PMID- 34000251
OWN - NLM
STAT- MEDLINE
DCOM- 20211027
LR  - 20220531
IS  - 1879-0518 (Electronic)
IS  - 0010-7824 (Linking)
VI  - 104
IP  - 3
DP  - 2021 Sep
TI  - Estetrol-drospirenone combination oral contraceptive: North American phase 3 
      efficacy and safety results.
PG  - 222-228
LID - S0010-7824(21)00149-9 [pii]
LID - 10.1016/j.contraception.2021.05.002 [doi]
AB  - OBJECTIVE: To assess efficacy, cycle control, and safety of an oral contraceptive 
      containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg. STUDY DESIGN: Women 
      aged 16 to 50 years with a body mass index </=35 kg/m(2) enrolled in this 
      multicenter, open-label, 13-cycle, phase 3 trial evaluating E4/DRSP in a 
      24-active/4-placebo regimen. Follow-up was scheduled at Cycles 2, 4, 7, and 10 
      and within 3 weeks of completing Cycle 13. Participants used daily diaries to 
      record pill use and vaginal bleeding. We evaluated efficacy outcomes in women 16 
      to 35 years and bleeding patterns and safety (adverse events [AEs]) in all 
      participants. We assessed overall and method-failure pregnancy rates using the 
      Pearl index (PI) and life-table analysis. Scheduled bleeding included spotting or 
      bleeding starting during the 4-day placebo period or first 3 days of the next 
      cycle. RESULTS: We enrolled 1864 women of whom 1674 were 16 to 35 years. Women 16 
      to 35 years had a PI of 2.65 (95% CI 1.73-3.88), method-failure PI of 1.43 (95% 
      CI 0.7-2.39) and 13-cycle life-table pregnancy rate of 2.1%. Scheduled bleeding 
      occurred in 82.9% to 87.0% of women per cycle; median duration was 4.5 days. 
      Unscheduled bleeding decreased from 30.3% in Cycle 1 to 21.3% to 22.1% during 
      Cycles 2 to 4 and remained stable (15.5% to 19.2%) thereafter. The most 
      frequently reported AEs were headache (5.0%) and metrorrhagia (4.6%). One-hundred 
      thirty-two (7.1%) women discontinued the study early for an AE, most commonly for 
      metrorrhagia (0.9%) and menorrhagia (0.8%). No thromboembolic events occurred. 
      CONCLUSION: E4/DRSP is an effective oral contraceptive with a predictable 
      bleeding pattern for most women and low AE rates. IMPLICATIONS STATEMENT: A new 
      oral contraceptive with a novel estrogen, estetrol, combined with drospirenone 
      has efficacy and safety within the range of other available oral contraceptives. 
      Large phase 4 studies will be needed to confirm if this combination is associated 
      with an improved adverse event profile or lower thrombosis risk.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Creinin, Mitchell D
AU  - Creinin MD
AD  - Department of Obstetrics and Gynecology, University of California, Davis, 
      Sacramento, CA, United States. Electronic address: mdcreinin@ucdavis.edu.
FAU - Westhoff, Carolyn L
AU  - Westhoff CL
AD  - Department of Obstetrics and Gynecology, Columbia University Medical Center, New 
      York, NY, United States.
FAU - Bouchard, Celine
AU  - Bouchard C
AD  - Clinique de Recherche en Sante des Femmes, Quebec City, QC, Canada.
FAU - Chen, Melissa J
AU  - Chen MJ
AD  - Department of Obstetrics and Gynecology, University of California, Davis, 
      Sacramento, CA, United States.
FAU - Jensen, Jeffrey T
AU  - Jensen JT
AD  - Department of Obstetrics and Gynecology, Oregon Health & Science University, 
      Portland, OR, United States.
FAU - Kaunitz, Andrew M
AU  - Kaunitz AM
AD  - Department of Obstetrics and Gynecology, University of Florida Jacksonville, 
      Jacksonville, FL, United States.
FAU - Achilles, Sharon L
AU  - Achilles SL
AD  - Department of Obstetrics, Gynecology, and Reproductive Sciences, University of 
      Pittsburgh/Magee-Womens Hospital, Pittsburgh, PA, United States.
FAU - Foidart, Jean-Michel
AU  - Foidart JM
AD  - Mithra Pharmaceuticals, Liege, Belgium; Department of Obstetrics and Gynecology, 
      University of Liege, Liege, Belgium.
FAU - Archer, David F
AU  - Archer DF
AD  - Department of Obstetrics and Gynecology, Eastern Virginia Medical School, 
      Norfolk, VA, United States.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210515
PL  - United States
TA  - Contraception
JT  - Contraception
JID - 0234361
RN  - 0 (Androstenes)
RN  - 0 (Contraceptives, Oral, Combined)
RN  - 0 (Estrogens)
RN  - 423D2T571U (Ethinyl Estradiol)
RN  - ENB39R14VF (Estetrol)
RN  - N295J34A25 (drospirenone)
SB  - IM
MH  - Androstenes
MH  - Contraceptives, Oral, Combined/adverse effects
MH  - *Estetrol
MH  - Estrogens
MH  - Ethinyl Estradiol/adverse effects
MH  - Female
MH  - Humans
MH  - North America
MH  - Pregnancy
OTO - NOTNLM
OT  - Drospirenone
OT  - Estetrol
OT  - Oral contraceptive
OT  - Pearl index
EDAT- 2021/05/18 06:00
MHDA- 2021/10/28 06:00
CRDT- 2021/05/17 20:16
PHST- 2021/03/15 00:00 [received]
PHST- 2021/04/19 00:00 [revised]
PHST- 2021/05/04 00:00 [accepted]
PHST- 2021/05/18 06:00 [pubmed]
PHST- 2021/10/28 06:00 [medline]
PHST- 2021/05/17 20:16 [entrez]
AID - S0010-7824(21)00149-9 [pii]
AID - 10.1016/j.contraception.2021.05.002 [doi]
PST - ppublish
SO  - Contraception. 2021 Sep;104(3):222-228. doi: 10.1016/j.contraception.2021.05.002. 
      Epub 2021 May 15.