CONJUGATED EQUINE ESTROGENS ALONE, BUT NOT IN COMBINATION WITH MEDROXYPROGESTERONE ACETATE, INHIBIT AORTIC CONNECTIVE-TISSUE REMODELING AFTER PLASMA-LIPID LOWERING IN FEMALE MONKEYS

The objective of this study was to determine the arterial responses to plasma lipid lowering alone or in combination with (1) estrogen repla cement therapy or (2) hormone replacement therapy in surgically postme nopausal female monkeys with preexisting;atherosclerosis. Eighty-eight female cynomolgus macaques were ovariectomized, fed an atherogenic di et for 24 months, and then assigned by randomized stratification into 4 groups. One group (baseline, n=20) was necropsied at the end of the atherogenic diet period; the remaining 3 groups were fed a plasma Lipi d-lowering diet (regression) for 30 months. These regression groups we re control (diet only), CEE (receiving conjugated equine estrogens alo ne), and CEE+MPA (receiving CEE and continuous medroxyprogesterone ace tate). A previous report described coronary artery functional and hist ological results; the present report describes biochemical and histolo gical results from the abdominal aorta. Aortic plaque size was not dif ferent between groups, similar to previous findings in the coronary ar teries. Aortic cholesterol content (milligrams per gram lipid-free dry weight) was lower in the regression groups compared with baseline, bo th for free cholesterol (mean, control=19.1, CEE=15.7, CEE+MPA=14.4, a nd baseline=32,7; P<0.001) and for esterified cholesterol (mean, contr ol=18.9, CEE=15.4, CEE+MPA=14.2, and bascline=58.7; P<0.001). This cho lesterol afflux could lead to increased plaque stability without chang ing the physical size of the lesion. Alterations in aortic connective tissue composition were observed in the regression groups. When expres sed as a percentage of the lipid-free tissue weight, the aortic elasti n content of the control (mean= 14.9) and the CEE+MPA (mean=14.0) grou ps was lower than that of the baseline group (mean= 19.0), which was n ot different from that of the CEE group (mean=15.8). Aortic collagen c ontent, as estimated by hydroxyproline content per milligram of lipid- free tissue, was higher in the control group (mean=67.4) and the CEE+M PA group (mean= 66.1) than in the baseline group (mean =56.2; P<0.05). Collagen content of the CEE group (mean=58.9) was not different from that of the baseline group. When the regression groups were considered separately, the aortic collagen content of the CEE group was lower th an that of the control group (P<0.05) and tended to be lower than that of the CEE+MPA group (P=0.10), suggesting that CEE therapy (but not C EE+MPA) inhibits potentially detrimental connective tissue alterations that accompany lesion regression. These results have implications for combinations of lipid-lowering and hormone replacement therapies in r elation to vascular remodeling and abdominal aortic aneurysm developme nt.