{"paper_id":"24576199-a895-48b1-bfa8-753802f821b2","body_text":"L Demetriou et al. 262–272\n3:4\nRESEARCH\nStressful experiences impact clinical \nsymptoms in people with endometriosis\nLysia Demetriou 1, Christian M Becker1, Beatriz Martínez-Burgo 1, Adriana L Invitti1,2, Marina Kvaskoff3, \nRazneen Shah1, Emma Evans4, Claire E Lunde1,5,6, Emma Cox7, Kurtis Garbutt1, Krina T Zondervan1,8, Elaine Fox9 and \nKaty Vincent1\n1Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK\n2Departamento de Ginecologia, Universidade Federal de São Paulo, São Paulo, Brazil\n3Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Gustave Roussy, ‘Exposome and Heredity’ Team, CESP, Villejuif, France\n4Oxford University Hospitals NHS Foundation Trust, Oxford, UK\n5Biobehavioral Pediatric Pain Lab, Department of Psychiatry, Boston Children’s Hospital, Boston, Massachusetts, USA\n6Pain and Affective Neuroscience Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital, Massachusetts, USA\n7Endometriosis UK, UK\n8Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK\n9Department of Experimental Psychology, University of Oxford, Oxford, UK\nCorrespondence should be addressed to L Demetriou: lysimachi.demetriou@wrh.ox.ac.uk\nAbstract\nEndometriosis is a chronic condition that affects ~10% of women globally. Its symptoms include chronic pelvic pain, \nheavy periods and tiredness/fatigue, which have been associated with poorer quality of life and mental health. We aim \nto explore the impact of the COVID-19 pandemic on pain and fatigue symptoms and their interactions with the impact \non mental health in people with endometriosis. This global cross-sectional online survey study collected data from \n4717 adults with self-reported surgical/radiological diagnosis of endometriosis between May and June 2020. The survey \nincluded questions on the current status and changes of endometriosis symptoms (pelvic pain, tiredness/fatigue, and \nbleeding patterns), mental health, pain catastrophising, and the impact of the COVID-19 pandemic on the respondents’ \nlives. Compared to 6 months earlier, Respondents reported a marked worsening of their endometriosis symptoms \n(endometriosis-associated pain (39.3%; 95% CI: 37.7, 40.5), tiredness/fatigue (49.9%; 95% CI: 48.4, 51.2) and bleeding \npatterns (39.6%; 95% CI: 38.2, 41)) and mental health (38.6%; 95% CI: 37.2, 39.9). Those with a pre-existing mental health \ndiagnosis (38.8%) were more likely to report their symptoms worsening. Worsening of pain and tiredness/fatigue was \nsignificantly correlated with worsening of mental health (P < 0.001). The relationship between changes in mental health \nand (a) change in pain and (b) change in fatigue was found to be weakly mediated by pain catastrophising scores (pain: \nB = 0.071, lower limit of confidence interval (LLCI) = 0.060, upper limit of confidence interval (ULCI) = 0.082, tiredness/\nfatigue: B = 0.050, LLCI = 0.040, ULCI = 0.060). This study demonstrates that stressful experiences impact the physical and \nmental health of people with endometriosis. The findings highlight the need to consider psychological approaches in the \nholistic management of people with endometriosis.\nLay summary\nEndometriosis is a chronic condition in which tissue similar to that of the lining of the womb grows outside it. It affects \naround 10% of women globally, and the symptoms often include persistent pelvic pain, heavy periods and tiredness/\nfatigue. These symptoms are associated with impaired mental health and life quality. This study used an online \nquestionnaire to assess the experiences of people with endometriosis during the first months of the pandemic. Results \nfrom 4717 adults revealed that pelvic pain, tiredness/fatigue and bleeding worsened in more than 39% of the participants. \nPoor mental health was also exacerbated and associated with worsening in tiredness/fatigue. Further analysis revealed \n-22-0028ID: XX-XXXX; \n3 4\nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2633:4\nthat this relationship could be partially explained by ‘pain catastrophising’, which measures how participants think about \ntheir pain. Our results suggest that stressful experiences like the pandemic negatively impact the already burdened mental \nhealth of people with endometriosis, who could benefit from psychological interventions.