New Evidence Implicates Estrogen Decline in the Onset of Migraines

Migraines are more prevalent in women, and have long been associated with sex hormones. In a study published last week in Neurology¹, researchers at Albert Einstein College of Medicine in New York, sought to monitor estrogen levels during the ovulatory cycle of women affected by migraines. Migraine attacks are both more prevalent and more severe in the 2 days preceding menstruation and in the first 3 days of menstruation². These observations led to the hypothesis that a link between “estrogen-withdrawal” and migraines was present, as estrogen levels drop at the end of the luteal phase which precedes menstruation.

Researchers sought to test the hypothesis that women experiencing migraines displayed distinct hormonal patterns, compared to non-migraineurs, by measuring within-woman, peak and daily hormone levels of estrogens, LH, FSH and pregnanediol-3-glucuronide in pre- and early perimenopausal women (114 migraineurs and 223 controls). In addition, daily headache diaries and migraine history were collected.

Results showed that migraineurs had greater within-woman absolute rates of decline in estrogen levels in the 2 days following the luteal peak (33.8 vs 23.1 pg/mgCr, p = 0.002, 2 sample t-tests) and percent change in estrogen levels (40% vs 30%, p < 0.001). Both the within-woman peaks of LH and FSH, and the absolute peaks and daily levels of all sex hormones were unaffected by migraines.

The present study adds evidence to the aforementioned “estrogen withdrawal” hypothesis, implicating the decline in estrogen levels in the onset of migraines. Estrogen peak levels and daily levels between women migraineurs and controls were unaffected; a difference in within-woman rate of estrogen decline was observed in the late luteal phase, but not in the peri-ovulatory phase, independent of migraine occurrence.

The study also provides an additional link between estrogen and peri-menstrual migraine: according to the authors, the distinct pattern of estrogen withdrawal observed in migraineurs does not initiate migraine by itself, but rather confers a neuroendocrine vulnerability. During this period of vulnerability, factors such as stress, disrupted sleep or specific foods might act as triggers for migraine.

 

References

1.Pavlović JM, Allshouse AA, Santoro NF, et al. Sex hormones in women with and without migraine: Evidence of migraine-specific hormone profiles. Neurology. 2016

2. Macgregor EA, Hackshaw A. Prevalence of migraine on each day of the natural menstrual cycle. Neurology. 2004;63(2):351-3.