Effect of sexual steroids on the calcium content of aortic atherosclerotic plaque of oophorectomized rabbits

Abstract

We determined the effect of conjugated equine estrogen plus medroxyprogesterone acetate on calcium content of aortic atherosclerotic lesions in oophorectomized adult New Zealand rabbits submitted to a cholesterol rich diet. Five groups of 10 animals each were studied: G1 = control, G2 = cholesterol diet only, G3 = diet plus conjugated equine estrogen (0.625 mg/day); G4 and G5 = diet, conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 and 10 mg/day, respectively). Mean weight varied from 2.7 ± 0.27 to 3.1 ± 0.20 kg (P = 0.38) between groups at the beginning and 3.1 ± 0.27 to 3.5 ± 0.20 kg (P = 0.35) at the end of the experiment. Cholesterol and triglyceride levels were determined at the time of oophorectomy, 21 days after surgery (time 0), and at the end of follow-up of 90 days. The planimetric method was used to measure plaque and caryometric method for histopathologic examination of the aorta. Calcium content was determined by the method of von Kossa. A similar increase in cholesterol occurred in all treated groups without differences between them at the end of the study. Groups G4 and G5 had smaller areas of atherosclerotic lesions (2.33 ± 2.8 and 2.45 ± 2.1 cm 2 , respectively) than the groups receiving no progestogens (G2: 5.6 ± 4 and G3: 4.6 ± 2.8 cm 2 ; P = 0.02). The relation between lesion area and total aorta area was smaller in groups treated with combined drugs compared to the groups receiving no progesterone (G4: 14.9 ± 13 and G5: 14.2 ± 13.4 vs G2: 35.8 ± 26 and G3: 25 ± 8 cm 2 , respectively; P = 0.017). Oral conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 or 10 mg/day) provoked a greater reduction in atherosclerotic plaque area and calcium content in treated groups, suggesting a dose-dependent effect.

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“…In view of the controversy between hormonal replacement in postmenopausal women and decreased cardiovascular morbidity and mortality, and the effects of estrogens associated with progesterones, or progesterone alone, we developed a protocol to evaluate the repercussions of hormone therapy with progesterone in oophorectomized rabbits submitted to the atherogenic diet, on the development of atherosclerotic lesions induced in animals. [1][2][3][4][5][6] The present study aims to report the effects of the addition of medroxyprogesterone acetate to the hypercholesterolemic diet, at doses of 5 and 10mg/day, given to oophorectomized New Zealand rabbits, regarding: serum cholesterol and triglycerides levels; analysis of atherosclerotic lesions of the aorta; analysis of atherosclerotic lesions in coronary arteries.…”