Advertisement

Menopause and Age-Related General Health Risk: A Woman’s Heart Needs Her Hormones

  • Adam Czyzyk
  • John C. StevensonEmail author
Chapter

Abstract

Cardiovascular disease (CVD) is a leading cause of mortality for women and men, but there is a strong relationship between menopause and incidence of coronary heart disease (CHD) in women. This is believed to be mainly due to the significant decrease of estrogen secretion after menopause. Estrogen receptors are abundant throughout the cardiovascular system and exert long-lasting and rapid actions on it. Experimental data shows that estrogens are cardioprotective and can protect against ischemia and adverse remodeling. In blood vessels, estrogens cause vasodilation and decrease atherogenesis. Therefore, it is understandable that after menopause arterial function deteriorates which, together with unfavorable metabolic alterations, causes an increase in the risk of CHD. Animal studies clearly showed the positive effect of estrogens on cardiovascular function. However, the first large randomized clinical trials of hormone replacement therapy (HRT) conducted in women with established CHD did not show a decreased risk. Analysis of data from subsequent trials revealed that there is a place for exogenous estrogens in the primary prevention of CHD. The timing hypothesis suggests that the introduction of HRT soon after menopause significantly reduces CHD and mortality in primary prevention.

Keywords

Estrogens Hormone replacement therapy Cardiovascular disease Coronary heart disease Menopause 

