EFFECTS OF POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY ON LIPOPROTEINSINCLUDING LIPOPROTEIN(A) AND LDL SUBFRACTIONS

The purpose of this study was to examine the effects on lipoprotein ri sk markers for CHD of oestradiol given alone and in combination with t he androgenic progestogen, norethisterone. Eighty postmenopausal women were randomly allocated to receive oestradiol (2 mg/day) alone or wit h continuous norethisterone (1 mg/day). Serum lipoprotein levels, incl uding lipoprotein(a), were monitored during 12 months on treatment in all the women, and in a sub-set of 32 patients cholesterol was measure d in the two major density subfractions of LDL. Oestradiol caused a tr ansient rise in triglycerides, a small decrease in LDL cholesterol (si gnificant only at 3 and 6 months, P < 0.05) and a consistent significa nt increase in HDL cholesterol (16%, P < 0.01). There was a downward t rend in lipoprotein(a) levels which did not achieve statistical signif icance. The combined preparation caused significant, sustained decreas es in triglycerides (31%, P < 0.01), total cholesterol (15%, P < 0.001 ), VLDL (42%, P < 0.01), LDL (9%, P < 0.05) and HDL (11%, P < 0.001). Lipoprotein(a) was also reduced (39%, P < 0.05). In the sub-set of pat ients in which LDL subfractions were measured, the reduction in LDL in duced by oestradiol monotherapy was significant only at the 3-month vi sit (6%, P < 0.05). This was due to a decrease in the 'light' (1.025 < d < 1.044 g/ml) subfraction (10%, P < 0.05) and resulted in an appare nt shift in subfraction distribution towards the 'heavy' (1.044 < d < 1.060 g/ml) subfraction, although there was no absolute increase in th e latter. None of these changes was statistically significant at 12 mo nths. Oestradiol/norethisterone caused sustained decreases in both 'li ght' (15%, P < 0.05) and 'heavy' (29%, P < 0.05) subfractions, with no significant change in the relative amounts. The changes in 'light' an d 'heavy' LDL in this group were highly correlated with changes in tri glyceride levels (r = -0.57, P < 0.05 and r = 0.82, P < 0.01 respectiv ely). Therefore, at the end of 1 year's treatment with unopposed oestr adiol the only statistically significant change was an increase in HDL cholesterol. Addition of norethisterone to the preparation reversed t his potentially beneficial change, but favourably influenced triglycer ides, VLDL, LDL subfraction profile and lipoprotein(a), which may coun teract the adverse effect on HDL.