Hormone Replacement Therapy and Cardiovascular Disease: Lessons from a Monkey Model of Postmenopausal Women

Concerns exist about the cardiovascular effects of hormone replacement therapy (HRT) in postmenopausal women be-cause results from the Women’s Health Initiative (WHI) and the Heart and Estrogen/Progestin Replacement Study (HERS) are contradictory. In both of these studies, post-menopausal conjugated equine estrogens + medroxyproges-terone acetate did not reduce risk, and somewhat increased the risk of myocardial infarction in both primary (WHI) and secondary (HERS) prevention. These results appear to con-tradict numerous observational clinical trials and animal studies, which reported profound beneficial effects of HRT on cardiovascular disease risk. Results of both human and monkey studies indicate that estrogen replacement therapy (ERT)/HRT is effective in inhibiting progression of early stage (fatty streak) atherosclerosis but that ERT/HRT is much less effective in inhibiting progression of more ad-vanced (established plaque) atherosclerosis. Results of these monkey studies are consistent with those of studies in women wherein ERT/HRT was initiated in postmenopausal women with different initial amounts of atherosclerosis. Based on these findings, it is speculated that ERT/HRT may be more cardioprotective in younger postmenopausal women with less coronary artery disease, and less effective in women with established coronary artery disease. Re-searchers are challenged to define the relative cardiovascu-lar risk/benefit in different populations of postmenopausal women based on differences in age, amounts of pre-existing atherosclerosis, and risk factors. Key Words: animal models; atherosclerosis; endothelial function; inflammation; plaque stability; risk factor