Summary
Increased serum levels of endogenous as well as exogenous estrogen are regarded to
be responsible for acquired activated protein C (APC) resistance. It was the objective
of this study to evaluate whether the physiological increase in serum estradiol concentration
during the normal menstrual cycle affects the individual’s sensitivity to APC. Seventy-two
women with normal menstrual cycles were included in the study. Blood samples for analysis
of estradiol (E2), progesterone (P4) and APC resistance were drawn at two time points
of the menstrual cycle (day 3–5 and day 22–25). Two methods of measuring APC resistance
were used: the activated partial thromboplastin time (aPTT)-based assay and the endogenous
thrombin potential (ETP)-based APC resistance test. Independent of the method used,
no changes in APC resistance were found, even though the E2 concentration increased
significantly between the two menstrual phases. No correlations between E2 levels
and APC resistance, P4 levels and APC resistance or changes in E2 concentrations and
changes in APC resistance were detected. Ten women were carriers of the factor VLeiden mutation. Their baseline APC resistance was increased, but their response to elevated
E2 during the menstrual cycle did not differ from that of non-carriers. In conclusion,
our observations suggest that physiological differences in serum levels of estradiol
and progesterone between the early follicular and the luteal phase in a normal menstrual
cycle do not have any significant impact on the individual’s sensitivity to APC.
Keywords
Menstrual cycle - APC resistance - ETP-based - aPTT-based - estradiol