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. 2024 Apr 9:5:1395863.
doi: 10.3389/fgwh.2024.1395863. eCollection 2024.

Experts' view on the role of oestrogens in combined oral contraceptives: emphasis on oestetrol (E4)

M D Creinin  1 , A Cagnacci  2 , R Z Spaczyński  3 , P Stute  4 , N Chabbert-Buffet  5 , T Korver  6 , T Simoncini  7
Affiliations

Experts' view on the role of oestrogens in combined oral contraceptives: emphasis on oestetrol (E4)

M D Creinin et al. Front Glob Womens Health. .

Abstract

Introduction: The evolution of contraception has been crucial for public health and reproductive well-being. Over the past 60 years, combined oral contraceptives (COCs) have remained an important part of the contraceptive landscape worldwide; continued development has worked toward maintaining efficacy and improving safety.

Methods: Seven global experts convened to discuss the clinical relevance of the oestrogen in COCs, focusing on the impact of the new oestrogen, oestetrol (E4). Participants then commented through an online forum on the summary content and other participants' feedback. We prepared this report to describe the experts' views, their follow-up from the open forum and the evidence supporting their views.

Results: Ethinylestradiol (EE) and oestradiol (E2) affect receptors similarly whereas E4 has differential effects, especially in the liver and breast. Adequate oestrogen doses in COCs ensure regular bleeding and user acceptability. EE and E4 have longer half-lives than E2; accordingly, COCs with EE and E4 offer more predictable bleeding than those with E2. Oestrogen type and progestin influence VTE risk; E2 poses a lower risk than EE; although promising, E4/DRSP VTE risk is lacking population-based data. COCs alleviate menstrual symptoms, impact mental health, cognition, libido, skin, and bone health.

Conclusion: Oestrogens play an important role in the contraceptive efficacy, bleeding patterns, and overall tolerability/safety of COCs. Recent studies exploring E4 combined with DRSP show promising results compared to traditional formulations, but more definitive conclusions await further research.

Keywords: E4; combined hormonal contraceptives; effectiveness; non-contraceptive benefits; oestetrol; oestrogens; oral contraception; safety.

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Conflict of interest statement

MC has received speaking honoraria from Gedeon Richter, Mayne and OLIC, served on Advisory Boards for Gedeon Richter and Mayne, has stock options with Femasys, and has consulted for Estetra SRL, and Medicines360. The Department of Obstetrics and Gynecology, University of California, Davis, receives contraceptive research funding for MDC from Chemo Research SL, Evofem, Medicines360, Merck, Sebela, and Sumitomo Pharma. AC has received speaking honoraria and served on Advisory Boards for Gedeon Richter, Bayer, Organon, Exeltis, and Italfarmaco. RS has received speaking honoraria from Gedeon Richter and Novo Nordisk Pharma, has consulted for Theramex Poland and Gedeon Richter, and participates in phase 4 clinical trial nr HUXX-NIS-E4DRSP-1/2020. PS has received speaking honoraria from Gedeon Richter, Max Zeller & Soehne, Jenapharm, Drossapharm, EFFIK, Labatec, Besins Healthcare, Astellas, Theramex, Schaer Pharma, Bayer and Exeltis. PS served on Advisory Boards for Gedeon Richter, Theramex and Astellas. NC-B has served on Advisory Boards for for BESINS, Exeltis, and Gedeon Richter. NC-B participates on clinical trial for Bayer and Organon. TK has received consulting fees from Hervana, TEVA, Osteopharma, Starodub, Eagle Rock, Merck, Luye, QPharma, Disphar, PantaRhei, Gedeon Richter, Mithra, IPM, Myovant and Organon. TS has received consulting fees from Abbott, Astellas, Gedeon Richter, Mitsubishi Tanabe, Sojournix, Estetra, Mithra, Actavis, Medtronic, Shionogi, Applied Medical and speakers’ honoraria from Shionogi, Gedeon Richter, Intuitive Surgical, Applied Medical and Theramex.

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Grants and funding

The authors declare the study received funding from Gedeon Richter Plc., Hungary. The funder had the following involvement in the study: support of forum, research of evidence, and publication.