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 oxidation. BACKGROUND Estrogen replacement therapy in postmenopausal women has an antioxidant effect that opposes oxidation of LDL particles. Estrogen-induced increases in plasma triglyceride concentrations, however, decrease LDL particle 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 concentrations and diameter of LDL particles were measured before and after therapy. Susceptibility of LDL to oxidation was determined by measuring the concentration of thiobarbituric acid-reactive substances (TBARS) after incubation with CuSO4. RESULTS Estrogen significantly decreased plasma concentrations of total cholesterol, LDL-cholesterol and apolipoprotein B, while increasing concentrations of triglyceride, high-density lipoprotein cholesterol and apolipoprotein A-I. Estrogen-induced changes in LDL particle diameter correlated negatively with changes in plasma triglyceride concentrations (r = −0.55, p < 0.005) and with changes in concentrations of LDL-derived TBARS (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 TBARS (p < 0.05). In contrast, estrogen significantly reduced the concentration of LDL-derived TBARS (p < 0.05) and caused no significant change in LDL particle diameter in subjects whose plasma triglyceride concentration was unchanged with estrogen therapy. CONCLUSIONS Because estrogen-induced plasma triglyceride increases may produce small LDL particles that are more susceptible to oxidation, antioxidant effects of estrogen might be offset in patients showing such a triglyceride increase.