Hormone Therapy and the Primary and Secondary Prevention of Cardiovascular Disease

  • Amos Pines
Part of the Endocrine Updates book series (ENDO, volume 8)

Abstract

The publication of the first results from the Heart and Oestrogen/progestin Replacement Study (HERS)(1) led to a turmoil in the perception of cardioprotection by hormone replacement therapy (HRT). Basically, the study showed that a continuous combined regimen (conjugated equine estrogen/medroxyprogesterone acetate) in women with documented coronary artery disease (CAD) was associated with higher mortality than in a placebo group during the first year of treatment. Later on this ill-effect was reversed and at years 4+5 of the study, the known benefit of HRT became evident. The possibility that HRT might be dangerous in prevention of CAD has been discussed quite extensively since the announcement of the HERS trial results. Questions like: “Are these findings really true? Can we extrapolate those results to the general postmenopausal population?” are presented in every forum on HRT. The following chapter will review the relevant data and discuss the various aspects of one of the most important issues in menopause medicine — cardioprotection by HRT.

Keywords

Postmenopausal Woman Honnone Replacement Therapy Estrogen Replacement Therapy Preventive Cardiology Documented Coronary Artery Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondaryprevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605–613.CrossRefPubMedGoogle Scholar
  2. 2.
    Tunstall-Pedoe H. Myth and paradox of coronary risk and the menopause. Lancet 1998; 351: 1425–1427.CrossRefPubMedGoogle Scholar
  3. 3.
    Mosca L, Manson JE, Sutherland SE, Langer RD, Manolio T, Barrett-Connor E. Cardiovascular disease in women. A statement for healthcare professionals from the American Heart Association. Circulation 1997; 96: 2468–2482.CrossRefPubMedGoogle Scholar
  4. 4.
    Rich-Edwards JW, Manson J’E, Hennekens CH, Buring JE. The primary prevention of coronary heart disease in women. N Engl J Med 1995; 332: 1758–1766.CrossRefPubMedGoogle Scholar
  5. 5.
    Grodstein F, Stampfer M. The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis 1995; 38: 199–210.CrossRefPubMedGoogle Scholar
  6. 6.
    Pines A, Mijatovic V, Mooren MJ, Kenemans P. Hormone replacement therapy and cardioprotection: basic concepts and clinical considerations. Eur J Obstet Gynecol Rep Biol 1997; 71: 193–197.CrossRefGoogle Scholar
  7. 7.
    Mendelsohn ME, Karas RH. Mechanisms of disease: the protective effects of estrogen on the cardiovascular system. N Engl J Med 1999; 340: 1801–1811.CrossRefPubMedGoogle Scholar
  8. 8.
    Greendale GA, Lee NP, Arriola ER. The menopause. Lancet 1999; 353: 571–580.CrossRefGoogle Scholar
  9. 9.
    Barrett-Connor E. Hormone replacement therapy. BMJ 1998; 317: 457–461.CrossRefPubMedGoogle Scholar
  10. 10.
    Rodstrom K, Bengtsson C, Lissner L, Bjorkelund C. Pre-existing risk factor profiles in users and nonusers of hormone replacement therapy: prospective cohort study in Gothenburg, Sweden. BMJ 1999; 319: 890–893.CrossRefPubMedGoogle Scholar
  11. 11.
    Matthews K, Kuller I, Wing R, Meilahn E, Plantinga P. Prior to use of estrogen replacement therapy: are users healthier than nonusers? Am J Epidemiol 1996; 143: 971–978.CrossRefPubMedGoogle Scholar
  12. 12.
    Grodstein F, Stampfer MJ, Manson JE, et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med, 1996; 335: 453–461.CrossRefPubMedGoogle Scholar
  13. 13.
    Bush TL, Barrett-Connor E, Cowan LD, et al. Cardiovascular mortality and noncontraceptive use of estrogen in women. Results from the Lipid Research Clinics Program Follow Up Study. Circulation 1987; 75: 1102–1109.CrossRefPubMedGoogle Scholar
  14. 14.
    Henderson BE, Paganini-Hill A, Ross RK. Reduced mortality in users of estrogen replacement therapy. Arch Intern Med 1991; 151: 75–78.CrossRefPubMedGoogle Scholar
  15. 15.
    Ettinger B, Friedman GD, Bush T, Quesenberry CP Jr. Decreased mortality associated with longterm postmenopausal estrogen therapy. Obstet Gynecol 1996; 87: 6–12.CrossRefPubMedGoogle Scholar
  16. 16.
    Sidney S, Petitti DB, Quesenberry CP Jr. Myocardial infarction and the use of estrogen and estrogenprogestogen in postmenopausal women. Ann Intern Med 1997; 127: 501–508.PubMedGoogle Scholar
  17. 17.
    Psaty BM, Heckbert SR, Atkins D, Lemaitre R, Koepsell TD, Wahl PW, Siscovick DS, Wagner EH. The risk of myocardial infarction associated with the combined use of estrogens and progestins in postmenopausal women. Arch Intern Med 1994; 154: 1333–1339.CrossRefPubMedGoogle Scholar
  18. 18.
