Plasma fibrin clot properties in postmenopausal women: effects of hormone therapy

Objective: Postmenopausal women are at risk of thromboembolic events. It is unclear whether menopause alters fibrin clot properties. The aim of our study was to assess the effects of menopause and hormone therapy on clot characteristics. Methods: Ex vivo plasma clot permeability, turbidity, and susceptibility to lysis were determined in 70 premenopausal and 70 postmenopausal women (a case-control study). From the postmenopausal group, 30 women were randomly assigned (1:1) to a 24-week oral or transdermal treatment with 17 beta-estradiol, combined with norethisterone acetate (2 mg + 1 mg/d or 0.05 mg + 5 mg/d, respectively). Results: Compared with premenopausal women (aged 29.2 +/- 2.60 y), postmenopausal women (aged 49.7 +/- 3.4 y; P = 0.009) were characterized by higher fibrinogen levels (by 36.8%), lower C-reactive protein levels (by 36.9%), and lower clot permeability (by 10.5%); also after adjustment for fibrinogen (all P < 0.05), with no difference in turbidimetric or fibrinolytic variables. Estrogen plus progestogen therapy led to higher maximal absorbency of fibrin gels by 6.0%(P < 0.05), whereas all other fibrin variables remained unchanged. Compared with transdermal hormone therapy, 24-week oral therapy was associated with higher absorbency of plasma clots by 16% (P < 0.05), without any other changes in fibrin characteristics. Conclusions: Menopause age is associated with the formation of denser fibrin clots. Estrogen plus progestogen therapy has a minor effect on plasma fibrin properties, but leads to the formation of thicker and more branched fibrin fibers, particularly during oral administration.