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 17β‐oestradiol, either orally (2 mg daily; n= 35) or transdermally (50 μg 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‐l, 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.