{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:10:24Z","timestamp":1793067024303,"version":"4.5.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T00:00:00Z","timestamp":1601596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T00:00:00Z","timestamp":1601596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Women's Health"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4\u2009mg in a regimen 24\/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three European and American multicenter clinical trials have been conducted in more than 2500 patients and more than 25,000\u2009cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9%) had a risk factor for VTE, while in the European studies, 261 patients (16.6%) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and\/or 85 to 90\u2009mm HG and no influence on ECG parameters were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The introduction of a new estrogen-free contraceptive with 4\u2009mg of non-micronized drospirenone in a 24\/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      EudraCT registration numbers:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/search?query=eudract_number:2010-021787-15\">2010\u2013021787-15<\/jats:ext-link>\n                      &amp;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/search?query=eudract_number:2011-002396-42\">2011\u2013002396-42<\/jats:ext-link>\n                      . Clincaltrials.gov:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02269241\">NCT02269241<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12905-020-01080-9","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T06:02:58Z","timestamp":1601618578000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4\u2009mg drospirenone alone in a 24\/4 regime"],"prefix":"10.1186","volume":"20","author":[{"given":"Santiago","family":"Palacios","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Colli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9551-2847","authenticated-orcid":false,"given":"Pedro-Antonio","family":"Regidor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,2]]},"reference":[{"key":"1080_CR1","unstructured":"WHO Medical eligibility criteria for contraceptive use. 5th edition 2015."},{"key":"1080_CR2","unstructured":"PRAC referral assessment report. Procedure under Article 31 of Directive 2001\/83\/EC resulting from pharmacovigilance data. Combined hormonal contraceptives containing medicinal products INN: chlormadinone, desogestrel, dienogest, drospirenone, etonogestrel, gestodene, nomegestrol, norelgestromin or norgestimate. Procedure number: EMEA\/H\/A-31\/1356. October 15 2013."},{"key":"1080_CR3","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.maturitas.2008.11.013","volume":"61","author":"AE Schindler","year":"2008","unstructured":"Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH. Classification and pharmacology of progestins. Maturitas. 2008;61:171\u201380.","journal-title":"Maturitas."},{"key":"1080_CR4","first-page":"41","volume":"11","author":"AE Schindler","year":"2013","unstructured":"Schindler AE. Non-contraceptive benefits of Oral hormonal contraceptives. Int J Endocrinol Metab. 2013;11:41\u20137.","journal-title":"Int J Endocrinol Metab"},{"issue":"47","key":"1080_CR5","doi-asserted-by":"publisher","first-page":"83334","DOI":"10.18632\/oncotarget19833","volume":"8","author":"PA Regidor","year":"2017","unstructured":"Regidor PA, Schindler AE. Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestins: dienogest and drospirenone. Oncotarget. 2017;8(47):83334\u201342. https:\/\/doi.org\/10.18632\/oncotarget19833 eCollection 2017 Oct 10. Review.","journal-title":"Oncotarget"},{"issue":"5","key":"1080_CR6","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.contraception.2015.07.014","volume":"92","author":"DF Archer","year":"2015","unstructured":"Archer DF, Ahrendt HJ, Drouin D. Drospirenone-only oral contraceptive: results from a multicenter noncomparative trial of efficacy, safety and tolerability. Contraception. 2015;92(5):439\u201344. https:\/\/doi.org\/10.1016\/j.contraception.2015.07.014 Epub 2015 July 29.","journal-title":"Contraception."},{"key":"1080_CR7","doi-asserted-by":"publisher","unstructured":"Palacios S, Colli E, Regidor PA. Multicenter, phase III trials on the contraceptive efficacy, tolerability and safety of a new drospirenone only pill. Acta Obstet Gynecol Scand. 20198. doi: https:\/\/doi.org\/10.1111\/aogs.13688.","DOI":"10.1111\/aogs.13688"},{"key":"1080_CR8","doi-asserted-by":"publisher","unstructured":"Kimble T, Burke AE, Barnhart KT, Archer DF, Colli E, Westhoff CL. A 1-year prospective, open-label, single-arm, multicenter, phase 3 trial of the contraceptive efficacy and safety of the oral progestin-only pill drospirenone 4 mg using a 24\/4-day regimen. Contracept X. 2020;2:100020. https:\/\/doi.org\/10.1016\/j.conx.2020.100020.","DOI":"10.1016\/j.conx.2020.100020"},{"issue":"6","key":"1080_CR9","doi-asserted-by":"publisher","first-page":"e0231856","DOI":"10.1371\/journal.pone.0231856","volume":"15","author":"S Palacios","year":"2020","unstructured":"Palacios S, Colli E, Regidor PA. Bleeding profile of women using a drospirenone only pill 4 mg over nine cycles in comparison with desogestrel 0.075 mg. PLoS ONE. 2020;15(6):e0231856. https:\/\/doi.org\/10.1371\/journal.pone.0231856.","journal-title":"PLoS ONE"},{"issue":"9","key":"1080_CR10","doi-asserted-by":"publisher","first-page":"749","DOI":"10.3109\/09513590.2016.1161743","volume":"32","author":"PA Regidor","year":"2016","unstructured":"Regidor PA, Colli E, Schindler AE. Drospirenone as estrogen-free pill and hemostasis: coagulatory study results comparing a novel 4\u2009mg formulation in a 24\u2009+\u20094 cycle with desogestrel 75\u2009\u03bcg per day. Gynecol Endocrinol. 