166 Chapter 8 ABSTRACT Background: Menstrual migraine (MM) is linked to hormonal fluctuations, but the precise role of sex hormones remains unclear. This study hypothesizes that women with MM experience a steeper decline in estradiol before menstruation. Methods: In this prospective cohort study, 28 women with MM and 18 healthy controls were followed over two menstrual cycles. Blood samples were collected on standardized cycle days based on the LH surge (day 0), specifically on days 1, 2, 3, 8, 10, 12, and 14 post-surge, covering mid- and late-luteal phases. The primary outcome was the peak estradiol level during the mid-luteal phase (day 8) and its subsequent decline from day 8 to day 14. Secondary outcomes included levels of other sex hormones such as steroids (progesterone, testosterone), gonadotropins, and androgens, as well as hormone pair ratios. Results: Women with MM had a 49% higher peak estradiol level during the luteal phase (2Estimate = 1·49, 95% CI: 1·03–1·87, p=0·04) and a 90% greater decline from mid- to late-luteal phase compared to controls (2Estimate = 1·90, 95% CI: 1·16–3·12, p=0·03). Pathway analysis confirmed these differences in peak estradiol (p = 0·04) and its decline (p = 0·02) between groups, with no differences observed in other sex hormones. Discussion: Women with MM have a higher peak estradiol and a more pronounced estradiol decline during the luteal phase compared to controls, indicating that interventions for women with MM need to focus on stabilizing estradiol fluctuations during the luteal phase for migraine attack prevention.
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