PMID- 36257374 OWN - NLM STAT- MEDLINE DCOM- 20221122 LR - 20230129 IS - 1879-0518 (Electronic) IS - 0010-7824 (Linking) VI - 116 DP - 2022 Dec TI - Tolerability and safety of the estetrol/drospirenone combined oral contraceptive: Pooled analysis of two multicenter, open-label phase 3 trials. PG - 44-50 LID - S0010-7824(22)00395-X [pii] LID - 10.1016/j.contraception.2022.10.004 [doi] AB - OBJECTIVES: To evaluate tolerability and safety of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg oral contraceptive using pooled data from two, multicenter, phase 3 trials. STUDY DESIGN: The two trials enrolled participants aged 16-50 years with a body mass index /=1 AE. Most participants with reported AEs had AEs that investigators rated as mild or moderate (n = 1665, 93.2%); of participants reporting AEs, 1105 (61.9%) did so during cycles 1 to 3. In total, 981 (28.7%) participants experienced >/=1 treatment-related AE, most frequently related to bleeding complaints (n = 323, 9.5%), breast pain or tenderness (n = 136, 4.0%), acne (n = 113, 3.3%), and mood disturbance (n = 111, 3.2%). Discontinuation due to treatment-related AEs occurred in 272 participants (8.0%), with only bleeding complaints (n = 97, 2.8%) and mood disturbance (n = 38, 1.1%) at rates exceeding 1%. Three participants experienced serious AEs, which the site investigators considered treatment-related: one venous thromboembolism, one worsening of depression, and one ectopic pregnancy. We found no clinically relevant changes in weight, blood pressure, heart rate, or laboratory parameters during treatment. CONCLUSIONS: E4/DRSP is associated with a favorable tolerability and safety profile. IMPLICATIONS STATEMENT: Pooling data allowed for a robust assessment of tolerability and safety, including relatively infrequent events. Other than bleeding complaints and mood disturbance, no adverse event resulted in E4/DRSP discontinuation at rates >1%. Post-marketing surveillance studies are needed to evaluate long-term safety of the E4/DRSP COC and population-based venous thromboembolism risks. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Chen, Melissa J AU - Chen MJ AD - Department of Obstetrics and Gynecology, University of California, Davis, Sacramento, California, USA. FAU - Jensen, Jeffrey T AU - Jensen JT AD - Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon, USA. FAU - Kaunitz, Andrew M AU - Kaunitz AM AD - Department of Obstetrics and Gynecology, University of Florida College of Medicine, Jacksonville, Jacksonville, Florida, USA. FAU - Achilles, Sharon L AU - Achilles SL AD - Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh and Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA. FAU - Zatik, Janos AU - Zatik J AD - Gynecological Praxis St. Anna, Debrecen, Hungary. FAU - Weyers, Steven AU - Weyers S AD - Department of Obstetrics and Gynecology, University Hospital, Gent, Belgium. FAU - Piltonen, Terhi AU - Piltonen T AD - Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland. FAU - Suturina, Larisa AU - Suturina L AD - Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russia. FAU - Apolikhina, Inna AU - Apolikhina I AD - National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Healthcare of the Russia, Moscow, Russia. FAU - Bouchard, Celine AU - Bouchard C AD - Clinique de Recherche en Sante de la Femme (RSF), Quebec, Canada. FAU - Archer, David F AU - Archer DF AD - Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia, USA. FAU - Jost, Maud AU - Jost M AD - Estetra SRL, an affiliate company of Mithra Pharmaceuticals, Liege, Belgium. Electronic address: mjost@mithra.com. FAU - Foidart, Jean-Michel AU - Foidart JM AD - Estetra SRL, an affiliate company of Mithra Pharmaceuticals, Liege, Belgium; Department of Obstetrics and Gynecology, University of Liege, Liege, Belgium. FAU - Creinin, Mitchell AU - Creinin M AD - Department of Obstetrics and Gynecology, University of California, Davis, Sacramento, California, USA. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20221017 PL - United States TA - Contraception JT - Contraception JID - 0234361 RN - ENB39R14VF (Estetrol) RN - 0 (Contraceptives, Oral, Combined) RN - N295J34A25 (drospirenone) RN - 0 (Androstenes) RN - 0 (Estrogens) RN - 423D2T571U (Ethinyl Estradiol) SB - IM MH - Humans MH - Pregnancy MH - Female MH - *Estetrol/adverse effects MH - Contraceptives, Oral, Combined/adverse effects MH - *Venous Thromboembolism/chemically induced MH - Androstenes/adverse effects MH - Estrogens MH - Ethinyl Estradiol/adverse effects OTO - NOTNLM OT - Combined Oral Contraceptive OT - Drospirenone OT - E4 OT - Estetrol OT - Oral Contraception OT - Safety OT - Tolerability EDAT- 2022/10/19 06:00 MHDA- 2022/11/23 06:00 CRDT- 2022/10/18 19:23 PHST- 2022/07/15 00:00 [received] PHST- 2022/10/04 00:00 [revised] PHST- 2022/10/09 00:00 [accepted] PHST- 2022/10/19 06:00 [pubmed] PHST- 2022/11/23 06:00 [medline] PHST- 2022/10/18 19:23 [entrez] AID - S0010-7824(22)00395-X [pii] AID - 10.1016/j.contraception.2022.10.004 [doi] PST - ppublish SO - Contraception. 2022 Dec;116:44-50. doi: 10.1016/j.contraception.2022.10.004. Epub 2022 Oct 17.