2016;32(9):749\u201351 Epub 2016 March 30.","journal-title":"Gynecol Endocrinol"},{"issue":"6","key":"1080_CR11","first-page":"1816","volume":"80","author":"W Oelkers","year":"1995","unstructured":"Oelkers W, Foidart JM, Dombrovicz N, Welter A, Heithecker R. Effects of a new oral contraceptive containing an antimineralocorticoid progestin, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism. J Clin Endocrinol Metab. 1995;80(6):1816\u201321.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1080_CR12","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/S0010-7824(02)00537-1","volume":"67","author":"U Gaspard","year":"2003","unstructured":"Gaspard U, Scheen A, Endrikat J, Buicu C, Lefebvre P, Gerlinger C, Heithecker R. A randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism. Contraception. 2003;67(6):423\u20139.","journal-title":"Contraception."},{"key":"1080_CR13","unstructured":"ICH Topic E 14 the clinical evaluation of QT\/QTc interval prolongation and Proarrhythmic potential for non-antiarrhythmic drugs. European Medicines Agency. 2005. CHMP\/ICH\/2\/04."},{"key":"1080_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0378-5122(96)00994-2","volume":"24","author":"H Kuhl","year":"1996","unstructured":"Kuhl H. Effects of progestogens on haemostasis. Maturitas. 1996;24:1\u201319.","journal-title":"Maturitas"},{"key":"1080_CR15","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/0378-5122(96)01027-4","volume":"24","author":"UH Winkler","year":"1996","unstructured":"Winkler UH. Hormone replacement therapy and haemostasis: principles of a complex interaction. Maturitas. 1996;24:131\u201345.","journal-title":"Maturitas"},{"key":"1080_CR16","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.maturitas.2003.09.016","volume":"46","author":"AE Schindler","year":"2003","unstructured":"Schindler AE. Differential effects on progestins on haemostasis. Maturitas. 2003;46:31\u2013373.","journal-title":"Maturitas"},{"key":"1080_CR17","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.contraception.2019.10.005","volume":"101","author":"WH Richter","year":"2020","unstructured":"Richter WH, Koytchev R, Kirkov V, Merki G, Colli E, Regidor P-A. Comparative pharmacokinetic estimates of Drospirenone alone and in combination with Ethinyl estradiol after single and repeated Oral Administration in Healthy Females. 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Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766\u201381. https:\/\/doi.org\/10.1016\/S0140-6736(14)60460-8 Epub 2014 May 29.","journal-title":"Lancet"}],"container-title":["BMC Women's Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-020-01080-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12905-020-01080-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-020-01080-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T20:00:34Z","timestamp":1633118434000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcwomenshealth.biomedcentral.com\/articles\/10.1186\/s12905-020-01080-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,2]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1080"],"URL":"https:\/\/doi.org\/10.1186\/s12905-020-01080-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-28911\/v3","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-28911\/v4","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-28911\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-28911\/v2","asserted-by":"object"}]},"ISSN":["1472-6874"],"issn-type":[{"value":"1472-6874","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,2]]},"assertion":[{"value":"12 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The overall approval for the trial 1 with the leading ethical committee was given the 01.07.2011 by the Ethikkommission des Landes Sachsen-Anhalt, Gesch\u00e4ftsstelle, number 10\/0607 EK. The overall approval for the trial 2 with the leading ethical committee was given the 13.07.2012 by the Landesamt f\u00fcr Gesundheit und Soziales Berlin, Gesch\u00e4ftstelle der Ethik Kommission des Landes Berlin, number 11\/0606 EK.The dates on which the records were first entered in the EudraCT database were between 2010 and 11-05 and 2011-04-14. The EudraCT is since the 2011-03-22 open and public available. As documented in the submitted protocol of study 1, the date the first subject entered was 2011-07-11. EudraCT registration numbers: 2010\u2013021787-15 & 2011\u2013002396-42. Registration was at Clincaltrials.gov: NCT02269241 for the USA trial.All participants consented written to participate in the clinical trials.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent for publication of identifying images or other personal or clinical details of participants that compromises anonymity:Not Applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Santiago Palacios is a consultant to Pfizer, Amgen, MSD, Gynea, Procare Health, Bayer, S\u00e9r\u00e9lys Shinogi, Exeltis, Abbott, and Gedeon Richter. Enrico Colli and Pedro Antonio Regidor are employees of Exeltis. Santiago Palacios is an editorial member of BMC Women\u2019s Health.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"218"}}