144 Chapter 7 ABSTRACT Background: Previous studies suggest the perimenstrual phase increases migraine risk without aura, while the link to the ovulatory phase remains unclear. Methods: We conducted a longitudinal cohort study among 554 women with migraine and a regular menstrual cycle. Participants completed a validated e-headache diary including also the menstrual cycle. Of these women, 31 (who participated in our Women Hormones Attacks and Treatment (WHAT)-hormone study) performed urine luteinizing hormone (LH) surge tests during two menstrual cycles to validate the estimation of the ovulation. The association between the ovulatory phase and migraine incidence was assessed using a mixed logistic model with patient as random effect, and the ovulatory and menstrual window as fixed effects. Secondary analyses included a case-crossover model and a self-controlled case series (SCCS) model to strengthen data robustness and control for time-invariant confounders. Findings: E-diary data from 2,522 menstrual cycles, including 58 from the WHAT-hormone subgroup, were analyzed. Across all three statistical models, the ovulatory window showed no higher incidence of migraine (with or without aura) compared to all other menstrual cycle days (mixed logistic model: OR 0.95, 95% CI 0.88–1.02; WHAT-hormone subgroup: OR 0.68, 95% CI 0.38–1.16). The perimenstrual window had the highest migraine incidence (SCCS model with luteal phase as reference: OR 2.57, 95% CI 1.51–4.39), followed by the follicular phase (OR 1.69, 95% CI 1.02–2.80). Interpretation: There is no increased incidence of migraine attacks (with or without aura) during the ovulatory window in women, but a higher incidence during the follicular phase compared to the luteal phase was confirmed, potentially linked to lingering effects of perimenstrual estrogen decline. Funding: This study is supported by grants from the Dutch Research Council (849200007) and the Dutch Brain Foundation (HA2017.01.05).
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