Menopause and Cardiovascular Risk

  • Angela H. E. M. MaasEmail author
  • C. Noel Bairey Merz


Men are at higher comparative CVD risk than women throughout their lifespan. During menopause transition the traditional CVD risk factors change into a more adverse direction in women with an up-regulation of hormonal systems such as the renin-angiotensin system (RAS) and the sympathetic nervous system. Primary ovarian insufficiency (POI) and persistent vasomotor symptoms are considered to be modest additive risk factors in women. Hypertension is a key-risk factor and may cause a variety of symptoms in middle-aged women that are often not well recognized. This chapter may be an eye-opener for many clinical cardiologists.


Arterial stiffness Blood pressure BRCA 1/2 mutation carriers Endometriosis Endothelial dysfunction Estrogen Hormone therapy (HT) Hypertension Hysterectomy Menopause Oral contraceptives Primary ovarian insufficiency (POI) Sex-hormones Symptoms hypertension Vasomotor symptoms (VMS) Vaginal bleeding Venous thrombo-embolism (VTE) 


  1. 1.
    Morabia A, Costanza MC. International variability in ages at menarche, first livebirth, and menopause. World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives. Am J Epidemiol. 1998;148(12):1195–205.PubMedCrossRefGoogle Scholar
  2. 2.
    Miller VM, Duckles SP. Vascular actions of estrogens: functional implications. Pharmacol Rev. 2008;60(2):210–41.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Menazza S, Murphy E. The expanding complexity of estrogen receptor signaling in the cardiovascular system. Circ Res. 2016;118(6):994–1007.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Salerni S, Di Francescomarino S, Cadeddu C, Acquistapace F, Maffei S, Gallina S. The different role of sex hormones on female cardiovascular physiology and function: not only oestrogens. Eur J Clin Investig. 2015;45(6):634–45.CrossRefGoogle Scholar
  5. 5.
    Turgeon JL, Carr MC, Maki PM, Mendelsohn ME, Wise PM. Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: insights from basic science and clinical studies. Endocr Rev. 2006;27(6):575–605.PubMedCrossRefGoogle Scholar
  6. 6.
    Cushman M, Legault C, Barrett-Connor E, Stefanick ML, Kessler C, Judd HL, et al. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation. 1999;100(7):717–22.PubMedCrossRefGoogle Scholar
  7. 7.
    Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, 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.PubMedCrossRefGoogle Scholar
  8. 8.
    Koh KK. Effects of estrogen on the vascular wall: vasomotor function and inflammation. Cardiovasc Res. 2002;55(4):714–26.PubMedCrossRefGoogle Scholar
  9. 9.
    Pradhan AD, Manson JE, Rossouw JE, Siscovick DS, Mouton CP, Rifai N, et al. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women’s Health Initiative Observational Study. JAMA. 2002;288(8):980–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297(13):1465–77.PubMedCrossRefGoogle Scholar
  11. 11.
    Clarkson TB, Melendez GC, Appt SE. Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future. Menopause. 2013;20(3):342–53.PubMedCrossRefGoogle Scholar
  12. 12.
    Clarkson TB. Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression. Menopause. 2007;14(3 Pt 1):373–84.PubMedCrossRefGoogle Scholar
  13. 13.
    Gierach GL, Johnson BD, Bairey Merz CN, Kelsey SF, Bittner V, Olson MB, et al. Hypertension, menopause, and coronary artery disease risk in the Women’s Ischemia Syndrome Evaluation (WISE) Study. J Am Coll Cardiol. 2006;47(3 Suppl):S50–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Schunkert H, Danser AH, Hense HW, Derkx FH, Kurzinger S, Riegger GA. Effects of estrogen replacement therapy on the renin-angiotensin system in postmenopausal women. Circulation. 1997;95(1):39–45.PubMedCrossRefGoogle Scholar
  15. 15.
    Yanes LL, Romero DG, Iliescu R, Zhang H, Davis D, Reckelhoff JF. Postmenopausal hypertension: role of the renin-angiotensin system. Hypertension. 2010;56(3):359–63.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Vongpatanasin W. Autonomic regulation of blood pressure in menopause. Semin Reprod Med. 2009;27(4):338–45.PubMedCrossRefGoogle Scholar
  17. 17.
    Freedman RR. Menopausal hot flashes: mechanisms, endocrinology, treatment. J Steroid Biochem Mol Biol. 2014;142:115–20.PubMedCrossRefGoogle Scholar
  18. 18.
    Maranon RO, Reckelhoff JF. Mechanisms responsible for postmenopausal hypertension in a rat model: roles of the renal sympathetic nervous system and the renin-angiotensin system. Physiol Rep. 2016;4(2):e12669.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Hart EC, Charkoudian N. Sympathetic neural regulation of blood pressure: influences of sex and aging. Physiology. 2014;29(1):8–15.PubMedCrossRefGoogle Scholar
  20. 20.
    van der Schouw YT, Grobbee DE. Menopausal complaints, oestrogens, and heart disease risk: an explanation for discrepant findings on the benefits of post-menopausal hormone therapy. Eur Heart J. 2005;26(14):1358–61.PubMedCrossRefGoogle Scholar
  21. 21.
    Gast GC, Grobbee DE, Pop VJ, Keyzer JJ, Wijnands-van Gent CJ, Samsioe GN, et al. Menopausal complaints are associated with cardiovascular risk factors. Hypertension. 2008;51(6):1492–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Gast GC, Pop VJ, Samsioe GN, Grobbee DE, Nilsson PM, Keyzer JJ, et al. Vasomotor menopausal symptoms are associated with increased risk of coronary heart disease. Menopause. 2011;18(2):146–51.PubMedGoogle Scholar
  23. 23.
    Jackson EA, El Khoudary SR, Crawford SL, Matthews K, Joffe H, Chae C, et al. Hot flash frequency and blood pressure: data from the study of Women’s Health Across the Nation. J Womens Health. 2016;25(12):1204–9.CrossRefGoogle Scholar
  24. 24.
    Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, Hess R, Matthews KA. Hot flashes and subclinical cardiovascular disease: findings from the Study of Women’s Health Across the Nation Heart Study. Circulation. 2008;118(12):1234–40.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, Hess R, Powell LH, Matthews KA. Hot flashes and carotid intima media thickness among midlife women. Menopause. 2011;18(4):352–8.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Thurston RC, Christie IC, Matthews KA. Hot flashes and cardiac vagal control during women’s daily lives. Menopause. 2012;19(4):406–12.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Hoikkala H, Haapalahti P, Viitasalo M, Vaananen H, Sovijarvi AR, Ylikorkala O, et al. Association between vasomotor hot flashes and heart rate variability in recently postmenopausal women. Menopause. 2010;17(2):315–20.PubMedCrossRefGoogle Scholar
  28. 28.
    Barnes JN, Hart EC, Curry TB, Nicholson WT, Eisenach JH, Wallin BG, et al. Aging enhances autonomic support of blood pressure in women. Hypertension. 2014;63(2):303–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Thurston RC, El Khoudary SR, Sutton-Tyrrell K, Crandall CJ, Sternfeld B, Joffe H, et al. Vasomotor symptoms and insulin resistance in the study of women’s health across the nation. J Clin Endocrinol Metab. 2012;97(10):3487–94.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Szmuilowicz ED, Manson JE, Rossouw JE, Howard BV, Margolis KL, Greep NC, et al. Vasomotor symptoms and cardiovascular events in postmenopausal women. Menopause. 2011;18(6):603–10.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Stearns V, Ullmer L, Lopez JF, Smith Y, Isaacs C, Hayes D. Hot flushes. Lancet. 2002;360(9348):1851–61.PubMedCrossRefGoogle Scholar
  32. 32.
    Collen AC, Manhem K, Sverrisdottir YB. Sympathetic nerve activity in women 40 years after a hypertensive pregnancy. J Hypertens. 2012;30(6):1203–10.PubMedCrossRefGoogle Scholar
  33. 33.
    Drost JT, van der Schouw YT, Herber-Gast GC, Maas AH. More vasomotor symptoms in menopause among women with a history of hypertensive pregnancy diseases compared with women with normotensive pregnancies. Menopause. 2013;20(10):1006–11.PubMedCrossRefGoogle Scholar
  34. 34.
