Impact of estetrol (E4) on hemostasis, metabolism and bone turnover in postmenopausal women

J Douxfils; U Gaspard; M Taziaux; M Jost; C Bouvy; R A Lobo; W H Utian; J-M Foidart

doi:10.1080/13697137.2022.2139599

Impact of estetrol (E4) on hemostasis, metabolism and bone turnover in postmenopausal women

J Douxfils, U Gaspard, M Taziaux, M Jost, C Bouvy, R A Lobo, W H Utian, J-M Foidart

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

Abstract

OBJECTIVE: This study aimed to determine the effects of estetrol (E4) on hemostasis, lipids, carbohydrate metabolism and bone turnover in postmenopausal women.

METHODS: This study was a multicenter, randomized, double-blind placebo-controlled phase 2 trial. Participants ( n = 180, age 43-64 years) received E4 2.5 mg, 5 mg, 10 mg and 15 mg or placebo once daily for 12 weeks. Changes from baseline at week 12 were evaluated versus placebo for hemostasis parameters, sex hormone binding globulin (SHBG), lipids, carbohydrate metabolism and bone markers.

RESULTS: Changes for hemostasis parameters were minimal with a small increase only in the normalized activated protein C sensitivity ratio in the E4 15 mg group versus placebo. SHBG increased in the E4 5 mg, 10 mg and 15 mg groups versus placebo. High-density lipoprotein cholesterol increased in all E4 groups; changes were not consistent for other lipids. Significant decreases versus placebo were seen for insulin resistance (E4 10 mg group), hemoglobin A1c (E4 15 mg group) and type 1 collagen C-terminal telopeptide (E4 10 mg and 15 mg groups). Small decreases in osteocalcin in the E4 5 mg, 10 mg and 15 mg groups were significant versus the increase observed in placebo.

CONCLUSION: E4 had limited impact on hemostasis and potentially beneficial effects on lipids, carbohydrate metabolism and bone turnover.

Original language	English
Pages (from-to)	55-63
Number of pages	9
Journal	Climacteric
Volume	26
Issue number	1
Early online date	18 Nov 2022
DOIs	https://doi.org/10.1080/13697137.2022.2139599
Publication status	Published - 2023

Keywords

activated protein C sensitivity ratio
bone turnover
carbohydrate metabolism
E4
Estetrol
hemostasis
hormone therapy
lipids
menopause

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/13697137.2022.2139599

Cite this

@article{e2bd409ea2e44d6b96a5a235a0eb902b,

title = "Impact of estetrol (E4) on hemostasis, metabolism and bone turnover in postmenopausal women",

abstract = "OBJECTIVE: This study aimed to determine the effects of estetrol (E4) on hemostasis, lipids, carbohydrate metabolism and bone turnover in postmenopausal women.METHODS: This study was a multicenter, randomized, double-blind placebo-controlled phase 2 trial. Participants ( n = 180, age 43-64 years) received E4 2.5 mg, 5 mg, 10 mg and 15 mg or placebo once daily for 12 weeks. Changes from baseline at week 12 were evaluated versus placebo for hemostasis parameters, sex hormone binding globulin (SHBG), lipids, carbohydrate metabolism and bone markers. RESULTS: Changes for hemostasis parameters were minimal with a small increase only in the normalized activated protein C sensitivity ratio in the E4 15 mg group versus placebo. SHBG increased in the E4 5 mg, 10 mg and 15 mg groups versus placebo. High-density lipoprotein cholesterol increased in all E4 groups; changes were not consistent for other lipids. Significant decreases versus placebo were seen for insulin resistance (E4 10 mg group), hemoglobin A1c (E4 15 mg group) and type 1 collagen C-terminal telopeptide (E4 10 mg and 15 mg groups). Small decreases in osteocalcin in the E4 5 mg, 10 mg and 15 mg groups were significant versus the increase observed in placebo.CONCLUSION: E4 had limited impact on hemostasis and potentially beneficial effects on lipids, carbohydrate metabolism and bone turnover.",

keywords = "activated protein C sensitivity ratio, bone turnover, carbohydrate metabolism, E4, Estetrol, hemostasis, hormone therapy, lipids, menopause",

author = "J Douxfils and U Gaspard and M Taziaux and M Jost and C Bouvy and Lobo, {R A} and Utian, {W H} and J-M Foidart",

note = "Funding Information: The trial was funded by Estetra SRL (subsidiary of Mithra Pharmaceuticals); Walloon region in Belgium [convention N°7492]. The authors wish to thank 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. Medical writing support was provided by Jan Egberts, Nazanin Hakimzadeh and Mireille Gerrits at Terminal 4 Communications, Hilversum, The Netherlands. Maud Hennion (Pharmalex Belgium) provided statistical support. Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2023",

doi = "10.1080/13697137.2022.2139599",

language = "English",

volume = "26",

pages = "55--63",

journal = "Climacteric",

issn = "1369-7137",

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TY - JOUR

T1 - Impact of estetrol (E4) on hemostasis, metabolism and bone turnover in postmenopausal women

