NORETHINDRONE ACETATE ENHANCES THE ANTIATHEROGENIC EFFECT OF 17-BETA-ESTRADIOL - A SECONDARY PREVENTION STUDY OF AORTIC ATHEROSCLEROSIS IN OVARIECTOMIZED CHOLESTEROL-FED RABBITS

The influence of progestogens in combination with 17 beta-estradiol (E 2) on cardiovascular disease remains controversial. This study investi gated the effect of norethindrone acetate (NETA) combined with E2 on a ortic atherosclerosis. Eighty mature female rabbits were ovariectomize d, then fed a cholesterol-rich diet (240 mg/d) for 14 weeks to induce aortic atherosclerosis. They were randomized to four equally large gro ups for the following 38-week intervention period. One group received placebo, another group oral E2 4 mg daily (E2), and the last two group s oral E2 4 mg daily combined with either NETA 1 mg (E2NETA1) or NETA 3 mg (E2NETA3). The cholesterol intake was reduced to a ''maintenance' ' level of 80 mg/d during the intervention period. Total serum cholest erol and ultracentrifuged lipoproteins were analyzed enzymatically thr oughout the study. The cholesterol content in the aortic wall was 2.76 +/-0.44 mu mol/cm(2) (mean+/-SEM) in the E2NETA1 group, 1.77+/-0.37 mu mol/cm(2) in the E2NETA3 group, 5.46+/-0.77 mu mol/cm(2) in the E2 gr oup, and 7.20+/-0.94 mu mol/cm(2) in the placebo group (ANOVA P<0.0001 ). The difference tin the aortic cholesterol accumulation) between the E2, and each of the combined E2/NETA groups was statistically signifi cant (P<0.01) but could only partly be explained by the differences in serum lipids and lipoproteins. In conclusion, NETA enhances the antia therogenic effect of E2 in cholesterol-fed rabbits. This effect is onl y partially mediated through changes in serum lipids and lipoproteins.