Abstract # 18:

Scheduled for Thursday, August 17, 2006 11:15 AM-11:30 AM: Session 2 (Regency East #2) Oral Presentation

Monkeys and the Postmenopausal Hormone Therapy Conundrum

J. R. Kaplan, M. R. Adams and T. B. Clarkson
Wake Forest University School of Medicine , Section on Comparative Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA
     Here we show how systematic research conducted in monkeys has helped unravel the controversy surrounding the health consequences of estrogen supplementation to menopausal women. This controversy began when randomized clinical trials found that hormone therapy initiated in women with an average age more than 60 does not provide cardiovascular protection. This finding contrasted with observational studies demonstrating a 50% reduction in heart disease risk. Studies using premenopausal cynomolgus monkeys (Macaca fascicularis) indicate that relative estrogen deficiency accelerates the development of coronary artery atherosclerosis, the pathological process underlying heart disease. Estrogen supplementation to such animals inhibits atherosclerosis exacerbation. Related studies demonstrate that atherosclerosis develops rapidly following surgical menopause (ovariectomy), a condition that can prevented by hormone replacement initiated immediately following ovariectomy. However, estrogen therapy provides no benefit if hormone replacement is delayed or if extensive atherosclerosis is already present. The monkey data suggest that estrogen is cardioprotective, but only in the early stages of atherosclerosis or when initiated at menopause. Newly emerging data from human studies support this hypothesis, suggesting hormone therapy does not adversely affect early menopausal women or those who are relatively atherosclerosis free. Because of the monkey studies and emerging human data, two new clinical trials have been initiated to test the hypothesis that early vs. late exposure to estrogen have contrasting effects on the cardiovascular system. Partially supported by HL45666 and HL79421.