Effects of estradiol, cyproterone acetate, tibolone and raloxifene on uterus and aorta atherosclerosis in oophorectomized cholesterol-fed rabbits.
BACKGROUND
Different hormonal replacement regimens are used for treating climacteric complaints; however, not all of them have the same clinical profile. Cardiovascular disease (CVD) is a major health problem and tibolone, raloxifene, estradiol (alone or with cyproterone acetate) have been added to cholesterol-fed rabbits to study atherosclerosis.


METHODS
A total of 48 cholesterol-fed New Zealand white rabbits were studied for 4 months. Forty rabbits underwent bilateral ovariectomy and the other eight were sham operated (group S). The ovariectomized rabbits were allocated to five groups of eight animals each receiving tibolone (Group T, 6 mg/day), raloxifene (R, 35 mg/day), estradiol valerate (E, 3 mg/day), estradiol valerate plus cyproterone acetate (EC, 3+0.5 mg/day, respectively), and no treatment for the control group (C). The sham group received no treatment too.


RESULTS
After 4 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, 17.9% in E group and 28.1% in EC group (P<0.05 T vs. C, R, EC). The aortic cholesterol content compared with aortic weight was 8.55 microg/mg in C group, 11.97 microg/mg in S group, 1.86 microg/mg in T group, 3.82 microg/mg in R group, 2.86 microg/mg in E group and 5.24 microg/mg in EC group (P<0.05 T vs. EC, C, S; R vs. C, S; E vs. C, S). Uterine weights in grams were: 1.89 (C group), 2.24 (S), 7.38 (T), 1.94 (R), 9.92 (E), and 5.94 (EC); P<0.05 (C, S, R, vs. T, E, EC; T vs. E; EC vs. T, E).


CONCLUSIONS
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. However, rabbits treated with tibolone showed an increased uterine weight, which is contrary to that observed in humans.
Sanjuán
A
A
Section of Gynecologic Oncology, Department of Gynecology and Obstetrics, Menopause Clinic, Hospital Clínic i Provincial, University of Barcelona, c/Villarroel 170, 08036 Barcelona, Spain.
Castelo-Branco
C
C
Colodrón
M
M
Ascaso
C
C
Vicente
J J
JJ
Ordi
J
J
Casals
E
E
Mercadé
I
I
Escaramís
G
G
Vanrell
J A
JA
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001161:Arteriosclerosis / Q000188:drug therapy*; D002791:Cholesterol, Dietary; D017373:Cyproterone Acetate / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D009652:Norpregnenes / Q000494:pharmacology* / Q000627:therapeutic use; D010052:Ovariectomy; D011817:Rabbits; D020849:Raloxifene Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use; D014599:Uterus / Q000187:drug effects*
D002791:Cholesterol, Dietary; D009652:Norpregnenes; D020849:Raloxifene Hydrochloride; D017373:Cyproterone Acetate; D004958:Estradiol; C027385:tibolone