Postmenopausal oestradiol-dydrogesterone therapy favourably affects fibrinolysis and Lp(a) in healthy women

Abstract

Background: Impaired fibrinolysis and increased lipoprotein (a) [Lp(a)] are major elements in the pathogenesis of atherothrombotic events. This study was undertaken to investigate the long-term effects of oestradioldydrogesterone therapy on fibrinolysis and lipoprotein (a) in healthy postmenopausal women. Methods: 27 women were randomized into a hormone-replacement therapy (HRT) group ( n=14) and a control group ( n=1313). During the first 12 months, the HRT group was treated with oral 17β-oestradiol (E2), 1 mg daily, sequentially combined with dydrogesterone 5 or 10 mg daily (14 days per 28-day treatment cycle). Thereafter these women received oral E2, 2 mg daily, sequentially combined with dydrogesterone, 10 mg daily (14 days per 28-day treatment cycle) for a period of 3 months. The control group received no treatment. Results: At baseline no significant differences were noted between the two groups. As compared to the control group (ANOVA for repeated measures with the baseline value as covariate), 15 months of HRT was associated with lower levels of plasma plasminogen activator inhibitor-1 (−26%; P=0.02) and serum Lp(a) (−46%; P<0.01), as well as with higher levels of plasma plasmin-antiplasmin (PAP) complexes (+8%; P=0.02). After 12 months of treatment with the 1 mg E2 regimen, similar significant results were found, except for PAP complexes. When compared to no treatment, HRT was not associated with differences in plasma levels of tissue plasminogen activator, thrombin-antithrombin complexes, prothrombin fragment 1+2, factor Vllc or factor Vlla. Conclusions: Long-term sequentially combined E2-dydrogesterone increases fibrinolytic potential and decreases serum Lp(a) levels without deterioration of the coagulation markers measured.