Several characteristics of the rabbit make it an excellent model for the study of lipoprotein metabolism and atherosclerosis. New Zealand White (NZW) rabbits have low plasma total cholesterol concentrations, high cholesteryl ester transfer protein activity, low hepatic lipase (HL) activity, and lack an analogue of human apolipoprotein (apo) A-II, providing a unique system in which to assess the effects of diets and therapies on plasma lipoproteins and atherosclerosis susceptibility. Cardiovascular disease is a major concern and the role of hormone replacement therapy in its prevention is controversial. For these reason we studied in cholesterol-fed rabbits how diet, tibolone, raloxifene and estradiol may affect atherosclerosis extension. For these reasons we studied a total of 40 cholesterol-fed New Zealand white rabbits for 4 months. Thirty-two rabbits underwent bilateral ovariectomy and the other 8 were sham operated (group S). The ovariectomized rabbits were allocated to 4 groups of 8 animals each receiving tibolone (Group T, 6 mg/day), raloxifene (R, 35 mg/day), estradiol valerate (E, 3 mg/day) and no treatment for the control group (C).

After four months the percentage of the extent of atherosclerosis in the aorta was 30.4% in C group, 24.5% in S group, 10.2% in T group, 30.3% in R group and 17.9% in E group (p<.05 T vs. C, R). The aortic cholesterol content compared to aortic weight was 8.55 µg/mg in C group, 11.97 µg/mg in S group, 1.86 µg/mg in T group, 3.82 µg/mg in R group, and 2.86 µg/mg in E group (p<.05 T vs. C, S; R vs. C, S; E vs. C, S).

In conclusion our study showed a decrease in the extent of aortic atherosclerosis in oophorectomized cholesterol-fed rabbits treated with tibolone or estradiol, and a decrease in aortic cholesterol content in rabbits treated with tibolone, raloxifene and estradiol.