    Folsom AR, Mink PJ, Sellers TA, Hong CP, Zheng W, Potter JD. Hormonal replacement therapy and morbidity and mortality in a prospective study of postmenopausal women. Am J Public Health 1995; 85: 1128–1132.CrossRefPubMedGoogle Scholar
  19. 19.
    Falkeborne M, Persson I, Adami H-O, Bergstrom R, Eaker E, Lithell H, Mohsen R, Naessen T. The risk of acute myocardial infarction after oestrogen and oestrogen-progestogen replacement. Br J Obstet Gynecol 1992; 99: 821–828.CrossRefGoogle Scholar
  20. 20.
    Sourander L, Rajala T, Raiha I, Maleinen J, Erkkola R, Helenius H. Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy (ERT). Lancet 1998; 352: 1965–1969.CrossRefPubMedGoogle Scholar
  21. 21.
    Grodstein F, Stampfer MJ, Coldiditz GA, et al. Postmenopausal hormone therapy and mortality. N Engl J Med 1997; 336: 1769–1775.CrossRefPubMedGoogle Scholar
  22. 22.
    Hemminki E, McPherson K. Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials. BMJ 1997; 315: 149–153.CrossRefPubMedGoogle Scholar
  23. 23.
    White MM, Zamudio S, Stevens T, Tyler R, Lindenfeld J, Leslie K, Moore LG. Estrogen, progesterone, and vascular reactivity: potential cellular mechanisms. Endocr Rev 1995; 6: 739–751.Google Scholar
  24. 24.
    Gruchow HW, Anderson AJ, Barboriak JJ, Sobocinsky KA. Postmenopausal use of estrogen and occlusion of coronary arteries. Am Heart J 1988; 115: 954–963.CrossRefPubMedGoogle Scholar
  25. 25.
    Hong MK, Romm PA, Reagen K, Green CE, Rackley CE. Effects of estrogen replacement therapy on serum lipid values and angiographically defined coronary artery disease in postmenopausal women. Am J Cardiol 1992; 69: 176–178.CrossRefPubMedGoogle Scholar
  26. 26.
    Newton KM, LaCroix AZ, McKnight B, Knopp RH, Siscovick DS, Heckbert SR, Weiss NS. Estrogen replacement therapy and prognosis after first myocardial infarction. Am J Epidemiol 1997; 145: 269–277.CrossRefPubMedGoogle Scholar
  27. 27.
    Sullivan JM, Vander Zwaag R, Hughes JP, Maddok V, Kroetz FW, Ramanathan KB, Mirvis DM. Estrogen replacement and coronary artery disease: effect in survival in postmenopausal women. Arch Intern Med 1990; 150: 2557–2562.CrossRefPubMedGoogle Scholar
  28. 28.
    Sullivan JM, El-Zeky F, Vander Zwaag R, Ramanathan KB. Effect on survival of estrogen replacement therapy after coronary artery bypass grafting. Am J Cardiol 1997; 79: 847–850.CrossRefPubMedGoogle Scholar
  29. 29.
    O’Keefe JH, Kim SC, Hall RR, Cochran VC, Lawhom SL, McCallister BD. Estrogen replacement therapy after coronary angioplasty in women. J Am Coll Cardiol 1997; 29: 1–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Herrington DM, Fong J, Sempos CT, et al. Comparison of the Heart and Estrogen/ Progestin Replacement Study (HERS) cohort with women with coronary disease from the National Health and Nutrition Examination Survey III (NHANES III). Am Heart J 1998; 136: 115–124.CrossRefPubMedGoogle Scholar
  31. 31.
    Adams MR, Register TC, Golden TL, Wagner JD, Williams JK. Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis. Arterioscler Thromb Vasc Biol 1997; 17: 217–221.CrossRefPubMedGoogle Scholar
  32. 32.
    Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 1995; 273: 199–208.CrossRefPubMedGoogle Scholar
  33. 33.
    Stevenson J, Samsioe G, Pines A, Huber J, Netelenbos C, de Roo G, Sitruk-Ware R, Barensten R, Palacios S, Koninckx PR. Critical comments on the HERS study. Maturitas 1998; 31: 77–87.CrossRefGoogle Scholar
  34. 34.
    Herrington DM. The HERS Trial results: paradigms lost? Ann Intern Med 1999; 131: 463–466.PubMedGoogle Scholar
  35. 35.
    Barrett-Connor E, Stuenkel C. Hormones and heart disease in womem: Heart and Estrogen/Progestin Replacement Study in perspective. J Clin Endocrinol Metab 1999; 84: 1848–1853.CrossRefPubMedGoogle Scholar
  36. 36.
    Alexander KP, Newby K, Harrington A, et al. Initiation of hormone replacement therapy after acute myocardial infarction is associated with more angina but less death/ml during follow-up. J Am Coll Cardiol 1999; 33 (suppl A): 315A.Google Scholar
  37. 37.
    Barrett-Connor E, Grady D: Hormone replacement therapy, heart disease, and other considerations. Annu Rev Public Health 1998; 19: 55–72.CrossRefPubMedGoogle Scholar
  38. 38.
    Clinical Synthesis Panel on HRT. Hormone replacement therapy. Lancet 1999; 354: 152–155.CrossRefGoogle Scholar
  39. 39.
    Mosca L, Grundy SM, Judelson D, et al. Guide to preventive cardiology for women. Circulation 1999; 99: 2480–2484.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Amos Pines
    • 1
  1. 1.The Department of Medicine “T”, Ichilov Hospital, affiliated to the Sackler Faculty of MedicineTel-Aviv University, and the Menopause Clinic, Ramat-Marpe HospitalRamat-GanIsrael

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