ObjectiveTo test whether hydrolysis of low-density lipoprotein (LDL) triglyceride by lipolytic enzymes decreases the size of LDL particles in women treated with estrogen replacement.MethodsFifteen postmenopausal women received 0.625 mg conjugated equine estrogens daily for 3 months. Plasma concentrations of total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol were measured before and after therapy. We also assayed levels of total, free, and esterified cholesterol, triglyceride, and protein in LDL. Plasma samples were incubated at 37C for 24 hours and LDL fractions were isolated by ultracentrifugation. After LDL samples were further incubated with or without lipoprotein lipase (500, 700, and 1000 ng/mL) at 37C for 24 hours, LDL triglyceride, LDL protein, and the diameter of LDL particles were measured.ResultsEstrogen decreased total cholesterol and increased triglyceride and HDL cholesterol in plasma. Estrogen treatment decreased the ratio of cholesteryl ester/protein, whereas the ratio of triglyceride/protein increased. Estrogen decreased LDL particle diameter. Incubation of plasma increased the ratio of LDL triglyceride/protein from 0.40 ± 0.14 to 0.48 ± 0.15 (P< .05) and decreased the ratio of LDL cholesteryl ester/protein from 1.17 ± 0.25 to 1.09 ± 0.22 (P< .05), but LDL particle diameter did not change. Incubation of LDL with lipoprotein lipase reduced the LDL triglyceride/protein ratio, and decreased the diameter of LDL particles from 25.61 ± 0.87 nm to 24.89 ± 0.88 nm (500 ng/mL,P< .05), 24.62 ± 1.20 nm (700 ng/mL,P< .05), and 24.67 ± 1.19 nm (1000 ng/mL,P< .05).ConclusionIn women treated with estrogen, hydrolysis of triglyceride in LDL particles might be accompanied by reduced particle size.