    De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010;376(9744):911–21.PubMedCrossRefGoogle Scholar
  35. 35.
    Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67(4):604–6.PubMedGoogle Scholar
  36. 36.
    Rosenberg L, Hennekens CH, Rosner B, Belanger C, Rothman KJ, Speizer FE. Early menopause and the risk of myocardial infarction. Am J Obstet Gynecol. 1981;139(1):47–51.PubMedCrossRefGoogle Scholar
  37. 37.
    Jacobsen BK, Heuch I, Kvale G. Age at natural menopause and all-cause mortality: a 37-year follow-up of 19,731 Norwegian women. Am J Epidemiol. 2003;157(10):923–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Lubiszewska B, Kruk M, Broda G, Ksiezycka E, Piotrowski W, Kurjata P, et al. The impact of early menopause on risk of coronary artery disease (PREmature Coronary Artery Disease In Women—PRECADIW case-control study). Eur J Prev Cardiol. 2012;19(1):95–101.PubMedCrossRefGoogle Scholar
  39. 39.
    Muka T, Oliver-Williams C, Kunutsor S, Laven JS, Fauser BC, Chowdhury R, et al. Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: a systematic review and meta-analysis. JAMA Cardiol. 2016;1(7):767–76.PubMedCrossRefGoogle Scholar
  40. 40.
    Atsma F, Bartelink ML, Grobbee DE, van der Schouw YT. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis. Menopause. 2006;13(2):265–79.PubMedCrossRefGoogle Scholar
  41. 41.
    Knauff EA, Westerveld HE, Goverde AJ, Eijkemans MJ, Valkenburg O, van Santbrink EJ, et al. Lipid profile of women with premature ovarian failure. Menopause. 2008;15(5):919–23.PubMedCrossRefGoogle Scholar
  42. 42.
    Parashar S, Reid KJ, Spertus JA, Shaw LJ, Vaccarino V. Early menopause predicts angina after myocardial infarction. Menopause. 2010;17(5):938–45.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Daan NM, Muka T, Koster MP, Roeters van Lennep JE, Lambalk CB, Laven JS, et al. Cardiovascular risk in women with premature ovarian insufficiency compared to premenopausal women at middle age. J Clin Endocrinol Metab. 2016;101(9):3306–15.PubMedCrossRefGoogle Scholar
  44. 44.
    Roeters van Lennep JE, Heida KY, Bots ML, Hoek A, Collaborators of the Dutch Multidisciplinary Guideline Development Group on Cardiovascular Risk Management After Reproductive D. Cardiovascular disease risk in women with premature ovarian insufficiency: a systematic review and meta-analysis. Eur J Prev Cardiol. 2016;23(2):178–86.PubMedCrossRefGoogle Scholar
  45. 45.
    Stolk L, Perry JR, Chasman DI, He C, Mangino M, Sulem P, et al. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nat Genet. 2012;44(3):260–8.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Rebbeck TR, Mitra N, Domchek SM, Wan F, Chuai S, Friebel TM, et al. Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers. Cancer Res. 2009;69(14):5801–10.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Arts-de Jong M, Maas AH, Massuger LF, Hoogerbrugge N, de Hullu JA. BRCA1/2 mutation carriers are potentially at higher cardiovascular risk. Crit Rev Oncol Hematol. 2014;91(2):159–71.PubMedCrossRefGoogle Scholar
  48. 48.
    Bae I, Fan S, Meng Q, Rih JK, Kim HJ, Kang HJ, et al. BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res. 2004;64(21):7893–909.PubMedCrossRefGoogle Scholar
  49. 49.
    Fridlich R, Annamalai D, Roy R, Bernheim G, Powell SN. BRCA1 and BRCA2 protect against oxidative DNA damage converted into double-strand breaks during DNA replication. DNA Repair. 2015;30:11–20.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Parker WH, Broder MS, Chang E, Feskanich D, Farquhar C, Liu Z, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses’ health study. Obstet Gynecol. 2009;113(5):1027–37.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Howard BV, Kuller L, Langer R, Manson JE, Allen C, Assaf A, et al. Risk of cardiovascular disease by hysterectomy status, with and without oophorectomy: the Women’s Health Initiative Observational Study. Circulation. 2005;111(12):1462–70.PubMedCrossRefGoogle Scholar
  52. 52.
