{"paper_id":"65ea11b4-9e80-4a27-b1e0-c96bae5a8ba8","body_text":"https://doi.org/10.1177/22840265241283520\nJournal of Endometriosis and  \nPelvic Pain Disorders\n2025, Vol. 17(1) 3 –11\n© The Author(s) 2024\nArticle reuse guidelines: \nsagepub.com/journals-permissions\nDOI: 10.1177/22840265241283520\njournals.sagepub.com/home/pev\nJEPPD\nJournal of\nEndometriosis and \nPelvic Pain\nDisorders\nIntroduction\nMigraine and endometriosis are disabling conditions with \nchronic pain affecting women during the reproductive \nyears. Oestrogens play a pivotal role in the pathophysiol-\nogy of both conditions and symptoms typically dissolve \nwith menopause.\n1 Some newer studies indicate in addition, \nthat both conditions are associated with breast cancer. 2,3 \nToday there is high evidence, that there is a shared genetic \nbackground, especially related to polymorphisms of sex \nhormones.\n4–6 Migraine prevalence was significantly higher \nin endometriosis patients compared with controls in a pop-\nulation-based study (1.7 fold).\n7 Survey-based case-control \nMenstrual migraine prevalence and \nfeatures in women with endometriosis: A \ncommon disabling comorbidity\nGabriele S Merki-Feld1 , Maria S Neumeier2,  \nHanna Dietrich1, Angela Niggli1 , Brigitte Leeners1,  \nChristoph J. Schankin3 , Gantenbein Andreas4,5 and \nPeter Sandor4\nAbstract\nIntroduction: Endometriosis is a highly prevalent disabling comorbidity of women with migraine. The aim of the \ncurrent study was to identify menstrual migraine prevalence and features in women with endometriosis.\nMethods: This observational study included data from patients visiting our outpatient clinic from 2015 to 2021. \nInformation was collected from charts and through structured phone interviews. Patients with surgically confirmed \nendometriosis and migraine were included.\nResults: A total of 92 from 344 endometriosis patients suffered from migraine and a subset of 35 from menstrual \nmigraine (MM). From the subset of women with MM 42.9% reported to have auras. Groups did not differ with regard \nto rASRM stage. Women with MM reported significantly more pain days/month at present and 5 years ago and more \noften a MIDAS Grade 4 (p < 0.01). Both groups had less migraine attacks/month now, compared with monthly attacks \n5 years ago. All women experienced endometriosis surgery in this interval. There was a trend towards more severe \ndysmenorrhoea with onset at menarche and towards higher use of analgesics for menstrual pain during the bleeding in \nthe MM group. Less deliveries were noted in the group with MM.\nConclusion: In women with similar endometriosis stages MM is associated with a higher migraine frequency, more \ndysmenorrhoea days and a higher burden of disease. Future studies are needed to better understand a potential influence \nof menstrual migraine on the number of deliveries. Our findings suggest, that close collaboration of neurologists with \ngynaecologists and shared treatment decisions might be of advantage for patients with the comorbidity.\nKeywords\nMigraine, endometriosis, medical treatment, ASRM stage, disability, dysmenorrhoea, menstrual migraine\nDate received: 8 December 2023; accepted: 25 August 2024\n1 Department of Reproductive Endocrinology, University Hospital \nZurich, Zurich, Switzerland\n2 Department of Neurology, University Hospital Zurich, Zurich, \nSwitzerland\n3 Department of Neurology, Inselspital, Bern University Hospital, \nUniversity of Bern, Bern, Switzerland\n4 Department of Neurology and Pain, Zurzach Care, Bad Zurzach, \nSwitzerland\n5Private Practice, Neurologie am Untertor, Bülach, Switzerland\nCorresponding author:\nGabriele S. Merki-Feld, Department of Gynaecologic Endocrinology, \nUniversity Hospital Zurich, Frauenklinikstrasse 26, Zurich 8091, \nSwitzerland. \nEmail: Gabriele.merki@usz.ch\n1283520 PEV0010.1177/22840265241283520Journal of Endometriosis and Pelvic Pain DisordersMerki-Feld et al.\nresearch-article2024\nOriginal Research Article\n\n\n4 Journal of Endometriosis and Pelvic Pain Disorders 17(1)\nstudies reported migraine in 29%–69% of endometriosis \npatients, which is far higher than the expected prevalence \nin the general female population.