Decreased synthesis of tissue plasminogen activator antigen in users of oral contraceptives

Abstract

Abstract Objective: To study why the plasma antigen concentrations of tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) are reduced in users of oral contraceptives (OCs). Design: Open, non-randomized study. Setting: University departments in Copenhagen and Esbjerg, Denmark. Subjects: Sixteen healthy female volunteers between 21 and 32 years of age. Eight women used an OC containing ethinyl estradiol and gestodene (OC group) and eight women used non-hormonal contraception (control group). Intervention: Determination of splanchnic plasma flow and total plasma volume; measurement of t-PA and PAI-1 antigen as well as active t-PA and PAI-1 in plasma from an artery and a liver vein Main outcome measures: Extraction, clearance, net rate of catabolism and mean transit time of t-PA and PAI-1 in the splanchnic circulation. Results: Arterial plasma concentrations of t-PA and PAI-1 antigen were reduced in the OC group whereas the concentrations of active t-PA and active PAI-I were similar. The arterio-venous (A-V) difference for t-PA antigen and active t-PA was positive in both groups. The net splanchnic catabolism of t-PA antigen was reduced in the OC group, while the extraction, clearance and mean transit time were similar. The extraction, clearance, net rate of catabolism and mean transit time of active t-PA did not differ between the two groups. For PAI-1, differences in the main outcome measures between the two groups could not be determined, as there was no statistically significant A-V difference for PAI-1 antigen in any of the groups and a significant A-V difference for active PAI-1 in the control group only. Conclusion: The reduced net splanchnic catabolism of t-PA antigen in the OC users probably reflects a decreased peripheral synthesis of t-PA, which may explain the low plasma concentration in these women. The mechanism underlying the reduced concentration of PAI-1 antigen in the OC users could not be determined by the present methodology.