The association between endometriosis and migraine: a systematic review and meta-analysis of observational studies

Endometriosis affects women of reproductive age. Increasing attention is being given to the characterization of comorbidities in endometriosis to enhance clinical phenotyping. Among these comorbidities, migraine has been reported to be significantly more common in individuals with endometriosis compared to the general population. However, the true epidemiological burden remains uncertain, and no conclusive evidence links specific subtypes of endometriosis to migraine.

Seven electronic databases were searched from inception until July 22nd, 2024, using combinations of relevant keywords. PROSPERO Registration CRD42023449492. Two independent reviewers screened the records according to inclusion/exclusion criteria and abstracted data. The risk of bias assessment was undertaken using the ROBINS-E tool. Random effects models were implemented to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between endometriosis and migraine. Fourteen studies were included in the qualitative synthesis, and 13 in the meta-analysis, accounting for a total of 331,655 individuals (32,489 with endometriosis vs. 299,166 controls). There was a serious risk of bias in the majority of the included studies, with 50% being at very high risk of bias. The risk of migraine was higher in individuals with endometriosis compared to those without (OR 2.25, 95%CI = 1.85-2.72; n = 13 studies; I² = 81%). This association remained significant in the sensitivity analyses: (i) when excluding studies at very high or high risk of bias (OR 2.64; 95%CI = 1.62-4.31; n = 4 studies; I² = 77%), (ii) when including only risk estimates adjusted for clinically relevant confounders (OR 2.35; 95%CI = 1.77-3.13; n = 6 studies; I² = 88%), and (iii) when including only risk estimates adjusted for hormonal therapy (OR 1.95; 95%CI = 1.42-2.66; n = 3; I² = 92%). Endometriosis was significantly associated with migraine without aura (OR 2.64, 95%CI 1.89-3.69; n = 3 studies; I² = 0%), but not migraine with aura (OR 3.47, 95%CI = 0.53-22.89; n = 3, I² = 73%).

This meta-analysis highlights the high prevalence of migraine in patients with endometriosis. However, due to observed high heterogeneity and risk of bias, caution is advised when interpreting and applying these findings in clinical practice. Future research should address these issues by limiting variations in diagnostic criteria, stratifying study populations, accounting for key confounders, and investigating potential underlying pathophysiological mechanisms to enhance understanding of the endometriosis-migraine relationship.