HORMONE REPLACEMENT THERAPY IN POSTMENOPAUSE AND CARDIOVASCULAR DISEASES: FACTS AND DILEMMAS
Abstract
Background. Hormonal replacement therapy (HRT) after menopause can affect cardiovascular system in a positive and negative way. Positive effects are exerted through estrogenic action on metabolic risk factors, such as lipids, glucose and insulin metabolism, as well as direct arterial effects, reducing atherogenesis. Negative effects are dose-dependent transient increase in coagulation activation and adverse vascular remodelling. Observational studies suggested that HRT might have a beneficial effect on the incidence of coronary heart disease, which is not in line with later randomized clinical trials. The main difference between both types of the studies is that participants in observational trials were in their fifties and in average ten years younger compared to randomized trials. Post-hoc analysis of the Women’s Health Initiative trial found a trend toward cardioprotective HRT in younger patients.
Conclusions. HRT is currently not recommended for the primary coronary prevention. But in women with menopausal symptoms, which are at the initiation of HRT younger than 60 years and are less than 10 years after menopause, HRT does seem not to increase cardiovascular events. Initiation of HRT early after menopause may reduce cardiovascular risk.
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References
Gordon T, Kannel WB, Hjortland MC, McNamara PM, et al.
Menopause and coronary heart disease: the Framingham Study.
Ann Intern Med 1978; 89: 157–61.
Stevenson JC. Menopausal hormone therapy. In: Wenger NK,
Collins P, eds. Women and heart disease. London: Taylor and
Francis; 2005. p. 375–90.
Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE,
Stampfer MJ. A prospective, observational study of postmenopausal
hormone therapy and primary prevention of cardiovascular
disease. Ann Intern Med 2000; 133: 933–41.
Grodstein F, Manson JE, Stampfer MJ. Postmenopausal hormone
use and secondary prevention of coronary events in the Nurses’
Health Study. Ann Intern Med 2001; 135: 1–138.
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
; 135: 939–53.
Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser
NL, et al. Estrogen plus progestin and the risk of coronary heart
disease. N Engl J Med 2003; 349: 523–34.
Stevenson JC. The metabolic basis for the effects of HRT on
coronary heart disease. Endocrine 2004; 24: 239–44.
Godsland IF. Effects of postmenopausal hormone replacement
therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations:
analysis of studies published from 1974–2000. Fertil Steril
; 75: 898–915.
Crook D, Cust MP, Gangar KF, Worthington M, Hillard TC, Stevenson
JC, et al. Comparison of transdermal and oral estrogen/
progestin hormone replacement therapy: effects on serum lipids
and lipoproteins. Am J Obstet Gynecol 1992; 166: 950–5.
Spencer CP, Godsland IF, Cooper AJ, Ross D, Whitehead MI,
Stevenson JC. Effects of oral and transdermal 17ß-estradiol with
cyclical oral norethindrone acetate on insulin sensitivity, secretion,
and elimination in postmenopausal women. Metabolism
; 49: 742–7.
Gambacciani M, Ciaponi M, Cappagli B, Piaggesi L, De Simone
L, Orlandi R, et al. Body weight, body fat distribution, and hormonal
replacement therapy in early postmenopausal women.
J Clin Endocrinol Metab 1997; 82: 414–7.
Winkler UH. Menopause, hormone replacement therapy and
cardiovascular disease: a review of haemostaseological findings.
Fibrinolysis 1992; 6 Suppl 3: 5–10.
Stevenson JC. Cardiovascular effects of estrogens. J Steroid
Biochem Mol Biol 2000; 74: 387–93.
Wingrove CS, Garr E, Godsland IF, Stevenson JC. 17ß-oestradiol
enhances release of matrix metalloproteinase-2 from human
vascular smooth muscle cells. Biochim Biophys Acta 1998; 1406:
–74.
Žegura B, Gužič Salobir B, Šebeštjen M, Keber I. The effect of various
menopausal hormone therapies on markers of inflammation,
coagulation, fibrinolysis, lipids, and lipoproteins in healthy
postmenopausal women. Menopause 2006; 13: 643–50.
Barret Connor E, Bush TL. Estrogen and coronary heart disease
in women. JAMA 1991; 265: 1861–7.
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:
–61.
Mikkola TS, Clarkson TB. Estrogen replacement therapy, atherosclerosis,
and vascular function. Cardiovasc Res 2002; 53:
–19.
Alexandersen P, Tankó LB, Bagger YZ,Qin G, Christiansen C.
The long term impact of 2–3 years of hormone replacement
therapy on cardiovascular mortality and atherosclerosis in
healthy women. Climacteric 2006; 9: 108–18.
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: 605–13.
Writing Group for the Women’s Health Initiative Investigators.
Risks and benefits of estrogen plus progestin in healthy postmenopausal
women. JAMA 2002; 288: 321–33.
Women’s Health Initiative Steering Committee. Effects of conjugated
equine estrogen in postmenopausal women with hysterectomy.
JAMA 2004; 291: 1701–12.
Stevenson JC. HRT and cardiovascular disease. Best Pract Res
Clin Obstet Gynaecol 2009; 23: 109–20.
Collins P, Flather M, Lees B, Mister R, Proudler AJ, Stevenson
JC, et al. Randomized trial of 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:
–53.
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;
: 1465–77.
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