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


METHODS
Combinations 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.


RESULTS
All 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.


CONCLUSIONS
The 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.
Good Biomarker Sciences, Zernikedreef 8, 2333CL, Leiden, the Netherlands. Electronic address: kluft@kluft.in.
Cornelis
C
Kluft
Pantarhei Bioscience, P.O. Box 464, 3700, AL, Zeist, the Netherlands. Electronic address: yz@pantarheioncology.nl.
Yvette
Y
Zimmerman
Estetra SPRL, Rue Saint Exupery, 4460 Grace-Hollogne, Belgium. Electronic address: mmawet@mithra.com.
Marie
M
Mawet
Dinox BV, Hanzeplein 1, 9713GZ, Groningen, the Netherlands. Electronic address: c.klipping@dinox.umcg.nl.
Christine
C
Klipping
Dinox BV, Hanzeplein 1, 9713GZ, Groningen, the Netherlands. Electronic address: i.j.m.duijkers@dinox.umcg.nl.
Ingrid J M
IJM
Duijkers
Good Biomarker Sciences, Zernikedreef 8, 2333CL, Leiden, the Netherlands. Electronic address: neuteboom@gbsleiden.nl.
Jacoline
J
Neuteboom
Estetra SPRL, Rue Saint Exupery, 4460 Grace-Hollogne, Belgium. Electronic address: jfevaconsulting@gmail.com.
Jean-Michel
JM
Foidart
Pantarhei Bioscience, P.O. Box 464, 3700, AL, Zeist, the Netherlands. Electronic address: hcb@pantarheibio.com.
Herjan Coelingh
HC
Bennink
D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000008:administration & dosage*; D000808:Angiotensinogen / Q000097:blood; D000925:Anticoagulants; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D003276:Contraceptives, Oral / Q000008:administration & dosage*; D004953:Estetrol / Q000008:administration & dosage*; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D055815:Young Adult
D000736:Androstenes; D000925:Anticoagulants; D015415:Biomarkers; D003276:Contraceptives, Oral; D005338:Fibrin Fibrinogen Degradation Products; D012738:Sex Hormone-Binding Globulin; C036309:fibrin fragment D; D000808:Angiotensinogen; D004997:Ethinyl Estradiol; D004953:Estetrol; C035144:drospirenone
Drospirenone; Estetrol; Estrogenicity; Ethinyl estradiol; Hemostasis; SHBG