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 disease, the mechanisms for this beneficial effect are largely unknown. Furthermore, the addition of progestins or androgens to estrogen replacement therapy is of concern. The objective of this study was to examine the effects of esterified estrogens alone or in combination with an androgen on arterial LDL metabolism and early atherogenesis in ovariectomized female cynomolgus monkeys. Arterial LDL metabolism was assessed by using dual-labeled LDL that was injected 24 hours before necropsy. Arterial LDL degradation was reduced by 64% to 84% and cholesteryl ester content was decreased by approximately 50% in the thoracic aorta in both treatment groups compared with controls. In addition, aortic lipid 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 lipoproteins, reduced LDL particle size, and increased total-body LDL catabolism. The combination of decreased arterial LDL metabolism, decreased arterial lipid peroxidation, and improved plasma lipoprotein metabolism may explain some of the protective effects of estrogens on coronary heart disease and indicate that beneficial actions extend to a combination of estrogen and androgen.