RESPONSE OF PLASMA LOW-DENSITY-LIPOPROTEIN SUBFRACTIONS TO ESTROGEN REPLACEMENT THERAPY FOLLOWING SURGICAL MENOPAUSE

OBJECTIVE Epidemiological studies suggest that postmenopausal oestroge n replacement reduces the incidence of cardiovascular disease. The pur pose of this study was to establish the effects of oestrogen replaceme nt therapy on subfractions of plasma low density lipoprotein in bilate rally oophorectomized women. DESIGN In a placebo controlled, double-bl ind study, patients were randomized on a two to one basis to receive e ither oestradiol valerate (2 mg/day) or placebo respectively for a per iod of 16 weeks. PATIENTS Seventeen women aged 28-51 years who had all had hysterectomy and bilateral oophorectomy at least 2 months before recruitment were assigned to either the active (n = 12) or placebo (n = 5) group. MEASUREMENTS Plasma lipids, lipoproteins, apolipoproteins and LDL subfractions were determined immediately before and after the treatment period. LDL subfractions were isolated directly from plasma by density gradient ultracentrifugation within 24 hours. Non-parametri c statistical analysis was carried out within each group using Wilcoxo n's signed rank test for matched pairs. RESULTS After 16 weeks of trea tment, HDL cholesterol, apo A-1 and HDL-2 were increased in the group receiving oestrogen (HDL cholesterol +12%, P < 0.01; apo A-I + 14%, P < 0.01; HDL-2 + 24% P < 0-01). While there were no significant changes in serum cholesterol, LDL cholesterol or triglycerides, the proportio n and concentration of the least dense LDL-I subfraction was decreased significantly (27%, P < 0.05). The LDL subfraction of intermediate de nsity (LDL-II) was decreased in eight subjects, while small, dense LDL -III was unaffected. Overall, these changes resulted in an apparent sh ift in the distribution of LDL subfractions towards small, dense LDL-I II, although there was no net increase in the latter. CONCLUSION In vi ew of a similar and characteristic response of LDL subfractions to hyp olipidaemic drugs that enhance the clearance of LDL via the LDL recept or, the present findings suggest that oestrogen promotes the preferent ial removal of LDL-I and II by activating LDL receptors. As this effec t is normally associated with a reduction in the circulating level of LDL, it should not be regarded as an unfavourable response to oestroge n replacement therapy.