{"paper_id":"232f0539-bdd7-4053-b6ff-4d561bc359cc","body_text":"Comment on ‘’Correlation between\nendometriosis and migraine features:\nResults from a prospective case-control\nstudy’‘\nWe read with great interest the recently published article by\nSelntigia et al. 1 The paper concludes that patients with\nco-occurrence of both endometriosis and migraine\n(EM-MG) have higher pain intensity compared to patients\nwith endometriosis only (EM-O) or migraine only\n(MG-O) and also the patients with both endometriosis\nand migraine has more severe gynaecological in filtrations\ncompared to endometriosis only patients. However, we\nhave several concerns regarding the overly assertive con-\nclusions, methodology, and statistical and power analysis\nof the study.\nOne primary issue is the study’s broad strokes in conclud-\ning that EM-MG patients suffer from more severe endometri-\nosis/adenomyosis compared to those with endometriosis\nalone. This simpli fication overlooks the complexity of\ndisease severity and the distinct classification systems for ade-\nnomyosis and deep in filtrating endometriosis (DIE). By\nequating the presence of adenomyosis or DIE with “more\nsevere gynecological infiltrations” without a systematic com-\nparison of endometrioma, DIE, and other lesions, the study\nfails to accurately capture disease severity. Furthermore, the\nsimilar frequency of DIE and endometrioma between the\nEM-MG and EM-O groups undermines the claim of inher-\nently greater disease severity in the comorbid group, espe-\ncially without a comparative analysis of severity.\nSecondly, the study ’s emphasis on the signi ficance of\nthe CGRP pathway is notable, yet it may overextend its con-\nclusions. The increased pain intensity observed in patients\nwith both endometriosis and migraine, as opposed to those\nwith just one condition, can be attributed to a variety of\nfactors including hormonal changes, chronic in flammation,\naltered pain sensitivity, genetic factors, psychological distress,\nfatigue, and both peripheral and central sensitization, along\nwith delayed diagnosis and treatment\n2. Therefore, focusing\nextensively on the CGRP pathway and asserting its targeting\nefficacy without direct pathophysiological evidence might\nexceed the study’s scope and be overly conclusive.\nThirdly, while the study points to a relationship between\nincreased migraine pain scores and speci fic endometriosis\nsubtypes (DIE and adenomyosis), it lacks direct correlation\nanalysis to substantiate this association.\nThe study ’s methodology also presents several notable\nissues. Initially, the approach is hindered by sampling\nbias due to its observational design and patient recruitment\nfrom two distinct departments: endometriosis and head-\nache. The selection criteria for patients with both endomet-\nriosis and migraine (EM-MG) lack clarity, particularly\nregarding their initial clinic of presentation. This oversight\nintroduces potential biases, as symptoms and severity\nreported by EM-MG patients could be skewed based on\nwhether they first sought treatment at the endometriosis or\nheadache clinic. Furthermore, treatment biases may exist;\nEM-only patients not receiving hormonal treatments\nlikely represent milder cases, while the hesitancy of clini-\ncians to use hormonal treatments in EM-MG patients, espe-\ncially those with migraine with aura, might mean this group\ndisproportionately represents more severe endometriosis\ncases. Additionally, the study ’s protocol speci fies that\neach EM-MG case was matched with two control patients\nfrom each of the EM-O and MG-O cohorts based on a\nstrict BMI matching criterion of ±1 unit range. However,\nthe actual reported mean BMI differences between the\nEM-MG group and the control groups exceed this thresh-\nold, with variations of up to 2 BMI units. This variation\nindicates a deviation from the described matching process\nand raises concerns about the study ’s methodological\nadherence and the reliability of its comparative analysis.\nLastly, the study ’s power analysis is compromised due\nto the absence of an effect size, crucial for assessing the\nability to identify meaningful differences, and incorrectly\nemploying the Kruskal-Wallis test for two-group compari-\nsons. Moreover, the statistical analysis presents concerns,\nas demonstrated by mean VAS scores (inherently non-\nnegative) having standard deviations larger than the\nmeans, indicating a non-normal distribution. This issue\nraises concerns about the appropriateness of utilizing\nt-tests for data analysis, suggesting a need for non-\nparametric tests or methods such as logarithmic transforma-\ntions to ensure a normal distribution for precise analysis.\nIn conclusion, while this study contributes to the under-\nstanding of the comorbidity between endometriosis and\nmigraine, these concerns highlight the need for cautious\nCreative Commons Non Commercial CC BY -NC: This article is distributed under the terms of the Creative Commons Attribution-\nNonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and dis-\ntribution of the work without further permission provided the original work is attributed as speci fied on the SAGE and Open Access page (https://us.\nsagepub.com/en-us/nam/open-access-at-sage).\nLetter to the Editor\nCephalalgia\n2024, Vol. 44(5) 1 –2\n© International Headache Society 2024\nArticle reuse guidelines:\nsagepub.com/journals-permissions\nDOI: 10.1177/03331024241254824\njournals.sagepub.com/home/cep\n\n\ninterpretation of the findings and call for further research to\naddress the complex relationship between these conditions\nmore comprehensively.\nReferences\n1. Selntigia A, Exacoustos C and Ortoleva C et al. Correlation between\nendometriosis and migraine features: Results from a prospective\ncase-control study. Cephalalgia 2024; 44: 3331024241235210.\n2024/03/04. DOI: 10.1177/03331024241235210.\n2. Morotti M, Vincent K and Becker CM. Mechanisms of pain\nin endometriosis.European Journal of Obstetrics & Gynecology\nand Reproductive Biology 2017; 209: 8 –13. DOI: 10.1016/j.\nejogrb.2016.07.497.\nUtku AKGOR 1 and Onur INCE 1\n1Department of Obstetrics and Gynecology, 64005Faculty\nof Medicine, Hacettepe University, Ankara, Turkey.\nCorresponding authors:\nUtku Akgör, Department of Obstetrics and Gynecology,\nFaculty of Medicine, Hacettepe University, 06230 Ankara,\nTurkey. Email: + 905495197799\n2 Cephalalgia 44(5)","source_license":"CC0","license_restricted":false}