The interplay between migraine, endometriosis and polycystic ovarian syndrome: A systematic review

Background

Results

Introduction

Results Included articles | Author, year country | Study design, sample size (n), age (years), mean ± SD | Endometriosis and migraine diagnosis | Main objective | Main results | |---|---|---|---|---| | Ferrero et al., 2004 Italy (4) | Cross-sectional Total N = 299 Cases EDM = 133. Age 34.0 ± 4.4 Controls WoEDM = 166. Age 34.4 ± 6.3 | EDM: Histological MG: Clinical interview by neurologist experienced in headache (ICHD-1) | To explore the prevalence and headache characteristics in females with EDM vs. females WoEDM | • MG prevalence was higher in the EDM group (38.3%, 95% CI = 30.1–47.2% vs. 15.1%, 95% CI = 10.0–21.4%; p < 0.001) • MA and MWoA were more frequent in individuals with EDM (MA 13.5% vs. 1.2%, p < 0.001; MWoA 24.8% vs. 13.9%, p = 0.016) • No differences in MG characteristics, treatments and MRM frequency were observed between groups • Females with MG + EDM experienced higher disability (reduction in work productivity of 46.7% ± 18.7% vs. 30.5% ± 8.6%, p < 0.001; missing working days due to dysmenorrhea or headache 51.4% vs. 22.7% p < 0.032) | | Nyholt et al., 2009 Australia (24) | Cross-sectional Families ≥ 2 sisters with EDM = 931. Age 50.35 Female twin pairs WoEDM = 815 MZ, 457 DZ. Age 56.88 | EDM: Surgical MG: Telephone interview (ICHD-1) | To determine the comorbidity of MG and EDM | • Greater risk of MG was observed in females with EDM vs. females WoEDM (using IHS criteria OR = 1.35, 95% CI = 0.94–1.95, p = 0.009) • Bivariate heritability analysis showed no evidence for common environmental factors affecting MG or EDM (rE = 0.08; 95% CI = 0–0.32) • No evidence of direct causality between MG and EDM were evidenced after applying statistics models | | Karp et al., 2011 USA (34) | Prospective cohort N Total = 108 Cases EDM = 81. Age 31.2 ± 0.8 Controls WoEDM = 27. Age 31.5 ± 1.4 | EDM: Laparoscopy and histological MG: Headache questionnaires and neurologist evaluation (ICHD-2) | To analyze headache in females with chronic pain with and without EDM | • MG was reported similarly in individuals with EDM compared to those WoEDM (66.7% in both, p = 1.0). • MG frequency, duration and severity were not related to EDM presence • Only 42% of females with MG had ever sought medical attention for headache. Only 33% of those asking for treatment received triptans | | Yang et al., 2012 China (31) | Retrospective cohort N Total = 283,987 Cases EDM = 20,220. Age 38.11 ± 8.32 Controls WoEDM = 263,767. Age 33.94 ± 9.56 | EDM: coding (clinical symptoms and medical signs, sometimes imaging). MG: coding. Independent group of physicians reviewed the charts and validated the diagnoses | To analyze the prevalence and relationship between EDM and MG in a large nationwide medical database (Taiwan) | • EDM was identified as an independent predictor of MG, with a 36–37% higher prevalence observed in individuals with EDM (AOR = 1.37, 95% CI = 1.27–1.47, p < 0.001 adjusting for age and hormone treatment). • MG was more frequently observed in females with pelvic pain (OR = 1.88; 1.80–1.96; p < 0.001) adjusting for EDM diagnoses | | Karamustafaoglu et al., 2019 Turkey (30) | Cross-sectional N Total =363 Cases EDM = 114. Age 31.86 ± 4.49 Cases WoEDM = 97. Age 28.95 ± 5.11 | EDM: Laparoscopy MG: 3-item screening questions, ID Migraine test | To determine the prevalence of MG in infertile females with EDM using the ID Migraine™ questionnaire | • MG prevalence was higher among EDM individuals (44.7% vs. 26.8%; p = 0.007) • Self-reported MRM was 45.1% in EDM vs. 30.8% in WoEDM (p = 0.275) | | Maitrot-Mantelet al., 2020 France (32) | Prospective case–control N Total = 314 Cases EDM = 182. Age 31.04 ± 5.06 Controls WoEDM = 132. Age 32.08 ± 5.70 | EDM: Histological MG: self-reported questionnaire applying ICHD-3 criteria checked by a physician | To assess the prevalence of MG in females with EDM (vs. WoEDM); analyze the risk of EDM in individuals with MG (vs. WoMG); and to determine the risk of EDM phenotypes linked to MG | • MG prevalence was greater in females with EDM vs. WoEDM (35.2% vs. 17.4%; p = 0.003). Females with MG had a notably greater risk of developing EDM (OR = 2.62, 95% CI = 1.43–4.79, p = nr) • The likelihood of having OMA (AOR = 2.78, 95% CI = 1.11–6.98) and DIE (AOR = 2.51, 95% CI = 1.25–5.07) was greater in females with MG compared to those WoEDM and WoMG • Higher VAS scores were obtained in females with EDM for chronic non-cyclic pain compared to females WoEDM (3.6 ± 2.9 vs. 2.3 ± 2.8; p = 