یائسگی و درمان هورمون وابسته به یائسگی در زنان Menopause and menopausal hormone therapy in women: cardiovascular benefits and risks

Cardiovascular disease is the leading cause of morbidity and mortality in the United States. The risk for heart disease increases exponentially with age for both men and women. For women, however, the risk is delayed by about 10 years, and becomes even more prominent after the onset of menopause.1 Endogenous estrogen during women’s reproductive years has many beneficial and protective effects.2 Estrogen has anti-atherosclerotic and anti-inflammatory properties,3 and may protect women from cardiovascular disease through halting the process of plaque formation and through modification of the lipid profile.2 Premenopausal women have higher HDL cholesterol and lower LDL cholesterol levels compared to men, which significantly reverses after menopause.4 Estrogen also has beneficial effects on the vascular endothelium and smooth muscle cells.2 Following menopause, impaired endothelium-mediated vasodilation contributes to increased cardiovascular risk. A progressive decline in endogenous estrogen levels may therefore contribute to the development of heart disease in post-menopausal women. Menopause (usually around the age of 50 years), and the postmenopausal period, may be risk factors for developing coronary heart disease in women, independent of increasing age. Specifically, following menopause, the loss of estrogen contributes to an increased development of hypertension, coronary artery disease, congestive heart failure and cerebrovascular disease.5 Early menopause (women younger than 40-45 years of age) and lower than average premenopausal levels of endogenous estrogen carry an even higher risk of cardiovascular disease, independent of other risk factors. The cardiac effects of surgical menopause with unilateral or bilateral oophorectomy remain unclear. The Nurses’ Health Study showed that surgical menopause increased cardiac risk, but natural menopause did not.6 Another research study which enrolled women who underwent bilateral oophorectomy also confirmed enhanced subclinical atherosclerosis, when assessed by the carotid artery intima media thickness, which carries an increased risk of cardiac events.7 Because the risk of heart disease in women increases after menopause, it was hypothesized that exogenous hormones (estrogen with or without progesterone) would have a protective role and would reduce the risk of heart disease. Although initial observational data8 supported this hypothesis, larger randomized clinical trials did not demonstrate that the use of menopausal hormone therapy would be beneficial for primary or secondary prevention of heart disease.