SummaryOBJECTIVE Epidemiological studies suggest that postmenopausal oestrogen replacement reduces the incidence of cardiovascular disease. The purpose of this study was to establish the effects of oestrogen replacement therapy on subfractions of plasma low density lipoprotein in bilaterally oophorectomized women.DESIGN In a placebo controlled, double‐blind study, patients were randomized on a two to one basis to receive either oestradiol valerate (2 mg/day) or placebo respectively for a period 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‐parametric statistical analysis was carried out within each group using Wilcoxon's signed rank test for matched pairs.RESULTS After 16 weeks of treatment, 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 proportion and concentration of the least dense LDL‐I subtraction was decreased significantly (‐27%, P < 0.05). The LDL subtraction of intermediate density (LDL‐II) was decreased in eight subjects, while small, dense LDL‐III was unaffected. Overall, these changes resulted in an apparent shift in the distribution of LDL subfractions towards small, dense LDL‐III, although there was no net increase in the latter.CONCLUSION In view of a similar and characteristic response of LDL subfractions to hypolipidaemic drugs that enhance the clearance of LDL via the LDL receptor, the present findings suggest that oestrogen promotes the preferential removal of LDL‐I and II by activating LDL receptors. As this effect is normally associated with a reduction in the circulating level of LDL, it should not be regarded as an unfavourable response to oestrogen replacement therapy.