Progestogens as a component of menopausal hormone therapy: the right molecule makes the difference

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John C Stevenson MB BS, FRCP, FESC, MFSEM, Serge Rozenberg MD, PhD, Silvia Maffei MD, Christian Egarter Prof Dr Med, Petra Stute Prof Dr Med, Thomas Römer Prof Dr Med

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Optimizing menopausal hormone therapy (MHT) requires an awareness of the benefits and risks associated with the available treatments. This narrative review, which is based on the proceedings of an Advisory Board meeting and supplemented by relevant articles identified in literature searches, examines the role of progestogens in MHT, with the aim of providing practical recommendations for prescribing physicians. Progestogens are an essential component of MHT in menopausal women with a uterus to prevent endometrial hyperplasia and reduce the risk of cancer associated with using unopposed estrogen. Progestogens include natural progesterone, dydrogesterone (a stereoisomer of progesterone), and a range of synthetic compounds. Structural differences and varying affinities for other steroid receptors (androgen, glucocorticoid, and mineralocorticoid) confer a unique biological and clinical profile to each progestogen that must be considered during treatment selection. MHT, including the progestogen component, should be tailored to each woman, starting with an estrogen and a progestogen that has the safest profile with respect to breast cancer and cardiovascular effects, while addressing patient-specific needs, risk factors, and treatment goals. Micronized progesterone and dydrogesterone appear to be the safest options, with lower associated cardiovascular, thromboembolic, and breast cancer risks compared with other progestogens, and are the first-choice options for use in ‘special situations,’ such as in women with high-density breast tissue, diabetes, obesity, smoking, and risk factors for venous thromboembolism, among others.

Keywords: menopausal hormone therapy, progesterone, progestogen

Citation: Stevenson JC, Rozenberg S, Maffei S, Egarter C, Stute P, Römer T. Progestogens as a component of menopausal hormone therapy: the right molecule makes the difference. Drugs in Context 2020; 9: 2020-10-1. DOI: 10.7573/dic.2020-10-1

Contributions: The authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article. The authors contributed to developing the concept of the review and critically reviewed and revised the manuscript at draft stages for intellectual content. The authors take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: John C Stevenson has received grants and research support from Abbott, Mylan, and Pfizer, speakers’ honoraria from Abbott, Bayer, Gedeon Richter, Menarini, Mylan, and Pfizer, and consulting fees from Abbott, Mylan, and Pfizer. Serge Rozenberg has received fees for advisory boards and lectures from Abbott, Gedeon Richter, Mylan, and UCB and research grants from Amgen, Gedeon Richter, Mylan, and UCB. Silvia Maffei received fees for lectures and advisory boards from Abiogen, Mylan, Theramex, Shionogi and MSD. Christian Egarter has received honoraria and reimbursement of expenses for attendance at advisory boards, lectures, and sponsored symposia from Bayer, Exeltis, and Mylan. Petra Stute declares having been invited as a speaker on the topic of menopausal hormone therapy by Gedeon Richter, Hexal, Jenapharm, Kade Besins, Labatec, and Mylan. Thomas Römer has received honoraria for lectures and advisory boards from Bayer, Exceltis, Gedeon Richter, Mylan, and Theramex. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at:

Acknowledgements: Editorial assistance was provided by Kerry Dechant on behalf of Content Ed Net (Madrid, Spain).

Funding declaration: Medical writing assistance was funded by Mylan Pharmaceuticals S.L., Barcelona, Spain.

Copyright: Copyright © 2020 Stevenson JC, Rozenberg S, Maffei S, Egarter C, Stute P, Römer T. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2020 Stevenson JC, Rozenberg S, Maffei S, Egarter C, Stute P, Römer T. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

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Correspondence: John C Stevenson, National Heart & Lung Institute, Imperial College London, Royal Brompton & Harefield NHS Foundation Trust, London SW3 6NP, UK.

Provenance: Submitted; externally peer reviewed.

Submitted: 1 October 2020; Peer review comments to author: 23 October 2020; Revised manuscript received: 13 November 2020; Accepted: 14 November 2020; Publication date: 2 December 2020.

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