Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity

A cross-sectional study of ninety six women was conducted to examine the effect of menopause and hormone replacement therapy (HRT) on plasma lipids, lipoproteins and oxidation of low density lipoproteins. The sample consisted of 26 premenopausal women, 26 postmenopausal women taking no replacement hormones and 43 postmenopausal women on hormone replacement therapy. Postmenopausal women not taking replacement hormones had significantly higher plasma cholesterol, low density lipoprotein (LDL) cholesterol and lipoprotein[a] (Lp[a]) levels compared to premenopausal women or postmenopausal women on HRT [6.00 +/- 0.15, 5.36 +/- 0.17 (P < 0.01), 5.63 +/- 0.13 (P < 0.05) mmol/l, respectively for total cholesterol; 4.13 +/- 0.15, 3.64 +/- 0.15 (P < 0.05), 3.82 +/- 0.12 (P < 0.05) mmol/l, respectively for LDL-cholesterol; 48.19 +/- 9.90, 26.59 +/- 5.53 (P < 0.03), 25.12 +/- 4.62 (P < 0.03) mg/dl, respectively for Lp[a]]. The differences in LDL cholesterol concentrations were inversely related to changes in LDL receptor activity (r = -0.27, P < 0.01). HRT use was found to be associated with a significantly smaller LDL particle size. Plasma triglyceride was significantly higher in women on HRT (1.16 +/- 0.07 mmol/l) than in the premenopausal group (0.96 +/- 0.07) or postmenopausal group not using HRT (0.87 +/- 0.06). There were no differences in LDL oxidation between the groups when LDL was oxidised in the presence of copper. Nor was there any difference in the uptake of copper-oxidised or macrophage-modified LDL into J774 macrophages. These results confirm the effect of menopause and exogenous hormones on plasma lipids and lipoproteins, and suggest that HRT modifies the activity of the LDL receptor. Hormone replacement did not appear to protect LDL from oxidation.