Effects of conventional or extended-cycle regimen of an oral contraceptive containing 30 mcg ethinylestradiol and 2 mg dienogest on various hemostasis parameters

Abstract 

Background

The study was conducted to investigate the effect of a combined oral contraceptive (COC) containing 30 mcg ethinylestradiol and 2 mg dienogest with two different regimens on various hemostasis variables.

Study Design

Hemostatic parameters were measured in 59 women treated with a monophasic COC containing 30 mcg ethinylestradiol and 2 mg dienogest (EE/DNG) either conventionally (13 cycles with 21 days of treatment+7 days without hormones) or with an extended-cycle regimen (4 extended cycles with 84 days of continuous administration of EE/DNG, followed by a hormone-free interval of 7 days). Blood samples were taken on Days 21–26 of the preceding control cycle and on Days 19–21 of the 3rd and 13th conventional cycle or on Days 82–84 of the first and fourth extended cycle.

Results

After 3 and 12 months, significant increases in fibrinogen (20%), factor VII antigen (50–60%), factor VII activity (45%), activated factor VII (30–45%) and factor VIII activity (10–20%) occurred in both treatment regimens. In both groups, there was a small but significant decrease in the level and activity of antithrombin, a 20–25% decrease in total and free protein S and a 15–20% rise in the level and activity of protein C, but no significant change of the thrombin-antithrombin complex. A significant over-time rise by about 25% of prothrombin fragment 1+2 occurred only in the extended-cycle group, but this effect did not differ significantly from that observed during conventional treatment. Plasminogen was elevated by 50% in both groups, while tissue-plasminogen activator (t-PA) activity rose by 15% in the conventional group and by 25–30% in the extended-cycle group. In both groups, t-PA antigen was reduced by about 30% and plasminogen activator inhibitor-1 by 40–60%. The levels of the plasmin-antiplasmin complex rose by 30–40% and those of D-dimers by 20–55%. The prothrombin time was slightly increased and the activated partial thromboplastin time was slightly decreased.

Conclusion

In general, these results were in agreement with those observed during treatment with other COCs. The study demonstrated that during conventional and extended-cycle treatment with EE/DNG, a steady-state in the effects on hemostasis variables was reached within 3 months, and that the effects observed after 3 and 12 months of treatment did not substantially differ between conventional and extended-cycle regimen.

Keywords: Dienogest, Ethinylestradiol, Hemostasis parameters, Extended-cycle regimen, Oral contraceptives