Effect of the cessation of long-term hormone replacement therapy on plasma plasminogen activator inhibitor-1 and fibrinogen

Objective: Hormone replacement therapy (HRT) has generally been documented to reduce plasminogen activator inhibitor-1 (PAI-1) and fibrinogen levels in plasma of postmenopausal women. We used a wash out protocol to study whether stopping long-term HRT with estrogen alone or a combination of estrogen-progestin have different effects on these markers of hemostasis. Study design: Thirty healthy postmenopausal women on HRT participated. Fifteen had estradiol valerate, and 15 had estradiol valerate and levonorgestrel. Each was studied after long-term HRT (period 1), four weeks after cessation of the treatment (period 2, wash out), and three weeks after reintroducing the therapy (period 3). Results: In the estrogen group, PAI-1 increased by 18% during the wash out period (P = 0.013) and decreased by 22% after reintroduction of therapy (P = 0.001). In the combined therapy group, there was a trend of PAI-1 to increase by 18% when therapy was discontinued (P = 0.17), and it decreased by 25% after reintroduction of hormone replacement therapy (P = 0.036). Fibrinogen was initially lower in the estrogen group compared with the combined therapy group (p = 0.014), and did not change during wash out. Conclusion: This wash out study shows that cessation of long-term HRT unfavorably increases PAI-1, but appears to have no adverse effect on fibrinogen. (c) 2005 Elsevier Ireland Ltd. All rights reserved.