To examine the interplay of hormonal, genetic, and therapeutic factors in menstrual migraine

Menstrual migraine is a common yet underrecognized migraine subtypes which results in inconsistent management and decreased quality of life. This type of migraine appears with cyclical hormonal fluctuation, particularly estrogen withdrawal; but timing of an attack, its intensity, and even response to treatment vary among patients, given their genetic susceptibilities or some other biological parameters. Recognizing these mechanisms enables one to target them with precision.

PubMed, Embase, and Scopus was searched systematically up to April 2025 using MeSH terms and free-text keywords related to menstrual migraine, hormonal modulation, genetic predisposition, and individualized therapies. Randomized controlled trials (RCTs), cohort studies, or observational studies investigating hormonal triggers, genetic markers, and treatment outcomes in MM were eligible. Study quality was assessed using Cochrane Risk of Bias Tool for RCTs, and Newcastle–Ottawa scale for observational studies.

Eighteen studies met the inclusion criteria. One major proposed factor for onset of migraine attacks has been estrogen withdrawal, along with increased severity and duration of attacks. Several studies have shown that high-dose estradiol supplementation decreased the frequency and intensity of MM attacks, but the data are scanty and need further confirmation. It was suggested that CGRP inhibitors help with symptoms, especially in the phase of decreasing estrogen levels. Genetic studies identified marker genes such as SYNE1 and TNF, suggesting pathways to precision treatment guided by estrogen sensitivity and inflammatory response.

Complex hormonal and genetic factors underpin menstrual migraine, affecting disease burden and treatment response. High-dose estradiol and CGRP inhibitors appear promising to improve patient outcome;however, there is a need for larger, well-designed studies on long-term efficacy and safety of these interventions. From clinical point of view, further advances in genetics will set the path for personal and mechanistic-driven treatment of this disabling migraine subtype.