\nKeywords:  endometriosis   COVID-19   survey   women   pandemic\nReproduction and Fertility (2022) 3 262–272\nIntroduction\nEndometriosis is a chronic condition that affects ~10% of \nwomen globally. It is classically associated with a variety \nof pelvic pain syndromes and subfertility; however, many \nsufferers also describe heavy periods and tiredness/fatigue \n(TF). The nature and longevity of these symptoms, along \nwith the currently long diagnostic delay of the disease, \nhave been associated with impairments in the quality \nof life, including mental health and work productivity \n(Nnoaham et  al. 2 011, Facchin et  al. 2017 , Zondervan \net  al. 2018). The symptoms of infertility and dyspareunia \nadd to the psychological burden of people suffering with \nendometriosis and increase the levels of perceived stress \nwhile also negatively affecting the patients’ self-esteem \nand relationship with their partners (Denny & Mann 2007, \nVitale et al. 2017). Fatigue has also been identified as one of \nthe most intense and frequent symptoms of endometriosis \n(Hansen et  al. 2013) and associated with pain, insomnia \nand depression ( Ramin-Wright et  al. 2018 ) but is often \noverlooked in clinics.\nThe coronavirus disease 2019 (COVID-19) that was \ndeclared as a pandemic by the World Health Organization \n(WHO) on 1 1 March 2020 ( World Health Organization \n2020) has been a disruptor to normal life and a source of \nsignificant stress (Kujawa et al. 2020). Studies have shown \nthat during the early weeks of government lockdowns, \nthere was a significant negative effect on mental health in \nthe general population (Brooks et al. 2020) and particularly \nin women in Italy ( Di Giuseppe et  al. 2020). In addition, \naccess to healthcare was severely affected at a global level. \nFor people with endometriosis, this meant cancelled \nappointments with gynaecologists and other specialists, \ndelayed or cancelled surgical procedures and fertility \ntreatments and difficulties accessing medication ( Yalçın \nBahat et al. 2020, Demetriou et al. 2021).\nUnderstanding the impact of the COVID-19 pandemic \non those with endometriosis could help us to better \nunderstand how other large-scale stressful events that \ncan disrupt access to normal healthcare and routines may \nimpact this population, potentially identifying those \nat risk of worsening symptoms during times of stress \nand informing the design of future multi-disciplinary \ntreatment protocols. The objective of the present study is \ntherefore to explore the impact of the early stages of the \nCOVID-19 pandemic on mental health and endometriosis-\nassociated symptomatology using data from a global \nsurvey. It is plausible that people with endometriosis \nare more adversely affected by an external stressor than \nan otherwise healthy population ( Petrelluzzi et  al.  \n2008, Sepulcri & do Amaral 2009 , Quiñones et  al. 2015, \nFacchin et al. 2017, Coxon et al. 2018) due to alterations in \nphysiological and psychological mechanisms underlying \nresilience and homeostasis ( Carbone et  al. 2021, Lubián-\nLópez et al. 2021).\nIn line with other population-based studies ( Brooks \net  al. 2020 , Di Giuseppe et  al. 2020 , Kujawa et  al. 2020 , \nYalçın Bahat et al. 2020), we expect to see a deterioration in \nmental health in our cohort. We hypothesise that in those \nwhose mental health worsens, pain and fatigue symptoms \nwill also increase. However, given the complex mechanisms \ninvolved in endometriosis-associated pain ( Morotti et  al. \n2017) and in fatigue more generally ( Norheim et al. 2 011), \nwe do not expect to see a direct relationship between \nmeasures of pain intensity and psychological well-being. \nWe will also explore the impact of the early stages of the \npandemic on bleeding patterns. Finally, any relationship \nbetween alterations in mental health and pain or fatigue \ncould be mediated by either intrinsic psychological factors \nor extrinsic factors. Therefore, we will explore whether \npain catastrophising (intrinsic) as a measure of how people \nperceive and worry about their pain, perceived stress or \nemotional support (both extrinsic) mediates any observed \nrelationships.