Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters

J. Douxfils; C. Klipping; I. Duijkers; V. Kinet; M. Mawet; C. Maillard; M. Jost; J. Rosing; J.M. Foidart

doi:10.1016/j.contraception.2020.08.015

Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters

J. Douxfils, C. Klipping, I. Duijkers, V. Kinet, M. Mawet, C. Maillard, M. Jost^*, J. Rosing, J.M. Foidart

^*Corresponding author for this work

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

Abstract

Objective: To assess the effect on hemostasis parameters of a new combined oral contraceptive (COC). Study design: In this randomized, single centre, open-label, exploratory study, healthy women received either 15 mg estetrol/3 mg drospirenone (E4/DRSP) (n = 39), 30 mcg ethinylestradiol/150 mcg levonorgestrel (EE/LNG) (n = 30), or 20 mcg ethinylestradiol/3 mg drospirenone (EE/DRSP) (n = 32) for six 28day cycles. Blood was collected at baseline, cycle 3, and cycle 6. Median change from baseline was evaluated for procoagulant, anticoagulant, and fibrinolytic parameters, and for sex hormone-binding globulin (SHBG).Results: Median change of endogenous thrombin potential (ETP) based activated protein C sensitivity resistance (APCr) at cycle 6 was +30% for E4/DRSP, +165% for EE/LNG (p-value <0.05 vs E4/DRSP), and +219% for EE/DRSP (p-value <0.05 vs E4/DRSP). Changes to prothrombin fragment 1 + 2 and SHBG for E4/DRSP, EE/LNG, and EE/DRSP were +23%, +71%, and +64% (p-value <0.05 vs E4/DRSP); and +55%, +74% and +251% (p-value <0.05 vs E4/DRSP), respectively. At cycle 6, changes to other hemostasis parameters for E4/DRSP were similar or smaller than for EE/LNG or EE/DRSP.Conclusions: In this study, changes in hemostasis parameters after treatment with 6 cycles of E4/DRSP were smaller or similar to those observed for EE/LNG. Similar, but more pronounced changes were also observed versus EE/DRSP, which supports the hypothesis that the effect of COCs on hemostasis parameters is mainly mediated by the estrogenic component. Further studies are needed to provide more insight into the venous thromboembolic risk of E4/DRSP.Implications statement: This study reports that the effects on hemostasis parameters of a COC containing 15 mg E4/3 mg DRSP are less or similar to those for EE/LNG or EE/DRSP. It also demonstrates that the choice of estrogen modulates the effects of COCs on hemostasis parameters. (C) 2020 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	396-402
Number of pages	7
Journal	Contraception
Volume	102
Issue number	6
DOIs	https://doi.org/10.1016/j.contraception.2020.08.015
Publication status	Published - 1 Dec 2020

Keywords

Activated protein C resistance
Contraception
Drospirenone
Estetrol
Ethinylestradiol
Hemostasis
Levonorgestrel
activated protein c resistance
contraception
drospirenone
estetrol
ethinylestradiol
hemostasis
levonorgestrel
VENOUS THROMBOSIS
RISK
PROFILE
CYCLE

Access to Document

10.1016/j.contraception.2020.08.015

Cite this

@article{9cd5b03439b844bb879311181f7d6a0f,

title = "Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters",

abstract = "Objective: To assess the effect on hemostasis parameters of a new combined oral contraceptive (COC). Study design: In this randomized, single centre, open-label, exploratory study, healthy women received either 15 mg estetrol/3 mg drospirenone (E4/DRSP) (n = 39), 30 mcg ethinylestradiol/150 mcg levonorgestrel (EE/LNG) (n = 30), or 20 mcg ethinylestradiol/3 mg drospirenone (EE/DRSP) (n = 32) for six 28day cycles. Blood was collected at baseline, cycle 3, and cycle 6. Median change from baseline was evaluated for procoagulant, anticoagulant, and fibrinolytic parameters, and for sex hormone-binding globulin (SHBG).Results: Median change of endogenous thrombin potential (ETP) based activated protein C sensitivity resistance (APCr) at cycle 6 was +30% for E4/DRSP, +165% for EE/LNG (p-value <0.05 vs E4/DRSP), and +219% for EE/DRSP (p-value <0.05 vs E4/DRSP). Changes to prothrombin fragment 1 + 2 and SHBG for E4/DRSP, EE/LNG, and EE/DRSP were +23%, +71%, and +64% (p-value <0.05 vs E4/DRSP); and +55%, +74% and +251% (p-value <0.05 vs E4/DRSP), respectively. At cycle 6, changes to other hemostasis parameters for E4/DRSP were similar or smaller than for EE/LNG or EE/DRSP.Conclusions: In this study, changes in hemostasis parameters after treatment with 6 cycles of E4/DRSP were smaller or similar to those observed for EE/LNG. Similar, but more pronounced changes were also observed versus EE/DRSP, which supports the hypothesis that the effect of COCs on hemostasis parameters is mainly mediated by the estrogenic component. Further studies are needed to provide more insight into the venous thromboembolic risk of E4/DRSP.Implications statement: This study reports that the effects on hemostasis parameters of a COC containing 15 mg E4/3 mg DRSP are less or similar to those for EE/LNG or EE/DRSP. It also demonstrates that the choice of estrogen modulates the effects of COCs on hemostasis parameters. (C) 2020 Elsevier Inc. All rights reserved.",

