Effects of hormone replacement modalities on low density lipoprotein composition and distribution in ovariectomized cynomolgus monkeys

This study was designed to determine the effect of several hormone replacement therapies on LDL size, density, heterogeneity, and composition in surgically postmenopausal cynomolgus monkeys fed an atherogenic diet. Groups (n = 5 each) of ovariectomized cynomolgus monkeys were untreated (control), or treated with conjugated equine estrogens, medroxyprogesterone acetate (progesterone), combined estrogen-progesterone, or tamoxifen for 9 weeks. There were no differences among treatment groups in total plasma, LDL, or HDL cholesterol or triglyceride concentrations. Plasma LDL were isolated by ultracentrifugation and size exclusion chromatography and subfractionated by density gradient centrifugation for subsequent chemical analysis. Estrogen treatment was associated with significantly smaller (measured as LDL molecular weight, 3.9 ± 0.2 g/μmol) and denser plasma LDL (1.034 g/ml peak density) compared with control (4.5 ± 0.1 g/μmol; 1.030 g/ml peak density) or progesterone-treated animals (4.6 ± 0.2; 1.029 g/ml peak density). LDL from the estrogen group were relatively enriched in protein and triglyceride and poor in cholesteryl ester and apolipoprotein E (apoE) compared to the control group. Triglyceride enrichment with estrogen treatment occurred predominantly in the lighter, larger LDL subfractions (d = 1.015-1.025 g/ml), which were reduced in concentration (26 ± 10 mg cholesterol/dl) compared to control (61 ± 19 mg/dl) or progesterone-treated animals (67 ± 16 mg/dl). Combined estrogen-progesterone or tamoxifen treatment resulted in changes in LDL that followed the same trend as those observed with estrogen treatment. We conclude that short-term estrogen treatment of ovariectomized cynomolgus monkeys results in changes in plasma LDL size, density, and composition while having no apparent effect on overall plasma lipid concentrations.