Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol

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• 作者：Cornelis Kluft^a ; ^{kluft@kluft.in} ; Yvette Zimmerman^b ; ^{yz@pantarheioncology.nl} ; Marie Mawet^c ; ^{mmawet@mithra.com} ; Christine Klipping^d ; ^{c.klipping@dinox.umcg.nl} ; Ingrid J.M. Duijkers^d ; ^{i.j.m.duijkers@dinox.umcg.nl} ; Jacoline Neuteboom^a ; ^{neuteboom@gbsleiden.nl} ; Jean-Michel Foidart^c ; ¹ ; ^{jfevaconsulting@gmail.com} ; Herjan Coelingh Bennink^b ; ¹ ; ^{hcb@pantarheibio.com}
• 关键词：Estetrol ; Ethinyl estradiol ; Drospirenone ; Hemostasis ; SHBG ; Estrogenicity
• 刊名：Contraception
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：95
• 期：2
• 页码：140-147
• 全文大小：518 K
• 卷排序：95

文摘

The effects of estetrol (E4), a natural fetal estrogen, combined with drospirenone (DRSP) were evaluated on plasma levels of sex hormone-binding globulin (SHBG), angiotensinogen and 12 hemostasis markers.Study designCombinations of 3 mg DRSP with 5 or 10 mg E4 were compared with YAZ® (20 mcg ethinyl estradiol and 3 mg DRSP; EE/DRSP) in parallel groups of 15–18 healthy young women. Main outcome was the relative change from pretreatment to the end (day 24±1) of the third treatment cycle.ResultsAll E4 combinations showed low estrogen impact compared to EE/DRSP. Effects on SHBG and angiotensinogen of 10 mg E4 combined with DRSP were 15%–20% that of EE/DRSP.Both E4/DRSP combinations reduced D-dimer level and the 5 mg E4/DRSP combination also decreased fragment 1+2.ConclusionsThe reduction in coagulation markers suggests an anticoagulant effect from DRSP.The indications of a low thrombosis risk for E4 preparations should be validated in larger studies.Implication statement The oral estrogens, 17-β-estradiol and ethinyl estradiol, are known for significant effects on estrogenic and hemostatic variables. Effects of oral estetrol (E4) combined with drospirenone (DRSP) are significantly less for these variables. This suggests a low procoagulant effect of E4/DRSP that should be clinically verified for low antithrombotic consequences.