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Thromb Res. 2008;121(6):757-61. Epub 2007 Oct 22.

Sensitivity to activated protein C during the menstrual cycle in women with and without factor VLeiden.

Author information

  • 1Department of Gynaecology, Division of Reproductive Medicine, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. haam.vliet@worldonline.nl



Activated protein C (APC) resistance is associated with an increased risk of venous thrombosis. High levels of estradiol and progesterone, e.g. during ovarian stimulation and pregnancy, as well as exogenously administered estrogens and progestagens during oral contraceptive use, induce an acquired form of APC resistance. Several coagulation factors display a cyclic pattern during the menstrual cycle due to the fluctuation of estradiol and progesterone. The aim of the study was to evaluate whether varying levels of estradiol and progesterone during the menstrual cycle are associated with differences in sensitivity to APC.


Normalized APC sensitivity ratios (nAPCsr) were determined with the thrombin generation-based APC-resistance test at six different time points during the menstrual cycle in thirteen wildtype women and six women with factor VLeiden.


Mean nAPCsr varied slightly during the menstrual cycle. Women without factor VLeiden were more likely to have lower nAPCsr at the beginning of the cycle than later on in the cycle (1.34 versus 1.54 and 1.58, Friedman ranking test p=0.009).


The sensitivity to APC differs between the different phases of the menstrual cycle. This cyclic variability could be useful in improving studies on APC resistance in women.

[PubMed - indexed for MEDLINE]
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