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-relate d enzymes in 45 postmenopausal women with type IIa hypercholesterolemia. Th ey 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 c oncentrations of cholesterol and triglyceride in the plasma, and in the ver y low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), l ow-density lipoprotein (LDL)1 (1.019 <d<1.045 g/ml) and LDL2 (1.045 <d<1.06 3 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 t reatments significantly lowered the plasma levels of total cholesterol, LDL 1 cholesterol, and apolipoprotein B, C-II, and E. In combination therapy, s ignificantly reduced levels of VLDL, IDL, and LDL2 cholesterol were also ob tained. Combination therapy lowered total and LDL1 cholesterol significantl y more than did estrogen alone. Estrogen and combination therapy significan tly increased the levels of cholesterol in the HDL2 subfraction, triglyceri de in the HDL2 and HDL3 subfractions, and apolipoprotein A-I and A-II. Estr ogen treatment, but not combination therapy, also significantly raised the levels of total and IDL triglyceride. Estrogen and combined therapies signi ficantly lowered the activities of hepatic triglyceride lipase and lecithin cholesterol acyltransferase. Findings indicate that combination therapy wi th estrogen plus simvastatin favorably affected lipid metabolism by reducin g the concentrations of VLDL and IDL particles as well as large and small L DL particles, increasing the concentration of HDL particles, and preventing estrogen-induced increases in plasma triglyceride levels. (C) 2000 Elsevie r Science Ireland Ltd. All rights reserved.