TRANSDERMAL ESTROGEN REPLACEMENT THERAPY - BENEFICIAL-EFFECTS ON HEMOSTATIC RISK-FACTORS FOR CARDIOVASCULAR-DISEASE

Objectives:. To assess the effect of estrogen replacement therapy on h emostatic risk factors for cardiovascular disease (CVD) in postmenopau sal women during 2 years of treatment. Methods: In an open prospective study, patients (n = 42) were investigated before and during 2 years of treatment, and compared to an untreated postmenopausal control grou p (n = 18) followed during the same period, healthy premenopausal wome n (n = 20) being included as a reference group for premenopausal value s. The patients underwent treatment with transdermal 17 beta-estradiol (E(2)) (50 mu g/24 h), oral medroxyprogesterone acetate (5 mg/day) be ing added for 12 days every second month. Results: After 2 years of tr eatment there was a significant increase in t-PA antigen (P = 0.01) an d a significant decrease in F VII antigen (P = 0.01). PAI-1 antigen co ncentrations decreased slightly. Fibrinogen concentrations were alread y significantly decreased at 3-month follow-up (P = 0.01), and were st ill low after 2 years. By contrast, at 2-year follow-up the postmenopa usal control group manifested significant increases in F VII and PAI-1 antigen and slight increases in fibrinogen, which resulted in signifi cant differences between patients and controls. Regression analysis sh owed the increase in the serum estradiol concentrations to be inversel y correlated to the decreases in the plasma concentrations of F VII an tigen (r = -0.34, P = 0.001) and fibrinogen (r = -0.35, P = 0.001). Th ere were no changes in AT III or protein C in any group. Conclusions: The increase in serum estradiol concentrations due to replacement ther apy did not adversely affect the studied components of the fibrinolyti c and protein C defense system against thrombosis, and resulted in ben eficial decreases in F VII antigen and fibrinogen. These findings may help to explain the beneficial effects of estrogen replacement therapy in terms of protection from cardiovascular disease.