References

  1. 1.
    Leening MJG, Ferket BS, Steyerberg EW, et al. Sex differences in lifetime risk and first manifestation of cardiovascular disease: prospective population based cohort study. BMJ. 2014;349:g5992.CrossRefGoogle Scholar
  2. 2.
    Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease. Lancet (London, England). 1999;353:89–92.CrossRefGoogle Scholar
  3. 3.
    Roach REJ, Lijfering WM, Rosendaal FR, Cannegieter SC, le Cessie S. Sex difference in risk of second but not of first venous thrombosis clinical perspective. Circulation. 2014;129:51–6.CrossRefGoogle Scholar
  4. 4.
    Eichinger S, Heinze G, Jandeck LM, Kyrle PA. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation. 2010;121:1630–6.CrossRefGoogle Scholar
  5. 5.
    dos Santos RL, da Silva FB, Ribeiro RF, Stefanon I. Sex hormones in the cardiovascular system. Horm Mol Biol Clin Investig. 2014;18:89–103.Google Scholar
  6. 6.
    Yakimchuk K, Jondal M, Okret S. Estrogen receptor α and β in the normal immune system and in lymphoid malignancies. Mol Cell Endocrinol. 2013;375:121–9.CrossRefGoogle Scholar
  7. 7.
    Feldman RD, Gros R. Rapid vascular effects of steroids-a question of balance? Can J Cardiol. 2010;26(Suppl A):22A–6A.CrossRefGoogle Scholar
  8. 8.
    Eyster KM. The estrogen receptors: an overview from different perspectives. New York: Humana Press; 2016. p. 1–10.CrossRefGoogle Scholar
  9. 9.
    Del Principe D, Ruggieri A, Pietraforte D, Villani A, Vitale C, Straface E, Malorni W. The relevance of estrogen/estrogen receptor system on the gender difference in cardiovascular risk. Int J Cardiol. 2015;187:291–8.CrossRefGoogle Scholar
  10. 10.
    Prabhavathi K, Selvi KT, Poornima KN, Sarvanan A. Role of biological sex in normal cardiac function and in its disease outcome—a review. J Clin Diagn Res. 2014;8:BE01–4.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Murphy E, Steenbergen C. Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury. Cardiovasc Res. 2007;75:478–86.CrossRefGoogle Scholar
  12. 12.
    Hayward C. The roles of gender, the menopause and hormone replacement on cardiovascular function. Cardiovasc Res. 2000;46:28–49.CrossRefGoogle Scholar
  13. 13.
    Brower GL, Gardner JD, Janicki JS. Gender mediated cardiac protection from adverse ventricular remodeling is abolished by ovariectomy. Mol Cell Biochem. 2003;251:89–95.CrossRefGoogle Scholar
  14. 14.
    Newton-Cheh C. Sex differences and genetic associations with myocardial infarction. JAMA. 2004;291:3008.CrossRefGoogle Scholar
  15. 15.
    Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF, Ghatei MA, Bloom SR. Central and peripheral administration of Kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol. 2004;16:850–8.CrossRefGoogle Scholar
  16. 16.
    Bae S. Gender differences in cardioprotection against ischemia/reperfusion injury in adult rat hearts: focus on Akt and protein kinase C Signaling. J Pharmacol Exp Ther. 2005;315:1125–35.CrossRefGoogle Scholar
  17. 17.
    Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999;340:1801–11.CrossRefGoogle Scholar
  18. 18.
    Lacka K, Czyzyk A. Hormones and the cardiovascular system. Endokrynol Pol. 2008;59:420–32.PubMedGoogle Scholar
  19. 19.
    Bilsel AS, Moini H, Tetik E, Aksungar F, Kaynak B, Ozer A. 17Beta-estradiol modulates endothelin-1 expression and release in human endothelial cells. Cardiovasc Res. 2000;46:579–84.CrossRefGoogle Scholar
  20. 20.
    Nickenig G, Strehlow K, Wassmann S, Bäumer AT, Albory K, Sauer H, Böhm M. Differential effects of estrogen and progesterone on AT 1 receptor gene expression in vascular smooth muscle cells. Circulation. 2000;102:1828–33.CrossRefGoogle Scholar
  21. 21.
    Chakrabarti S, Lekontseva O, Davidge ST. Estrogen is a modulator of vascular inflammation. IUBMB Life. 2008;60:376–82.CrossRefGoogle Scholar
  22. 22.
    Knowlton AA, Lee AR. Estrogen and the cardiovascular system. Pharmacol Ther. 2012;135:54–70.CrossRefGoogle Scholar
  23. 23.
    Luoto R, Kaprio J, Uutela A. Age at natural menopause and sociodemographic status in Finland. Am J Epidemiol. 1994;139:64–76.CrossRefGoogle Scholar
  24. 24.
    Yen SS. The biology of menopause. J Reprod Med. 1977;18:287–96.PubMedGoogle Scholar
  25. 25.
    Muniyappa R, Wong KA, Baldwin HL, Sorkin JD, Johnson ML, Bhasin S, Harman SM, Blackman MR. Dehydroepiandrosterone secretion in healthy older men and women: effects of testosterone and growth hormone administration in older men. J Clin Endocrinol Metab. 2006;91:4445–52.CrossRefGoogle Scholar
  26. 26.
    Samaan SA, Crawford MH. Estrogen and cardiovascular function after menopause. J Am Coll Cardiol. 1995;26:1403–10.CrossRefGoogle Scholar
  27. 27.
    Matthews KA, Meilahn E, Kuller LH, Kelsey SF, Caggiula AW, Wing RR. Menopause and risk factors for coronary heart disease. N Engl J Med. 1989;321:641–6.CrossRefGoogle Scholar
  28. 28.
    Snowdon DA, Kane RL, Beeson WL, Burke GL, Sprafka JM, Potter J, Iso H, Jacobs DR, Phillips RL. Is early natural menopause a biologic marker of health and aging? Am J Public Health. 1989;79:709–14.CrossRefGoogle Scholar
  29. 29.
    Wenger NK, Arnold A, Bairey Merz CN, et al. Hypertension across a woman’s life cycle. J Am Coll Cardiol. 2018;71:1797–813.CrossRefGoogle Scholar
  30. 30.
    Cooper GS, Sandler DP. Age at natural menopause and mortality. Ann Epidemiol. 1998;8:229–35.CrossRefGoogle Scholar
  31. 31.
