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Several small studies suggest a beneficial effect of combined oral contraceptives, but no large randomized controlled trial has been performed. As proof of efficacy is lacking and usage may be accompanied by potentially severe side effects, there is a great need for clarity on this topic.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Women with menstrual migraine (<jats:italic>n<\/jats:italic>\u2009=\u2009180) are randomly assigned (1:1) to ethinylestradiol\/levonorgestrel 30\/150\u00a0\u03bcg or vitamin E 400\u00a0IU. Participants start with a baseline period of 4\u00a0weeks, which is followed by a 12-week treatment period. During the study period, a E-headache diary will be used, which is time-locked and includes an automated algorithm differentiating headache and migraine days.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The primary outcome will be change in monthly migraine days (MMD) from baseline (weeks\u2009\u2212\u20094 to 0) to the last 4\u00a0weeks of treatment (weeks 9 to 12). Secondary outcomes will be change in monthly headache days (MHD) and 50% responder rates of MMD and MHD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The WHAT! trial aims to investigate effectivity and safety of continuous combined oral contraceptive treatment for menstrual migraine. Immediate implementation of results in clinical practice is possible.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>Clinical trials.gov <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/study\/NCT04007874\">NCT04007874<\/jats:ext-link>. Registered 28 June 2019.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-024-07955-8","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T15:03:09Z","timestamp":1708009389000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Continuous combined oral contraceptive use versus vitamin E in the treatment of menstrual migraine: rationale and protocol of a randomized controlled trial (WHAT!)"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8999-0087","authenticated-orcid":false,"given":"Britt W. 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Verhagen, A. MaassenVanDenBrink and G.M. Terwindt report independent support from the Netherlands Organization for Health Research (849200007) and the Dutch Brain Foundation (HA2017.01.05). A. MaassenVanDenBrink reports consultancy or industry support from Novartis, Lillyand Teva, and Allergan\/Abbvie and independent support from the Dutch Research Council (Vici grant) and the Dutch Heart Foundation. G.M. Terwindt reports consultancy or industry support from Novartis, Lilly and Teva, Allergan\/Abbvie, and Lundbeck and independent support from the European Community, Dutch Heart Foundation, IRRF and Dioraphte.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"123"}}