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

B. V. D. van der Arend, I. Verhagen, Daphne S. van Casteren, J. Goeman, J. Laven, S. V. D. van den Berg, A. Maassenvandenbrink, G. Terwindt

European Journal of Endocrinology, 2026

46 participants

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 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…

How strong is the evidence?

Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 46 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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