106 Chapter 5 contraception use on migraine frequency, headache severity and attack duration. Effect of hormonal contraception on migraine was determined in women reporting current or past use of oral contraception. In the questionnaire, no distinction was made between a regimen with hormone-free intervals versus continuous use. Results were stratified by migraine diagnosis. Patients with MA were divided into two subgroups: high frequent MA if they registered ≥1 times visual aura symptoms within a period of at least two months, and otherwise as low frequent MA. Women with MA additionally reported about the influence of contraceptive pill use, pregnancy and menstruation on the frequency of their aura symptoms. Statistical analyses The relation between migraine attacks with and without aura and the menstrual cycle was explored in women diagnosed with MO and MA by plotting the incidence of migraine attacks with and without aura on each day of the menstrual cycle. For creation of these plots menstrual cycles were standardized to 28 days; the perimenstrual days of the menstrual cycle were fixed to 5 days, while the non-perimenstrual days were standardized to 23 (28-5) days by dividing by the remaining of the cycle length and multiplying by 23. Note that consequently, for women with a menstrual cycle length > 28 days, some days of the menstrual cycle contain multiple datapoints per cycle. For all other analyses the menstrual window was treated as a binary variable and standardization was not used. Differences in the effect of the perimenstrual window on migraine attacks in women with MO compared to MA were assessed using a mixed effects logistic regression model, with migraine attack (including migraine headache and aura symptoms) as dependent variable and migraine subtype (MO versus MA), perimenstrual window and an interaction-term (migraine subtype*perimenstrual window) as fixed effects and patient as a random effect. The interaction term indicates whether the perimenstrual window has a different effect on migraine attack occurrence in women with MO versus MA on a multiplicative scale. A similar analysis was performed with migraine attacks without aura as dependent variable. The relation between migraine attacks with aura and the menstrual cycle was assessed by fitting a mixed effects logistic regression model with migraine attack with aura as dependent variable and perimenstrual window as fixed effect and patient as random effect in patients with MA. Finally, the effect of oral contraceptive use, pregnancy and breastfeeding on migraine frequency, headache severity and attack duration in women with MO compared to MA were assessed using chi-square
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