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Thromb Haemost. 2009 Apr;101(4):691-5.

The effect of the levonorgestrel-releasing intrauterine system on the resistance to activated protein C (APC).

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Department of Gynaecology and Reproductive Medicine, Leiden University Medical Center, Leiden, The Netherlands.


Exogenously administered estrogens and progestogens as during combined oral contraceptive use increase the risk of venous thrombosis. The thrombin generation-based APC resistance assay is a global coagulation test that enables quantification of the net prothrombotic effect of combined oral contraceptives and that predicts the risk of thrombosis. The thrombotic risk of the levonorgestrel-releasing intrauterine system is unknown. It was the objective of this study to evaluate the thrombotic risk by comparing the APC resistance before and after insertion of a levonorgestrel-releasing or a copper-containing intrauterine device. We measured normalized APC-sensitivity ratios (nAPCsr) before and three months after insertion of the levonorgestrel-intrauterine system in 56 women and the copper-intrauterine device in 18 women. In women without hormonal contraceptive use or a pregnancy in the three months before collection of the baseline samples, nAPCsr were lower three months after insertion of the levonorgestrel-intrauterine system than at baseline (difference -0.29; 95% CI -0.04 to -0.53) and hardly changed after insertion of the copper-intrauterine device (difference -0.11; 95% CI -1.03 to 0.82). In women who switched from a combined oral contraceptive to the levonorgestrel-system the difference was more pronounced (-1.48; 95% CI -0.85 to -2.11). In this study we observed that the levonorgestrel-intrauterine system decreases the resistance to APC which indicates that the levonorgestrel-intrauterine system does not have a prothrombotic effect.

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