147 Migraine attack incidence in relation to ovulation 7 Data collection Participants were monitored using validated headache e-diaries imbedded in the Patient Journey App for at least two menstrual cycles. 16, 17 Each morning at 8 a.m. participants received a notification to complete the questionnaire referring to the previous 24 hours (midnight to midnight). The questionnaire included 6-31 questions, depending on the responses, covering the presence of headache and/or visual aura symptoms and their characteristics, use of acute medication, changes in prophylactic medication or use of hormones, and menstruation. If the e-diary was not completed by afternoon, a reminder was sent at 6 p.m. Once submitted, entries could not be edited, and questionnaires were time-locked after two days.16, 17 An automated algorithm calculated for each day if it was classified as a migraine day according to the ICHD-3 criteria.18, 19 In the WHAT-hormone subgroup, participants conducted daily ovulation tests (Clearblue Digital Ovulation Test, SPD Development Company, Bedford, UK) each morning at home, beginning on the 5th day after the onset of menstruation and continuing until a positive result was obtained. These WHAT-hormone subgroup participants sent their ovulation dates to the researchers via WhatsApp, and this information was registered for each participant. DATA ANALYSES AND STATISTICS The primary outcome was migraine attack incidence, which is defined as the numer of new migraine attacks occuring per cycle phase, measured per participant. Since on migraine attack can consist of multiple consecutive migraine days, only the first day of each attack was counted to determine migraine attack incidence. The incidence of migraine attacks iwthin the ovulatory window was then compared to the incidence outside the ovulatory window. The ovulation day for each individual cycle was calculated as 14 days before the onset of the following menstruation. For the WHAT-hormone subgroup the precise measured day of ovulation was used. The ovulatory window was then defined as the day of ovulation until the 5th day post-ovulation. This window was carefully selected with the estrogen-withdrawal theory in mind, as the decline in estrogen starts on the day of ovulation, unlike the perimenstrual window, where the decline starts two days before menstruation.15, 20, 21 The period duration of five days was aligned with the perimenstrual window, which has consistently been defined as five days in prior studies.3, 5, 11, 13
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