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Diary data from 155 women were analyzed using within-woman analysis. Compared with all other times of the cycle, migraine was 1.7 times more likely to occur during the 2 days before menstruation and 2.1 times more likely to be severe and 2.5 times more likely to occur during the first 3 days of menstruation and 3.4 times more likely to be severe. This confirms that migraine at menstruation is different from nonmenstrual attacks, even within individuals.

Objective: To investigate the association between urinary hormone levels and migraine, with particular reference to rising and falling levels of estrogen across the menstrual cycle in women with menstrual and menstrually related migraine. Methods: Women with regular menstrual cycles, who were not using hormonal contraception or treatments and who experienced between one and four migraine attacks per month, one of which regularly occurred on or between days 1 Ϯ 2 of menstruation, were studied for three cycles. Women used a fertility monitor to identify ovulation, conducting a test each day as requested by the monitor, using a sample of early morning urine. Urine samples were collected daily for assay of estrone-3-glucuronide, pregnanediol 3-glucuronide, follicle-stimulating hormone, and luteinizing hormone. All women kept a daily migraine diary and continued their usual treatment for migraine. Results: Of 40 women recruited, data from 38 women were available for analysis. Compared with the expected number of attacks, there was a significantly higher number of migraine attacks during the late luteal/early follicular phase of falling estrogen and lower number of attacks during rising phases of estrogen. Conclusion: These findings confirm a relationship between migraine and changing levels of estrogen, supporting the hypothesis of perimenstrual but not postovulatory estrogen "withdrawal" migraine. In addition, rising levels of estrogen appear to offer some protection against migraine. NEUROLOGY 2006;67:2154-2158 During the female reproductive years, migraine is up to three times more common in women than in men of similar age. 1 This sex difference is generally considered to be due to the additional hormonal trigger in women. In specialist clinics and in populationbased studies, 50% of women report an association between migraine and menstruation. 2,3 The peak time for migraine is on or between 2 days before the start of menstruation and the first 3 days of bleeding. [4][5][6][7][8] Identification of the underlying mechanisms of menstrual migraine could enable more effective treatment strategies to be developed. However, despite clinical evidence for the effect of hormonal events, the pathophysiology remains poorly understood.The main hormones considered have been progesterone and estrogen. Levels of both these hormones fall in the late luteal phase of the menstrual cycle, preceding the increase in menstrual attacks of migraine.Evidence for the importance of progesterone in migraine is conflicting. 9-12 A greater body of evidence suggests that migraine is associated at least in some women, with the "withdrawal" of exogenous and endogenous estrogen. [13][14][15][16][17][18][19] However, results from studies assessing serum or urinary hormones levels and headache risk are based on limited data. Further, headache risk has been analyzed according to standard menstrual, follicular, and luteal phases of the menstrual cycles rather than specifically analyzing risk during rising and falling hormone phases. 20 We here present...