Norethindrone acetate enhances the antiatherogenic effect of 17beta-estradiol: a secondary prevention study of aortic atherosclerosis in ovariectomized cholesterol-fed rabbits.
The influence of progestogens in combination with 17beta-estradiol (E2) on cardiovascular disease remains controversial. This study investigated the effect of norethindrone acetate (NETA) combined with E2 on aortic atherosclerosis. Eighty mature female rabbits were ovariectomized, then fed a cholesterol-rich diet (240 mg/d) for 14 weeks to induce aortic atherosclerosis. They were randomized to four equally large groups for the following 38-week intervention period. One group received placebo, another group oral E2 4 mg daily (E2), and the last two groups 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 cholesterol and ultracentrifuged lipoproteins were analyzed enzymatically throughout the study. The cholesterol content in the aortic wall was 2.76+/-0.44 micromol/cm2 (mean+/-SEM) in the E2NETA1 group, 1.77+/-0.37 micromol/cm2 in the E2NETA3 group, 5.46+/-0.77 micromol/cm2 in the E2 group, and 7.20+/-0.94 micromol/cm2 in the placebo group (ANOVA P<0.0001). The difference (in the aortic cholesterol accumulation) between the E2 and each of the combined E2/NETA groups was statistically significant (P<0.01) but could only partly be explained by the differences in serum lipids and lipoproteins. In conclusion, NETA enhances the antiatherogenic effect of E2 in cholesterol-fed rabbits. This effect is only partially mediated through changes in serum lipids and lipoproteins.
Alexandersen
P
P
Center for Clinical & Basic Research, Ballerup Byvej, Ballerup, Denmark.
Haarbo
J
J
Sandholdt
I
I
Shalmi
M
M
Lawaetz
H
H
Christiansen
C
C
D000818:Animals; D001011:Aorta; D001161:Arteriosclerosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008074:Lipoproteins / Q000097:blood; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D010052:Ovariectomy; D011817:Rabbits
D002791:Cholesterol, Dietary; D008074:Lipoproteins; D004958:Estradiol; D002784:Cholesterol; D000077563:Norethindrone Acetate; D009640:Norethindrone