Systematic review and meta-analysis show hormonal-free intervals elevate migraine frequency in women using hormonal contraceptives, indicating a need for further randomized trials.
Migraines affect a substantial proportion of female migraineurs in a menstrual pattern, yet the relationship between hormonal contraceptive use and migraine outcomes remains unclear. No prior systematic review has comprehensively synthesized quantitative data on migraine frequency and severity in hormonal contraceptive users. We systematically searched multiple electronic databases for studies reporting quantitative migraine outcomes in women using hormonal contraceptives. Random-effects meta-analyses using standardized mean differences examined within-subject comparisons (hormone-free interval versus hormone phase) separately from between-group comparisons (users versus non-users). Several studies of varying designs and sample sizes were included. The overall pooled estimate for migraine frequency showed no significant effect, with substantial heterogeneity across studies. Subgroup analysis revealed significant effect modification by comparison type. Within-subject studies demonstrated a marked increase in migraine frequency during the hormone-free interval, whereas between-group comparisons showed no significant difference between contraceptive users and non-users. Acute medication use was also significantly elevated during the hormone-free interval. These findings indicate that the hormone-free interval, rather than hormonal contraceptive use per se, represents a period of heightened migraine burden. Substantial heterogeneity and observational designs limit causal inference, and randomized trials comparing contraceptive regimens are needed to establish definitive conclusions.
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Alju et al. (2026) studied this question.
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