    Eapen DJ, Kalra GL, Rifai L, Eapen CA, Merchant N, Khan BV. Raising HDL cholesterol in women. Int J Womens Health. 2010;1:181–91.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Lobo RA, Pickar JH, Stevenson JC, Mack WJ, Hodis HN. Back to the future: hormone replacement therapy as part of a prevention strategy for women at the onset of menopause. Atherosclerosis. 2016;254:282–90.  https://doi.org/10.1016/j.atherosclerosis.2016.10.005.CrossRefPubMedGoogle Scholar
  33. 33.
    Stevenson JC, Rioux JE, Komer L, Gelfand M. 1 and 2 mg 17β-estradiol combined with sequential dydrogesterone have similar effects on the serum lipid profile of postmenopausal women. Climacteric. 2005;8:352–9.CrossRefGoogle Scholar
  34. 34.
    Spencer CP, Godsland IF, Cooper AJ, Ross D, Whitehead MI, Stevenson JC. Effects of oral and transdermal 17β-estradiol with cyclical oral norethindrone acetate on insulin sensitivity, secretion, and elimination in postmenopausal women. Metabolism. 2000;49:742–7.CrossRefGoogle Scholar
  35. 35.
    Gambacciani M, Ciaponi M, Cappagli B, Piaggesi L, De Simone L, Orlandi R, Genazzani AR. Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women. J Clin Endocrinol Metab. 1997;82:414–7.CrossRefGoogle Scholar
  36. 36.
    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;288:321–33.CrossRefGoogle Scholar
  37. 37.
    Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013;310:1353.CrossRefGoogle Scholar
  38. 38.
    Clarkson TB, Anthony MS, Jerome CP. Lack of effect of raloxifene on coronary artery atherosclerosis of postmenopausal monkeys. J Clin Endocrinol Metab. 1998;83:721–6.PubMedGoogle Scholar
  39. 39.
    Clarkson TB, Anthony MS, Morgan TM. Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens. J Clin Endocrinol Metab. 2001;86:41–7.PubMedGoogle Scholar
  40. 40.
    Williams JK, Anthony MS, Honoré EK, Herrington DM, Morgan TM, Register TC, Clarkson TB. Regression of atherosclerosis in female monkeys. Arterioscler Thromb Vasc Biol. 1995;15:827–36.CrossRefGoogle Scholar
  41. 41.
    Hodis HN, Mack WJ, Henderson VW, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016;374:1221–31.CrossRefGoogle Scholar
  42. 42.
    Grossman DC, Curry SJ, Owens DK, et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal women. JAMA. 2017;318:2224.CrossRefGoogle Scholar
  43. 43.
    Mebane-Sims. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the postmenopausal estrogen/progestin interventions (PEPI) trial. J Am Med Assoc. 1994;273:199–208.Google Scholar
  44. 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;343:522–9.CrossRefGoogle Scholar
  45. 45.
    Gallagher JC, Fowler SE, Detter JR, Sherman SS. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab. 2001;86:3618–28.CrossRefGoogle Scholar
  46. 46.
    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;135:939–53.CrossRefGoogle Scholar
  47. 47.
    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;288:2432–40.CrossRefGoogle Scholar
  48. 48.
    Anderson GL. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures. The Women’s Health Initiative randomized trial. JAMA. 2003;290:1739.CrossRefGoogle Scholar
  49. 49.
    Greenspan SL, Resnick NM, Parker RA. The effect of hormone replacement on physical performance in community-dwelling elderly women. Am J Med. 2005;118:1232–9.CrossRefGoogle Scholar
  50. 50.
    Veerus P, Hovi S-L, Fischer K, Rahu M, Hakama M, Hemminki E. Results from the Estonian postmenopausal hormone therapy trial [ISRCTN35338757]. Maturitas. 2006;55:162–73.CrossRefGoogle Scholar
  51. 51.
    Tierney MC, Oh P, Moineddin R, Greenblatt EM, Snow WG, Fisher RH, Iazzetta J, Hyslop PSG, MacLusky NJ. A randomized double-blind trial of the effects of hormone therapy on delayed verbal recall in older women. Psychoneuroendocrinology. 2009;34:1065–74.CrossRefGoogle Scholar
  52. 52.
    Vickers MR, MacLennan AH, Lawton B, et al. Main morbidities recorded in the women’s international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. BMJ. 2007;335:239.CrossRefGoogle Scholar
  53. 53.
    Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, Køber L, Jensen J-EB. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012;345:e6409.CrossRefGoogle Scholar
  54. 54.
    Rossouw JE, Manson JE, Kaunitz AM, Stefanick ML. Study had insufficient power to investigate safety. BMJ. 2012;345:e8146; author reply e8164.CrossRefGoogle Scholar
  55. 55.
    Langer RD, Simon JA, Pines A, Lobo RA, Hodis HN, Pickar JH, Archer DF, Sarrel PM, Utian WH. Menopausal hormone therapy for primary prevention: why the USPSTF is wrong. Climacteric. 2017;20:402–13.CrossRefGoogle Scholar
  56. 56.
    National Collaborating Centre for Women’s and Children’s Health (UK). Menopause. London: National Institute for Health and Care Excellence (UK); 2015.Google Scholar
  57. 57.
    Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of Estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s health initiative randomized controlled trial. JAMA. 2002;288:321–33.CrossRefGoogle Scholar
  58. 58.
    Goulis DG, Lambrinoudaki I. Menopausal hormone therapy for the prevention of cardiovascular disease: evidence-based customization. Maturitas. 2015;81:421–2.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.The Fertility Partnership, Vitrolive Fertility ClinicSzczecinPoland
  2. 2.National Heart and Lung InstituteImperial College London, Royal Brompton HospitalLondonUK

Personalised recommendations