Effect over coagulation and fibrinolysis parameters of a prolonged release 24 + 4 daily use regime contraceptive formulation containing 2 mg dienogest/0.02 mg ethinylestradiol.

Abstract

Background: A prolonged release combined oral contraceptive (COC) pill, containing 2 mg dienogest (DNG)/0.02 mg ethinylestradiol (EE) in a 24 + 4 daily dosing regimen has recently been approved in Europe.

Objective: To determine if this COC impacts coagulation and fibrinolytic factors in comparison to an immediate release COC containing 3 mg drospirenone (DRSP)/0.02 mg EE.

Method: Forty-four patients received the novel product, and forty-seven the comparator (immediate release formulation) during nine complete cycles. Coagulation and fibrinolytic parameters were evaluated: activated protein C resistance ratio, Antithrombin III (AT III), C-reactive protein, Factor VII, Factor VIII, and D-Dimer.

Results: Compared to baseline, at the end of the study both groups displayed significantly higher mean values for AT III: 1.06 mg/mL (standard deviation [SD], 95% CI, 0.98-1.15) for the DNG/EE formulation and 1.04 mg/mL (SD 95% CI, 0.96-1.12) for the comparator (p = 0.0006 and p = 0.0009, respectively). D-dimer showed a non-significant slight reduction in the DNG/EE group, from 276.62 ng/mL (SD, 95% CI, 228.92-334.26) before treatment to 243.98 ng/mL (SD, 95% CI, 192.45-309.31) ng/mL after treatment. Contrarily, the comparator displayed a non-significant rise in D-dimer values from 246.46 ng/mL (SD, 95% CI, 205.44-295.66) ng/mL to 275.30 ng/mL (SD, 95% CI 219.21-345.75; p = 0.4520). All other parameters showed no significant differences before and after the treatment for both groups.

Conclusion: The COC 2 mg DNG/0.02 mg EE was not associated with any meaningful changes in the analyzed coagulation and fibrinolytic parameters indicating that a prolonged release formulation does not impact on these factors.

Clinical trial registry: EudraCT: 2019-0018-77-97.