EFFECTS OF SHORT-TERM HORMONE REPLACEMENT THERAPIES ON LOW-DENSITY-LIPOPROTEIN METABOLISM IN CYNOMOLGUS MONKEYS

Estrogen replacement therapy reduces the risk of coronary heart diseas e in women and decreases the extent of atherosclerosis in monkeys. In our previous studies, estrogen treatment decreased arterial LDL degrad ation and accumulation, thus indicating one mechanism by which estroge n inhibits the progression of atherosclerosis. The influence of proges tins on these processes remains unclear. The objective of this study w as to determine the effects of oral estrogen (conjugated equine estrog ens) and progestin (medroxyprogesterone acetate) alone or in combinati on on arterial LDL metabolism after 12 weeks of atherogenic stimulus. This relatively short period of treatment was chosen to determine effe cts on arterial LDL metabolism before substantial subendothelial macro phage accumulation. In contrast to previous studies (16 to 18 weeks of treatment), when macrophages were present in the intima, neither estr ogen nor progestin (nor their combination) had any effect on any index of arterial LDL metabolism. These results suggest that estrogen may p referentially reduce LDL metabolism in macrophages with little effect on cells of the normal artery. In contrast to arterial LDL metabolism, hepatic LDL uptake was significantly increased in animals treated wit h estrogen or estrogen plus progestin. Despite the increased LDL uptak e by the liver, hepatic lipid content was significantly decreased by a pproximate to 50% in both estrogen and estrogen-plus-progestin treatme nt compared with control and progestin-treated animals. The decrease i n hepatic cholesterol content is hypothesized to be due to increased b iliary secretion of cholesterol.