Effect of estrogen and simvastatin on low-density lipoprotein subclasses in hypercholesterolemic postmenopausal women

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Abstract
Objective: To identify the effects of estrogen and simvastatin, individually and in combination, on the levels of low-density lipoprotein (LDL) subclasses in postmenopausal women with type IIa hypercholesterolemia. Methods: Fifty-five postmenopausal women with type IIa hypercholesterolemia were assigned randomly to 0.625 mg of conjugated equine estrogen (n = 20), 5 mg of simvastatin (n = 18), or both (n = 17) daily for 3 months. Cholesterol, triglyceride, and apolipoprotein B levels in the plasma and in the LDL1 (density 1.019–1.045 g/mL) and LDL2 (density 1.045–1.063 g/mL) fractions were measured before and after treatment. Results: Estrogen treatment significantly reduced LDL1 cholesterol and LDL1 apolipoprotein B levels by 18.4% and 20.8%, respectively; simvastatin treatment by 21.9% and 29.2%, respectively; and combination therapy by 38.5% and 34.4%, respectively. In contrast to estrogen or simvastatin treatment, the combination therapy also significantly lowered the levels of LDL2 cholesterol by 19.5% and LDL2 apolipoprotein B by 30.5%. Posttreatment levels of total cholesterol, LDL1 cholesterol, and LDL1 apolipoprotein B were significantly lower after combination treatment than after estrogen treatment. Estrogen treatment, but not combination therapy, significantly increased total plasma triglyceride levels (103.1 ± 26.0 mg/dL to 138.8 ± 75.6 mg/dL, P < .01). Significantly more patients receiving combination therapy than those receiving estrogen had total and LDL cholesterol concentrations reduced to target levels. Conclusion: Combination therapy with estrogen and simvastatin favorably affected lipid metabolism by reducing large and small LDL particles and prevented the estrogen-induced increase in plasma triglyceride levels.

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