ESTERIFIED ESTROGENS WITH AND WITHOUT METHYLTESTOSTERONE DECREASE ARTERIAL LDL METABOLISM IN CYNOMOLGUS MONKEYS

Although both epidemiological and experimental evidence suggests that estrogen replacement therapy reduces the risk of coronary heart diseas e, the mechanisms for this beneficial effect are largely unknown. Furt hermore, the addition of progestins or androgens to estrogen replaceme nt therapy is of concern. The objective of this study was to examine t he effects of esterified estrogens alone or in combination with an and rogen on arterial LDL metabolism and early atherogenesis in ovariectom ized female cynomolgus monkeys. Arterial LDL metabolism was assessed b y using dual-labeled LDL that was injected 24 hours before necropsy. A rterial LDL degradation was reduced by 64% to 84% and cholesteryl este r content was decreased by approximate to 50% in the thoracic aorta in both treatment groups compared with controls. In addition, aortic lip id peroxidation products, as assessed by thiobarbituric acid reaction, were significantly lower in animals treated with esterified estrogens , with a similar trend for combined estrogen androgen treatment. Both treatments also reduced plasma concentrations of apoB-containing lipop roteins, reduced LDL particle size, and increased total-body LDL catab olism. The combination of decreased arterial LDL metabolism, decreased arterial lipid peroxidation, and improved plasma lipoprotein metaboli sm may explain some of the protective effects of estrogens on coronary heart disease and indicate that beneficial actions extend to a combin ation of estrogen and androgen.