Investigation of the hemostatic effect of a transdermal patch containing 0.55 mg ethinyl estradiol and 2.1 mg gestodene compared with a monophasic oral contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel: an open-label, randomized, crossover study

Abstract

Background: Transdermal delivery of contraceptives offers several advantages over combined oral contraceptives (COCs), including effective absorption and the provision of relatively constant serum concentrations. Ethinyl estradiol (EE) and the progestin gestodene are well-absorbed through the skin and, therefore, well-suited for use in a transdermal contraceptive patch.

Objective: The objective of this study was to investigate the impact of a once-weekly transparent, transdermal patch delivering low doses of EE and gestodene equivalent to a COC containing 0.02 mg EE and 0.06 mg gestodene on hemostasis parameters compared with a monophasic COC containing 0.03 mg EE and 0.15 mg levonorgestrel.

Methods: In this single-center, open-label, randomized, crossover study, 30 women (aged 18-35 years) received three cycles of each treatment, separated by a two-cycle washout period. The primary outcome measure was the absolute change from baseline in prothrombin fragments 1 + 2 and D-dimer.

Results: For both treatments, prothrombin fragments 1 + 2 remained stable during the first treatment period, and increased only slightly in the second period (mean absolute change 0.025 and 0.028 nmol/L in the novel Bayer patch and COC groups, respectively). Increases in D-dimer were observed in both periods (mean absolute change 107.0 ± 147.2 ng/L for the novel Bayer patch and 113.7 ± 159.0 ng/L for the COC). There were no statistically significant treatment differences in prothrombin 1 + 2 or D-dimer (p = 0.667 and p = 0.884, respectively) and no statistically significant treatment sequence or period effects.

Conclusion: A COC containing 0.03 mg EE and 0.15 mg levonorgestrel and the novel Bayer patch have comparable influence on hemostatic endpoints. Both treatments were well-tolerated by subjects.

Figures

Fig. 1

Study overview. a If the subject is a hormonal contraceptive starter (i.e., has not used hormonal contraceptives for a period of 3 months before starting the study), no washout period was necessary; b Treatment sequence A: novel Bayer patch containing 0.55 mg EE and 2.1 mg GSD in period 1, COC containing 0.03 mg EE and 0.15 mg LNG in period 2; c Treatment sequence B: COC containing 0.03 mg EE and 0.15 mg LNG in period 1, novel Bayer patch containing 0.55 mg EE and 2.1 mg GSD in period 2. COC combined oral contraceptive, EE ethinyl estradiol, EOT end of treatment, GSD gestodene, LNG levonorgestrel, SOT start of treatment (on the first day of bleeding), V1 screening visit, V2 baseline–washout cycle 2 (days 15–21), V3 treatment period 1–treatment cycle 3 (days 15–21), V4 washout cycle 3 (days 15–21), V5 washout cycle 4 (days 15–21) or baseline for treatment period 2, V6 treatment period 2–treatment cycle 6 (days 15–21), V7 up to 2 weeks after EOT, but at least 2 days after the end of the withdrawal bleeding that follows treatment cycle 6

Fig. 2

Disposition of subjects. a Subjects using the novel Bayer patch were regarded as having completed treatment if there were ≥77 days between “Last day patch removed” and “First day patch worn” in period 2; b The study was completed only if the subject had completed the treatment period and had performed the follow-up visit. COC combined oral contraceptive