AU - Douxfils, J

AU - Gaspard, U

AU - Taziaux, M

AU - Jost, M

AU - Bouvy, C

AU - Lobo, R A

AU - Utian, W H

AU - Foidart, J-M

N1 - Funding Information: The trial was funded by Estetra SRL (subsidiary of Mithra Pharmaceuticals); Walloon region in Belgium [convention N°7492]. The authors wish to thank 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. Medical writing support was provided by Jan Egberts, Nazanin Hakimzadeh and Mireille Gerrits at Terminal 4 Communications, Hilversum, The Netherlands. Maud Hennion (Pharmalex Belgium) provided statistical support. Publisher Copyright: © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

PY - 2023

Y1 - 2023

N2 - OBJECTIVE: This study aimed to determine the effects of estetrol (E4) on hemostasis, lipids, carbohydrate metabolism and bone turnover in postmenopausal women.METHODS: This study was a multicenter, randomized, double-blind placebo-controlled phase 2 trial. Participants ( n = 180, age 43-64 years) received E4 2.5 mg, 5 mg, 10 mg and 15 mg or placebo once daily for 12 weeks. Changes from baseline at week 12 were evaluated versus placebo for hemostasis parameters, sex hormone binding globulin (SHBG), lipids, carbohydrate metabolism and bone markers. RESULTS: Changes for hemostasis parameters were minimal with a small increase only in the normalized activated protein C sensitivity ratio in the E4 15 mg group versus placebo. SHBG increased in the E4 5 mg, 10 mg and 15 mg groups versus placebo. High-density lipoprotein cholesterol increased in all E4 groups; changes were not consistent for other lipids. Significant decreases versus placebo were seen for insulin resistance (E4 10 mg group), hemoglobin A1c (E4 15 mg group) and type 1 collagen C-terminal telopeptide (E4 10 mg and 15 mg groups). Small decreases in osteocalcin in the E4 5 mg, 10 mg and 15 mg groups were significant versus the increase observed in placebo.CONCLUSION: E4 had limited impact on hemostasis and potentially beneficial effects on lipids, carbohydrate metabolism and bone turnover.

AB - OBJECTIVE: This study aimed to determine the effects of estetrol (E4) on hemostasis, lipids, carbohydrate metabolism and bone turnover in postmenopausal women.METHODS: This study was a multicenter, randomized, double-blind placebo-controlled phase 2 trial. Participants ( n = 180, age 43-64 years) received E4 2.5 mg, 5 mg, 10 mg and 15 mg or placebo once daily for 12 weeks. Changes from baseline at week 12 were evaluated versus placebo for hemostasis parameters, sex hormone binding globulin (SHBG), lipids, carbohydrate metabolism and bone markers. RESULTS: Changes for hemostasis parameters were minimal with a small increase only in the normalized activated protein C sensitivity ratio in the E4 15 mg group versus placebo. SHBG increased in the E4 5 mg, 10 mg and 15 mg groups versus placebo. High-density lipoprotein cholesterol increased in all E4 groups; changes were not consistent for other lipids. Significant decreases versus placebo were seen for insulin resistance (E4 10 mg group), hemoglobin A1c (E4 15 mg group) and type 1 collagen C-terminal telopeptide (E4 10 mg and 15 mg groups). Small decreases in osteocalcin in the E4 5 mg, 10 mg and 15 mg groups were significant versus the increase observed in placebo.CONCLUSION: E4 had limited impact on hemostasis and potentially beneficial effects on lipids, carbohydrate metabolism and bone turnover.

KW - activated protein C sensitivity ratio

KW - bone turnover

KW - carbohydrate metabolism

KW - E4

KW - Estetrol

KW - hemostasis

KW - hormone therapy

KW - lipids

KW - menopause

UR - http://www.scopus.com/inward/record.url?scp=85142287025&partnerID=8YFLogxK

U2 - 10.1080/13697137.2022.2139599

DO - 10.1080/13697137.2022.2139599

M3 - Article

C2 - 36399023

SN - 1369-7137

VL - 26

SP - 55

EP - 63

JO - Climacteric

JF - Climacteric

IS - 1

ER -

Impact of estetrol (E4) on hemostasis, metabolism and bone turnover in postmenopausal women

Abstract

Keywords

UN SDGs

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Clinical Pharmacology Research Group

The HIC Project : Evaluation of hormone-induced coagulopathy

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Impact of estetrol (E4) on hemostasis, metabolism and bone turnover in postmenopausal women

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Clinical Pharmacology Research Group

The HIC Project : Evaluation of hormone-induced coagulopathy

Cite this