{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:41:29Z","timestamp":1792611689292,"version":"4.5.0"},"reference-count":250,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Many different progestogens are used by millions of women worldwide for oral contraception, either alone (Progestogen-only Pills [POPs]) or as combined oral contraceptives (COCs) comprising a synthetic estrogen (ethinyl estradiol [EE]), or a natural estrogen (estradiol and its valerate [E2; E2V] or estetrol [E4]), associated with a progestogen. This review describes first the three families of progestogens derived either from testosterone, 17 alpha-hydroxyprogesterone or spironolactone. Their pharmacokinetic parameters are largely differing, but also their metabolism, potency and efficacy via many steroid receptors, thereby confirming the absence of a class effect of these progestogens. In the pharmacodynamic section, POPs will be described in detail, showing high efficacy and safety, though low cyclic tolerance. When different progestogens are combined with EE in COCs, and despite high efficacy, tolerability and improved cyclic tolerance compared with POPs, safety is hampered, among other by vascular thromboembolism risks (venous [VTE] as well as arterial [ATE]). These will be analyzed with the help of most recent results establishing that EE\/levonorgestrel (LNG) entails less adverse vascular events than other EE-containing COCs. Also, in the last 15 years, COCs containing natural estrogens (E2V\/dienogest (DNG) and E2\/nomegestrol acetate (NOMAC)) have shown through meta-analyses of clinical thrombotic events and adequate hemostatic studies, a lower VTE risk than with use of EE\/LNG. Moreover, another natural estrogen-containing COC, E4\/drospirenone (DRSP), predicts also a low level of risk through global hemostasis assessments, disproportionality analyses and other studies. So, a new possibility arises that the safest COCs in terms of thrombotic risk might be the natural estrogen-containing COCs, where the estrogen is combined to one of three different non-androgenic progestogens.<\/jats:p>","DOI":"10.3389\/fendo.2026.1730768","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:23:26Z","timestamp":1774502606000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A detailed review of pharmacokinetics\/pharmacodynamics of progestogens in oral contraception"],"prefix":"10.3389","volume":"17","author":[{"given":"Ulysse","family":"Gaspard","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Liege","place":["Liege, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Chatel","sequence":"additional","affiliation":[{"name":"Estetra SRL, a member of Gedeon Richter PLC","place":["Liege, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Douxfils","sequence":"additional","affiliation":[{"name":"Research Unit in Clinical Pharmacology and Toxicology (URPC), NAmur Research Institute for LIfe Sciences (NARILIS), Faculty of Medicine, University of Namur","place":["Namur, Belgium"]},{"name":"QUALIresearch, Qualiblood s.a","place":["Li\u00e8ge, Belgium"]},{"name":"Department of Biological Hematology, Centre Hospitalier Universitaire Clermont-Ferrand, H\u00f4pital Estaing","place":["Clermont-Ferrand, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Z.","family":"Stanczyk","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Southern California","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1210\/er.2012-1008","article-title":"Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects","volume":"34","author":"Stanczyk","year":"2013","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.23736\/S2724-606X.21.04881-8","article-title":"Clinical pharmacology of progestins","volume":"74","author":"Capozzi","year":"2022","journal-title":"Minerva Obstet Gynecol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2003.08.003","article-title":"All progestins are not created equal","volume":"68","author":"Stanczyk","year":"2003","journal-title":"Steroids"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.21392","article-title":"Contraception selection, effectiveness, and adverse effects: A review","volume":"326","author":"Teal","year":"2021","journal-title":"JAMA"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/13625187.2020.1736546","article-title":"Evaluation of different antiandrogenic progestins on clinical and biochemical variables in polycystic ovary syndrome","volume":"25","author":"Morgante","year":"2020","journal-title":"Eur J Contracept Reprod Health Care"},{"key":"B6","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1097\/01.AOG.0000175834.77215.2e","article-title":"Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder","volume":"106","author":"Yonkers","year":"2005","journal-title":"Obstet Gynecol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1080\/13625187.2024.2317295","article-title":"Health benefits of combined oral contraceptives - 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