keywords = "Activated protein C resistance, Contraception, Drospirenone, Estetrol, Ethinylestradiol, Hemostasis, Levonorgestrel, activated protein c resistance, contraception, drospirenone, estetrol, ethinylestradiol, hemostasis, levonorgestrel, VENOUS THROMBOSIS, RISK, PROFILE, CYCLE",

author = "J. Douxfils and C. Klipping and I. Duijkers and V. Kinet and M. Mawet and C. Maillard and M. Jost and J. Rosing and J.M. Foidart",

note = "Funding Information: Conflict of interest: J. Douxfils is the director and founder of Qualiblood, a contract research organization that received funding from Mithra for the conduct of the study. He also reports personal fees from Daiichi-Sankyo, Diagnostica Stago, Portola, Roche and Roche Diagnostics. J. Rosing has provided expert witness testimony relating to effects of hormonal contraceptives on blood coagulation and his laboratory executed several industry-sponsored studies on the effects of female sex hormones on coagulation. He reports personal fees from Mithra and from Pantharei Bioscience and Oncology.C. Klipping and I. Duijkers are directors of Dinox BV, a contract research organization that received funding from Mithra for the conduct of the study. V. Kinet, M. Mawet, C. Maillard and M. Jost are employees of Mithra. JM Foidart is a member of the board at Mithra and received financial support for the supervision of this study. Funding Information: The study was sponsored by Estetra SPRL, an affiliate's company of Mithra Pharmaceuticals , Li{\`e}ge, Belgium. Medical writing support was provided by Mireille Gerrits PharmD, at Terminal 4 Communications, Hilversum, the Netherlands. Statistical support was provided by Pharmalex Belgium, Mont-Saint-Guibert, Belgium. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = dec,

day = "1",

doi = "10.1016/j.contraception.2020.08.015",

language = "English",

volume = "102",

pages = "396--402",

journal = "Contraception",

issn = "0010-7824",

publisher = "Elsevier Science",

number = "6",

}

TY - JOUR

T1 - Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters

AU - Douxfils, J.

AU - Klipping, C.

AU - Duijkers, I.

AU - Kinet, V.

AU - Mawet, M.

AU - Maillard, C.

AU - Jost, M.

AU - Rosing, J.

AU - Foidart, J.M.

