The applicability of hormonal effects on atherosclerosis in animals to heart disease in postmenopausal women.

The discrepancy between estrogen's beneficial cardiovascular effects found in animal studies and observational studies in women compared with the recently published randomized clinical trials have stimulated a great deal of controversy. Possibilities for the discrepancy include the age of the women, number of years postmenopausal, and amount of atherosclerotic complication (necrosis and inflammation) present when hormone therapy is initiated. Many of the previous benefits of estrogens noted in both animal studies and observational studies were found in primary prevention studies that experimentally refer to a decrease in the progression of atherosclerosis extent rather than prevention of clinical events, which often occur in women with undiagnosed atherosclerotic plaques. In support of this notion, animal studies in which artery damage was present prior to hormone treatment, due to either consumption of an atherogenic diet or balloon injury of the endothelium, found no benefit with estrogen treatment. These animal studies are consistent with the lack of protection found in secondary prevention studies in women. Other areas of concern deal with the route of hormone delivery or dose of hormones used. Higher doses of oral estrogens may result in increased risk of inflammation and thrombosis. Future studies should be directed at studying hormone therapy in relevant ages of women (perimenopausal women) using the lowest effective doses of hormones and comparing oral and parenteral forms of delivery.