Cardiovascular consequences of hormone therapy in postmenopausal women: Messages to clinicians Authors
Review Article Endocrinology
Received: 04 September 2004 Accepted: 10 September 2004 DOI:
10.1007/BF03016133 Cite this article as: Ylikorkala, O. & Mikkola, T. Reprod Med Biol (2005) 4: 1. doi:10.1007/BF03016133
Results from the recent randomized clinical trials indicating that hormone therapy (HT) does not provide cardiovascular protection, but potentially harm are in profound disagreement with the sound evidence from numerous observational and experimental studies. While the observational studies have mainly assessed symptomatic recently menopausal women, the randomized trials have studied symptomless elderly postmenopausal women with established coronary heart disease or various risk factors for cardiovascular disease. Therefore, the recent trials have only revealed that HT does not provide secondary cardiovascular benefits. Since primary cardiovascular benefits of HT are rational but not yet proven in clinical trials, new studies are in demand. Until more data from recently menopausal symptomatic women are available, we need to base our decisions on existing evidence and good clinical practice. Although the potential of HT to provide cardiovascular benefits is decreased by advancing age and time since menopause, this should not preclude the use of individualized HT in younger postmenopausal women.
hormone replacement therapy
Women’s Health Initiative
The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative Randomized Controlled Trial.
2004; 291: 1701–1712.
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.
2002; 288: 321–333.
Genazzani AR, Gambacciani M. A personal initiative for women’s health: to challenge the Women’s Health Initiative.
2002; 16: 255–257.
Mikkola TS, Clarkson TB. Estrogen replacement therapy, atherosclerosis, and vascular function.
2002; 53: 605–619.
Stampfer MJ, Willett WC, Colditz GA
. A prospective study of postmenopausal estrogen therapy and coronary heart disease.
N Engl J Med
1985; 313: 1044–1049.
Grodstein F, Manson JE, Colditz GA
. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease.
Ann Intern Med
2000; 133: 933–941.
Grady D, Rubin SM, Petitti DB
. Hormone therapy to prevent disease and prolong life in postmenopausal women.
Ann Intern Med
1992; 117: 1016–1037.
Hulley S, Grady D, Bush T
. 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.
1998; 280: 605–613.
Herrington DM, Reboussin DM, Brosnihan KB et al. Effects of estrogen replacement on the progression of coronaryartery atherosclerosis.
N Engl J Med
2000; 343: 522–529.
Viscoli CM, Brass LM, Kernan WN
. A clinical trial of estrogen-replacement therapy after ischemic stroke.
N Engl J Med
2001; 345: 1243–1249.
Mikkola TS, Clarkson TB, Notelovitz M. Postmenopausal hormone therapy before and after the women’s health initiative: what consequences?
2004; 36: 1–12.
Garbe E, Suissa S. Issues to debate on the Women’s Health Initiative (WHI) study. Hormone replacement therapy and acute coronary outcomes. Methodological issues between randomized and observational studies.
2004; 19: 8–13.
Manson JE, Hsia J, Johnson KC
. Estrogen plus progestin and the risk of coronary heart disease.
N Engl J Med
2003; 349: 523–534.
Gambacciani M, Genazzani AR. The missing R.
2003; 17: 91–94.
Raggi P, Callister TQ, Cooil B
. Identification of patients at increased risk of first unheralded acute myocaridal infarction by electron-beam computed tomography.
2000; 101: 850–855.
Karas RH, Clarkson TB. Considerations in interpreting the cardiovascular effects of hormone replacement therapy observed in the WHI: timing is everything.
Menopausal Med 2003; 10: 8–12.
Zanger D, Yang BK, Ardans J et al. Divergent effects of hormone therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical management.
J Ant Coll Cardiol
2000; 36: 1797–1802.
Kah KK, Ahn JY, Kang MH
. Effects of hormone replacement therapy on plaque stability, inflammation, and fibrinolysis in hypertensive or overweight postmenopausal women.
Am J Cardiol
2001; 88: 1423–1426.
Herrington DM, Vittinghoff E, Lin F
. Statin therapy, cardiovascular events, and total mortality in the heart and estrogen/progestin replacement study (HERS).
2002; 105: 2962–2967.
Langer RD. Legend meets reality: estrogen plus progestin and coronary heart disease in the Women’s Health Initiative.
Menopausal Med 2003; 10: 5–7.
Naftolin F, Taylor HS, Karas R et al. The Women’s Health Initiative could not have detected cardioprotective effects of starting hormone therapy during the menopausal transition.
2004; 81: 1498–1501.
Ylikorkala O. Balancing between observational studies and randomized trials in prevention of coronary heart disease by estrogen replacement: HERS study was no revolution.
Acta Obstet Gynecol Scand
2000; 79: 1029–1036.
Beljic T, Babic D, Marinkovic J
. Effect of estrogen replacement therapy on cardiac function in postmenopausal women with and without flushes.
1999; 13: 104–112.
De Kleijn MJJ, Bots ML, Bak AAA et al. Hormone replacement therapy in perimenopausal women and 2-year change of carotid intima-media thickness.
1999; 32: 195–204.
Akhrass F, Evans AT, Wang Y
. Hormone replacement therapy is associated with less coronary atherosclerosis in postmenopausal women.
J Clin Endocrinol Metab
2003; 88: 5611–5614.
Herrington DM, Howard TO, Hawkins GA
. Estrogenreceptor polymorphism and effects of estrogen replacement on high-density lipoprotein cholesterol in women with coronary disease.
N Engl J Med
2002; 346: 967–974.
Lu H, Higashikata T, Inazu A
. Association of estrogen receptor-a gene polymorphisms with coronary artery disease in patients with familial hypercholesterolemia.
Arterioscler Thromb Vasc Biol
2002; 22: 817–823.
Grady D. Postmenopausal hormones— therapy for symptoms only.
N Eng J Med
2003; 348: 1–3.
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