EFFECT OF ESTROGEN AND SIMVASTATIN ON LOW-DENSITY-LIPOPROTEIN SUBCLASSES IN HYPERCHOLESTEROLEMIC POSTMENOPAUSAL WOMEN

Objective: To identify the effects of estrogen and simvastatin,individ ually and in combination, on the levels of low-density lipoprotein (LD L) subclasses in postmenopausal women with type IIa hypercholesterolem ia. Methods: Fifty-five postmenopausal women with type IIa hypercholes terolemia were assigned randomly to 0.625 mg of conjugated equine estr ogen (n = 20), 5 mg of simvastatin (n = 18), or both (n = 17) daily fo r 3 months. Cholesterol, triglyceride, and apolipoprotein B levels in the plasma and in the LDL1 (density 1.019-1.045 g/mL) and LDL2 (densit y 1.045-1.063 g/mL) fractions were measured before and after treatment . Results: Estrogen treatment significantly reduced LDL1 cholesterol a nd LDL1 apolipoprotein B levels by 18.4% and 20.8%, respectively; simv astatin treatment by 21.9% and 29.2%, respectively; and combination th erapy by 38.5% and 34.4%, respectively. In contrast to estrogen or sim vastatin 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, an d LDL1 apolipoprotein B were significantly lower after combination tre atment than after estrogen treatment. Estrogen treatment, but not comb ination therapy, significantly increased total plasma triglyceride lev els (103.1 +/- 26.0 mg/dL to 138.8 +/- 75.6 mg/dL, P < .01). Significa ntly more patients receiving combination therapy than those receiving estrogen had total and LDL cholesterol concentrations reduced to targe t levels. Conclusion: Combination therapy with estrogen and simvastati n favorably affected lipid metabolism by reducing large and small LDL particles and prevented the estrogen-induced increase in plasma trigly ceride levels. (Obstet Gynecol 1998;92:367-72. (C) 1998 by The America n College of Obstetricians and Gynecologists.).