\n8–10 Endometriosis is an \ninflammatory proliferative chronic disease affecting 5%–\n10% of women of reproductive age.\n11–13 A combination of \nimmunological, environmental and anatomical factors are \ndiscussed as pathomechanisms for the ectopic growth of \nendometrial tissue.\n11 Endometrial tissue in affected patients \nmay release Calcitonin Gene-Related Peptide (CGRP) and \nshows an increased density of CGRP-positive sensory \nnerve fibres.\n14,15 Endometriosis pain is strongly related to \nthe period of menstrual bleeding with dysmenorrhoea and \npelvic pain being the most disabling symptoms.\n16 Other \nendometriosis associated symptoms may occur at any type \nof the cycle. Menstrual migraine (MM) is a special sub-\ntype of migraine occurring at days 1 ± 2 in at least two of \nthree cycles and associated with oestrogen withdrawal in \nthe natural cycle or in the pill break in users of combined \nhormonal contraceptives.\n17 MM attacks are more severe, \nof longer duration and less responsive to acute therapy \nwith, for example, triptans or short-term prevention.\n18–27 \nTheir high negative impact on quality of life has been \ndescribed many times.\n28 Between 18% and 25% of women \nwith migraine report MM, while the prevalence and fea-\ntures of MM in endometriosis patients with migraine as a \ncomorbidity is unknown.\n29–31 This is despite the probable \nhigh burden caused by the combination of disabling symp-\ntoms from endometriosis and MM during the days of the \nmenstrual cycle. It is still unknown, if MM onset in women \nwith endometriosis already occurs with the initiation of \ndysmenorrhoea during the early years of puberty. Such a \ncoincidence could facilitate earlier diagnosis and treatment \npotentially contributing to avoiding the development of \ncentral pain sensitisation (CPS). CPS leads in patients with \nchronic pain conditions to pain hypersensitivity.\n32 Migraine \nas well as endometriosis respond to continuous therapy \nwith some progestins in dosages which inhibit ovula-\ntion.\n33–36 With the present study we aim to improve to iden-\ntify MM features in women with endometriosis, as well as \nMM prevalence and burden of disease. Considering not \nonly the strong genetic background, but also the high influ-\nence of oestrogens on both conditions, we were interested \nto evaluate, if certain endometriosis features might differ \nin these patients, and if MM onset and dysmenorrhoea \nonset are timely connected. Higher awareness of women at \nrisk for the comorbidity might contribute to earlier diagno-\nsis, prevent CPS and decrease burden of disease.\nMaterials and methods\nThis cross-sectional study was conducted at the Clinic for \nReproductive Endocrinology in the Department of \nGynaecology of the University Hospital of Zurich. Data \nwere collected from patient records and supplemented \nthrough telephone interviews. In order to assure correctness \nof our data, two persons from medical staff were trained in \n50 interviews prior to start of the study. The presented data \nderive from a broader study investigating the characteristics \nof endometriosis in women with migraine anddepression.\n37\nData collection\nPatients with the diagnosis of endometriosis and migraine \nwere preselected by searching charts from all endometrio-\nsis patients treated in our outpatient clinic from January \n2015 to July 2021. Included were premenopausal patients \naged >18 years with histopathological examination results \nconfirming endometriosis, who in addition suffered from \nmigraine (Figure 1). Migraine, menstrual migraine and \npure menstrual migraine diagnosis was clarified during a \ntelephone interview using the criteria of the International \nClassification of Headache Disorders (third version, \nICHD-3).