Hormone replacement therapy and cardiovascular disease

Current Opinion in Lipidology

Volumn 10, Issue 5, 1999, Pages 429-434

  Rossouw, Jacques E ^a  

^a NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ESTROGEN; GESTAGEN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIPOPROTEIN A; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEDROXYPROGESTERONE; PLASMINOGEN ACTIVATOR INHIBITOR 1; RALOXIFENE; SIMVASTATIN; TRIACYLGLYCEROL;

CARDIOVASCULAR DISEASE; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; FEMALE; HORMONE SUBSTITUTION; HUMAN; ISCHEMIC HEART DISEASE; LIPOPROTEIN BLOOD LEVEL; PRIORITY JOURNAL; REVIEW; TRIACYLGLYCEROL BLOOD LEVEL; VASCULAR ENDOTHELIUM; VEIN THROMBOSIS;

CARDIOVASCULAR DISEASES; ESTROGEN REPLACEMENT THERAPY; FEMALE; HUMANS; LIPIDS; LIPOPROTEINS; RANDOMIZED CONTROLLED TRIALS; RECEPTORS, ESTROGEN;

EID: 0033394709     PISSN: 09579672     EISSN: None     Source Type: Journal    
DOI: 10.1097/00041433-199910000-00007     Document Type: Review

References (25)

