Impaired Procoagulant-anticoagulant Balance during Hormone Replacement Therapy?

W. Marchien van Baal; Jef J. Emeis; Marius J. van der Mooren; Hilda Kessel; Peter Kenemans; Coen D. A. Stehouwer

doi:10.1055/s-0037-1613752

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 83(01): 29-34
DOI: 10.1055/s-0037-1613752

Commentary

Schattauer GmbH

Impaired Procoagulant-anticoagulant Balance during Hormone Replacement Therapy?

A Randomised, Placebo-controlled 12-week Study

W. Marchien van Baal

¹Department of Obstetrics & Gynaecology, Leiden, The Netherlands

,

Jef J. Emeis

²Department of Gaubius Laboratory, TNO-PG, Leiden, The Netherlands

,

Marius J. van der Mooren

¹Department of Obstetrics & Gynaecology, Leiden, The Netherlands

,

Hilda Kessel

¹Department of Obstetrics & Gynaecology, Leiden, The Netherlands

,

Peter Kenemans

¹Department of Obstetrics & Gynaecology, Leiden, The Netherlands

,

Coen D. A. Stehouwer

³Department of Internal Medicine, University Hospital Vrije Universiteit, Amsterdam, Leiden, The Netherlands

› Author Affiliations

Abstract

Summary

In this randomised, placebo-controlled 12-week study, sixty healthy postmenopausal women received either placebo (N = 16) or daily 2 mg micronised oestradiol, either unopposed (N = 16, E₂ group) or combined with a progestagen for 14 days of each cycle (N = 28, E₂+P group).

Results

As compared to placebo, plasma levels of AT III were reduced only in the E₂ group (∼28%), plasma levels of protein C decreased only in the E₂+P group (∼4%) and plasma levels of protein S decreased in both the E₂ and E₂+P group (∼21%). In both the E₂ and E₂+P groups, the plasma levels of factor VII (antigen and activity) showed a borderline significant increase (∼10%), whereas no significant change was observed in active factor VII. Plasma levels of tissue-type plasminogen activator (∼22%), urokinase plasminogen activator (∼25%) and plasminogen activator inhibitor type-1 (∼43%) decreased in the E₂ and E₂+P groups, whereas those of plasminogen increased (∼12%). Treatment was associated with an increase in levels of prothrombin fragment 1+2 (∼31%), but levels of thrombin-antithrombin III complexes, and of plasmin-α₂-antiplasmin complexes and total fibrin(ogen) degradation products did not change significantly.

Conclusion

Short-term E₂ and E₂+P treatment is associated with a shift in the procoagulant-anticoagulant balance towards a procoagulant state. A substantial proportion of women do not have a net increase in fibrinolytic activity. These data may be relevant in explaining the increased risk of venous thromboembolism associated with ERT and HRT, and possibly also in explaining the negative results of the Heart and Estrogen/progestin Replacement Study.

Key words

Hormone replacement therapy - coagulation - fibrinolysis - postmenopausal

Full Text

References

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