    Ingelsson E, Lundholm C, Johansson AL, Altman D. Hysterectomy and risk of cardiovascular disease: a population-based cohort study. Eur Heart J. 2011;32(6):745–50.PubMedCrossRefGoogle Scholar
  53. 53.
    Mu F, Rich-Edwards J, Rimm EB, Spiegelman D, Missmer SA. Endometriosis and risk of coronary heart disease. Circ Cardiovasc Qual Outcomes. 2016;9(3):257–64.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Moreau KL, Hildreth KL, Meditz AL, Deane KD, Kohrt WM. Endothelial function is impaired across the stages of the menopause transition in healthy women. J Clin Endocrinol Metab. 2012;97(12):4692–700.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Bechlioulis A, Kalantaridou SN, Naka KK, Chatzikyriakidou A, Calis KA, Makrigiannakis A, et al. Endothelial function, but not carotid intima-media thickness, is affected early in menopause and is associated with severity of hot flushes. J Clin Endocrinol Metab. 2010;95(3):1199–206.PubMedCrossRefGoogle Scholar
  56. 56.
    Robinson JG, Wallace R, Limacher M, Ren H, Cochrane B, Wassertheil-Smoller S, et al. Cardiovascular risk in women with non-specific chest pain (from the Women’s Health Initiative Hormone Trials). Am J Cardiol. 2008;102(6):693–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Gulati M, Cooper-DeHoff RM, McClure C, Johnson BD, Shaw LJ, Handberg EM, et al. Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women’s Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. Arch Intern Med. 2009;169(9):843–50.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol. 2014;34(3):509–15.PubMedCrossRefGoogle Scholar
  59. 59.
    Matsuzawa Y, Guddeti RR, Kwon TG, Lerman LO, Lerman A. Treating coronary disease and the impact of endothelial dysfunction. Prog Cardiovasc Dis. 2015;57(5):431–42.PubMedCrossRefGoogle Scholar
  60. 60.
    Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, et al. The assessment of endothelial function: from research into clinical practice. Circulation. 2012;126(6):753–67.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, et al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation. 2010;121(4):505–11.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, Bos ML, Schalekamp MA, et al. Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation. 2006;113(5):657–63.PubMedCrossRefGoogle Scholar
  63. 63.
    Ong P, Athanasiadis A, Sechtem U. Patterns of coronary vasomotor responses to intracoronary acetylcholine provocation. Heart. 2013;99(17):1288–95.PubMedCrossRefGoogle Scholar
  64. 64.
    Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26(5):1235–41.PubMedCrossRefGoogle Scholar
  65. 65.
    Sade LE. Vascular function tests in women with no obstructive CAD: a few pieces of the puzzle. JACC Cardiovasc Imaging. 2016;9(4):418–20.PubMedCrossRefGoogle Scholar
  66. 66.
    Cutler JA, Sorlie PD, Wolz M, Thom T, Fields LE, Roccella EJ. Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988–1994 and 1999–2004. Hypertension. 2008;52(5):818–27.PubMedCrossRefGoogle Scholar
  67. 67.
    Hage FG, Mansur SJ, Xing D, Oparil S. Hypertension in women. Kidney Int Suppl. 2013;3(4):352–6.CrossRefGoogle Scholar
  68. 68.
    Ljungman C, Kahan T, Schioler L, Hjerpe P, Hasselstrom J, Wettermark B, et al. Gender differences in antihypertensive drug treatment: results from the Swedish Primary Care Cardiovascular Database (SPCCD). J Am Soc Hypertens. 2014;8(12):882–90.PubMedCrossRefGoogle Scholar
  69. 69.
    Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, et al. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension. 1995;25(3):305–13.PubMedCrossRefGoogle Scholar
  70. 70.