1. 1 Barrett-Connor E, Grady D. Hormone replacement therapy, heart disease, and other considerations. Annu Rev Public Health 1998; 19:55-72. This is a carefully conducted meta-analysis that considers the various potential health effects of HRT, and cautions about the potential biases in the observational data.
2. 2 Rossouw JE. What we still need to learn about hormone replacement therapy. Infertility and Reproductive Medicine Clinics of North America. Menopause: Curr Issues Treat Options 1999; 10:189-209. This is an evidence-based review of what is known and not known about HRT that focuses on the size of the potential biases in observational studies and the effect that they might have on the overall health outcome.
3. 3 Espeland MA, Marcovina SM, Miller V, Wood PD, Wasilauskas C, Sherwin R, et al. Effect of postmenopausal hormone therapy on lipoprotein (a) concentration. Circulation 1998; 97:979-986. This reports results of a large clinical trial of four HRT regimens, all having conjugated equine estrogen as the estrogen, which quantifies the degree of lipoprotein (a) lowering and shows that it persists for at least 3 years.
4. 4 Su W, Campos H, Judge H, Walsh BW, Sacks FM. Metabolism of apo (a) and apo B100 of lipoprotein (a) in women: effect of postmenopausal estrogen replacement. J Clin Endocrinol Metabol 1998; 83:3267-3276. This is a metabolic study suggesting that estrogen administration lowers the production rate of apolipoprotein (a).
5. 5 Rosenson RS, Tangney CC, Mosca LJ. Hormone replacement therapy improves cardiovascular risk by lowering plasma viscosity in postmenopausal women. Arterioscler Thromb Vasc Biol 1998; 18:1902-1905. This small and inconclusive trial studied the effects of estradiol on triglycerides, fibrinogen and plasma viscosity.
6. 6 Grady D, Sawaya G. Postmenopausal hormone therapy increases risk of deep vain thrombosis and pulmonary embolism. Am J Med 1998; 105:41-43. This reviews the relatively recent evidence from observational studies and clinical trials that has changed the previous perception that HRT does not increase the risk for venous thromboembolism. The clinical evidence that HRT is procoagulant is more persuasive than the metabolic studies, and the concept may have implications for arterial as well as venous thrombosis.
7. 7 Koh KK, Horne MK, Csako G, Waclawiw MA, Cannon RO. Relation of fibrinolytic potentiation by estrogen to coagulation pathway activation in postmenopausal women. Am J Cardiol 1999; 83:466-469. Reductions in PAI-1 and activation of the fibrinolytic pathway by estrogen do not appear to be in reaction to activation of coagulation. This may cause an imbalance between coagulation and fibrinolysis in some individuals, potentially putting them at higher risk of coagulation.
8. 8 Giri S, Thompson PD, Taxel P, Contois JHG, Otvos J, Allen R, et al. Oral estrogen improves serum lipids, homocysteine and fibrinolysis in elderly men. Atherosclerosis 1998; 137:359-366. Few studies have looked at the effects of estrogen on CHD risk factors in men. In this trial, the effects on blood lipids, lipoproteins, coagulation factors, and homocysteine levels were similar to those reported in women. However, estrogen did not lower lipoprotein (a) levels in men as it does in women.
9. 9 Koh KK, Cardillo C, Bui MM, Hathaway L, Csako G, Waclawiw MA, et al. Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women. Circulation 1999; 99:354-360. This trial compared the effects of conjugated equine estrogen and simvastatin on lipids, lipoproteins, coagulation factors, and vascular markers of inflammation. Conjugated equine estrogen was found to be better at raising HDL-cholesterol, while simvastatin was better at lowering LDL-cholesterol, and when the drugs were given in combination the effects were less than fully additive.
10. 10 Lekakis J, Papamichael C, Mavrikakis M, Voutsas A, Stamatelopoulos S. Effect of long-term estrogen therapy on brachial arterial endothelium-dependent basodilation in women with Raynaud's phenomenon secondary to systemic sclerosis. Am J Cardiol 1998; 82:1555-1557. Conjugated equine estrogen improves vascular endothelium function in women with systemic sclerosis.
11. 11 Anderson TJ. Acute effect of estrogen on metabolic coronary vasodilator responseses to atrial pacing in postmenopausal women. Am J Cardiol 1998; 82:236-239. The acute adminstration of estradiol did not improve the coronary blood flow in response to pacing.
12. 12 Al-Khalili F, Landgren BM, Eksborg S, Franco-Cereceda A, Schenck-Gustafsson K. Does sublingual 17β-oestradiol have any effects on exercise capacity and myocardial ischaemia in post-menopausal women with stable coronary artery disease? Eur Heart J 1998; 19:1019-1026. The acute administration of sublingual estradiol did not improve exercise-induced myocardial ischemia.
13. 13 Webb CM, Rosano GMC, Collins P. Oestrogen improves exercise-induced myocardial ischaemia in women. Lancet 1998; 351:1556-1557. Short-term administration of oral estrodiol improved exercise-induced myocardial ischemia.
14. 14 Bush DE, Jones CE, Bass KM, Walters GK, Bruza JM, Ouyang P. Estrogen replacement reverses endothelial dysfunction in postmenopausal women. Am J Med 1998; 104:552558. Short term estrogen (mostly conjugated equine estrogen) improved flow mediated dilatation in women with endothelial dysfunction, but not in those with normal function. Medroxyprogesterone did not attenuate the estrogen effect.
15. 15 Sorensen KE, Dorup I, Hermann AP, Mosekilde L. Combined hormone replacement therapy does not protect women against the age-related decline in endothelium-dependent vasomotor function. Circulation 1998; 97:1234-1238. In this large and long term (3 year) randomized clinical trial endothelial function in the group on oral estradiol and norethisterone did not differ from the group on placebo. Baseline endothelial function tests were not performed, but both groups had worse function than an external reference group of premenopausal women.
16. 16 Gerhard M, Walsh BW, Tawakol A, Haley EA, Creager SJ, Seely EW, et al. Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. Circulation 1998; 98:1158-1163. This report is of interest because of the physiologic doses of estradiol and progesterone used, and the transdermal and vaginal route of administration. Endothelial function was improved, and could not be explained by the modest changes in lipids and lipoproteins observed.
17. 17 Dubuisson JT, Wagenknecht LE, D'Agostino RB, Haffner SM, Rewers M, Saad MF, et al. Association of hormone replacement therapy and carotid wall thickness in women with and without diabetes. Diabetes Care 1998; 21:1790-1796. In an observational study, current and former users of HRT had healthier carotid arteries, irrespective of the presence of diabetes. In current users, the effects on the carotid artery were explained by a better lipid profile.
18. 18 Abu-Halawa SA, Thompson K, Kirkeeide RL, Vaughn WK, Rosales O, Fujisi K, et al. Estrogen replacement therapy and outcome of coronary balloon angioplasty in postmenopausal women. Am J Cardiol 1998; 82:409-413. This retrospective study of women undergoing balloon angioplasty suggests that current users had a lower mortality than never-users. The results may be subject to substantial biases, and rates of restenosis did not differ by HRT use.
19. 19 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. JAMA 1998; 280:605-613. An important study, because it is the first report of a large placebo-controlled randomized controlled clinical trial of HRT (conjugated equine estrogen and medroxyprogesterone) in women with prior CHD HRT did not reduce CHD risk, but did increase the risk for venous thromboembolism and gallbladder disease.
20. 20 Petitti DB. Hormone replacement therapy and heart disease prevention: experimentation trumps observation [editorial]. JAMA 1998; 280:650-651. This editorial accompanied the HERS publication, and makes the point that observational studies may be misleading.
21. 21 Bush TL. Lessons from HERS: the null and beyond [editorial]. J Women's Health 1998; 7:781-783. This editorial attempts to reconcile the HERS findings with those of the observational studies.
22. 22 Walsh BW, Kuller LH, Wild RA, Paul S, Farmer M, Lawrence JB, et al. Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women. JAMA 1998; 279:1445-1451. This trial compares the effects of raloxifene and HRT (conjugated equine estrogen and medroxyprogesterone) on lipids and coagulation factors. The effects on LDL-cholesterol were similar, but raloxifene was less effective at raising HDL-cholesterol and lowering PA-1.
23. 23 Clarkson TB, Anthony MS, Jerome CP. Lack of effect of reloxifene on coronary artery atherosclerosis of postmenopausal monkeys. J Clin Endocrinol Metab 1998; 83:721-726. This trial in non-human primates showed a reduction of diet-induced atherosclerosis on conjugated equine estrogen but not on two doses of raloxifene.
24. 24 Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 1998; 90:1371-1388. Tamoxifen did not appear to reduce the risk for CHD in a large randomized placebo-controlled clinical trial (primary outcome: prevention of breast cancer). Tamoxifen increased the risk for venous thromboembolism to approximately the same extent as HRT.
25. 25 Schrott HF, Bitter V, Vittinghof E, Hulley S. Adherence to National Cholesterol Education Program treatment goals in postmenopausal women with heart disease. The Heart and Estrogen/Progestin Replacement Study (HERS). JAMA 1997; 277:1281-1286.