Hypercholesterolemia in Postmenopausal Women

Abstract

<h3>Objective.</h3> —To determine the metabolic mechanisms underlying hypercholesterolemia in postmenopausal women and to determine whether a low dose of lovastatin will correct this abnormality. <h3>Design.</h3> —In the first part of the study, turnover rates of autologous low-density lipoprotein (LDL) were measured in hypercholesterolemic and control women. In the second part, hypercholesterolemic women participated in a placebo-controlled, randomized, double-blind study using lovastatin as the therapeutic agent. <h3>Setting.</h3> —The General Clinical Research Center of the University of Texas Southwestern Medical Center, Dallas, utilizing inpatient and outpatient facilities, and the Veterans Affairs Medical Center, Dallas, Tex. <h3>Patients.</h3> —For the LDL turnover study, 26 postmenopausal women with moderate hypercholesterolemia (mean±SD LDL cholesterol, 4.78±0.59 mmol/L [185 ±23 mg/dL]) and 13 postmenopausal women with normal levels of plasma lipids and lipoproteins (mean±SD LDL cholesterol, 3.31 ±0.39 mmol/L [128±15 mg/dL]) were studied. Sixteen postmenopausal women participated in the drug study. <h3>Interventions.</h3> —In the drug study, patients received blindly both lovastatin (10 mg/d) and placebo. <h3>Main Outcome Measures.</h3> —In the first study, kinetic parameters of LDL metabolism; in the second study, response in lipids and lipoproteins to lovastatin therapy. <h3>Results.</h3> —In the LDL turnover study, mean (±SD) input (production) rates for LDL apolipoprotein B (apo B) were similar for hypercholesterolemic women and control women (12.4 [±3.2] mg/kg per day and 11.1 [±2.2] mg/kg per day, respectively). In contrast, mean (±SD) fractional catabolic rates for LDL apo B in hypercholesterolemic women (0.29 [±0.04] pools per day) were significantly lower than those in normolipidemic women (0.35 [±0.03] pools per day). In the drug trial, lovastatin therapy reduced mean (±SD) total cholesterol and LDL cholesterol from 7.03 (±1.16) mmol/L (272 [±45] mg/dL) and 4.42 (±0.80) mmol/L (171 [±31] mg/dL, respectively, to 5.70 (±1.03) mmol/L (221 [±40] mg/dL) and 3.46 (±0.85) mmol/L (134 [±33] mg/dL). <h3>Conclusions.</h3> —The turnover data suggest that hypercholesterolemia in postmenopausal women is primarily attributable to a reduced activity of LDL receptors. In accord, the hypercholesterolemia in these women was effectively lowered by low doses of lovastatin. Thus, a low dose of lovastatin appears highly effective for treatment of moderate hypercholesterolemia in most postmenopausal women, presumably because it reverses the reduction in LDL receptor activity associated with menopause. (<i>JAMA</i>. 1994;271:453-459)