Britt van der Arend (Leiden/ NL; Rotterdam/ NL), Iris Vehagen (Leiden/ NL; Rotterdam/ NL), Daphne van Casteren (Leiden/ NL), Antoinette Maassen van den Brink (Rotterdam/ NL), Gisela Terwindt (Leiden/ NL)
Abstract text (incl. figure legends and references)
Introduction – Currently, there is no evidence-based hormonal treatment for migraine in women. Several small studies suggested a beneficial effect of hormonal 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 research on this topic. In a small study a beneficial effect of vitamin E with respect to pain severity and functional disability was described, which was suggested to be mediated by a reduction of prostaglandin production in the endometrium.
Objectives – To study the efficacy of continuous daily use of ethinylestradiol/levonorgestrel (30/150 µg/day) compared to vitamin E (400 IU/day) in the treatment of menstrual migraine.
Methods – Women with menstrual migraine (n=180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150µg or vitamin E 400IU. The study is open-label since we consider it practically and ethically not feasible to blind participants. Vitamin E is chosen as an active comparator. Participants start with a baseline period of 4 weeks, which is followed by a 12-week treatment period. During the study period, participants fill out our headache E-Diary, which is time-locked and includes an automated algorithm differentiating headache and migraine days based on ICHD-3 criteria. The Stanford Expectations of Treatment Scale (SETS) will be used to help assess expectancy effects of both interventions.
Results – Primary outcome will be change in monthly migraine days (MMD) from baseline (week -4 to 0) to the last 4 weeks of treatment (weeks 9-12). Secondary outcomes will be change in monthly headache days (MHD), and 50% responder rates of MMD and MHD.
Conclusion – The WHAT!-Trial aims to investigate superiority of continuous oral contraceptive treatment for menstrual migraine. Results may be implemented in clinical practice at short notice.
Trial registration: Clinical trials.gov NCT04007874