Tibolone inhibits aortic atherosclerotic lesionformation in oophorectomized cholesterol-fed rabbits

Tibolone is a synthetic steroid effective for the treatment of climacteric symptoms and osteoporosis. Long term treatment with tibolone is associated with a significant decrease in cholesterol levels due to a parallel decrease in high-density lipoprotein. However, the effect of these changes on atherogenesis is not known.

To investigate the effect of tibolone therapy on aorta atherogenesis.

Thirty-two New Zealand white rabbits were fed cholesterol-rich feed and studied for four months. The rabbits underwent laparotomy and were randomly assigned to four groups. Twenty-four rabbits underwent bilateral ovariectomy; of these, eight received tibolone (group T), eight received estradiol valerate (group E), eight received placebo after sterilization (group C), and eight were sham operated (group S).

After receiving the cholesterol-rich diet, total levels of cholesterol increased in group C from 3.17+/-0.72 mmol/L to 35.36+/-9.01 mmol/L, in group S from 2.88+/-0.9 mmol/L to 28.76+/-9.442 mmol/L, in group E from 1.69+/-0.44 mmol/L to 1.69+/-0.44 mmol/L and in group T from 2.03+/-0.22 mmol/L to 26.33+/-13.45 mmol/L (no significant differences were observed among the groups at the end of the study). At four months, the cholesterol- rich diet caused atherosclerotic lesions in both treated and untreated rabbits, affecting 30.47+/-12.2%, 24.51+/-16.1%, 17.91+/-10.19% and 10.21+/-6.8% of the aortic surface for groups C, S, E and T, respectively (P<0.01 for treated groups).

The principal result from this study was that treatment with tibolone in cholesterol-fed ovariectomized rabbits reduces aortic atherosclerotic lesion formation and that this reduction is not related to plasma lipid levels.