0.007) | | Sultana et al. 2024 Bangladesh (29) | Prospective case–control N Total = 380 Cases EDM = 190. Age 30 ± 6.04 Controls WoEDM = 190. Age 30.7 ± 4.25 | EDM: Laparoscopy/ laparotomy MG: medicine or neuromedicine specialist diagnosis | To determine the association between EDM and MG among females of reproductive age in Bangladesh. | • MG prevalence was greater in females with EDM vs. WoEDM (14.2% vs. 2.6%; 95% CI = 2.50–18.41, p < 0.001) • A one-year increase in age increased the odds of having MG by 23% (OR = 1.23; 95% CI = 1.13–1.16; p ≤ 0.001) • Females with EDM have AOR = 5.35 of having MG (2.11–16.4, p < 0.001) | | Wu et al., 2022 China (33) | Prospective case–control N Total = 357 Cases EDM = 167. Age 33.5 ± 4.8 Controls WoEDM = 190. Age 32.9 ± 4.2 | MG: ID MigraineTM screening followed by an interview by headache specialist (ICHD-3) EDM: laparoscopy AM: TUS by ≥ 2 experienced sonographers | To assess whether individuals with severe EDM have greater risk of MG; to evaluate the presence of MG in cases of EDM with/without AM | • MG prevalence was greater among females with EDM vs. WoEDM (29.9% vs. 12.1%; p = 0.000) • Individuals with MG were more likely to have severe (AOR = 4.6, 95% CI = 2.7–8.1; p < 0.001) and moderate EDM (AOR = 3.6, 95% CI = 2.1–6.2, p < 0.001) • Females with MG had greater risk of EDM coexisting with AM (AOR = 5.4, 95% CI = 3.0–9.5, p < 0.05) and EDM without AM (AOR = 2.2, 95% CI = 1.2–3.8, p < 0.05) compared to females WoEDM • The VAS scores for MG were higher in individuals with EDM compared to those WoEDM (7.3 ± 1.4 vs. 5.6 ± 2.2, p = 0.002) | | Author, year, Country | Study type, sample size (n), age (years), mean ± SD | Endometriosis and migraine diagnosis | Main objective | Main results | |---|---|---|---|---| | Tietjen et al., 2006 USA (36) | Prospective case–control N Total = 102 Cases MG = 50. Age 37.6 ± 8.4 Controls WoMG = 52. Age 36.9 ± 6.1 | EDM: Laparoscopy MG: Neurologist with semi-structured questionnaire (ICHD-1) | To assess the prevalence of menorrhagia and EDM in a population with MG | • EDM prevalence was higher in MG individuals (MG 30% vs. WoMG 4%, p = 0.001). AOR of 10.5 (95% CI = 2.2–51.4) for association of MG-EDM • Menorrhagia prevalence was higher in MG individuals (63% vs. controls 37%, p = 0.009) • MG individuals presented higher indicators of heavy menstrual bleeding (total number of tampons and/or pads in a period 20 ± 9.6 vs. 16 ± 9.4, p = 0.027; clothes stained by menses 35% vs. 8%, p = 0.003) • MG individuals reported that their menstrual periods caused a greater amount of interference in their daily lives than HC (p = 0.003) | | Tietjen et al., 2007 USA (16) | Cross-sectional Sample size Cases MG = 171. Age 37.6 ± 10 Controls WoMG = 104. Age 40.6 ± 12 | EDM: Self-reported EDM confirmed by laparoscopy MG: Headache specialist (ICHD-2) | To determine headache characteristics in females with MG + EDM vs. females with only MG. To assess the association of EDM with other comorbid conditions in females with MG and HCs | • EDM was more prevalent in MG individuals (22% vs. 9.6%; p < 0.01) • Individuals with MG + EDM presented higher headache frequency ( 60 81% vs. 74%: p = 0.025). • Individuals with MG reported higher menorrhagia (68% vs. 43%; p < 0.05) and dysmenorrhea history (54% vs. 23%; p < 0.05) vs WoMG • Individuals with MG + EDM self-reported greater comorbidities:interstitial cystitis (OR = 10.6, 95% CI = 1.9–56.5; p < 0.05), chronic fatigue syndrome (OR = 3.6, 95% CI = 1.1–11.5; p < 0.05), anxiety (OR = 2.2; 95% CI = 1.0–4.7; p < 0.05) | | Author, year, Country | Study type, sample size(n), age (years), mean ± SD, country | Endometriosis and migraine diagnosis | Main objective | Main results | |---|---|---|---|---| | Raffaelli et al., 2021 Germany (38) | Cross-sectional (with prospective collection of repeated hormonal measures) N Total = 122. MG = 31. Age 32.74 ± 1.31 EDM = 30. Age 31.90 ± 1.02 MG + EDM =30. Age 35.70 ± 1.32 HC = 31. Age 31.55 ± 1.71 | EDM: Histological MG: Headache specialist (ICHD-3) | To assess CGRP concentrations (pg/ml) between the menstrual (PM) and ovulatory phases (PO) in all study groups | • CGRP plasma levels differed significantly between the PM and PO periods across the groups (p = 0.007) • Females with EDM + MG showed an absolute increase in CGRP levels during PM (+6.32; –3.64 to 13.60) compared to the PO period, whereas HCs experienced a decrease of –10.14 (–22.45 to –0.91; p = 0.004). • Individuals with MG + EDM showed greater days with EDM-related pain, pain intensity and MG attack duration compared to EDM only • Higher