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)	1-9
Number of pages	9
Journal	Climacteric
DOIs	https://doi.org/10.1080/13697137.2023.2292066
Publication status	E-pub ahead of print - 19 Jan 2024

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10.1080/13697137.2023.2292066

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Clinical Pharmacology Research Group
Douxfils, J., Dogne, J., Musuamba Tshinanu, F., Masereel, B., Wieërs, G., Haguet, H., RONVAUX, L., Donis, N., Morimont, L., Evrard, J., Siriez, R., Gillot, C., FAVRESSE, J., BOUVY, C., Djokoto, H., Didembourg, M., David, C., Melchionda, S., Maloteau, V., Boucher, A., Devel, P., Modaffari, E., Vandeputte, M., De Messemaeker, A., Decarpentrie, J., Vassart, J. & De Groote, A.
1/04/22 → …
Project: Research Axis
The HIC Project : Evaluation of hormone-induced coagulopathy
Dogne, J., Douxfils, J., Morimont, L., Didembourg, M. & Evrard, J.
1/09/19 → 31/08/23
Project: Research

Cite this

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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.",

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",

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doi = "10.1080/13697137.2023.2292066",

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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

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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.

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DO - 10.1080/13697137.2023.2292066

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EP - 9

JO - Climacteric

JF - Climacteric

ER -

Low thrombin generation in postmenopausal women using estetrol

Abstract

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Clinical Pharmacology Research Group

The HIC Project : Evaluation of hormone-induced coagulopathy

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