Low thrombin generation in users of a contraceptive containing estetrol and drospirenone

Laure Morimont, Maud Jost, Ulysse Gaspard, Jean Michel Foidart, Jean Michel Dogné, Jonathan Douxfils

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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.

Original languageEnglish
Pages (from-to)135-143
Number of pages9
JournalThe Journal of clinical endocrinology and metabolism
Issue number1
Early online date13 Sept 2022
Publication statusPublished - 17 Dec 2022


  • contraception
  • drospirenone
  • estetrol
  • ethinylestradiol
  • levonorgestrel
  • thrombin generation


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