Current Obstetrics and Gynecology Reports

, Volume 3, Issue 4, pp 217–222 | Cite as

Menopausal Hormonal Therapy and Cardiovascular Disease

Management of Menopause (K-E Huang, Section Editor)
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Abstract

Cardiovascular disease is the leading cause of death in women. Older observational studies suggested a significant protective effect of menopausal hormone therapy (MHT) for coronary heart disease (CHD) when prescribed for women at the onset of menopause; and this also translated into a significant reduction in mortality as well. Multiple mechanisms have been found to support these findings. Various secondary prevention trials and the use of hormones in older women have shown negative findings and a trend for more coronary events in these women with atherosclerotic plaque. Data from the Women’s Health Initiative in younger women confirm the data in the observational studies showing a protective effect on CHD and mortality for conjugated equine estrogens (CEE) alone, whereas the data with CEE and medroxyprogesterone acetate do not show as positive an effect. Recent trials testing the “timing” hypothesis also have confirmed these data for benefit in younger women, but not in older women. Because prevention of diseases after menopause should be a major goal of providers of health care for women, the consideration of using MHT, particularly the use of estrogen, may once again be considered as part of this prevention strategy.

Keywords

Coronary heart disease Mortality Menopause Estrogen Progestogen Prevention 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Statistical Fact Sheet 2014 Update.www.heart.org.
  2. 2.
    Weiss NS. Relationship of menopause to serum cholesterol and arterial blood pressure: the United States health examination survey of adults. Am J Epidemiol. 1972;96:237–41.Google Scholar
  3. 3.
    Davis SR, Castelo-Branco C, Chedraui P, et al. Understanding weight gain at menopause. Climacteric. 2012;15:419–29.PubMedCrossRefGoogle Scholar
  4. 4.
    Mendelsohn ME, Karas RH. Mechanisms of disease: the protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999;340:1801–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science. 2005;308:1583–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Lobo RA. Effects of hormonal replacement on lipids and lipoproteins in postmenopausal women. J Clin Endocrinol Metab. 1991;73:925–30.PubMedCrossRefGoogle Scholar
  7. 7.
    Stampfer MJ, Coldit GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med. 1991;20:47–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Henderson BE, Paganini-Hill A, Ross RK. Decreased mortality in users of estrogen replacement therapy. Arch Intern Med. 1991;151:75–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Altern Med. 1991;117:1016–37.Google Scholar
  10. 10.
    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;280:605–13.PubMedCrossRefGoogle Scholar
  11. 11.
    Herrington DM, Reboussin DM, Brosnihan KB, et al. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med. 2000;343:522–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Manson JE, Hsia J, Johnson KC, et al. Women’s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Hsia J, Langer RD, Manson JE, et al. Conjugated equine estrogens and coronary heart disease; the Women’s Health Initiative. Arch Intern Med. 2006;166:357–65.PubMedCrossRefGoogle Scholar
  14. 14.
    Post WS, Goldschmidt-Clermont PJ, Wilhide CC, et al. Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system. Cardiovascular. 1999;43(4):985–91.CrossRefGoogle Scholar
  15. 15.
    Umetani M, Domoto H, Gormley AK, et al. 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med. 2007;10:1185–92.CrossRefGoogle Scholar
  16. 16.
    Hu P, Greendale GA, Palla SL, et al. The effects of hormone therapy on the markers of inflammation and endothelial function and plasma matrix metalloproteinase-9 level in postmenopausal women: the Postmenopausal Estrogen Progestin Intervention (PEPI) trial. Atherosclerosis. 2006;185:347–52.PubMedCrossRefGoogle Scholar
  17. 17.
    Galis ZS, Sukhova GK, Lark MV, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994;94:2493–503.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Lobo RA. Evaluation of cardiovascular event rates with hormone therapy in healthy postmenopausal women: results from four large clinical trials. Arch Intern Med. 2004;164:48–84.CrossRefGoogle Scholar
  19. 19.
    Stevenson JC, Hodis HN, Pickar JH, Lobo RA. Coronary heart disease and menopause management: the Swinging Pendulum of HRT. Atherosclerosis. 2009;207:336–3401.PubMedCrossRefGoogle Scholar
  20. 20.•
    Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended post stopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013;310:1353–68. This is the most recent follow-up of the hormone trials from the WHI. The data in the 50–59-year-old group with CEE alone show significant benefit. The conclusion of the authors that there is no role in prevention should be challenged.PubMedCrossRefGoogle Scholar
  21. 21.
    Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465–77.PubMedCrossRefGoogle Scholar
  22. 22.
    Manson JE, Allison MA, Rossouw JE, et al. WHI and SHI-CACS Investigators. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007;356:2591–602.PubMedCrossRefGoogle Scholar
  23. 23.
    LaCroix AZ, Chlebowski RT, Manson JE, et al. WHI Investigators. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011;305:1305–14.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Salpeter SR, Walsh JM, Greyber E, Salpeter EE. Brief report: coronary heart disease events associated with hormone therapy in younger and older women. A meta-analysis. J Gen Intern Med. 2006;21:363–6.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Salpeter SR, Cheng J, Thabane, et al. Bayesian meta-analysis of hormone therapy and mortality in younger post-menopausal women. Am J Med. 2009;122:1016–22.PubMedCrossRefGoogle Scholar
  26. 26.
    Harmon SM, Black DM, Naftolin F, et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women in the Kronos Early Estrogen Prevention study (KEEPS): A randomized controlled trial. Annals of Int Med. 2014Google Scholar
  27. 27.
    Hodis HN. ELITE – Does the trial outcome confirm or refute the timing hypothesis of hormone therapy? Cancun: Presented at the 14th World Congress on Menopause of the International Menopause Society; 2014.Google Scholar
  28. 28.•
    Schierbeck IL, Renmark L, Tofteng CL, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomized trial. BMJ. 2012;345:e6409. Prospective trial in 1,006 women at the onset of menopause treated with MHT for 10 years, followed for up to 16 years, and showing a significant reduction in CHD.PubMedCrossRefGoogle Scholar
  29. 29.
    Lobo RA. Where are we 10 years after the Women’s Health Initiative? J Clin Endocrinol Metab. 2013;98(5):1771–80.PubMedCrossRefGoogle Scholar
  30. 30.
    Hodis HN, Mack WJ. Hormone replacement therapy and the association with coronary heart disease and overall mortality: clinical application of the timing hypothesis. J Steroid Biochem Mol Biol. 2014;142:68–75.PubMedCrossRefGoogle Scholar
  31. 31.
    Canonico M, Plu-Bureau G, Lowe GD, et al. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ. 2008;336:1227–31.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Canonico M, Olger E, Plu-Bureau G, et al. Estrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of administration and progestogens: the ESTER study. Circulation. 2007;115:840–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Lidegaard O, Lokkegaard EA, Jensen A, et al. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med. 2012;366:2257–66.PubMedCrossRefGoogle Scholar
  34. 34.
    Lobo RA, Clarkson TB. Different mechanisms for benefit and risk of coronary heart disease and stroke in early postmenopausal women: a hypothetical explanation. Menopause. 2011;18:237–40.PubMedCrossRefGoogle Scholar
  35. 35.
    Sare GM, Gray LJ, Bath PM. Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis. Eur Heart J. 2008;29:2031–41.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Henderson VW, Lobo RA. Hormone therapy and the risk of stroke: perspectives 10 years after the Women’s Health Initiative trials. Climacteric. 2012;15(3):229–34. Review.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Sweetland V, Beral A, Balkwill B, et al. Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J Thromb Haemost. 2012;10:2277–86.PubMedCrossRefGoogle Scholar
  38. 38.
    Sturdee DW, Pines A, IMS Writing Group, et al. Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health. Climacteric. 2011;14:302–20.PubMedCrossRefGoogle Scholar
  39. 39.
    Fournier, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008;107:103–11.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Lewandowski KC, Komorowski J, Mikhalidis DP, et al. Effects of hormone replacement therapy type and route of administration on plasma matrix metalloproteinases and their tissue inhibitors in postmenopausal women. J Clin Endocrinol Metab. 2006;91(8):3123.PubMedCrossRefGoogle Scholar
  41. 41.
    de Villiers TJ, Gass ML, Haines CJ, et al. Global consensus statement on menopausal hormone therapy. Climacteric. 2013;16:203–4.PubMedCrossRefGoogle Scholar
  42. 42.
    Sarrel PM, Njike V, Vinante V, Katz DL. The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women age 50 to 59. Am J Public Health. 2013;103:1583–8.PubMedCrossRefGoogle Scholar
  43. 43.•
    Lobo RA, Davis SR, De Villiers TJ, et al. Prevention of diseases after menopause. Climacteric. 2014;17:1–17. This is a “white” paper written on behalf of the International Menopause Society for the 2014 theme of World Menopause Day. It stresses the role of prevention for women after menopause and explores in detail the potential beneficial role of estrogen as part of this strategy.Google Scholar
  44. 44.
    Panay N, Fenton A. The ‘window of opportunity’ – should we be taking it? Climacteric. 2014;17:211–2.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyColumbia University Medical CenterNew YorkUSA

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