University of Oulu

Jensen, J. T., Kaunitz, A. M., Achilles, S. L., Zatik, J., Weyers, S., Piltonen, T., Suturina, L., Apolikhina, I., Bouchard, C., Chen, M. J., Apter, D., Jost, M., Foidart, J., & Creinin, M. D. (2022). Pooled efficacy results of estetrol/drospirenone combined oral contraception phase 3 trials. Contraception, 116, 37–43.

Pooled efficacy results of estetrol/drospirenone combined oral contraception phase 3 trials

Saved in:
Author: Jensen, Jeffrey T.1; Kaunitz, Andrew M.2; Achilles, Sharon L.3;
Organizations: 1Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA
2Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville, Jacksonville, FL, USA
3Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh and Magee–Womens Research Institute, Pittsburgh, PA, USA
4Szent Anna Szuleszeti, Nogyogyaszati es Ultrahang Maganrendelo, Debrecen, Hungary
5Department of Obstetrics and Gynaecology, Ghent University Hospital, Ghent, Belgium
6Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Centre, Oulu University Hospital, Oulu, Finland
7Department of Reproductive Health Protection, Scientific Center for Family Health and Human Reproduction, Irkutsk, Russia
8National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russia
9Clinique de Recherche en Santé de la femme (RSF) Inc., Québec City, Québec, Canada
10Department of Obstetrics and Gynecology, University of California, Davis, Sacramento, CA, USA
11VL–Medi Clinical Research Center, Helsinki, Finland
12Estetra SRL, an affiliated company of Mithra Pharmaceuticals, Liège, Belgium
13Department of Obstetrics and Gynecology, University of Liège, Liège, Belgium
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
Persistent link:
Language: English
Published: Elsevier, 2022
Publish Date: 2023-05-31


Objective: To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen.

Study design: We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors.

Results: Analyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m². The pooled PI was 1.52 (95% confidence interval 1.04‐2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%‐1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94‐2.57) and 1.43 (0.78‐2.40), respectively; in new starters and switchers of 1.88 (1.09‐3.00) and 1.24 (0.68‐2.08), respectively; and by BMI <25 kg/m², 25 to 29.9 kg/m², and ≥30 kg/m² of 1.14 (0.64‐1.88), 2.19 (1.05‐4.03), and 2.27 (0.83‐4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56–8.38]), Black race (HR 4.61[1.97‐10.80]), age 16 to 25 years (HR 2.37[1.09‐5.15]) and compliance <99% of expected pills (HR 4.21[2.04‐8.66]) with conception.

Conclusions: E4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, contraceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable.

Implications Statement: Pooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non–modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure.

see all

Series: Contraception
ISSN: 0010-7824
ISSN-E: 1879-0518
ISSN-L: 0010-7824
Volume: 116
Pages: 37 - 43
DOI: 10.1016/j.contraception.2022.07.009
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: Estetra SRL (an affiliated company of Mithra Pharmaceuticals) funded this study. Participants received the study treatment free of charge.
Copyright information: © 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (