Gemzell-Danielsson, K, Apter, D, Zatik, J, Weyers, S, Piltonen, T, Suturina, L, Apolikhina, I, Jost, M, Creinin, MD, Foidart, J-M. Estetrol-Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia. BJOG 2022; https://doi.org/10.1111/1471-0528.16840. 129: 63– 71
Estetrol-drospirenone combination oral contraceptive : a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia
|Author:||Gemzell-Danielsson, K.1; Apter, D.2; Zatik, J.3;|
1Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
2VL-Medi Clinical Research Centre, Helsinki, Finland
3Gynaecological Praxis St Anna, Debrecen, Hungary
4Department of Obstetrics and Gynaecology, University Hospital, Gent, Belgium
5Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
6Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russia
7Kulakov National Medical Research Centre for Obstetrics, Gynaecology, and Perinatology, Moscow, Russia
8Estetra SRL, an affiliate Company of Mithra Pharmaceuticals, Liège, Belgium
9Department of Obstetrics and Gynecology, University of California, Davis, Sacramento, CA, USA
10Department of Obstetrics and Gynaecology, University of Liège, Liège, Belgium
|Online Access:||PDF Full Text (PDF, 0.8 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022030922683
John Wiley & Sons,
|Publish Date:|| 2022-03-09
Objectives: To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.
Design: Multicenter, open-label, phase 3 trial.
Setting: Sixty-nine sites in Europe and Russia.
Population: Sexually active women aged 18–50 years with regular menstrual cycles and body mass index ≤35 kg/m².
Methods: E4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary.
Main outcome measures: Pearl Index (PI) for women 18–35 years (overall and method-failure), bleeding pattern and AEs.
Results: A total of 1553 women aged 18–50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15–1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06–0.83). Scheduled bleeding/spotting occurred in 91.9–94.4% of women over Cycles 1 to 12 and lasted a median of 4–5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to <16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment-related serious AE was reported, a lower extremity venous thromboembolism. One-hundred and forty-one (9.1%) women discontinued study participation because of treatment-related adverse events.
Conclusions: E4/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile.
Tweetable abstract: A phase 3 trial with E4/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.
BJOG. An international journal of obstetrics and gynaecology
|Pages:||63 - 71|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3123 Gynaecology and paediatrics
The study was funded by Estetra SRL, an affiliate company of Mithra Pharmaceuticals. Estetra SRL was involved in the phase 3 trial design. PRA Health Sciences managed the trial execution, including monitoring and reporting, as well as data analysis. Study treatment was provided free of charge to participants.
© 2021 Estetra SRL. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.