Menopause; NCT02834312; activated protein C resistance; coagulation; estetrol; hemostasis; thrombin generation; Estetrol; Thrombin; Estrogen Receptor alpha; Estrogens; Female; Humans; Postmenopause; Estetrol/pharmacology; Obstetrics and Gynecology
Abstract :
[en] OBJECTIVE: Estetrol (E4) represents a novel estrogen of interest to relieve vasomotor symptoms. E4 activates the nuclear estrogen receptor α (ERα) but antagonizes the estradiol ERα-dependent membrane-initiated steroid signaling pathway. The distinct pharmacological properties of E4 could explain its low impact on hemostasis. This study aimed to assess the effect of E4 on coagulation in postmenopausal women, using the thrombin generation assay (TGA).
METHODS: Data were collected from a multicenter, randomized, placebo-controlled, dose-finding study in postmenopausal women (NCT02834312). Oral E4 (2.5 mg, n = 42; 5 mg, n = 29; 10 mg, n = 34; or 15 mg, n = 32) or placebo (n = 31) was administered daily for 12 weeks. Thrombograms and TGA parameters were extracted for each subject at baseline and after 12 weeks of treatment.
RESULTS: After 12 weeks of treatment, all treatment groups showed a mean thrombogram (±95% confidence interval [CI] of the mean) within the reference ranges, that is, the 2.5th-97.5th percentile of all baseline thrombograms (n = 168), as well as for TGA parameters.
CONCLUSIONS: The intake of E4 15 mg for 12 weeks led to significant but not clinically relevant changes compared to baseline as the mean values (±95% CI of the mean) remained within reference ranges, demonstrating a neutral profile of this estrogen on hemostasis.
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Morimont, L; QUALIresearch, Qualiblood s.a, Namur, Belgium ; Clinical Pharmacology and Toxicology Research Unit (CPRU), Namur Research Institute for LIfe Sciences (NARILIS), Faculty of Medicine, University of Namur, Namur, Belgium
Didembourg, M; Clinical Pharmacology and Toxicology Research Unit (CPRU), Namur Research Institute for LIfe Sciences (NARILIS), Faculty of Medicine, University of Namur, Namur, Belgium
Jost, M; Estetra SRL, An affiliate Company of Mithra Pharmaceuticals, Liège, Belgium
Taziaux, M; Estetra SRL, An affiliate Company of Mithra Pharmaceuticals, Liège, Belgium
Oligschlager, Y; Estetra SRL, An affiliate Company of Mithra Pharmaceuticals, Liège, Belgium
van Rooijen, M ; Estetra SRL, An affiliate Company of Mithra Pharmaceuticals, Liège, Belgium
Gaspard, Ulysse ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie-Obstétrique
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques
Douxfils, J ; QUALIresearch, Qualiblood s.a, Namur, Belgium ; Clinical Pharmacology and Toxicology Research Unit (CPRU), Namur Research Institute for LIfe Sciences (NARILIS), Faculty of Medicine, University of Namur, Namur, Belgium ; Department of Biological Hematology, Centre Hospitalier Universitaire Clermont-Ferrand, Hôpital Estaing, Clermont-Ferrand, France
Language :
English
Title :
Low thrombin generation in postmenopausal women using estetrol.
Publication date :
2024
Journal title :
Climacteric: the Journal of the International Menopause Society
The authors would like to thank the technical teams of QUALIblood s.a., the medical affairs team of Mithra Pharmaceuticals, the Walloon region in Belgium and the investigators in the participating centers for conducting the E4Relief trial [17]. The authors also thank the members of the Donesta Scientific Advisory Boards for their valuable advice. Original data generated and analyzed during this study are included in this published article or in the data repositories listed in the references.The trial was funded by Estetra SRL (affiliate company of Mithra Pharmaceuticals); Walloon region in Belgium [convention N\u00B07492].
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