Effects of combination therapy with estrogen plus simvastatin on lipoprotein metabolism in postmenopausal women with type IIa hypercholesterolemia.

We investigated the effects of estrogen and simvastatin, administered both alone and in combination, on the plasma lipid levels and lipoprotein-related enzymes in 45 postmenopausal women with type IIa hypercholesterolemia. They received 0.625 mg conjugated equine estrogen (n=15), 5 mg simvastatin (n=15), or the combination (n=15) daily for 3 months. We measured the concentrations of cholesterol and triglyceride in the plasma, and in the very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL)1 (1.019<d<1.045 g/ml) and LDL2 (1.045<d<1.063 g/ml), and high-density lipoprotein (HDL)2 (1.063<d<1.125 g/ml) and HDL3 (1.125<d<1.210 g/ml) subfractions, and apolipoproteins, and the activities of lipoprotein-metabolizing enzyme before and after treatment. All three treatments significantly lowered the plasma levels of total cholesterol, LDL1 cholesterol, and apolipoprotein B, C-II, and E. In combination therapy, significantly reduced levels of VLDL, IDL, and LDL2 cholesterol were also obtained. Combination therapy lowered total and LDL1 cholesterol significantly more than did estrogen alone. Estrogen and combination therapy significantly increased the levels of cholesterol in the HDL2 subfraction, triglyceride in the HDL2 and HDL3 subfractions, and apolipoprotein A-I and A-II. Estrogen treatment, but not combination therapy, also significantly raised the levels of total and IDL triglyceride. Estrogen and combined therapies significantly lowered the activities of hepatic triglyceride lipase and lecithin cholesterol acyltransferase. Findings indicate that combination therapy with estrogen plus simvastatin favorably affected lipid metabolism by reducing the concentrations of VLDL and IDL particles as well as large and small LDL particles, increasing the concentration of HDL particles, and preventing estrogen-induced increases in plasma triglyceride levels.