    Wassertheil-Smoller S, Anderson G, Psaty BM, Black HR, Manson J, Wong N, et al. Hypertension and its treatment in postmenopausal women: baseline data from the Women’s Health Initiative. Hypertension. 2000;36(5):780–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Staessen J, Bulpitt CJ, Fagard R, Lijnen P, Amery A. The influence of menopause on blood pressure. J Hum Hypertens. 1989;3(6):427–33.PubMedGoogle Scholar
  72. 72.
    Boggia J, Thijs L, Hansen TW, Li Y, Kikuya M, Bjorklund-Bodegard K, et al. Ambulatory blood pressure monitoring in 9357 subjects from 11 populations highlights missed opportunities for cardiovascular prevention in women. Hypertension. 2011;57(3):397–405.PubMedCrossRefGoogle Scholar
  73. 73.
    Vasan RS, Larson MG, Leip EP, Evans JC, O'Donnell CJ, Kannel WB, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001;345(18):1291–7.PubMedCrossRefGoogle Scholar
  74. 74.
    O'Brien E, Parati G, Stergiou G, Asmar R, Beilin L, Bilo G, et al. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J Hypertens. 2013;31(9):1731–68.PubMedCrossRefGoogle Scholar
  75. 75.
    Franklin SS, Thijs L, Hansen TW, O'Brien E, Staessen JA. White-coat hypertension: new insights from recent studies. Hypertension. 2013;62(6):982–7.PubMedCrossRefGoogle Scholar
  76. 76.
    Margolis KL, Asche SE, Bergdall AR, Dehmer SP, Groen SE, Kadrmas HM, et al. Effect of home blood pressure telemonitoring and pharmacist management on blood pressure control: a cluster randomized clinical trial. JAMA. 2013;310(1):46–56.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    McManus RJ, Mant J, Haque MS, Bray EP, Bryan S, Greenfield SM, et al. Effect of self-monitoring and medication self-titration on systolic blood pressure in hypertensive patients at high risk of cardiovascular disease: the TASMIN-SR randomized clinical trial. JAMA. 2014;312(8):799–808.PubMedCrossRefGoogle Scholar
  78. 78.
    James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20.PubMedCrossRefGoogle Scholar
  79. 79.
    SPRINT Research Group, Wright Jr JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103–16.CrossRefGoogle Scholar
  80. 80.
    Egan BM, Li J, Wagner CS. Systolic Blood Pressure Intervention Trial (SPRINT) and target systolic blood pressure in future hypertension guidelines. Hypertension. 2016;68(2):318–23.PubMedCrossRefGoogle Scholar
  81. 81.
    Lopez-Jaramillo P, Coca A, Sanchez R, Zanchetti A. Hypertension guidelines: is it time to reappraise blood pressure thresholds and targets? Position statement of the Latin American Society of Hypertension. Hypertension. 2016;68(2):257–62.PubMedCrossRefGoogle Scholar
  82. 82.
    Wenger NK, Ferdinand KC, Bairey Merz CN, Walsh MN, Gulati M, Pepine CJ, et al. Women, hypertension, and the systolic blood pressure intervention trial. Am J Med. 2016;129(10):1030–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Franklin SS, Gustin W, Wong ND, Larson MG, Weber MA, Kannel WB, et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation. 1997;96(1):308–15.PubMedCrossRefGoogle Scholar
  84. 84.
    Denton KM, Hilliard LM, Tare M. Sex-related differences in hypertension: seek and ye shall find. Hypertension. 2013;62(4):674–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Sandberg K, Ji H. Sex differences in primary hypertension. Biol Sex Differ. 2012;3(1):7.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Staessen JA, van der Heijden-Spek JJ, Safar ME, Den Hond E, Gasowski J, Fagard RH, et al. Menopause and the characteristics of the large arteries in a population study. J Hum Hypertens. 2001;15(8):511–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Cadeddu C, Franconi F, Cassisa L, Campesi I, Pepe A, Cugusi L, et al. Arterial hypertension in the female world: pathophysiology and therapy. J Cardiovasc Med. 2016;17(4):229–36.CrossRefGoogle Scholar
  88. 88.
