The clinical impact of estrogen loss on cardiovascular disease in menopausal females
Main Article Content
Abstract
According to the CDC (2017), more women than men have died from heart disease over the last 20-25 years. On the contrary, premenopausal women are protected against heart and cardiovascular disease (CVD) compared to men. Following menopause, there is sharp rise in CVD mortality and morbidity in women compared to men indicating that women lose protection against CVD during menopause. This loss of CVD protection in women drives the CDC statistics. Life expectancy of women has now reached 82 (almost 35 years longer than at the turn of the 20th century). Yet, women typically undergo menopause at 50-60 years of age, which means that women spend over 40% of their life in menopause. Therefore, menopausal women, and associated CVD risk, must be considered as distinct from an aging or senescent woman. Despite longstanding knowledge that premenopausal women are protected from CVD, our fundamental understanding regarding the shift in CVD risk with menopause remains inadequate and impedes our ability to develop sex-specific therapeutic strategies to combat menopausal susceptibility to CVD. This review provides a critical overview of clinical trials attempting to address CVD susceptibility postmenopausal using hormone replacement therapy. Next, we outline key deficiencies in pre-clinical menopause models and introduce an alternative to overcome these deficiencies. Finally, we discuss a novel connection between AMPK and estrogen-dependent pathways that may serve as a potential solution to increased CVD susceptibility in menopausal women.
Keywords:
cardiovascular disease, menopause, perimenopause, estrogen, estrogen receptors hormone replacement therapy, AMP-activated protein kinase, ovariectomy, timing hypothesis
Article Details
How to Cite
LOPEZ-PIER, Marissa A. et al.
The clinical impact of estrogen loss on cardiovascular disease in menopausal females.
Medical Research Archives, [S.l.], v. 6, n. 2, feb. 2018.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1663>. Date accessed: 14 nov. 2024.
doi: https://doi.org/10.18103/mra.v6i2.1663.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Writing Group M, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al. Executive Summary: Heart Disease and Stroke Statistics--2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):447-54.
4. Mosca L, Mochari-Greenberger H, Dolor RJ, Newby LK, Robb KJ. Twelve-year follow-up of American women's awareness of cardiovascular disease risk and barriers to heart health. Circ Cardiovasc Qual Outcomes. 2010;3(2):120-7.
5. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, et al. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119(3):480-6.
6. Schocken DD, Arrieta MI, Leaverton PE, Ross EA. Prevalence and mortality rate of congestive heart failure in the United States. J Am Coll Cardiol. 1992;20(2):301-6.
7. Dubey RK, Oparil S, Imthurn B, Jackson EK. Sex hormones and hypertension. Cardiovasc Res. 2002;53(3):688-708.
8. Lima R, Wofford M, Reckelhoff JF. Hypertension in postmenopausal women. Curr Hypertens Rep. 2012;14(3):254-60.
9. Rosano GM, Vitale C, Marazzi G, Volterrani M. Menopause and cardiovascular disease: the evidence. Climacteric. 2007;10 Suppl 1:19-24.
10. Yang XP, Reckelhoff JF. Estrogen, hormonal replacement therapy and cardiovascular disease. Curr Opin Nephrol Hypertens. 2011;20(2):133-8.
11. Konhilas JP, Leinwand LA. The effects of biological sex and diet on the development of heart failure. Circulation. 2007;116(23):2747-59.
12. Diamond-Stanic MK, Romero-Aleshire MJ, Hoyer PB, Greer K, Hoying JB, Brooks HL. Midkine, a heparin-binding protein, is increased in the diabetic mouse kidney postmenopause. Am J Physiol Renal Physiol. 2011;300(1):F139-46.
13. Riazi S, Maric C, Ecelbarger CA. 17-beta Estradiol attenuates streptozotocin-induced diabetes and regulates the expression of renal sodium transporters. Kidney Int. 2006;69(3):471-80.
14. Romero-Aleshire MJ, Diamond-Stanic MK, Hasty AH, Hoyer PB, Brooks HL. Loss of ovarian function in the VCD mouse-model of menopause leads to insulin resistance and a rapid progression into the metabolic syndrome. Am J Physiol Regul Integr Comp Physiol. 2009;297(3):R587-92.
15. Mankhey RW, Bhatti F, Maric C. 17beta-Estradiol replacement improves renal function and pathology associated with diabetic nephropathy. Am J Physiol Renal Physiol. 2005;288(2):F399-405.
16. Xue B, Zhao Y, Johnson AK, Hay M. Central estrogen inhibition of angiotensin II-induced hypertension in male mice and the role of reactive oxygen species. Am J Physiol Heart Circ Physiol. 2008;295(3):H1025-H32.
