104 Chapter 5 true for attacks with aura. High, stable levels of estradiol, such as during pregnancy, clinically associated with an improvement of MO, have been suggested to increase susceptibility to migraine attacks with aura. MA is also suggested to worsen or develop for the first time during hormonal contraception use.9-12 The evidence is however limited to case series and self-reported questionnaire studies with small to moderate sample sizes. Differences in migraine course during hormonal milestones have not been consistently reported for MO and MA in all studies. Inconsistencies between studies may result from differences in certainty of (self-reported or verified by a headache specialist) diagnoses or because women with MA often additionally experience attacks without aura. It may be necessary to distinguish effects on migraine attacks with and without aura when determining the exact relationship between hormonal milestones and migraine course. The aim of the current study is to determine the relation between menstruation and occurrence of migraine attacks with and without aura. Additionally, differences in migraine course during hormonal milestones are explored between women with MO versus MA. METHODS We conducted a longitudinal electronic diary (E-diary) study including also a one-time questionnaire at baseline.5, 13 Data were collected between October 2018 and July 2022. The study was approved by the medical ethics committee of the Leiden University Medical Center (P18.181). All participants provided written informed consent. Premenopausal women diagnosed with migraine were considered eligible. Patients with coexisting primary or secondary headache disorders other than episodic tension-type headache were excluded. Women who were postmenopausal, pregnant or breastfeeding were excluded. Women who were using combined oral hormonal contraception were eligible provided that they included hormone-free intervals each month with a maximum duration of 7 days. No minimum length was specified. Women using intrauterine devices (IUD) and progestogen only pills were excluded by definition, as they do not insert hormone-free intervals. Final diagnoses were based on the ICHD-3 criteria for MO or MA and were established during a clinical interview with a researcher with headache expertise (IV, BvdA, DvC) and in case of uncertainty in consultation with a neurologist with headache expertise (GMT).4 Patients with coexisting cluster headache were excluded.
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