Sex differences in migraine: bridging pathophysiology and clinical care in women

Migraine affects women at various life stages, with its frequency and severity influenced by fluctuations in ovarian hormones. The pathophysiology of migraine involves activation of the trigeminovascular system, brain stem regions, and diencephalic nuclei, with neurotransmitters and neuropeptides like serotonin (5-HT), γ-aminobutyric acid (GABA), noradrenaline, and calcitonin gene-related peptide (CGRP) playing key roles in maintenance of pain. Estrogen modulates these pathways and has a significant impact on migraine pathophysiology in females. Menstrual migraines, linked to estrogen withdrawal and prostaglandin release, can be managed with short-term prophylactic therapies such as selective serotonin agonists, initiated a few days before the expected onset of menstruation, and with nonsteroidal anti-inflammatory drugs or triptans for breakthrough headaches. During pregnancy, migraines often subside because of stable hormone levels, whereas perimenopause can exacerbate symptoms. Breastfeeding may improve migraine symptoms temporarily. Hormone replacement therapy can reduce migraine frequency in women during the perimenopausal period. A tailored, individualized approach is essential for effective management of migraines in women.NEW & NOTEWORTHY Recent advances in migraine research have deepened understanding of its complex pathophysiology. Sex hormones modulate the neural pathways involved in migraine generation, and explain the higher prevalence and fluctuating pattern of migraine observed in females across different life stages. Consequently, a sex-specific, individualized therapeutic approach is recognized as essential for optimizing management of migraine in women.