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Different mechanisms for benefit and risk of coronary heart disease and stroke in early postmenopausal women: a hypothetical explanation

Lobo, Rogerio A. MD1; Clarkson, Tom B. DVM2

doi: 10.1097/gme.0b013e3181e9e538
Personal Perspective

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.

In young postmenopausal women receiving estrogen therapy, there is no evidence for early coronary harm and the possibility of a decrease in coronary risk, but there may be a small increase in the risk of ischemic stroke. The hypothesis that there are different mechanisms explaining this difference, with thrombotic mechanisms predominantly explaining ischemic stroke risk.

From the 1Department of Obstetrics and Gynecology, Columbia University, New York, NY; and 2Department of Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.

Received May 14, 2010; revised and accepted May 26, 2010.

Financial disclosure/conflicts of interest: None reported for this study. Research funds for other studies for T.B.C. (Pfizer) and R.A.L. (Pfizer, Kronos).

Address correspondence to: Rogerio A. Lobo, MD, Department of Obstetrics and Gynecology, Columbia University Medical Center, 622 West 168th Street, New York, NY 10032. E-mail:

©2011The North American Menopause Society