Low thrombin generation in postmenopausal women using estetrol

L Morimont; M Didembourg; C Bouvy; M Jost; M Taziaux; Y Oligschlager; M van Rooijen; U Gaspard; J-M Foidart; J Douxfils

doi:10.1080/13697137.2023.2292066

Low thrombin generation in postmenopausal women using estetrol

L Morimont
, M Didembourg
, C Bouvy
, M Jost
, M Taziaux
, Y Oligschlager
, M van Rooijen
, U Gaspard
, J-M Foidart
, J Douxfils

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	193-201
Number of pages	9
Journal	Climacteric
Volume	27
Issue number	2
Early online date	19 Jan 2024
DOIs	https://doi.org/10.1080/13697137.2023.2292066
Publication status	Published - 2024

Funding

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°7492].

Funders
medical affairs team of Mithra Pharmaceuticals
Estetra SRL

Keywords

estetrol
activated protein C resistance
Menopause
hemostasis
thrombin generation
coagulation
NCT02834312

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10.1080/13697137.2023.2292066

Cite this

@article{6f4343119a70427381a609c55bac04c2,

title = "Low thrombin generation in postmenopausal women using estetrol",

abstract = "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.",

keywords = "estetrol, activated protein C resistance, Menopause, hemostasis, thrombin generation, coagulation, NCT02834312",

author = "L Morimont and M Didembourg and C Bouvy and M Jost and M Taziaux and Y Oligschlager and \{van Rooijen\}, M and U Gaspard and J-M Foidart and J Douxfils",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Published by Informa UK Limited, trading as Taylor \& Francis Group.",

year = "2024",

doi = "10.1080/13697137.2023.2292066",

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TY - JOUR

T1 - Low thrombin generation in postmenopausal women using estetrol

AU - Morimont, L

AU - Didembourg, M

AU - Bouvy, C

AU - Jost, M

AU - Taziaux, M

AU - Oligschlager, Y

AU - van Rooijen, M

AU - Gaspard, U

AU - Foidart, J-M

AU - Douxfils, J

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - estetrol

KW - activated protein C resistance

KW - Menopause

KW - hemostasis

KW - thrombin generation

KW - coagulation

KW - NCT02834312

UR - https://www.scopus.com/pages/publications/85184699572

U2 - 10.1080/13697137.2023.2292066

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SN - 1369-7137

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SP - 193

EP - 201

JO - Climacteric

JF - Climacteric

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ER -

Low thrombin generation in postmenopausal women using estetrol

Abstract

Funding

Keywords

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Clinical Pharmacology Research Group

The HIC Project : Evaluation of hormone-induced coagulopathy

Cite this

Low thrombin generation in postmenopausal women using estetrol

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Projects

Clinical Pharmacology Research Group

The HIC Project : Evaluation of hormone-induced coagulopathy

Cite this