The combination of 15 mg estetrol and 3 mg drospirenone resulted in a significantly lower endogenous thrombin potential compared to ethinylestradiol/levonorgestrel after 6 cycles of treatment.
RCT (n=98)
Open-label
Computerized random allocation sequence
No
Does 15 mg estetrol combined with 3 mg drospirenone improve thrombin generation parameters compared to ethinylestradiol-containing products in healthy females?
The combination of 15 mg estetrol and 3 mg drospirenone demonstrates a neutral profile on hemostasis, avoiding the prothrombotic changes seen with ethinylestradiol-containing contraceptives.
Absolute Event Rate: 1456% vs 1588%
p-value: p=0.0042
OBJECTIVE: To compare the impact on thrombin generation of the new combined oral contraceptive containing 15 mg estetrol and 3 mg drospirenone with ethinylestradiol (30 or 20 mcg) associated either with 150 mcg levonorgestrel or with 3 mg drospirenone. METHODS: Data were collected from the "E4/DRSP Endocrine Function, Metabolic Control and Hemostasis Study" (NCT02957630). Overall, the per-protocol set population included 24 subjects in the ethinylestradiol/levonorgestrel arm, 28 subjects in the ethinylestradiol/drospirenone arm, and 34 subjects in the estetrol/drospirenone arm. Thrombograms and thrombin generation parameters (lag time, peak, time to peak, endogenous thrombin potential, and mean velocity rate index) were extracted for each subject at baseline and after 6 cycles of treatment. RESULTS: After 6 cycles of treatment, ethinylestradiol-containing products arms show a mean thrombogram outside the upper limit of the reference range, that is the 97.5th percentile of all baseline thrombograms. On the other hand, the mean thrombogram of estetrol/drospirenone is within this reference interval. After 6 cycles of treatment, all thrombin generation parameters are statistically less affected by estetrol/drospirenone than ethinylestradiol-containing products. CONCLUSIONS: In conclusion, an association of 15 mg estetrol with 3 mg drospirenone does not have an impact on thrombin generation compared with ethinylestradiol-containing products that, either associated with levonorgestrel or drospirenone, are able to increase the production of procoagulant factors and decrease the production of anticoagulant ones, shifting the patient to a prothrombotic state. Ethinylestradiol-containing products thus generate prothrombotic environments contrary to estetrol which demonstrates a neutral profile on hemostasis.
Morimont et al. (Tue,) conducted a rct in Healthy females requiring contraception (n=98). Estetrol and drospirenone (E4/DRSP) vs. Ethinylestradiol/levonorgestrel (30 mcg/150 mcg) or Ethinylestradiol/drospirenone (20 mcg/3 mg) was evaluated on Endogenous thrombin potential (ETP) at cycle 6 (p=0.0042). The combination of 15 mg estetrol and 3 mg drospirenone resulted in a significantly lower endogenous thrombin potential compared to ethinylestradiol/levonorgestrel after 6 cycles of treatment.