Long term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): A randomised study

Objective To assess the influence of three different postmenopausal hormone replacement therapies on levels of serum lipids and lipoprotein(a) [Lp(a)]. Design Open, randomised, controlled study. Participants One hundred and forty healthy, early postmenopausal women. Interventions The women were randomised to receive continuous 17 beta-oestradiol, either orally (2 mg daily; n = 35) or transdermally (50 mu g daily;n = 35), plus 10 mg dydrogesterone daily for 14 days of each 28-day cycle; or 2.5 mg tibolone daily (n = 35). Thirty-five untreated women acted as controls. Main outcome measures Fasting blood samples were analysed at baseline, 6, 12 and 24 months for low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, very low density lipoprotein (VLDL), total cholesterol, triglycerides, lipoprotein(a) [Lp(a)], apolipoproteins A-1, A-2 and B, fibrinogen, and antithrombin factor III. Results At 24 months oral oestradiol increased mean HDL cholesterol (7%; 95% CI 1-14), compared with no change in the transdermal group and a decrease of 26.8% in the tibolone group (95% CI 22.9-30.5); oral oestradiol decreased mean LDL cholesterol (11.8%; 95% CI 6.3-19), compared with no change in the tibolone group. Changes in apolipoprotein A-1 and B showed a similar pattern to HDL and LDL cholesterol, respectively Oral oestradiol increased serum triglycerides (30%; 95% CI 18-42) after 24 months, compared with no change in the tibolone and transdermal oestradiol groups. Tibolone decreased serum Lp(a) by 36.6% after 24 months (95% CI 8.3-56.2), oral oestradiol decreased levels by 29.4% (95% CI 2-51.1), compared with no change in the transdermal oestradiol group. Conclusions Oral and to a lesser extent transdermal oestradiol when sequentially combined with dydrogesterone, showed a beneficial influence on serum lipids regarding the cardiovascular disease risk, which was not seen with tibolone. The significance of Lp(a) levels on cardiovascular disease risk remains to be determined.