a) and coronary heart disease. Chem Phys Lipids 1994; 67-68: 389–98

    Article  PubMed  CAS  Google Scholar 

  52. Shlipak MG, Simon JA, Vittinghoff E, et al. Estrogen and progestin, lipoprotein (a), and the risk of recurrent coronary heart disease events after menopause. JAMA 2000; 283(14): 1845–52

    Article  PubMed  CAS  Google Scholar 

  53. Orth-Gomer K, Mittleman MA, Schenck-Gustafsson K, et al. Lipoprotein (a) as a determinant of coronary heart disease in young women. Circulation 1997; 95(2): 329–34

    Article  PubMed  CAS  Google Scholar 

  54. Kornhauser C, Malacara JM, Garay ME, et al. The effect of hormone replacement therapy on blood pressure and cardiovascular risk factors in menopausal women with moderate hypertension. J Hum Hypertens 1997; 11(7): 405–11

    Article  PubMed  CAS  Google Scholar 

  55. Harrison-Bernard LM, Raij L. Postmenopausal hypertension. Curr Hypertens Rep 2000; 2(2): 202–7

    Article  PubMed  CAS  Google Scholar 

  56. Pines A, Mijatovic V, van der Mooren MJ, et al. Hormone replacement therapy and cardioprotection: basic concepts and clinical considerations. Eur J Obstet Gynecol Reprod Biol 1997; 71(2): 193–7

    Article  PubMed  CAS  Google Scholar 

  57. Mijatovic V, van der Mooren MJ, Stehouwer CD, et al. Postmenopausal hormone replacement, risk estimators for coronary artery disease and cardiovascular protection. Gynecol Endocrinol 1999; 13(2): 130–44

    Article  PubMed  CAS  Google Scholar 

  58. Nogawa N, Sumino H, Ichikawa S, et al. Effect of long-term hormone replacement therapy on angiotensin-converting enzyme activity and bradykinin in postmenopausal women with essential hypertension and normotensive postmenopausal women. Menopause 2001; 8(3): 210–5

    Article  PubMed  CAS  Google Scholar 

  59. Lip GY, Beevers M, Churchill D, et al. Hormone replacement therapy and blood pressure in hypertensive women. J Hum Hypertens 1994; 8(7): 491–4

    PubMed  CAS  Google Scholar 

  60. Pfeffer RI, Kurosaki TT, Charlton SK. Estrogen use and blood pressure in later life. Am J Epidemiol 1979; 110(4): 469–78

    PubMed  CAS  Google Scholar 

  61. Scuteri A, Bos AJ, Brant LJ, et al. Hormone replacement therapy and longitudinal changes in blood pressure in postmenopausal women. Ann Intern Med 2001; 135(4): 229–38

    PubMed  CAS  Google Scholar 

  62. Szekacs B, Vajo Z, Acs N, et al. Hormone replacement therapy reduces mean 24-hour blood pressure and its variability in postmenopausal women with treated hypertension. Menopause 2000; 7(1): 31–5

    Article  PubMed  CAS  Google Scholar 

  63. Harvey PJ, Molloy D, Upton J, et al. Dose response effect of conjugated equine oestrogen on blood pressure in postmenopausal women with hypertension. Blood Press 2000; 9(5): 275–82

    Article  PubMed  CAS  Google Scholar 

  64. Espeland MA, Hogan PE, Fineberg SE, et al. Effect of postmenopausal hormone therapy on glucose and insulin concentrations. PEPI Investigators: postmenopausal estrogen/progestin interventions. Diabetes Care 1998; 21(10): 1589–95

    Article  PubMed  CAS  Google Scholar 

  65. Fineberg SE. Glycaemic control and hormone replacement therapy: implications of the Postmenopausal Estrogen/Progestogen Intervention (PEPI) study. Drugs Aging 2000; 17(6): 453–61

    Article  PubMed  CAS  Google Scholar 

  66. Simon JA, Hsia J, Cauley JA, et al. Postmenopausal hormone therapy and risk of stroke: The Heart and Estrogen-progestin Replacement Study (HERS). Circulation 2001; 103(5): 638–42

    Article  PubMed  CAS  Google Scholar 

  67. Viscoli CM, Brass LM, Kernan WN, et al. A clinical trial of estrogen-replacement therapy after ischemic stroke. N Engl J Med 2001; 345(17): 1243–9

    Article  PubMed  CAS  Google Scholar 

  68. The Women’s Health Initiative Study Group. Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials 1998; 19(1): 61–109

    Article  Google Scholar 

  69. Wren BG. Megatrials of hormonal replacement therapy. Drugs Aging 1998; 12(5): 343–8

    Article  PubMed  CAS  Google Scholar 

  70. Mitka M. New advice for women patients about hormone therapy and the heart. JAMA 2001; 286(8): 907

    Article  PubMed  CAS  Google Scholar 

  71. Tunstall-Pedoe H. Myth and paradox of coronary risk and the menopause. Lancet 1998; 351(9113): 1425–7

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We acknowledge the support of the City Hospital Research & Development Programme for the Haemostasis Thrombosis and Vascular Biology Unit.

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  1. Haemostasis Thrombosis and Vascular Biology Unit, T16/10/2001, University Department of Medicine, City Hospital, Birmingham, B18 7QH, England

    Aun-Yeong Chong &  Gregory Y. H. Lip

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Correspondence to Gregory Y. H. Lip.

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Chong, AY., Lip, G.Y.H. Hormone Replacement Therapy and Cardiovascular Risk. Mol Diag Ther 1, 95–103 (2002). https://doi.org/10.2165/00024677-200201020-00003

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