17. Widder J, Pelzer T, von Poser-Klein C, Hu K, Jazbutyte V, Fritzemeier KH, et al. Improvement of endothelial dysfunction by selective estrogen receptor-alpha stimulation in ovariectomized SHR. Hypertension. 2003;42(5):991-6.
18. Cavasin MA, Sankey SS, Yu AL, Menon S, Yang XP. Estrogen and testosterone have opposing effects on chronic cardiac remodeling and function in mice with myocardial infarction. Am J Physiol Heart Circ Physiol. 2003;284(5):H1560-9.
19. van Eickels M, Grohe C, Cleutjens JP, Janssen BJ, Wellens HJ, Doevendans PA. 17beta-estradiol attenuates the development of pressure-overload hypertrophy. Circulation. 2001;104(12):1419-23.
20. Sharkey LC, Holycross BJ, Park S, Shiry LJ, Hoepf TM, McCune SA, et al. Effect of ovariectomy and estrogen replacement on cardiovascular disease in heart failure-prone SHHF/Mcc- fa cp rats. J Mol Cell Cardiol. 1999;31(8):1527-37.
21. de Jager T, Pelzer T, Muller-Botz S, Imam A, Muck J, Neyses L. Mechanisms of estrogen receptor action in the myocardium. Rapid gene activation via the ERK1/2 pathway and serum response elements. The Journal of biological chemistry. 2001;276(30):27873-80.
22. Grady D, Applegate W, Bush T, Furberg C, Riggs B, Hulley SB. Heart and Estrogen/progestin Replacement Study (HERS): design, methods, and baseline characteristics. Control Clin Trials. 1998;19(4):314-35.
23. 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.
24. Vickers MR, MacLennan AH, Lawton B, Ford D, Martin J, Meredith SK, 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(7613):239.
25. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291(14):1701-12.
26. Manson JE, Aragaki AK, Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials. JAMA. 2017;318(10):927-38.
27. Reis SE, Holubkov R, Young JB, White BG, Cohn JN, Feldman AM. Estrogen is associated with improved survival in aging women with congestive heart failure: analysis of the vesnarinone studies. J Am Coll Cardiol. 2000;36(2):529-33.
28. Lindenfeld J, Ghali JK, Krause-Steinrauf HJ, Khan S, Adams K, Goldman S, et al. Hormone replacement therapy is associated with improved survival in women with advanced heart failure. J Am Coll Cardiol. 2003;42(7):1238-45.
29. Bibbins-Domingo K, Lin F, Vittinghoff E, Barrett-Connor E, Hulley SB, Grady D, et al. Effect of hormone therapy on mortality rates among women with heart failure and coronary artery disease. Am J Cardiol. 2005;95(2):289-91.
30. Manson JE. The 'timing hypothesis' for estrogen therapy in menopausal symptom management. Womens Health (Lond). 2015;11(4):437-40.
31. Hodis HN, Mack WJ, Shoupe D, Azen SP, Stanczyk FZ, Hwang-Levine J, et al. Methods and baseline cardiovascular data from the Early versus Late Intervention Trial with Estradiol testing the menopausal hormone timing hypothesis. Menopause. 2015;22(4):391-401.
32. Santoro N, Allshouse A, Neal-Perry G, Pal L, Lobo RA, Naftolin F, et al. Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: the Kronos Early Estrogen Prevention Study. Menopause. 2017;24(3):238-46.
33. Peter I, Kelley-Hedgepeth A, Fox CS, Cupples LA, Huggins GS, Housman DE, et al. Variation in estrogen-related genes associated with cardiovascular phenotypes and circulating estradiol, testosterone, and dehydroepiandrosterone sulfate levels. J Clin Endocrinol Metab. 2008;93(7):2779-85.
34. Fox EM, Andrade J, Shupnik MA. Novel actions of estrogen to promote proliferation: integration of cytoplasmic and nuclear pathways. Steroids. 2009;74(7):622-7.
35. Herrington DM, Reboussin DM, Brosnihan KB, Sharp PC, Shumaker SA, Snyder TE, et al. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med. 2000;343(8):522-9.
36. Hodis HN, Mack WJ, Azen SP, Lobo RA, Shoupe D, Mahrer PR, et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med. 2003;349(6):535-45.
37. Hodis HN, Mack WJ, Lobo RA, Shoupe D, Sevanian A, Mahrer PR, et al. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2001;135(11):939-53.
38. 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.
39. Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002;288(1):49-57.
40. Mayer LP, Devine PJ, Dyer CA, Hoyer PB. The follicle-deplete mouse ovary produces androgen. Biol Reprod. 2004;71(1):130-8.
41. Hu X, Christian PJ, Thompson KE, Sipes IG, Hoyer PB. Apoptosis induced in rats by 4-vinylcyclohexene diepoxide is associated with activation of the caspase cascades. Biol Reprod. 2001;65(1):87-93.
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