    Reckelhoff JF, Fortepiani LA. Novel mechanisms responsible for postmenopausal hypertension. Hypertension. 2004;43(5):918–23.PubMedCrossRefGoogle Scholar
  89. 89.
    Coylewright M, Reckelhoff JF, Ouyang P. Menopause and hypertension: an age-old debate. Hypertension. 2008;51(4):952–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Khalil RA. Sex hormones as potential modulators of vascular function in hypertension. Hypertension. 2005;46(2):249–54.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Reckelhoff JF. Gender differences in the regulation of blood pressure. Hypertension. 2001;37(5):1199–208.PubMedCrossRefGoogle Scholar
  92. 92.
    Ashraf MS, Vongpatanasin W. Estrogen and hypertension. Curr Hypertens Rep. 2006;8(5):368–76.PubMedCrossRefGoogle Scholar
  93. 93.
    Pechere-Bertschi A, Burnier M. Gonadal steroids, salt-sensitivity and renal function. Curr Opin Nephrol Hypertens. 2007;16(1):16–21.PubMedCrossRefGoogle Scholar
  94. 94.
    Tominaga T, Suzuki H, Ogata Y, Matsukawa S, Saruta T. The role of sex hormones and sodium intake in postmenopausal hypertension. J Hum Hypertens. 1991;5(6):495–500.PubMedGoogle Scholar
  95. 95.
    Kim JM, Kim TH, Lee HH, Lee SH, Wang T. Postmenopausal hypertension and sodium sensitivity. J Menopausal Med. 2014;20(1):1–6.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Pechere-Bertschi A, Burnier M. Female sex hormones, salt, and blood pressure regulation. Am J Hypertens. 2004;17(10):994–1001.PubMedCrossRefGoogle Scholar
  97. 97.
    Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159–219.PubMedCrossRefGoogle Scholar
  98. 98.
    Drost JT, Arpaci G, Ottervanger JP, de Boer MJ, van Eyck J, van der Schouw YT, et al. Cardiovascular risk factors in women 10 years post early preeclampsia: the Preeclampsia Risk EValuation in FEMales study (PREVFEM). Eur J Prev Cardiol. 2012;19(5):1138–44.PubMedCrossRefGoogle Scholar
  99. 99.
    Regnault V, Thomas F, Safar ME, Osborne-Pellegrin M, Khalil RA, Pannier B, et al. Sex difference in cardiovascular risk: role of pulse pressure amplification. J Am Coll Cardiol. 2012;59(20):1771–7.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Regitz-Zagrosek V, Brokat S, Tschope C. Role of gender in heart failure with normal left ventricular ejection fraction. Prog Cardiovasc Dis. 2007;49(4):241–51.PubMedCrossRefGoogle Scholar
  101. 101.
    Coutinho T. Arterial stiffness and its clinical implications in women. Can J Cardiol. 2014;30(7):756–64.PubMedCrossRefGoogle Scholar
  102. 102.
    Cleland JG, Swedberg K, Follath F, Komajda M, Cohen-Solal A, Aguilar JC, et al. The EuroHeart Failure survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J. 2003;24(5):442–63.PubMedCrossRefGoogle Scholar
  103. 103.
    Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J. 2011;32(6):670–9.PubMedCrossRefGoogle Scholar
  104. 104.
    Merz AA, Cheng S. Sex differences in cardiovascular ageing. Heart. 2016;102(11):825–31.PubMedCrossRefGoogle Scholar
  105. 105.
    Maas AH, Franke HR. Women’s health in menopause with a focus on hypertension. Neth Heart J. 2009;17(2):68–72.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Davies PF. Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nat Clin Pract Cardiovasc Med. 2009;6(1):16–26.PubMedCrossRefGoogle Scholar
  107. 107.
    Brandes RP. Endothelial dysfunction and hypertension. Hypertension. 2014;64(5):924–8.PubMedCrossRefGoogle Scholar
  108. 108.
    Oparil S. Women and hypertension: what did we learn from the Women’s Health Initiative? Cardiol Rev. 2006;14(6):267–75.PubMedCrossRefGoogle Scholar
  109. 109.
