Estradiol and other sex hormone dynamics in menstrual migraine: pathway analysis of hormones in a case-control follow-up study.

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 total, 413 standardized serum hormone measurements were collected from 87 menstrual cycles contributed by 46 participants (28 with MM, 18 healthy controls) in this prospective cohort study. Blood samples were collected on standardized cycle days based on the luteinizing hormone 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 (1.49, 95% CI: 1.03-1.87, P = .04) and a 90% greater decline from mid- to late-luteal phase compared to controls (1.90, 95% CI: 1.16-3.12, P = .03). Secondary pathway analysis showed no differences in other sex hormones, although progesterone showed high variability and a peak difference of similar magnitude to estradiol. 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.