\n17 Postmenopausal women and those with adeno-\nmyosis or scar endometriosis were excluded. We further -\nmore excluded patients, if no histology was available and \nthose in which the stage of endometriosis and localisation \nwere not clearly documented. During a phone contact, we \ninformed patients about the study and asked if they were \ninterested in participating. Those willing to participate \nreceived an information sheet and thereafter provided oral \nconsent. Details about the inclusion process can be found \nin Figure 1. During the interview we collected headache \ndata on age at migraine onset, migraine frequency in the \npast and at present, aura, menstrual attacks, duration of \nattacks, migraine triggers, acute and prophylactic medica-\ntion, family history, history of medication overuse head-\nache, history of status migrainosis and quality of life, using \nthe Migraine Disability Assessment questionnaire \n(MIDAS).\n38 Endometriosis stage according to the \nAmerican Society for Reproductive Medicine classifica-\ntion (rASRM stage) was identified from the surgery \nreport.\n39 Further gynaecological information and informa-\ntion on comorbidities was collected in the interview using \na shortened and adapted to our needs version of the \n‘Women’s Health Symptom Survey Questionnaire’ recom-\nmended from the World Endometriosis Research \nFoundation.\n40 We collected data on medical conditions, \noperations, family history, pregnancies, deliveries, poten-\ntial symptoms of endometriosis and medications used at \npresent. Furthermore, we collected detailed information on \nthe menstrual cycle, we focussed on menstrual pain days \nduring adolescence and at present, dysmenorrhoea onset \nand intensity, number of pregnancies and deliveries, num-\nber and timing of endometriosis surgery and number of \npain days during the cyclic bleeding as well as use of hor-\nmones and analgesics. Pain intensity was rated on a scale \nfrom 0 to 3 with 0 meaning no pain and 3 severe pain. The \nstudy was approved by the cantonal ethics commission of \nZurich (BASEC Nr. 2021-00285) and registered on clini-\ncal Trials.gov (NCT04816357).\n\nMerki-Feld et al. 5\nStatistical analysis\nData was analysed using SPSS® statistics (IBM®, Armonk, \nNew York, United States Version 27.0.1.0.). Shares in per-\ncent were used for categorical variables and means includ-\ning standard deviation (SD) were used for numeric \nvariables. To compare categorical variables among groups, \nwe used Chi-Square or Fisher’s exact test (expected fre-\nquencies <5), depending on expected frequencies. To \ncompare numeric variables between two groups, we used \nthe independent sample t-test for normally distributed var-\niables and Wilcoxon-Mann-Whitney test for not normally \ndistributed variables. In addition, binary logistic regres-\nsion was used to evaluate a potential association between \nage and menarche and migraine onset in both subgroups. A \ntwo-tailed p-value ⩽0.05 was considered statistically \nsignificant.\nResults\nIn this study involving 375 premenopausal patients with \nendometriosis and 92 patients suffered from both, endo-\nmetriosis and migraine (Figure 1). About 38% (n = 35) of \nthe migraineurs experienced menstrual migraine and 61% \n(n = 57) reported non-menstrual migraine (nMM; Table 1). \nOnly two women in the menstrual migraine group suffered \nfrom pure menstrual migraine indicating, that they only \nexperienced migraine attacks at cycle days 1 ± 2 and never \non any other day. The groups did not differ with regard to \nage, but BMI was slightly lower in the MM group. Age at \nmenarche and age at first severe dysmenorrhoea did not \ndiffer (p = 0.66 and 0.56). A higher percentage of women in \nthe MM group experienced severe dysmenorrhoea onset \nwith menarche 48.6% versus 36.8% (p < 0.1). A similar \ntrend was seen for the number of monthly pain days during \nthe bleeding and use of analgesics for bleeding-related \npain (p ⩽ 0.1). There were no differences between the two \ngroups with regard to the ASRM stage or the number of \nsurgeries (p = 0.28 and 0.22; Table 1). Nevertheless, \nwomen with MM had less pregnancies and significantly \nless deliveries (p = 0.09 and 0.04). The groups did not dif-\nfer with regard to a history of depression or treatment for a \npsychic condition (p = 0.35 and 0.66). Table 2 demon-\nstrates migraine characteristic for both groups. There were \nno differences with regard to age at migraine onset \n(p = 0.8). Women with menstrual migraine suffered from a \nhigher migraine frequency, now and in the past, but not \nduring adolescence (p = 0.001, 0.002 and 0.36). In both \ngroups the rate of women having migraine with aura (MA) \nwas high with (41.2%–42.9%; p = 0.9). Frequency of med-\nication overuse headache, or history of status migrainosus \ndid not differ between groups (p = 0.44 and 0.3). The only \nmigraine trigger, which was significantly higher in the \nMM group was menstrual bleeding (p > 0.001). In more \nthan 50% of the women migraine was not present before \nstarting use of combined hormonal contraceptives (CHC). \nThis was more pronounced in the group of women without \nmenstrual migraine (p = 0.057; Table 2). Hormone use at \nthe time of the interview did not differ between groups \n(CHC 6.8 % nMM, 14.3% MM; progestin-only methods \nFigure 1. Flow Chart of participants.\n\n6 Journal of Endometriosis and Pelvic Pain Disorders 17(1)\n15.3% nMM 2.9% MM, no hormones 77.9% nMM; \n82.8%). A correlation between age at menarche and \nmigraine onset (p = 0.7 and 0.5) or between age at menarche \nand onset of severe dysmenorrhoea (p = 0.6 and 0.68) \ncould not be observed in the whole group, nor in the two \nsubgroups. Most of MIDAS associated quality of life items \nwas lower in the women with MM. Both average MIDAS \nGrade and MIDAS Score were higher in women with MM \n(0.01; Table 3).\nCurrently, 59% of the patients did not use prophylactic \nagents, 37% used magnesium or riboflavin on a regular \nbasis, while 3.1% used onabotulinumtoxin A or beta-\nblockers. Pain medication was prescribed from neurolo-\ngists in 18.5% and GPs in 35.1%. Another 35.1% of the \nTable 1. Baseline characteristics and endometriosis-related gynaecologic features.\nCharacteristics Menstrual migraine n = 35 Non menstrual migraine n = 57 p Value=\nMean ± SD/% (n) Mean ± SD/% (n)\nAge 37.0 ± 7.5 36.1 ± 7.6 0.57\n0 n.r. 0 n.r.  \nBMI 22.2 ± 2.8 23.7 ± 3.9 0.05\n0 n.r 0 n.r.  \nAge at menarche 12.8 ± 1.6 12.7 ± 1.5 0.66\n1 n.r. 0 n.r.  \nAge at first severe dysmenorrhoea* 18.7 ± 7.4 17.7 ± 7.2 0.56\n2 n.r 9 n.r  \nSevere dysmenorrhoea at menarche (scores 2 \nand 3)*\n48.6 (17) 36.8 (21) 0.10\n3 n.r. 0 n.r.  \nHeavy menstrual bleeding 65.7 (23) 63.2 (36) 0.80\n0 n.r. 0 n.r.  \nNumber of pregnancies 0.5 ± 0.7 1.0 ± 1.2 0.09\n1 n.r. 1 n.r.  \nNumber of deliveries 0.2 ± 0.4 0.75 ± 1.0 0.04\n1 n.r. 1 n.r.  \nEver treatment for psychic problems 57.1 (20) 50.9 (29) 0.66\n0 n.r. 0.n.r.  \nDiagnosis of depression 34.4 (10) 27.6 (13) 0.35\n6 n.r. 10 n.r.  \nMaximum of monthly days with endometriosis \npain during menstrual bleeding\n4.4 ± 2.3 3.6 ± 2.4 0.10\n0 n.r 3 n.r  \nMonthly days with use of analgesics during the \nmenstrual bleeding\n3.8 ± 3.8 2.7 ± 2.4 0.09\n2 n.r. 8 n.r.  \nrASRM stage 0.28\n 1 10 (28.6%) 14 (24.6%)  \n 2 6 (17.1%) 14 (24.6%)  \n 3 5 (14.3%) 15 (26.3%)  \n 4 14 (40.0%) 14 (24.6%)  \n0 n.r. 0 n.r.  \nrASRM stages 3 or 4 0.75\n 19 (54.3%) 29 (50.9%)  \n 0 n.r. 0 n.r.  \nAge at first EM surgery 0.91\n Mean (SD) 31.49 ± 6.26 31.33 ± 8.05  \n Range 18–42 15–48  \n0 n.r. 0 n.r.  \nFirst surgery at age 0–20 3 (8.6%) 5 (8.8%) 0.97\n0 n.r. 0 n..  \nNumber of EM surgeries 0.22\n Mean (SD) 1.57 (1.26) 1.86 (1.26)\n Range 0 n.r. 0 n.r.\nn.r.:no response \n\nMerki-Feld et al. 7\nparticipants bought the medication in the pharmacy with-\nout prescription or received it from other sources (11.3%).\nDiscussion\nEndometriosis and migraine are frequent, highly disabling, \noestrogen-dependent comorbidities with a shared genetic \nbackground.\n4–6 It is possible that women with endometrio-\nsis might differ from those without endometriosis with \nregard to MM course and features. Oestrogen interacts \nwith the local inflammatory process involving sensory \nnerve fibres and macrophages produced in the endometrio-\nsis lesions.