In younger postmenopausal women,
estrogen is thought to be protective against
coronary heart disease. The mechanism for this effect is likely to be an inhibition of the development of
atherosclerosis. However, in older postmenopausal women with established
atherosclerosis, the initiation of
estrogen therapy may cause coronary artery plaque instability and
rupture, resulting in
coronary thrombosis and
myocardial infarction. Compared with these findings of
coronary disease prevention in younger women,
estrogen therapy has been linked to an increased risk of
ischemic stroke in both younger and older postmenopausal women, although the risk is small and the event rate in younger women is considered to be rare. Here, we provide an argument that the mechanism for
stroke risk in younger women is not based on atherosclerotic disease, as occurs in older women for both
coronary disease and
stroke, but is related to
thrombosis. Susceptibility for
stroke is increased in women, and various factors leading to
thrombosis may explain this risk. This notion is supported by data that
estrogen regimens that decrease the risk of
venous thrombosis (lower oral doses and transdermal
therapy) may not be associated with an increase in
ischemic stroke risk.