115 Migraine with and without aura in relation to the menstrual cycle 5 linked to increased incidence of migraine attacks (with aura), also not in this present study. However, determining the exact timing of ovulation without measuring the preceding luteinizing hormone (LH) surge is difficult, so conclusive evidence is scarce. Moreover, there may be a critical concentration of estradiol above which aura may be triggered in women, but there are large interindividual and interindividual variations.30 We found that women with MA more often reported increased migraine frequency during pregnancy and breastfeeding compared to women with MO, although differences were small. No differences were found during the use of hormonal contraception, but in the questionnaire no distinction was made between different types of contraceptive pills, or between continuous use and a regime with hormone-free intervals, which may have obscured the effect, since differences in formulations and dosages lead to different estradiol plasma levels.31 Furthermore, differences in effect of hormonal milestones may mainly lie in the frequency of migraine attacks with aura and without aura and not so much in differences on a patient level (MO versus MA), as was also the case in the present study for the relation with menstruation. Future studies should therefore attempt to differentiate at migraine attack level and not solely at a patient diagnosis level. For this study, we used detailed diary data, which poses a number of challenges, such as how to define a migraine day and how to distinguish individual attacks. With the increasing number of diary studies, there is a need for consensus on these issues. For the current study, we have largely based our definitions on the ICHD-3 criteria, although they were not developed for discriminating days with or without migraine, but for the classification of patients.4 We considered consecutive migraine days with a maximum migraine free period of 24 hours as one attack, while the current guidelines on preventive treatments recommend to include migraine free periods of up to 48 hours.32 In a separate validation study we have assessed several migraine day definitions and further address these issues.33 Our study provides interpretable and conclusive results on the relation between menstruation and migraine attacks with and without aura. However, influence of pregnancy, breastfeeding and hormonal contraception was inferred from crosssectional data and our results therefore provide less certainty about the influence of hormonal milestones on MO and MA. Differences in outcomes could also be interpreted as a more frequent improvement of migraine frequency in women with MO, due to more stable hormone levels, rather than more frequent deterioration in women with MA. Ideally, final conclusions should be reached based on a prospective
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