EHP-30 scores were referred in females EDM + MG vs EDM only in 5/6 domains | | Neumeier et al., 2023 Switzerland (39) | Cross-sectional N total = 344 Cases EDM + MG = 94. Age 36.78 ± 7.64 Controls EDM = 250. Age 36.10 ± 7.18 | EDM: Histological MG: Telephone interview with structured questionnaire (ICHD-3 adapted) | To examine EDM features among females with EDM + MG vs. females with EDM only | • MG had a prevalence of 27.33% in females with EDM • Individuals with EDM + MG suffered less frequently advanced EDM (ASRM stages 3–4: EDM 64.4% vs. EDM + MG 52.1%; p = 0.038) • Individuals with EDM + MG reported more history of dysmenorrhea (48.8% vs 36.6%, p = 0.044), dyschezia (60.6 vs. 40.0%, p < 0.001), pain days during menstruation (3.93 ± 2.38 vs. 3.39 ± 2.84; p = 0.039), heavy menstrual bleeding days lasting ≥2 days (68.3% vs. 48.2%, p = 0.009) | | Pasquini et al., 2023 Italy (35) | Prospective case–control N Total = 131. Age 33 ± 7.4 Cases EDM + MG = 70 Controls EDM = 61 | EDM: surgical or clinical symptoms plus imaging (TVS ± MR). MG: headache questionnaire and posterior confirmation at headache centre (ICHD-3) | To explore MG subtypes in individuals with EDM; to analyze their potential association with EDM phenotypes, clinical symptoms, and comorbidities | • MG prevalence was 53.4%. MG was mainly episodic (84.3%, mean HDM of 3 ± 2.9 days). PMM was observed in 18.6% and MRM in 45.70% females • Dysmenorrhea (94.3% vs 82.0%) and dysuria (27.1% vs. 9.8%) were greater reported in cases (p = 0.03; p = 0.01). • Only 11.4% of females with EDM + MG reported triptans use (8/70) | | Selntigia et al., 2024 Italy (37) | Prospective case–control N Total = 250 Cases EDM/AM + MG = 50. Age 33.46 ± 8.98 Control EDM =100. Age 32.94 ± 5.49 Control MG = 100. Age 33.60 ± 8.26 | EDM: clinical symptoms and TVS MG: Headache expert face-to-face interview (ICHD-3) | To examine in females with EDM/AM + MG vs. females with only MG or EDM the following: Variations in EDM lesions subtypes and AM severity; MG characteristics; associations between disease severity and disability | • Mean VAS scores for dysmenorrhea, dyspareunia, dyschezia, dysuria, bowel symptoms and heavy menstrual bleeding were higher in EDM + MG vs. EDM • Higher percentage of severe AM (14% vs. 4%: p = 0.02), posterior (48% vs. 30%, p = 0.031) and anterior (10% vs. 2% p = 0.029) DIE was observed in females EDM + MG • Higher MG pain intensity (8.44 ± 1.18 vs. 7.74 ± 1.47; p = 0.004), MMD and mean of HIT-6 score (62.33 ± 9.44 vs. 57.38 ± 11.83; p = 0.010) were reported in EDM + MG compared to MG only • Only 8% of females EDM + MG used triptans | Migraine and endometriosis Prevalence and risk factors Migraine clinical features and treatment Endometriosis clinical features Migraine, EDM and calcitonin gene related peptide (CGRP) Comorbidity and disability associated with migraine and EDM Heterogeneity of the included studies Migraine and PCOS

Study limitations Clinical implications

Key findings Acknowledgments Declaration of conflicting interests Funding ORCID iDs Data availability statement

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Data availability statement Authors Author contributions Metrics and citations Metrics Publication usage* Total views and downloads: 2285 *Publication usage tracking started in December 2016 Altmetric See the impact this article is making through the number of times it’s been read, and the Altmetric Score. Learn more about the Altmetric Scores Publications citing this one Receive email alerts when this publication is cited Web of Science: 2 view articles Opens in new tab Crossref: 4 - A review on shared genetic architecture of endometriosis and migraine: from pleiotropy to convergent inflammatory pathways - Vascular risk at menopause: The importance of a cardio-gynecological program - Identification of common genetic and molecular signatures in migraine and comorbid conditions - Impact of fertility treatments on headache disorders: a systematic review with an overview of treatment modalities Figures and tables Figures & Media Tables View Options View options PDF/EPUB View PDF/EPUBAccess options If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below: loading institutional access options IHS members can access this journal content using society membership credentials. IHS members can access this journal content using society membership credentials. Alternatively, view purchase options below: Purchase 24 hour online access to view and download content. Access journal content via a DeepDyve subscription or find out more about this option.