Benefit/risk of estrogen therapy in cardiovascular disease: current knowledge and future challenges.

Abstract

In the United States, cardiovascular disease represents the leading cause of death among women. A majority of the deaths are due to coronary disease. In addition, the incidence of heart attacks increases with age. Among those who are 65 years of age or older, the estimated heart attack rate is 374,000 per year for women, compared with 440,000 per year for men. In the past three decades, a number of observational studies have suggested that estrogen therapy can reduce the risk of coronary disease in postmenopausal women. This protective effect appears to be much greater in women who have existing coronary disease. These observational data point to the potential usefulness of estrogen therapy in preventing cardiovascular death among women. Although large, well-controlled, clinical trials are needed to confirm the benefit of estrogen therapy, several important findings strongly support the cardioprotective effect of estrogen therapy. For example, in monkeys estrogen prevents the accumulation of low-density lipoprotein (LDL) cholesterol (a known risk factor for heart disease) in coronary arteries, and estrogen has also been shown to increase high-density lipoprotein (HDL) cholesterol (a known cardioprotective factor). Estrogen also possesses a vasodilating property, which can improve cardiac performance in ischemic heart disease. In addition, recent studies have demonstrated that estrogens (especially equilin) exhibit a high antioxidant effect, which may also be related to cardioprotectivity. Although estrogen therapy has been observed to decrease the risk of coronary disease, long-term estrogen therapy has also been found to increase the risk of uterine carcinoma; the addition of progesterone to estrogen therapy may lessen this undesirable risk, however. On the other hand the addition of progesterone to estrogen therapy may decrease estrogen's beneficial effect on HDL cholesterol. What should be the present position on estrogen therapy in postmenopausal women? What is the best dosage regimen? Should it be used alone or in combination with a progesterone? These important issues are discussed, as are several current clinical trials addressing the issue of estrogen therapy in postmenopausal women.