RALOXIFENE INHIBITS AORTIC ACCUMULATION OF CHOLESTEROL IN OVARIECTOMIZED, CHOLESTEROL-FED RABBITS

Background The beneficial effect of long-term hormone replacement ther apy in terms of a decreased risk of cardiovascular disease is now gene rally accepted. Raloxifene, a selective estrogen receptor modulator, h as demonstrated hypolipidemic properties while leaving the endometrium unstimulated. Methods and Results For our study of the effects of ral oxifene on atherosclerosis, 75 rabbits were ovariectomized and treated with either raloxifene, 17 beta-estradiol, or placebo; 25 rabbits wer e sham operated and treated with placebo. After 45 weeks, the raloxife ne group had two thirds of the aortic atherosclerosis, as evaluated by the cholesterol content of the proximal inner part of the aorta, foun d in the placebo group (placebo, 577 +/- 55.1 nmol/mg protein; raloxif ene, 397 +/- 53.6 nmol/mg protein; P < .05); the estrogen group had on e third of the aortic atherosclerosis in the placebo group (estrogen, 177 +/- 32.1 nmol/mg protein; P < .001). The sham-operated group (473 +/- 59.6 nmol/mg protein) was not significantly different from placebo . These effects were only partly explained by the changes in serum lip ids and lipoproteins, and treatment with both estrogen and raloxifene independently predicted the response in aorta cholesterol. Because pla sma levels of total raloxifene were low relative to clinical values in postmenopausal women, dose-response data for raloxifene are required. Conclusions Our findings indicate that raloxifene hydrochloride has a potentially important antiatherogenic effect, analogous to that obser ved with estrogen in this model.