Repercussions of raloxifen, tamoxifen and estrogen on aortic atherosclerotic lesions of female rabbits submitted to ovariectomy and hypercholesterol diet.

Background: The role of hormone-replacement therapy in decreasing the risk of cardiovascular disease in women has not been firmly established. Recent studies have shown that the selective estrogen receptor modulators raloxifene, and tamoxifene, posses hypolipidemic and antiatherogenic properties.

Methods And Results: Forty-three adult female rabbits were submitted to ovariectomy (moment 1). Three weeks after surgical recovery, they were grouped in five groups as follows (moment 2): control group (9)--normal diet; cholesterol group (8)--0.5% cholesterol added to diet; raloxifen group (8); tamoxifen group (9); estrogen group (9)--diet added by 0.5% cholesterol and 60 mg raloxifen, 20 mg tamoxifen or 0.625 mg equine conjugated estrogen. The animals from all groups were sacrificed after 13 weeks (moment 3) and the thoracic and abdominal aortas were studied. We collected digital images of the observed atherosclerotic lesions in the vessel lumen by means of a computerized method. We analyzed serum levels of total cholesterol and fractions (HDL, VLDL, and LDL), as well as triglycerides. Among the animals that received hyper cholesterol diet and medication, we noticed a reduction of the total area of atherosclerotic plaques in the tamoxifen (P < 0.05) or estrogen group (P < 0.05) compared to the cholesterol group. Serum levels of total, LDL- and HDL-cholesterol were higher for the raloxifen, tamoxifen, estrogen, and cholesterol (P = 0.0001).

Conclusion: Female rabbits treated with a high cholesterol diet associated to tamoxifen or estrogen had a statistically significant reduction in aortic atherosclerotic plaques. Even though there was a significant increase in cholesterol levels, we did not find any correlation between cholesterol levels and degree of aortic atherosclerotic lesion.