Estrogen-induced small low density lipoprotein particles may be atherogenic in postmenopausal women

Objectives The purpose of this study was to investigate the susceptibility of estrogen-induced small low density lipoprotein (LDL) particles to oxidat ion. Background Estrogen replacement therapy in postmenopausal women has an anti oxidant effect that opposes oxidation of LDL particles. Estrogen-induced in creases in plasma triglyceride concentrations, however, decrease LDL partic le size, which may act counter to this antioxidant effect. It has not been evaluated whether estrogen-induced small LDL particles are atherogenic. Methods In 24 lean and healthy postmenopausal women treated with conjugated equine estrogen (0.625 mg daily) for three months, plasma lipid concentrat ions and diameter of LDL particles were measured before and after therapy. Susceptibility of LDL to oxidation was determined by measuring the concentr ation of thiobarbituric acid-reactive substances (TBARS) after incubation w ith CuSO4. Results Estrogen significantly decreased plasma concentrations of total cho lesterol, LDL-cholesterol and apolipoprotein B, while increasing concentrat ions of triglyceride, high-density lipoprotein cholesterol and apolipoprote in A-I. Estrogen-induced changes in LDL particle diameter correlated negati vely with changes in plasma triglyceride concentrations (r = -0.55, p < 0.0 05) and with changes in concentrations of LDL derived TEARS (r = -0.49, p < 0.005). In subjects with substantial estrogen induced plasma triglyceride increases, estrogen significantly reduced the diameter of LDL particles (p < 0.05) and significantly increased the concentration of LDL-derived TEARS (p < 0.05). In contrast, estrogen significantly reduced the concentration o f LDL-derived TEARS (p < 0.05) and caused no significant change in LDL part icle diameter in subjects whose plasma triglyceride concentration was uncha nged with estrogen therapy. Conclusions Because estrogen-induced plasma triglyceride increases may prod uce small LDL particles that are more susceptible to oxidation, antioxidant effects of estrogen might be offset in patients showing such a triglycerid e increase. (C) 2001 by the American College of Cardiology.