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Migraine attack incidence in relation to the post-ovulatory estrogen decline: A prospective cohort study

van der Arend BWH, Bakker S, van Casteren DS, Verhagen IE, Pelzer N, de Boer I, Cannegieter SC, MaassenVanDenBrink A et al.

Cephalalgia : an international journal of headache, 2026

563 participants

Abstract

Background Previous studies suggest the perimenstrual phase increases migraine without aura risk, attributed to the decline of estrogen in this phase. However, the link to the decline of estrogen in the post-ovulatory phase remains unclear. Methods We conducted a longitudinal cohort study among 563 women with migraine and a regular natural menstrual cycle. Participants completed a validated e-headache diary also including menstrual cycle tracking. 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 post-ovulatory estrogen decline. The association between the post-ovulatory estrogen decline and migraine incidence was assessed using a mixed logistic model with patient as random effect, and the post-ovulatory and menstrual window as fixed effects. Secondary analyses included a case-crossover model and a self-controlled case series (SCCS) model to strengthen robustness and control for time-invariant confounders. Results E-diary data from 2627 menstrual cycles, including 58 from the WHAT-hormone subgroup, were analyzed. Across all three statistical models, the post-ovulatory window showed no higher incidence of migraine (with or without aura) than other menstrual cycle days (mixed logistic model: OR 0.95, 95% CI 0.89–1.02; WHAT-hormone subgroup: OR 0.68, 95% CI 0.38–1.16). The perimenstrual window had the highest…

How strong is the evidence?

Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 563 participants or records.

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