Controversies about HRT--lessons from monkey models.
Lessons from monkey models contribute significantly to a better understanding of the controversies in reconciling the differences in postmenopausal hormone treatment outcomes between observational and randomized trial data. Monkey studies brought attention to premenopausal estrogen deficiency with resulting premature coronary artery atherosclerosis. Recently, those monkey studies were confirmed for premenopausal women in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) Study. Monkey studies have provided convincing evidence for the primary prevention of coronary artery atherosclerosis when estrogens are administered soon after the development of estrogen deficiency. Equally convincing are the data from monkey studies indicating the total loss of these estrogens beneficial effects if treatment is delayed for a period equal to six postmenopausal years for women. An attempt has been made using the monkey model to identify the hormone treatment regimen most effective in preventing the progression of coronary artery atherosclerosis. By a substantial margin, the most effective approach is that of using estrogen containing oral contraceptive during the perimenopausal transition, followed directly by hormone replacement therapy postmenopausally. Because of similarities between human and nonhuman breast, monkeys have had a major role in clarifying controversies surrounding the breast cancer risk of estrogen only versus estrogen plus progestin therapies. The results of monkey studies suggest little or no effects of estrogen only treatment; whereas, estrogen+progestin clearly increases breast cancer risk.
Clarkson
Thomas B
TB
Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1040, USA. tclarkso@wfubmc.edu
Appt
Susan E
SE
D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced; D003324:Coronary Artery Disease / Q000139:chemically induced / Q000517:prevention & control; D004195:Disease Models, Animal; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D000882:Haplorhini; D006801:Humans; D008593:Menopause / Q000187:drug effects*; D011322:Primary Prevention; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors