Coagulation Activation Following Estrogen Administration to Postmenopausal Women

Abstract

SummaryWe investigated coagulation system activation following estrogen treatment in 29 healthy postmenopausal women. Study participants received conjugated estrogens at 0.625 and 1.25 mg per day, and placebo for 3-month periods in a randomized crossover protocol. Blood samples were obtained on two consecutive days at the end of each treatment period for immunoassays of F1+2 and fibrinopeptide A (FPA), markers of factor Xa action on prothrombin and thrombin action on fibrinogen in vivo, respectively. Treatment with estrogens at a dose of 0.625 or 1.25 mg resulted in significant increases in mean F1+2 levels of 40 and 98%, respectively, and in mean FPA levels of 37 and 71%, respectively. The measurements of F1+2 were significantly higher in women receiving 1.25 mg of estrogen than 0.625 mg. We also observed significant declines in the levels of antithrombin III and total protein S antigen. Immunologic levels of protein C increased modestly at only the 1.25 mg estrogen dose level. These data indicate that low doses of oral estrogens (≤1.25 mg per day) frequently increase the amount of thrombin generated in vivo. Our observations may help to explain the increased thrombotic risk that has been observed with higher doses of this medication (≥2.5 mg).

Assessment of hypercoagulability markers and lipid levels in postmenopausal women undergoing either oral or transdermal hormone replacement therapy

“…Controversial results have been reported regarding the effect of HRT on the activation of coagulation and the activity of the fibrinolytic system, although VTE is one of the major adverse effects of HRT. Increased levels of thrombin generation markers have been reported in women using oral HRT [15,23,24]. In the present study, Brazilian women using oral HRT for a period of 3 months also presented a significant increase in F1+2 and DDi levels and a decrease in PS levels.…”

Sex steroids as inflammatory regulators

“…Indeed, this has been demonstrated [90]. Furthermore, 1 month's estrogen treatment reduced systemic fibrinolysis in a randomized trial performed on postmenopausal women [80].…”

Controversies regarding hormone therapy: Insights from inflammation and hemostasis

“…There is evidence for activation of the coagulation system even with low estrogen doses used orally in HT. Caine et al [56] show that administration of CEE 0.625 mg or 1.25 mg daily increases indices of thrombin generation [prothrombin fragment 1 + 2 ( F 1 + 2 ) and fibrinopeptide A] in a dose-dependent manner. Moreover, CEE decreases levels of inhibitors of thrombin generation (antithrombin III and protein S).…”