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

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 migraine incidence (SCCS model with luteal phase as reference: OR 1.67, 95% CI 1.60–1.75), followed by the follicular phase (OR 1.31, 95% CI 1.26–1.37). Discussion In contrast to what many women with migraine believe, there is no increased incidence of migraine attacks (with or without aura) during the post-ovulatory window, but a higher incidence during the follicular phase compared to the luteal phase was confirmed.