\n41 In the present study we found, that 40% of \nmigraine patients with endometriosis suffered from MM. \nWithin this subgroup 42% reported migraine with aura. In \ncomparison with the nMM group the MM group experi-\nenced a higher frequency of monthly migraine attacks and \nhad a significantly lower quality of life with more days \ncharacterised by more days with reduced productivity at \nwork, missed leisure activities and without the ability to \nperform household work. Also, the MIDAS Grade was \nsignificantly higher (Table 3). This was observed despite \nno significant differences in the ASRM stage between \nwomen with MM and nMM. Regarding endometriosis \ncomplaints the patients with MM reported more often \nsevere dysmenorrhoea onset with menarche already \n(48.6% vs 35.8% p = 0.1) and more endometriosis-related \npain days during the menstrual bleeding (p = 0.1). The \ndelivery rate was significantly lower in the MM group \n(p = 0.04).\nMenstrual migraine frequency, onset and aura\nConsidering both, the high genetic background of the \ncomorbidity based amongst others on oestrogen-receptor \npolymorphisms, and the relevant role of oestrogens in the \npathophysiology of endometriosis we expected, that the \nmajority of women might suffer from MM and that \nmigraine onset might have a relation to age at menarche \nand onset of dysmenorrhoea. Insofar we were surprised \nTable 2. Migraine characteristics. .\nCharacteristics Menstrual migraine n = 35 Non menstrual migraine n = 57 p\nMean ± SD/% (n) Mean ± SD/%(n)\nAge at migraine onset 20.0 ± 7.9 19.5 ± 8.8 0.80\nn.r. 0 n.r. 0.n.r.  \nMigraine with Aura 42.9 (15) 42.1 (24) 0.9\nn.r. 0 n.r. 0 n.r.  \nCurrent migraine frequency (attacks/month) 2.7 ± 3.3 0.6 ± 1.7 0.001\nn.r. 0 n.r. 0 n.r.  \nMigraine frequency 5 years ago (attacks /month) 4.4 ± 5.7 1.7 ± 3.4 0.002\nn.r. 0 n.r. 0 n.r.  \nMigraine frequency at age under 20 years (attacks/\nmonth)\n1.6 ± 2.3 1.5 ± 3.0 0.36\nn.r. 1 n.r 4 n.r  \nCurrent migraine frequency >2 attacks/month 40.0 (35) 8.8 (5) 0.001\nn.r. 0 n.r. 1 n.r.  \nMean duration of migraine attacks/h 19.8 ± 22.3 14.7 ± 17.0 0.43\nn.r. 1.n.r. 2.n.r.  \nFamily history first degree relative with migraine 42.9 (15) 40.7 (24)  \nn.r. 0 n.r. 0 n.r.  \nMedication overuse headache ever 11.4 (4) 7.0 (4) 0.44\nn.r. 0 n.r. 1 n.r.  \nStatus migrainosus ever 28.6 (10) 19.3 (11) 0.30\nn.r. 0 n.r. 1 n.r  \nMigraine was present before CHC start 28.6 (10) 42.1 (24) 0.057\nn.r. 0 n.r. 3 n.r.  \nMigraine trigger  \nn.r 0 n.r. 0 n.r.  \nStress 54.2 (19) 38.6 (22) 0.19\nTiredness 28.5 (10) 43.8 (25) 0.18\nMenstruation 100 (35) 26 (15) >0.001\nSleep deficiency 20.0 (7) 24.5 (14) 0.79\nSkipping meals 14.2 (5) 7.0 (4) 0.29\nAlcohol 11.4 (4) 7.0 (4) 0.47\n\n8 Journal of Endometriosis and Pelvic Pain Disorders 17(1)\nthat migraine onset also in endometriosis patients is quite \nlate (age around 20 years) in relation to age at menarche \n(12.7–12.8 years) and also age at first severe dysmenor -\nrhoea (age 17–18 years). This is around 5–6 years after \nmenarche. Interesting is, that migraine onset and severe \ndysmenorrhoea onset are timely related in both groups. \nFurther studies are needed to understand if initiation of \nsevere dysmenorrhoea in endometriosis patients has an \nimpact on the course of migraine. It is also noteworthy, \nthat around 50% of our MM patients suffered from severe \ndysmenorrhoea already at the time of menarche.\nThe comorbidity does not seem to be associated with \nonset of symptoms already during early adolescence, but \nthe in general high rate of severe dysmenorrhoea with \nmenarche could be an indication for the clinician to check \nfor a history or family history of migraine. Even more rel-\nevant might be the choice of a contraceptive or hormone \nfor endometriosis treatment, if there is an indication for a \nbidirectional comorbidity.\nIn a recent high-quality diary-based study with migraine \npatients recruited in a headache centre, the prevalence of \nMM was around 15% higher than in our cross-sectional \nstudy, while the , prevalence of migraine with aura did not \ndiffer from ours with 40%.\n42 The study did check report if \nparticipants suffered from endometriosis. Another recently \npublished gene-based study found substantial genetic cor-\nrelation between migraine with aura and migraine without \naura, suggesting that both conditions might be more alike \nthan dissimilar.\n43 Menstrual migraine has been described \nto be typically without aura, however migraines with aura \ncould occur during the non-menstrual attacks of these \nwomen.\n18,24,29 Newer diary-based data confirm the notion, \nthat typically auras reported from patients with MM do not \noccur during the perimenstrual time frame of cycle days \n1 ± 2.