N1 - Funding Information: Conflict of interest: J. Douxfils is the director and founder of Qualiblood, a contract research organization that received funding from Mithra for the conduct of the study. He also reports personal fees from Daiichi-Sankyo, Diagnostica Stago, Portola, Roche and Roche Diagnostics. J. Rosing has provided expert witness testimony relating to effects of hormonal contraceptives on blood coagulation and his laboratory executed several industry-sponsored studies on the effects of female sex hormones on coagulation. He reports personal fees from Mithra and from Pantharei Bioscience and Oncology.C. Klipping and I. Duijkers are directors of Dinox BV, a contract research organization that received funding from Mithra for the conduct of the study. V. Kinet, M. Mawet, C. Maillard and M. Jost are employees of Mithra. JM Foidart is a member of the board at Mithra and received financial support for the supervision of this study. Funding Information: The study was sponsored by Estetra SPRL, an affiliate's company of Mithra Pharmaceuticals , Liège, Belgium. Medical writing support was provided by Mireille Gerrits PharmD, at Terminal 4 Communications, Hilversum, the Netherlands. Statistical support was provided by Pharmalex Belgium, Mont-Saint-Guibert, Belgium. Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Objective: To assess the effect on hemostasis parameters of a new combined oral contraceptive (COC). Study design: In this randomized, single centre, open-label, exploratory study, healthy women received either 15 mg estetrol/3 mg drospirenone (E4/DRSP) (n = 39), 30 mcg ethinylestradiol/150 mcg levonorgestrel (EE/LNG) (n = 30), or 20 mcg ethinylestradiol/3 mg drospirenone (EE/DRSP) (n = 32) for six 28day cycles. Blood was collected at baseline, cycle 3, and cycle 6. Median change from baseline was evaluated for procoagulant, anticoagulant, and fibrinolytic parameters, and for sex hormone-binding globulin (SHBG).Results: Median change of endogenous thrombin potential (ETP) based activated protein C sensitivity resistance (APCr) at cycle 6 was +30% for E4/DRSP, +165% for EE/LNG (p-value <0.05 vs E4/DRSP), and +219% for EE/DRSP (p-value <0.05 vs E4/DRSP). Changes to prothrombin fragment 1 + 2 and SHBG for E4/DRSP, EE/LNG, and EE/DRSP were +23%, +71%, and +64% (p-value <0.05 vs E4/DRSP); and +55%, +74% and +251% (p-value <0.05 vs E4/DRSP), respectively. At cycle 6, changes to other hemostasis parameters for E4/DRSP were similar or smaller than for EE/LNG or EE/DRSP.Conclusions: In this study, changes in hemostasis parameters after treatment with 6 cycles of E4/DRSP were smaller or similar to those observed for EE/LNG. Similar, but more pronounced changes were also observed versus EE/DRSP, which supports the hypothesis that the effect of COCs on hemostasis parameters is mainly mediated by the estrogenic component. Further studies are needed to provide more insight into the venous thromboembolic risk of E4/DRSP.Implications statement: This study reports that the effects on hemostasis parameters of a COC containing 15 mg E4/3 mg DRSP are less or similar to those for EE/LNG or EE/DRSP. It also demonstrates that the choice of estrogen modulates the effects of COCs on hemostasis parameters. (C) 2020 Elsevier Inc. All rights reserved.

AB - Objective: To assess the effect on hemostasis parameters of a new combined oral contraceptive (COC). Study design: In this randomized, single centre, open-label, exploratory study, healthy women received either 15 mg estetrol/3 mg drospirenone (E4/DRSP) (n = 39), 30 mcg ethinylestradiol/150 mcg levonorgestrel (EE/LNG) (n = 30), or 20 mcg ethinylestradiol/3 mg drospirenone (EE/DRSP) (n = 32) for six 28day cycles. Blood was collected at baseline, cycle 3, and cycle 6. Median change from baseline was evaluated for procoagulant, anticoagulant, and fibrinolytic parameters, and for sex hormone-binding globulin (SHBG).Results: Median change of endogenous thrombin potential (ETP) based activated protein C sensitivity resistance (APCr) at cycle 6 was +30% for E4/DRSP, +165% for EE/LNG (p-value <0.05 vs E4/DRSP), and +219% for EE/DRSP (p-value <0.05 vs E4/DRSP). Changes to prothrombin fragment 1 + 2 and SHBG for E4/DRSP, EE/LNG, and EE/DRSP were +23%, +71%, and +64% (p-value <0.05 vs E4/DRSP); and +55%, +74% and +251% (p-value <0.05 vs E4/DRSP), respectively. At cycle 6, changes to other hemostasis parameters for E4/DRSP were similar or smaller than for EE/LNG or EE/DRSP.Conclusions: In this study, changes in hemostasis parameters after treatment with 6 cycles of E4/DRSP were smaller or similar to those observed for EE/LNG. Similar, but more pronounced changes were also observed versus EE/DRSP, which supports the hypothesis that the effect of COCs on hemostasis parameters is mainly mediated by the estrogenic component. Further studies are needed to provide more insight into the venous thromboembolic risk of E4/DRSP.Implications statement: This study reports that the effects on hemostasis parameters of a COC containing 15 mg E4/3 mg DRSP are less or similar to those for EE/LNG or EE/DRSP. It also demonstrates that the choice of estrogen modulates the effects of COCs on hemostasis parameters. (C) 2020 Elsevier Inc. All rights reserved.

KW - Activated protein C resistance

KW - Contraception

KW - Drospirenone

KW - Estetrol

KW - Ethinylestradiol

KW - Hemostasis

KW - Levonorgestrel

KW - activated protein c resistance

KW - contraception

KW - drospirenone

KW - estetrol

KW - ethinylestradiol

KW - hemostasis

KW - levonorgestrel

KW - VENOUS THROMBOSIS

KW - RISK

KW - PROFILE

KW - CYCLE

U2 - 10.1016/j.contraception.2020.08.015

DO - 10.1016/j.contraception.2020.08.015

M3 - Article

C2 - 32956694

SN - 0010-7824

VL - 102

SP - 396

EP - 402

JO - Contraception

JF - Contraception

IS - 6

ER -