Abstract
Purpose of Review
Cardiovascular disease (CVD) is known to be an increasing cause of mortality among women, particularly postmenopausal women. Hormone replacement therapy (HRT) is a topic that has been investigated over the past decade for its known impact on the cardiovascular system. This review summarizes the evidence and current opinion on the associations between HRT and CVD, evidence both supporting and against HRT use as a prevention to the development of coronary heart disease (CHD).
Recent Findings
The majority of the new data available suggests the use of HRT has the potential to be more beneficial in the prevention of CVD if started in women at younger ages. Current studies also suggest that while starting HRT in older postmenopausal women may be associated with an initial slight increase in CVD, the overall lifetime occurrence rate is not increased. Several studies have also started to use the “timing hypothesis” to suggest that HRT initiated soon after menopause has the potential of being the greatest cardiovascular benefit to the patient. Overall, the data support the finding that HRT should be used only for symptomatic treatment, not in an attempt to slow progression of CVD.
Summary
Current evidence does not support the use of HRT for either primary or secondary prevention of CHD. HRT has different implications based on the temporal relationship in which it is initiated in relation to the onset of menopause. Overall, the use of HRT should be an individualized decision with each patient on the basis of the individual’s symptoms and overall risk profile.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance
Mozaffarian D, Benjamin EJ, Arnett DK, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29–322.
Gholizadeh L, Davidson P. More similarities than differences: an international comparison of CVD mortality and risk factors in women. Health Care Women Int. 2008;29:3–22.
Chakrabarti S, Morton JS, Davidge ST. Mechanisms of estrogen effects on the endothelium: an overview. Can J Cardiol. 2014;30(7):705–12.
Khalil RA. Sex hormones as potential modulators of vascular function in hypertension. Hypertension. 2005;46(2):249–54.
Mendelsohn ME, Karas RH. The Protective Effects of Estrogen on the Cardiovascular System. N Engl J Med. 1999;340(23):1801–11.
Hermeneglido C, Oviedo PJ, Cano A. Cyclooxygenases regulation by estradiol on the endothelium. Curr Pharm Des. 2006;12(2):205–15.
Gilligan DM, Badar DM, Panza JA, et al. Acute vascular effects of estrogen in postmenopausal women. Circulation. 1994;90:786–91.
Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW, Liao JK. Interaction of oestrogen receptor with the regulatory subunit of phoshatidyllinisitol 3 kinase. Nature. 2000;407(6803):538–41.
Chan SH, Chan JY. Brain stem NOS and ROS in neural mechanisms of hypertension. Antioxid Redox Signal. 2015;20(1):146–83.
Kaludercic N, Deshwal S, Di Lisa F. Reactive oxygen species and redox compartmentalization. Front Physiol. 2014;5:285.
Rubattu S, Bianchi F, Busceti CL, et al. Differential modulation of AMPK/PPARalpha/UCP2 axis in relation to hypertension and aging in the brain, kidneys and heart of two closely related spontaneously hypertensive rat strains. Oncotarget. 2015;6(22):18800–18.
Whitcroft SI, Crook D, Marsh MS, et al. Long-term effects of oral and transdermal hormone replacement therapies on serum lipid and lipoprotein concentrations. Obstet Gynecol. 1994;84(2):222–6.
Feingold KM, Brinton EA., Grunfeld C. The effect of endocrine disorders on lipids and lipoproteins. In: De Groot LJ, Chrousos G., et al., Endotext (internet). South Dartmouth (MA): MD text.com, Inc., 2000. 2017 Feb 24.
Rossouw JE, Anderson GL, Prentice RL, et al. 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.
Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hia J, et al. Estrogen therapy and coronary-artery calcification. WHI and WHI-CACS investigators. N Engl J Med. 2007;356:2591–602.
Allison MA, Manson JE, Langer RD, Carr JJ, Rossouw JE, Pettinger MB, et al. Oophorectomy, hormone therapy, and subclinical coronary artery disease in women with hysterectomy: the women’s health initiative coronary artery calcium study. women’s health initiative and women’s health initiative coronary artery calcium study investigators. Menopause. 2008;15:639–47.
Bernstein P, Pohost G. Progesterone, progestins, and the heart. Rev Cardiovasc Med. 2010;11:228–36.
Lee DY, Kim JY, Kim JH, Choi DS, Kim DK, Koh KK, et al. Effects of hormone therapy on ambulatory blood pressure in postmenopausal Korean women. Climacteric. 2011;14:92–9.
Fahraeus L, Larsson-Cohn U, Wallentin L. L-norgestrel and progesterone have different influences on plasma lipoproteins. Eur J Clin Investig. 1983;13:447–53.
Schierbeck LL, Rejnmark L, Tofteng CL, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomized trial. Br Med J. 2012;e6409:345.
Collins P, Flather M, Lees B, et al. Randomized trial effects of continuous combined HRT on markers of lipids and coagulation in women with acute coronary syndromes: WHISP pilot study. Eur Heart J. 2006;27:2046–53.
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;280:605–13.
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). HERS Research Group [published erratum appears in JAMA] 2002; 288:1064. JAMA. 2002;288:49–57.
Salpeter SR, Walsh JME, Greyber E, Salpeter EE. Coronary heart disease events associated with hormone therapy in younger and older women. J Gen Intern Med. 2006;21:363–6.
• Boardman HM, Hartley L, Eisinga A et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev. 2015:10(3). A large updated Cochrane review that reviewed the effects of hormone therapy for prevention of cardiovascular disease.
• Hodis HN, Mack WJ, Henderson VW. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016;374:1221–31 A good study evaluating the atherosclerotic progression based on timing of hormorne replacement therapy.
Hodis NH, 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.
Barker C, Manson JE. The Kronos Early Estrogen Prevention Study. Women Health. 2013;9(1):9–11.
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(13):1353–68.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Carson Keck and Marian Taylor declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
This article is part of theTopical Collection on Women and Ischemic Heart Disease
Rights and permissions
About this article
Cite this article
Keck, C., Taylor, M. Emerging Research on the Implications of Hormone Replacement Therapy on Coronary Heart Disease. Curr Atheroscler Rep 20, 57 (2018). https://doi.org/10.1007/s11883-018-0758-2
Published:
DOI: https://doi.org/10.1007/s11883-018-0758-2