\n42 Prevalence of menstrual migraine did in the latter \nstudy not differ between women with migraine with or \nwithout aura what is in line with our findings.\nStill, it is noteworthy, that in our study neither age at \nmigraine onset was earlier, nor was family history more \nfrequently positive in women suffering from MM.\n44\nThe percentage of women, who have ever been treated \nfor a psychological condition (51%–57%) was higher in \nour trial including endometriosis patients, than in studies \nwith migraine patients, but did not differ so much from the \npercentages in the Verhagen trial, which reported the per -\ncentage of lifetime depressions in migraineurs with 38%–\n43%.\n42,45,46 Major depression rate in our trial was 25% and \ndid not differ between groups, but there was a high rate of \nnon-responders.\nThe monthly migraine frequency (MMF) did not differ \nbetween groups during adolescence. In the later course of \nlife MMF was significantly higher in women with MM \n(Table 2). For the latter group we found in addition a trend \nto more days with endometriosis pain days during the men-\nstrual bleeding, what may contribute to the probably higher \nburden of disease. We can only speculate, why for both \ngroups the MMF was 40%–50% lower at the time of the \ninterview in comparison to the frequency 5 years earlier \n(Table 2). As only 3.1% of the patients used prophylactic \nagents apart from magnesium or riboflavin, the observed \ndecrease in MMF is rather not related to the new-start of \nprophylactic agents. All participants in our study underwent \nTable 3. MIDAS Parameters in women with Endometriosis and Menstrual or Non-menstrual Migraine.\nWomen with menstrual \nmigraine (n = 35)\nWomen with non-menstrual \nmigraine (n = 57)\np Value >\n Mean/% Standard deviation Mean Standard deviation\nMIDAS score 2.23 1.37 0.87 0.12  \nMIDAS 1 day missed at work 1.67 3.46 0.42 0.86 0.16\nMIDAS 2 days with >50% reduced productivity at \nwork\n3.34 4.62 1.49 4.49 0.01\nMIDAS 3 days without household work 5.26 9.42 0.84 1.86 0.01\nMIDAS 4 days with >50% reduced productivity in \nhousehold work\n0.89 2.61 1.07 4.28 0.52\nMIDAS 5 days when family, social or leisure \nactivities are missed (60)\n4.00 5.80 1.67 4.56 0.01\nMIDAS Headache days (61) 6.77 8.27 2.09 4.58 0.001\nMIDAS Pain intensity (scale1–10) 5.34 3.16 3.93 3.67 0.01\nMIDAS Grade 2.23 1.37 0.87 0.12 0.01\nMIDAS Grade >1 55.8% 24.0% 0.002\nMIDAS Grade 4 32% 7.0% 0:01\nQuestions in this table are given in a shortened form. The observation time for MIDAS includes a 90 day interval. Data were compared using non-\nparametric Wilcoxon test.\n\nMerki-Feld et al. 9\nendometriosis surgery within the recent years. There are two \nmechanisms how endometriosis surgery could impact the \ncourse of migraine. On one hand the CGRP release, an \nimportant trigger for migraine attacks, from endometriosis \nlesions is diminished. On the other hand, reduction in pelvic \npain might contribute to reverse central pain sensitisation. \nTherefore, we hypothesize that endometriosis surgery might \nnot only reduce dysmenorrhoea and pelvic pain, but also \nmight have had a positive impact on the course of both types \nof migraine.\nBurden of disease, surgery and pregnancies\nIn accordance with findings in migraine patients without \nthe comorbidity we found for endometriosis patients with \nMM that reduction in quality of life was much more pro-\nnounced than in those with nMM (Table 3). The high nega-\ntive impact of MM on the private life is reflected in the \nnumber of days when family/social activities are missed. If \nthis burden is the reason, why the pregnancy and delivery \nrate in this subgroup is lower requires further investiga-\ntion. It is well known, that endometriosis is associated with \ninfertility.\n47 Infertility rates in migraine patients have not \nyet been investigated. As neither ASRM stages nor the age \nat first endometriosis operation or the number of endome-\ntriosis operations differ, we suggest, that the higher burden \nof disease in our MM-subpopulation is a main cause for \nthe lower delivery rate. This hypothesis is in accordance \nwith a recently published narrative review postulating that \nmigraine may influence fertility related to the obstacles \npatients face stemming the impact of migraine on their \nsocial relationships.