    Gerber LM, Sievert LL, Warren K, Pickering TG, Schwartz JE. Hot flashes are associated with increased ambulatory systolic blood pressure. Menopause. 2007;14(2):308–15.PubMedCrossRefGoogle Scholar
  110. 110.
    Ikeda H, Inoue T, Uemura S, Kaibara R, Tanaka H, Node K. Effects of candesartan for middle-aged and elderly women with hypertension and menopausal-like symptoms. Hypertens Res. 2006;29(12):1007–12.PubMedCrossRefGoogle Scholar
  111. 111.
    Oelkers WH. Drospirenone in combination with estrogens: for contraception and hormone replacement therapy. Climacteric. 2005;8(Suppl 3):19–27.PubMedCrossRefGoogle Scholar
  112. 112.
    Rautaharju PM, Kooperberg C, Larson JC, LaCroix A. Electrocardiographic predictors of incident congestive heart failure and all-cause mortality in postmenopausal women: the Women’s Health Initiative. Circulation. 2006;113(4):481–9.PubMedCrossRefGoogle Scholar
  113. 113.
    Farmer RD, Lawrenson RA, Thompson CR, Kennedy JG, Hambleton IR. Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet. 1997;349(9045):83–8.PubMedCrossRefGoogle Scholar
  114. 114.
    van Hylckama VA, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ. 2009;339:b2921.CrossRefGoogle Scholar
  115. 115.
    Lidegaard O, Lokkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ. 2009;339:b2890.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Shufelt CL, Bairey Merz CN. Contraceptive hormone use and cardiovascular disease. J Am Coll Cardiol. 2009;53(3):221–31.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Pomp ER, Rosendaal FR, Doggen CJ. Smoking increases the risk of venous thrombosis and acts synergistically with oral contraceptive use. Am J Hematol. 2008;83(2):97–102.PubMedCrossRefGoogle Scholar
  118. 118.
    Tanis BC, van den Bosch MA, Kemmeren JM, Cats VM, Helmerhorst FM, Algra A, et al. Oral contraceptives and the risk of myocardial infarction. N Engl J Med. 2001;345(25):1787–93.PubMedCrossRefGoogle Scholar
  119. 119.
    Cibula D, Gompel A, Mueck AO, La Vecchia C, Hannaford PC, Skouby SO, et al. Hormonal contraception and risk of cancer. Hum Reprod Update. 2010;16(6):631–50.PubMedCrossRefGoogle Scholar
  120. 120.
    Merz CN, Johnson BD, Berga S, Braunstein G, Reis SE, Bittner V, et al. Past oral contraceptive use and angiographic coronary artery disease in postmenopausal women: data from the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation. Fertil Steril. 2006;85(5):1425–31.PubMedCrossRefGoogle Scholar
  121. 121.
    Weill A, Dalichampt M, Raguideau F, Ricordeau P, Blotiere PO, Rudant J, et al. Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study. BMJ. 2016;353:i2002.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Roos-Hesselink JW, Cornette J, Sliwa K, Pieper PG, Veldtman GR, Johnson MR. Contraception and cardiovascular disease. Eur Heart J. 2015;36(27):1728–34, 34a–34b.Google Scholar
  123. 123.
    Kaunitz AM. Clinical practice. Hormonal contraception in women of older reproductive age. N Engl J Med. 2008;358(12):1262–70.PubMedCrossRefGoogle Scholar
  124. 124.
    Martinelli I, Lensing AW, Middeldorp S, Levi M, Beyer-Westendorf J, van Bellen B, et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood. 2016;127(11):1417–25.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Maas AH, Euler M, Bongers MY, Rolden HJ, Grutters JP, Ulrich L, et al. Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy. Maturitas. 2015;82(4):355–9.PubMedCrossRefGoogle Scholar
  126. 126.
    Oldgren J, Wallentin L, Alexander JH, James S, Jonelid B, Steg G, et al. New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis. Eur Heart J. 2013;34(22):1670–80.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Dans AL, Connolly SJ, Wallentin L, Yang S, Nakamya J, Brueckmann M, et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013;127(5):634–40.PubMedCrossRefGoogle Scholar
  128. 128.
    Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med. 1991;20(1):47–63.PubMedCrossRefGoogle Scholar
  129. 129.
