Combined oral contraceptives alter ectonucleotidase and adenosine deaminase activities in peripheral blood cells

Hormonal contraceptives, one of the most widely used contraceptive methods, are associated with the development of thromboembolism. Purinergic mediators such as soluble agonists, ectonucleotidases, and receptors play a prominent role in regulating hemostasis. This study aimed to evaluate E-NTPDase, E-5'-NT, and E-ADA activities in lymphocytes and platelets from women using combined oral contraceptives. Participants used third-generation (3G) oral contraceptives, such as drospirenone or cyproterone acetate, or fourth-generation (4G) oral contraceptives, such as gestodene or desogestrel, both combined with ethinylestradiol. The findings indicated decreased adenosine (ADO) deamination in lymphocytes (78%, p < 0.001) and decreased AMP hydrolysis (69%, p < 0.01) and ADO deamination (66%, p < 0.001) in platelets from women using 3G contraceptives compared with the control. Furthermore, the results showed decreased ADO deamination (66%, p < 0.05) in lymphocytes and decreased ATP hydrolysis (52%, p < 0.05) and decreased ADO deamination (57%, p < 0.001) in platelets from women using 4G contraceptives compared with the control. The observed patterns of AMP hydrolysis are compatible with an ADO-poor vascular microenvironment. Likewise, the decrease in E-ADA activity may be associated with lower concentrations of ADO in the vascular microenvironment, which has antiplatelet and anti-inflammatory effects. Overall, the findings demonstrated that hormonal contraceptives alter the activity of purinergic ectoenzymes, which might be related to their effects on hemostasis and a predisposition to thromboembolic events.