4.6 Review

Hormonal influences in migraine - interactions of oestrogen, oxytocin and CGRP

Journal

NATURE REVIEWS NEUROLOGY
Volume 17, Issue 10, Pages 621-633

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41582-021-00544-2

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Reproductive hormones influence migraine in women but the basis of these effects is unknown. In this Review, the authors discuss what is known about sex hormones and their receptors in migraine-related areas of the CNS and the trigeminovascular pathway and propose a simple model to explain how hormones influence menstrual migraine.
Migraine is ranked as the second highest cause of disability worldwide and the first among women aged 15-49 years. Overall, the incidence of migraine is threefold higher among women than men, though the frequency and severity of attacks varies during puberty, the menstrual cycle, pregnancy, the postpartum period and menopause. Reproductive hormones are clearly a key influence in the susceptibility of women to migraine. A fall in plasma oestrogen levels can trigger attacks of migraine without aura, whereas higher oestrogen levels seem to be protective. The basis of these effects is unknown. In this Review, we discuss what is known about sex hormones and their receptors in migraine-related areas in the CNS and the peripheral trigeminovascular pathway. We consider the actions of oestrogen via its multiple receptor subtypes and the involvement of oxytocin, which has been shown to prevent migraine attacks. We also discuss possible interactions of these hormones with the calcitonin gene-related peptide (CGRP) system in light of the success of anti-CGRP treatments. We propose a simple model to explain the hormone withdrawal trigger in menstrual migraine, which could provide a foundation for improved management and therapy for hormone-related migraine in women. Reproductive hormones influence migraine in women but the basis of these effects is unknown. In this Review, the authors discuss what is known about sex hormones and their receptors in migraine-related areas of the CNS and the trigeminovascular pathway and propose a simple model to explain how hormones influence menstrual migraine.

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