    Grodstein F, Stampfer MJ, Manson JE, Colditz GA, Willett WC, Rosner B, et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med. 1996;335(7):453–61.PubMedCrossRefGoogle Scholar
  130. 130.
    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, 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(3):321–33.PubMedCrossRefGoogle Scholar
  131. 131.
    Salpeter SR, Cheng J, Thabane L, Buckley NS, Salpeter EE. Bayesian meta-analysis of hormone therapy and mortality in younger postmenopausal women. Am J Med. 2009;122(11):1016–22. e1PubMedCrossRefGoogle Scholar
  132. 132.
    Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012;345:e6409.PubMedCrossRefGoogle Scholar
  133. 133.
    Maas AH, van der Schouw YT, Grobbee DE, van der Graaf Y. Rise and fall of hormone therapy in postmenopausal women with cardiovascular disease. Menopause. 2004;11(2):228–35.PubMedCrossRefGoogle Scholar
  134. 134.
    Harman SM, Black DM, Naftolin F, Brinton EA, Budoff MJ, Cedars MI, et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med. 2014;161(4):249–60.PubMedCrossRefGoogle Scholar
  135. 135.
    Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016;374(13):1221–31.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Bergendal A, Kieler H, Sundstrom A, Hirschberg AL, Kocoska-Maras L. Risk of venous thromboembolism associated with local and systemic use of hormone therapy in peri- and postmenopausal women and in relation to type and route of administration. Menopause. 2016;23(6):593–9.PubMedCrossRefGoogle Scholar
  137. 137.
    Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, Levesque H, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007;115(7):840–5.PubMedCrossRefGoogle Scholar
  138. 138.
    Gleason CE, Dowling NM, Wharton W, Manson JE, Miller VM, Atwood CS, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS-Cognitive and Affective Study. PLoS Med. 2015;12(6):e1001833; discussion e.Google Scholar
  139. 139.
    Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2651–62.PubMedCrossRefGoogle Scholar
  140. 140.
    Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA. 2004;291(24):2947–58.PubMedCrossRefGoogle Scholar
  141. 141.
    Rees MC. HRT in premature menopause. BMJ. 2008;337:a1668.PubMedCrossRefGoogle Scholar
  142. 142.
    North American Menopause Society. The 2012 hormone therapy position statement of: the North American Menopause Society. Menopause. 2012;19(3):257–71.CrossRefGoogle Scholar
  143. 143.
    Manson JE, Kaunitz AM. Menopause management—getting clinical care back on track. N Engl J Med. 2016;374(9):803–6.PubMedCrossRefGoogle Scholar
  144. 144.
    Geukes M, van Aalst MP, Nauta MC, Oosterhof H. The impact of menopausal symptoms on work ability. Menopause. 2012;19(3):278–82.PubMedCrossRefGoogle Scholar
  145. 145.
    Sarrel PM. Women, work, and menopause. Menopause. 2012;19(3):250–2.PubMedCrossRefGoogle Scholar
  146. 146.
    Neves ECM, Birkhauser M, Samsioe G, Lambrinoudaki I, Palacios S, Borrego RS, et al. EMAS position statement: the ten point guide to the integral management of menopausal health. Maturitas. 2015;81(1):88–92.CrossRefGoogle Scholar
  147. 147.
    de Villiers TJ, Hall JE, Pinkerton JV, Perez SC, Rees M, Yang C, et al. Revised global consensus statement on menopausal hormone therapy. Maturitas. 2016;91:153–5.PubMedCrossRefGoogle Scholar
  148. 148.
    Mintziori G, Lambrinoudaki I, Goulis DG, Ceausu I, Depypere H, Erel CT, et al. EMAS position statement: Non-hormonal management of menopausal vasomotor symptoms. Maturitas. 2015;81(3):410–3.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Cardiology, Women’s Cardiac Health ProgramRadboud University Medical CenterNijmegenThe Netherlands
  2. 2.Barbra Streisand Women’s Heart Center, Linda Joy Pollin Women’s Heart Health Program, Director Preventive Cardiac Center, Cedars-SinaiLos AngelesUSA

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