on November 7, 2002
Published online before print November 7, 2002, doi: 10.1161/01.ATV.0000046033.32478.6D
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Submitted on September 17, 2002
Accepted on October 25, 2002
Hormone Replacement Therapy and Risk of Cardiovascular Disease. Implications of the Results of the Women's Health Initiative
Lewis H. Kuller *
From the Department of Epidemiology, University of Pittsburgh, Pa.
* To whom correspondence should be addressed. E-mail: kullerl{at}edc.pitt.edu.
Abstract—The higher rates of coronary heart disease (CHD), stroke, and venous thrombosis among women taking estrogen and progesterone (E+P) compared with placebo in the Women's Health Initiative clinical trial have important implications for women's health. Previous studies in both men and women have shown that estrogen therapy lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol. The changes in these lipoproteins should be associated with at least a 30% decline in CHD risk. Estrogens increased very-low-density lipoprotein (VLDL) triglyceride levels and C-reactive protein. There is evidence that estrogens increase thrombin generation and fibrinolysis. The increase in VLDL triglycerides may enhance thrombotic risk as well as higher levels of atherogenic lipoproteins, such as dense low-density lipoprotein. Genetic variations in estrogen receptors and thrombosis or fibrinolysis may also be important in risks associated with E+P therapy. The increased risk of CHD and stroke with E+P therapy may be attributable to rise in VLDL triglycerides and thrombosis.
Key words: coronary heart disease • hormones • estrogen • stroke • clinical trials
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