| Summary: | Research into the association between migraine and menstruation has been hampered by lack of an agreed definition for 'menstrual' migraine. This thesis presents evidence for increased risk of migraine without aura on or between the two days before menstruation and the first three days of bleeding. Within individual women menstrual attacks differ from attacks at other times of the cycle, being longer and more severe. These findings led to the development of definitions for 'pure menstrual migraine' and 'menstrually-related migraine', which have subsequently been adopted by the International Headache Society. Further research identified an inverse relationship between oestrogen and migraine incidence. The follicular phase oestrogen rise was associated with reduced risk of migraine late luteal oestrogen 'withdrawal' at menstruation was associated with increased risk of migraine. In order to counteract the luteal phase oestrogen drop and prevent menstrual attacks, oestrogen supplements were used from the luteal phase oestrogen peak (day-6) through to the early follicular rise of endogenous oestrogen (day +2). Identification of ovulation using a fertility monitor enabled prediction of menstruation and accurate timing of oestrogen supplements, despite a wide inter- and intra-individual range in cycle length. The results showed that use of oestrogen supplements was associated with a significant reduction in migraine days compared to placebo. However, the benefits were offset by delayed oestrogen 'withdrawal' migraine. In women with migraine in the pill-free interval of combined hormonal contraceptives, there was a trend for oestrogen supplements to prevent 'menstrual' attacks, although the dose used was suboptimal. These findings support the hypotheses that menstrual migraine is a discrete clinical entity and is associated with oestrogen 'withdrawal'. Further, oestrogen 'withdrawal' migraine can be independent of menstruation and independent of ovulation. Oestrogen 'withdrawal' migraine can be prevented with oestrogen supplements, although the optimal regime has yet to be established.
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