Continuous combined oral contraceptive use versus vitamin E in the treatment of menstrual migraine: rationale and protocol of a randomized controlled trial (WHAT!).

Publisher: BioMed Central Country of Publication: England NLM ID: 101263253 Publication Model: Electronic Cited Medium: Internet ISSN: 1745-6215 (Electronic) Linking ISSN: 17456215 NLM ISO Abbreviation: Trials Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2006-

Contraceptives, Oral, Combined*/adverse effects ; Migraine Disorders*/diagnosis ; Migraine Disorders*/drug therapy; Humans ; Female ; Headache ; Randomized Controlled Trials as Topic

Background: Currently, there is no evidence-based hormonal treatment for migraine in women. 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.
Methods: Women with menstrual migraine (n = 180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150 μg or vitamin E 400 IU. Participants start with a baseline period of 4 weeks, 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.
Results: The primary outcome will be change in monthly migraine days (MMD) from baseline (weeks - 4 to 0) to the last 4 weeks of treatment (weeks 9 to 12). Secondary outcomes will be change in monthly headache days (MHD) and 50% responder rates of MMD and MHD.
Conclusions: 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.
Trial Registration: Clinical trials.gov NCT04007874 . Registered 28 June 2019.
(© 2024. The Author(s).)

Curr Pain Headache Rep. 2011 Aug;15(4):289-94. (PMID: 21465113)
Intern Med. 2012;51(22):3119-23. (PMID: 23154716)
Lancet Neurol. 2005 Sep;4(9):533-42. (PMID: 16109360)
Neurology. 2005 Mar 22;64(6):1020-6. (PMID: 15781820)
Neurology. 2006 Dec 26;67(12):2159-63. (PMID: 17190936)
Contraception. 2013 Sep;88(3):369-75. (PMID: 23453784)
Cells. 2022 Apr 15;11(8):. (PMID: 35456034)
Med Sci Monit. 2009 Jan;15(1):CR16-9. (PMID: 19114966)
Neurology. 2006 Dec 26;67(12):2154-8. (PMID: 16971700)
Cephalalgia. 2021 May;41(6):643-648. (PMID: 33203218)
Eur J Obstet Gynecol Reprod Biol. 2014 Dec;183:178-82. (PMID: 25461375)
Int J Womens Health. 2015 Aug 20;7:773-82. (PMID: 26316824)
Cephalalgia. 2022 Oct;42(11-12):1184-1193. (PMID: 35514214)
Cephalalgia. 2003 Apr;23(3):197-205. (PMID: 12662187)
Neurology. 2021 Oct 26;97(17):e1661-e1671. (PMID: 34493613)
Cephalalgia. 2020 Oct;40(12):1355-1362. (PMID: 32588652)
Headache. 2007 Jan;47(1):27-37. (PMID: 17355491)
Neurology. 1972 Apr;22(4):355-65. (PMID: 5062827)
South Med J. 2004 Sep;97(9):819-22. (PMID: 15455962)
Fertil Steril. 2011 Oct;96(4):917-20. (PMID: 21843889)
J Headache Pain. 2018 Aug 31;19(1):76. (PMID: 30171365)
Neurology. 1999 Aug 11;53(3):537-42. (PMID: 10449117)
Headache. 1972 Oct;12(3):93-102. (PMID: 5075463)
J Womens Health (Larchmt). 2014 Apr;23(4):310-7. (PMID: 24450487)
Neurology. 2004 Jul 27;63(2):351-3. (PMID: 15277635)
Clin Trials. 2012 Dec;9(6):767-76. (PMID: 23169874)
Neurologist. 2008 Mar;14(2):108-19. (PMID: 18332840)
Cephalalgia. 2023 May;43(5):3331024231166625. (PMID: 37021643)
Cephalalgia. 2021 Oct;41(11-12):1161-1171. (PMID: 33938248)

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Keywords: Combined oral contraceptive pill; Headache; Hormones; Migraine; Treatment

ClinicalTrials.gov NCT04007874

0 (Contraceptives, Oral, Combined)

Date Created: 20240215 Date Completed: 20240219 Latest Revision: 20240219

20240219

PMC10870678

10.1186/s13063-024-07955-8

38360739