Hypercholesterolemia in postmenopausal women. Metabolic defects and response to low-dose lovastatin

To determine the metabolic mechanisms underlying hypercholesterolemia in postmenopausal women and to determine whether a low dose of lovastatin will correct this abnormality.

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 placed-controlled, randomized, double-blind study using lovastatin as the therapeutic agent.

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.

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.

In the drug study, patients received blindly both lovastatin (10 mg/d) and placebo.

In the first study, kinetic parameters of LDL metabolism; in the second study, response in lipids and lipoproteins to lovastatin therapy.

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).

The turnover data suggest that hypercholesterolemia in post-menopausal 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.