{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:35:56Z","timestamp":1788510956296,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15\u2009mg and drospirenone (DRSP) 3\u2009mg.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Multicenter, open\u2010label, phase 3 trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Sixty\u2010nine sites in Europe and Russia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Population<\/jats:title>\n                    <jats:p>\n                      Sexually active women aged 18\u201350\u2009years with regular menstrual cycles and body mass index \u226435\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>E4\/DRSP was administered in a 24 active\/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding\/spotting, use of other contraceptive methods and sexual intercourse on a daily diary.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>Pearl Index (PI) for women 18\u201335\u2009years (overall and method\u2010failure), bleeding pattern and AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 1553 women aged 18\u201350\u2009years, including 1353 from 18 to 35\u2009years old, received the study medication. PI was 0.47 pregnancies\/100 woman\u2010years (95% CI 0.15\u20131.11); method failure PI was 0.29 pregnancies\/100 woman\u2010years (95% CI 0.06\u20130.83). Scheduled bleeding\/spotting occurred in 91.9\u201394.4% of women over Cycles 1 to 12 and lasted a median of 4\u20135\u2009days per cycle. The percentage of women with unscheduled bleeding\/spotting episodes decreased from 23.5% in Cycle 1 to &lt;16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment\u2010related serious AE was reported, a lower extremity venous thromboembolism. One\u2010hundred and forty\u2010one (9.1%) women discontinued study participation because of treatment\u2010related adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>E4\/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Tweetable abstract<\/jats:title>\n                    <jats:p>A phase 3 trial with E4\/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1471-0528.16840","type":"journal-article","created":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T13:55:43Z","timestamp":1625925343000},"page":"63-71","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Estetrol\u2010Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia"],"prefix":"10.1111","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-1444","authenticated-orcid":false,"given":"K","family":"Gemzell\u2010Danielsson","sequence":"first","affiliation":[{"name":"Department of Women's and Children's Health Karolinska Institutet Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Apter","sequence":"additional","affiliation":[{"name":"VL\u2010Medi Clinical Research Centre Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Zatik","sequence":"additional","affiliation":[{"name":"Gynaecological Praxis St Anna Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Weyers","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University Hospital Gent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Piltonen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology PEDEGO Research Unit Medical Research Center Oulu University Hospital University of Oulu Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Suturina","sequence":"additional","affiliation":[{"name":"Scientific Centre for Family Health and Human Reproduction Problems Irkutsk Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Apolikhina","sequence":"additional","affiliation":[{"name":"Kulakov National Medical Research Centre for Obstetrics, Gynaecology, and Perinatology Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Jost","sequence":"additional","affiliation":[{"name":"Estetra SRL, an affiliate Company of Mithra Pharmaceuticals Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MD","family":"Creinin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of California Davis, Sacramento CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u2010M","family":"Foidart","sequence":"additional","affiliation":[{"name":"Estetra SRL, an affiliate Company of Mithra Pharmaceuticals Li\u00e8ge Belgium"},{"name":"Department of Obstetrics and Gynaecology University of Li\u00e8ge Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"299","article-title":"Pharmacological profile of estrogens in oral contraception","volume":"63","author":"Bitzer J","year":"2011","journal-title":"Minerva Ginecol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-14-0527"},{"key":"e_1_2_7_4_1","first-page":"CD010813","article-title":"Combined oral contraceptives: venous thrombosis","volume":"3","author":"Bastos M","year":"2014","journal-title":"Cochrane Database Syst Rev."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f5298"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2012.662547"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jfprhc-2013-100605"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/acta.0.0490207"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404112"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2016"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.008950"},{"issue":"1","key":"e_1_2_7_12_1","article-title":"Estetrol (E4) is a unique estrogen with selective actions in tissues which are distinctly different from the actions of SERMs","volume":"3","author":"Foidart JM","year":"2019","journal-title":"J Endocrine Soc"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-14-0549"},{"key":"e_1_2_7_14_1","first-page":"463","article-title":"Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives","volume":"20","author":"Mawet M","year":"2015","journal-title":"Eur J Contracept Reprod Health Care"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2016.08.018"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/13625187.2015.1044082"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2016.04.015"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/13625187.2017.1336532"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2021.05.002"},{"key":"e_1_2_7_20_1","volume-title":"Establishing Effectiveness and Safety for Hormonal Drug Products Intended to Prevent Pregnancy","author":"FDA draft Guidance for Industry","year":"2019"},{"key":"e_1_2_7_21_1","unstructured":"The EMEA CHMP guideline on clinical investigation of steroid contraceptives in women. [https:\/\/www.ema.europa.eu\/en\/clinical\u2010investigation\u2010steroid\u2010contraceptives\u2010women]. Accessed 22 December 2020."},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0b013e318159bf8a"},{"key":"e_1_2_7_23_1","first-page":"15","volume-title":"Medical eligibility criteria for contraceptive use","author":"World Health Organization","year":"2009"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/ejc.8.2.87.92"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2006.08.012"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genhosppsych.2004.06.003"},{"key":"e_1_2_7_27_1","first-page":"52","article-title":"A case of pulmonary embolism associated with escitalopram","volume":"4","author":"Yong WK","year":"2007","journal-title":"Psychiatr Invest"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/13625187.2020.1743828"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmw016"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2009.03.018"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2009.11.001"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d6423"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2006.12.018"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e4944"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2016.1161743"}],"container-title":["BJOG: An International Journal of Obstetrics &amp; Gynaecology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1471-0528.16840","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1471-0528.16840","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1471-0528.16840","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T15:49:40Z","timestamp":1692978580000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/1471-0528.16840"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,9]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1111\/1471-0528.16840"],"URL":"https:\/\/doi.org\/10.1111\/1471-0528.16840","archive":["Portico"],"relation":{},"ISSN":["1470-0328","1471-0528"],"issn-type":[{"value":"1470-0328","type":"print"},{"value":"1471-0528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,9]]},"assertion":[{"value":"2021-01-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}