The effect of fenofibrate on HDL cholesterol and HDL particle concentration in postmenopausal women on tibolone therapy

Summary Background  Low high-density lipoprotein (HDL) cholesterol and particle concentration are risk factors for coronary heart disease in women. Tibolone lowers HDL cholesterol and HDL particle concentration, an effect that could be reversed by the peroxisome proliferator-activator receptor-α agonist fenofibrate. Objective  To assess the effects of fenofibrate on plasma HDL particles in postmenopausal women taking tibolone therapy. Design and participants  Randomized crossover study conducted in a women’s health clinic. Fourteen postmenopausal women taking tibolone 2·5 mg daily for menopausal symptoms were randomized to either fenofibrate 160 mg daily or no treatment for 8 weeks, followed by a 3- week wash-out for fenofibrate and then crossed over to alternate therapy for another 8 weeks. The main outcome measure was changes in plasma HDL cholesterol concentration, apoA-I and apoA-II, LpA-I and LpA-I-A-II. Results  After 8 weeks of fenofibrate therapy, there was no change in HDL cholesterol, 1·13 ± 0·06 v 1·16 ± 0·06 mmol/l (P = 0·47) or apoA-I, 1·19 ± 0·05 v 1·20 ± 0·05 g/l (P = 0·23). LpA-I fell significantly 0·35 ± 0·03 v 0·29 ± 0·02 (P = 0·02) but there was a rise in apoA-II, 0·35 ± 0·01 v 0·39 ± 0·01 g/l (P = 0·01). There was a significant fall in total cholesterol, triglycerides, low-density lipoprotein cholesterol and apoB. Conclusion  In women taking tibolone, fenofibrate increases plasma apoA-II concentration and effects a redistribution of HDL subfractions but does not correct tibolone-induced changes in HDL cholesterol or HDL particle concentration. The mechanism and significance of this require further investigation.