Hormone replacement therapy has been associated with a reduction in cardiovascular disease. One possible mechanism may be the effects of hormone replacement on the clotting factors, including the anticoagulant, protein S. In a double-blind, prospective study, 41 postmenopausal women were randomly assigned to one of four groups: (1) unopposed conjugated equine estrogen (CEE) 0.625 mg daily (E alone, n = 9), (2) CEE 0.625 mg daily and medroxyprogesterone acetate (MPA) 5.0 mg sequentially for the last 14 days of each 28-day cycle (E/P 5.0S, n = 11), (3) CEE 0.625 mg and MPA 2.5 mg continuously (E/P 2.5C, n = 10), and (4) CEE 0.625 mg and MPA 5.0 mg continuously (E/P 5.0C, n = 11). Blood samples for coagulation factors and fibrinolysis were assessed at baseline and during the last week of the 13th treatment cycle and included antithrombin III, plasminogen, factor VII, factor X, and protein S. Demographic and baseline hormonal profiles did not differ among groups. A slight increase (p < 0.05) was observed for levels of plasminogen in groups E/P 5.0C and E/P 5.0S, and a larger increase (p < 0.05) was observed for factors VII and X in all groups. Total protein S decreased (p < 0.03) only in the E/P 2.5C and E Alone groups. CEE alone was associated with significant increases in factors VII and X activity, a significant decrease in protein S, and nonsignificant changes in plasminogen and antithrombin III activities. The addition of MPA, however, resulted in dose-dependent favorable changes in coagulation parameters: (1) augmentation of the CEE-induced increase in plasminogen activity and (2) amelioration of the CEE-induced reduction in protein S. These data suggest that the combination of CEE and MPA may be more protective against thromboembolic occurrences than CEE alone in postmenopausal women. However, further studies with larger sample sizes must be completed before any definitive statement can be made.
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