Estrogen, atherosclerosis and cardiovascular disease in women : epidemiological studies on menopause and hormone replacement therapy

A therosclerosis, the principal cause of ischemic heart disease, stroke and peripheral arterial disease, is the fllost important cause of morbidity and Inortality in Western countries. Atherosclerosis and cardiovascular disease are diseases of the elderly. Demographic data predict that the number of elderly people in our countIy as well as in most Western countries, will increase in the coming years, especially among women. This means the absolute number of deaths from cardiovascular disease in women is bound to increase, and an increasing awareness of the importance of cardiovascular disease as a major issue in women is warranted. Premenopausal women seem to be protected from cardiovascular disease compared to postmenopausal women. What part menopause plays in the increased risk of cardiovascular disease after middle age is still debated. One might expect that women experiencing an early menopause have more time to develop atherosclerosis and thus cany a high risk of coronary heart disease. But data on the association between menopause and coronmy heart disease are conflicting. The inconsistency might be the result of a methodological problem; incidence of cardiovascular disease in women shortly after menopause is quite low, and increases only after age 70. This lag time of 10 to 20 years between menopause and the occurrence of coronary healt disease in women makes the effect of menopause difficult to disentangle from that of age. A better approach to study the role of menopause might be to study its association with atherosclerosis, as the latter is present long before symptomatic coronmy hemt disease develops. Only few studies have focussed on non-invasively measured atherosclerosis in relation to menopause. Obselvational studies consistently show a marked reduction of coronary heart disease associated with the use of hormone replacement therapy. Although results from observational studies are strong, consistent and biologically plausible, potential biases are large and most would be expected to spuriously enhance the observed cardioprotective effect. Nonetheless, because coronmy healt disease is the most conunon and most deadly disease of women, any significant reduction in coronaty hean disease risk due to hormone replacement therapy would strongly affect the benefit-risk scale. The mechanisms by which hormone replacement therapy exerts its effect on the cardiovascular system have not yet been fully explained. It is not known, whether the effect is based on influencing atherosclerosis or on other, direct effects, and whether these effects remain present after discontinuation of therapy. The aim of this thesis is to gain insight into the role of menopause in the increase of cardiovascular disease in women after middle age. FUlthermore, in search of possibilities for prevention, it addresses the effect of hormone replacement therapy.

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