Effects of tibolone or continuous combined oestradiol and norethisterone acetate on lipids, high-density lipoprotein subfractions and apolipoproteins in postmenopausal women in a two-year, randomized, double-blind, placebo-controlled trial.

Objective: To compare the effects of (a) tibolone, (b) continuous combined oestrogen plus progestogen and (c) placebo on plasma lipid and lipoprotein markers of cardiovascular risk in healthy postmenopausal women.

Study Design: Randomized, single-centre, placebo-controlled, double-blind study.

Patients: One hundred and one postmenopausal women were randomized (1:1:1) into one of three groups taking daily 2.5 mg tibolone, continuous oral oestradiol-17β 2 mg plus norethisterone acetate 1 mg daily (E /NETA) or placebo.

Main Outcome Measures: Fasting serum lipid, lipoprotein and apolipoprotein concentrations measured at baseline and after 6, 12 and 24 months of treatment.

Results: Both tibolone and E /NETA lowered plasma total cholesterol concentrations relative to placebo. With tibolone, high-density lipoprotein cholesterol (HDL-C) was reduced (-27% at 24 months, P < .001), the greatest effect being in the cholesterol-enriched HDL subfraction (-40%, P < .001). Tibolone's effect on HDL concentrations was also apparent in the principal HDL protein component, apolipoprotein AI (-29% at 24 months, P < .001). However, there was no significant effect of tibolone on low-density or very low-density lipoprotein cholesterol (LDL-C and VLDL-C, respectively). By contrast, the greatest reduction in cholesterol with E /NETA was in LDL-C (-22% at 24 months, P = .008). E /NETA reduced HDL-C to a lesser extent than tibolone (-12% at 24 months, P < .001). Effects on HDL apolipoproteins were similarly diminished relative to tibolone. E /NETA had no effect on VLDL-C or on the protein component of LDL, apolipoprotein B.

Conclusion: Tibolone reduces serum HDL. E /NETA reduces LDL cholesterol but not apolipoprotein B, suggesting decreased cholesterol loading of LDL. Any impact these changes may have on CVD risk needs further investigation.