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 2 /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 2 /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 2 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 2 /NETA was in LDL‐C (−22% at 24 months, P = .008). E 2 /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 2 /NETA had no effect on VLDL‐C or on the protein component of LDL, apolipoprotein B. Conclusion Tibolone reduces serum HDL. E 2 /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.