{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T18:46:56Z","timestamp":1757616416217,"version":"3.44.0"},"reference-count":29,"publisher":"BMJ","issue":"3","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Fam Plann Reprod Health Care"],"accepted":{"date-parts":[[2013,4,3]]},"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:p>Initial oral contraceptive regimens were characterised by high doses of ethinylestradiol (EE) and a progestogen in a 21-day regimen that either included seven additional hormone-free tablets or simply the 21\u2005days of combination hormonal tablets. These regimens were developed to ensure high contraceptive effectiveness, regular and predictable withdrawal bleeding episodes to mimic a menstrual cycle, and minimal unscheduled vaginal bleeding. However, these regimens were associated with adverse tolerability and safety issues resulting from the dose and characteristics of their hormonal components. Attempts to ameliorate these adverse issues included the development of lower-dose EE regimens, the incorporation of new progestogens, multiphasic regimens, and reduced hormone-free interval regimens. However, the EE component has remained a constant until the recent approval of combination oral contraceptives with an estrogen component other than EE. The development and introduction of an estradiol-based oral contraceptive regimen is presented in this review.<\/jats:p>","DOI":"10.1136\/jfprhc-2013-100605","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T20:56:01Z","timestamp":1369428961000},"page":"211-216","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Changing convention in combination oral contraceptives: estradiol and nomegestrol acetate in a monophasic 24\/4 regimen"],"prefix":"10.1136","volume":"39","author":[{"given":"Lee P","family":"Shulman","sequence":"first","affiliation":[{"name":"Anna Ross Lapham Professor in Obstetrics and Gynecology and Chief, Division of Clinical Genetics, Department of Obstetrics and Gynecology, Feinberg School of Medicine of Northwestern University, Chicago, IL, USA"},{"name":"Adjunct Professor of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2013,5,24]]},"reference":[{"key":"2025090511341442000_39.3.211.1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c927"},{"key":"2025090511341442000_39.3.211.2","doi-asserted-by":"publisher","DOI":"10.1783\/147118910793048665"},{"key":"2025090511341442000_39.3.211.3","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1517\/14656561003724713","article-title":"Evaluation of a new estradiol oral contraceptive: estradiol valerate and dienogest","volume":"11","author":"Jensen","year":"2010","journal-title":"Expert Opin Pharmacother"},{"key":"2025090511341442000_39.3.211.4","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/S0940-2993(98)80034-1","article-title":"Approaches to the replacement of ethinylestradiol by natural 17beta-estradiol in combined oral contraceptives","volume":"50","author":"Hoffmann","year":"1998","journal-title":"Exp Toxicol Pathol"},{"key":"2025090511341442000_39.3.211.5","first-page":"109","article-title":"Oral combined contraception: is there any difference between ethinyl-estradiol and estradiol","volume":"40","author":"Tremollieres","year":"2012","journal-title":"Gynecol Obstet Fertil"},{"key":"2025090511341442000_39.3.211.6","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3109\/09513590.2012.662547","article-title":"An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate\/dienogest","volume":"28","author":"Fruzzetti","year":"2012","journal-title":"Gynecol Endocrinol"},{"key":"2025090511341442000_39.3.211.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2008.05.004"},{"key":"2025090511341442000_39.3.211.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2009.08.010"},{"key":"2025090511341442000_39.3.211.9","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5122(82)90064-0"},{"key":"2025090511341442000_39.3.211.10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2147\/IJWH.S22645","article-title":"Estradiol valerate and dienogest: a new approach to oral contraception","volume":"3","author":"Kiley","year":"2011","journal-title":"Int J Womens Health"},{"key":"2025090511341442000_39.3.211.11","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/0002-9378(82)90218-6","article-title":"Comparison of pharmacodynamic properties of various estrogen formulations","volume":"144","author":"Mashchak","year":"1982","journal-title":"Am J Obstet Gynecol"},{"key":"2025090511341442000_39.3.211.12","doi-asserted-by":"publisher","DOI":"10.3109\/13625187.2011.604450"},{"key":"2025090511341442000_39.3.211.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2004.03.004"},{"key":"2025090511341442000_39.3.211.14","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0039-128X(91)90055-Z","article-title":"Interaction of [3H]nomegestrol acetate with cytosolic progesterone receptors from the rat uterus","volume":"56","author":"Duc","year":"1991","journal-title":"Steroids"},{"key":"2025090511341442000_39.3.211.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2011.02.002"},{"key":"2025090511341442000_39.3.211.16","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S0022-3565(25)23767-3","article-title":"Regulation of rat uterine steroid receptors by nomegestrol acetate, a new 19-nor-progesterone derivative","volume":"248","author":"Botella","year":"1989","journal-title":"J Pharmacol Exp Ther"},{"key":"2025090511341442000_39.3.211.17","doi-asserted-by":"publisher","DOI":"10.2165\/11532130-000000000-00000"},{"key":"2025090511341442000_39.3.211.18","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/S1701-2163(16)34746-6","article-title":"SOGC Clinical Practice Guideline No. 252, December 2010. 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