Women’s Heart and Estrogens

In the 21st century, cardiovascular disease has become a global cause of morbidity and a main contributor to mortality in most countries, regardless of the important actions which have been endorsed for primary and secondary prevention. Concerning women's cardiovascular mortality, in all age groups it is more frequent and even greater than it is due to breast cancer. In this chapter, the stages of atherogenesis, the factors that induce atherogenesis (environmental and genetic), the effects of estrogens on the stages of atherogenesis, and finally, the effects of estrogens on those components will be analyzed.

The actions of estrogens on the cardiovascular system occur either indirectly through the modification of cardiovascular risk factors [reduction of plasma LDL cholesterol, elevation of HDL cholesterol, effect on hemostatic factors (reduction of fibrinogen and inhibitors of fibrinolysis)] or directly mediated by the estrogen receptors (ERs, defined as genomic action of estrogens) or other receptors. In this chapter, the overall actions of estrogens on the cardiovascular system and particularly on the vascular wall, as well as actions of estrogens on many different metabolic pathways affecting the cardiovascular system will be analyzed. The indirect actions of estrogen on the circulatory and hematological system, body composition, lipids and glucose metabolisms will be analyzed. There are several causes leading to the development of early onset of coronary heart disease in young women. These causes can be classified into five categories: 1) Vasculitis and autoimmune diseases, 2) Hypercoagulable states, 3) Non-atherosclerotic coronary heart disease, 4) Myocardial infarction in hallucinogenic drug abusers, and 5) Atherosclerotic coronary heart disease. The causes leading to an early onset of coronary heart disease in young women will be analyzed.

Natural menopause occurs during the early 50s of a woman’s life. The last two decades life expectancy for men and women has risen nationwide. This supports the hypothesis that women may live more than 30 years after the onset of menopause. The decline of estrogens production leads to various, usually annoying, vasomotor symptoms, to other conditions such as obesity, urogenital atrophy, cognition disturbances and eventually to an increased risk for developing degenerative diseases like osteoporosis, cardiovascular and others. The differences observed in the lipid profile of peri- or post-menopausal women are not only due to the decline levels of estradiol and raised levels of estrone, but also due to the changes of body weight. Central obesity, usually observed in peri- and post-menopausal women is associated with elevated plasma triglycerides and low HDL cholesterol concentrations. The organic system, which is affected significantly by menopause, is the cardiovascular one. Alterations in the cardiovascular system due to the rapid decline in endogenous estrogens production will be discussed.

Studies evaluating cardiovascular events solely in women are fewer in comparison with studies evaluating solely in men. Clinical data on the efficacy of antihypertensive, hypolipidemic or antidiabetic treatment are not many. Studies involving women were mainly focused on the influence of hormone replacement therapy on cardiovascular events. Some of these studies were challenged for their design. Many scientists believe that women included in these studies were too old and the period of time after the onset of menopause was too long. In this chapter, studies evaluating cardiovascular outcomes in women receiving hormone replacement therapy will be summarized. Hormone replacement therapy should not be recommended routinely for all postmenopausal women, as it is not clear if it presents cardioprotection and the detectable elevated risk of cardiovascular disease and breast cancer surpasses the benefits in asymptomatic women, by the time the newer data would become available.

The increase awareness of cardiovascular risk factors is an important concern and may help to avoid or to moderate an aggressive management of cardiovascular events in the future. The factors (healthy diet, physical activities, body weight reduction and smoking cessation), whose modification could improve the cardiovascular disease outcomes in women, will be analyzed.

Clinical trials that involved women under treatment for dyslipidemia, diabetes mellitus or arterial hypertension will be also analyzed. Moreover, data of hormone replacement therapy in women as well as in animal models will be discussed.

The most common cause of death in menopausal women is cardiovascular disease with sudden death as the more severe complication. It is noteworthy to mention that two out of the three women who die suddenly, have been asymptomatic before.

More than one in three American women have some form of cardiovascular disease (coronary heart disease, cerebrovascular disease, peripheral artery disease, rheumatic heart disease, congenital heart disease, deep vein thrombosis, and pulmonary embolism). One in 31 women die of breast cancer, one in three die from cardiovascular disease.

This data led medical societies to suggest more intensive primary and secondary prevention of cardiovascular disease in women. The results from the Women’s Health Initiative and Heart and Estrogen/progestin Replacement Study studies trigger a lot of discussion. Both unexpectedly reported an association between hormone replacement therapy and increased cardiovascular disease risk incidence.

Thus, the need for cardiovascular disease strategy prevention in women other than hormone replacement therapy, based on documented evidence and a critical review was required. The guidelines/scientific statements, which have been reported by various medical societies for the prevention of cardiovascular disease in women, will be analyzed.