\n48 Looking at the balanced age distri-\nbution of both groups (women >35 years; MM = 52%; \nnMM = 54%) we regard it as unlikely that a difference in \nthe distribution of age between the groups could bias this \nresult. Staying without children might in addition diminish \npsychological well-being.\n49 As both migraine and endo-\nmetriosis are associated with depression we checked in the \ninterview, if women had ever experienced treatment for \npsychic problems or a depression. In spite of the higher \nburden of disease reported for our MM patient we did not \nfind a difference in psychiatric comorbidity between \ngroups, however the percentage of such a treatment was \nstrikingly high (>50%) for both groups (Table 1). The \nmajority of data related to migraine and depression do not \ndiscriminate between migraine subtypes and do not con-\nsider fertility or endometriosis, but this topic requires more \nattention.\n50–53\nFinally, we found a trend towards more monthly days \nwith endometriosis pain during the menstrual bleeding in \nMM patients, what could be the cause for the higher num-\nber of days using analgesics in this period (p < 0.1; Table \n1). The progestin desogestrel exerts a positive impact on \nmenstrual and non-menstrual migraine and might insofar \nbe considered as an important option for the treatment of \nboth conditions.\n35,54,55 It is still not clear today, if the oes-\ntrogen-induced disabling migraine attacks during the peri-\nmenstrual phase would also improve with treatment \noptions like physiotherapy or stress relaxation.\nLimitations\nStrength of this study are the inclusion of only women \nwith histologic confirmed endometriosis and a clear stag-\ning, and the collection of migraine data by skilled experts \nin a phone interview. However, potentially data related to \npain and migraine frequency in the past might be affected \nto recall bias. Insofar our data have to be confirmed in pro-\nspective studies. Women were recruited from a specialised \nendometriosis clinic and not a headache clinic. This might \nexplain, why the overall frequency of migraine/month was \nrather low. However, we do not expect that the general out-\ncomes related to high burden, migraine onset in relation to \nmenarche, low delivery rate and course of MM are much \naffected from this.\nConclusions\nIn women with similar ASRM endometriosis stages MM is \nassociated with a higher migraine frequency, a lower deliv-\nery rate, more dysmenorrhoea days and a much lower \nquality of life in comparison to nMM. In neither group age \nof migraine onset correlated with onset of severe dysmen-\norrhoea or age at menarche. Future studies are needed to \nbetter understand a potential influence of menstrual \nmigraine or its burden on the number of deliveries. \nOestrogen-free hormonal treatment options can be useful \nfor both conditions and may contribute to reduce the bur -\nden of disease. Our findings suggest that collaboration \nbetween neurologists and gynaecologists and shared treat-\nment decisions might be of advantage in endometriosis/\nmigraine patients.\nAcknowledgement\nThe authors thank all patients who agreed to participate in this \nstudy.\nData Availability Statement\nData sharing not applicable to this article as no datasets were \ngenerated or analysed during the current study.\nDeclaration of conflicting interests\nThe author(s) declared no potential conflicts of interest with \nrespect to the research, authorship, and/or publication of this \narticle.\nFunding\nThe author(s) received no financial support for the research, \nauthorship, and/or publication of this article.\n\n10 Journal of Endometriosis and Pelvic Pain Disorders 17(1)\nORCID iDs\nGabriele S Merki-Feld  https://orcid.org/0000-0002-8644- \n773X\nAngela Niggli  https://orcid.org/0009-0002-4385-2468\nChristoph J Schankin  https://orcid.org/0000-0003-4668- \n6098\nReferences\n 1. 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