\nMethods\nThis was an online cross-sectional study conducted between \n1 1 May 2020 and 8 June 2020, and the data were collected \nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2643:4\nvia a global online survey study (Jisc: https ://ww w.jis c.ac. \nuk/on line- surve ys). The research was internally funded \nby the University of Oxford. The study obtained approval \nby The Central University Research Ethics Committee, \nUniversity of Oxford (reference number: R69636/RE001) \nand was advertised widely on social media by endometriosis \nsupport groups around the world and by endometriosis \nand women’s health researchers and clinicians.\nThe survey was designed in collaboration with the \nsupport group Endometriosis UK and consisted of both \nvalidated outcome measures (see section titled ’Domains \nassessed’) and relevant multiple-choice questions, some \nof which had an extra option for a free text response if \nthe answer was not already provided. It assessed a variety \nof areas relevant to endometriosis symptoms, mental \nhealth, and the impact of COVID-19 on the respondent’s \nlives (available as Supplementary material online, see \nsection on supplementary materials  given at the end of \nthis article). Whilst specific core outcome sets were not \nused, we aimed to assess all domains recommended for \nstudies of chronic pain and endometriosis ( Dworkin et al. \n2005, Rogers et al. 2009). Many of the questions were taken \ndirectly from the EPHEct Clinical Covariates Questionnaire \n(Vitonis et  al. 2014). The survey was prepared in English \nand then translated by native speakers into French, \nGerman, Spanish, and Portuguese. All free text responses \nwere translated into English by these native speakers and \ncategorised by two researchers (LD and KV). None of the \nquestions was mandatory; therefore, the total number of \nrespondents for each varies.\nParticipants\nA total of 7246 respondents completed the survey, with \n6729 of them meeting the inclusion criteria of age ( ≤18 \nyears old) and confirmed endometriosis diagnosis by \nsurgery or imaging. In addition, as per the inclusion/\nexclusion criteria, the participants needed to be able to \nread, write and understand one of the languages that \nthe questionnaire was available in (thereby excluding \nparticipants with severe cognitive impairments) and \nhave access to a computer, tablet or smartphone with \ninternet connection. Additionally, for the purposes of the \npresent analysis, exclusions were made if the respondents \nreported a change in their hormone treatments or if they \nhad a change in their pregnancy or breastfeeding status \ncompared to 6 months ago as changes in hormonal status \nsuch as these would be expected to influence endometriosis \nsymptoms. The final dataset used for the analysis included \n4717 respondents (mean age =  33.2).\nDomains assessed\nEndometriosis symptoms\nThe survey assessed a variety of pelvic pain symptoms, \nbleeding and TF . Pain was assessed with numerical rating \nscales (NRSs) for pain intensity anchored with 0 =  no pain \nand 10 =  worst pain imaginable. NRSs have been widely used \nin the pain literature and proven to have high sensitivity \nand reliability for assessing pain ( Williamson & Hoggart \n2005, Karcioglu et  al. 2018 ). The self-reported change \nin pain and TF compared to 6 months ago was assessed \nwith ordinal scales with the following response options \navailable: very marked worsening, marked worsening, \nminimal worsening, no change, minimal improvement, \nmarked improvement, I did not experience any pain/\nTF due to endometriosis and this has not changed. An \nextensive set of responses was provided for changes in the \nregularity and frequency of bleeding pattern to allow all \npossible options to be assessed (Supplementary Appendix \n1. Question B.6).\nMental health measures\nSelf-reported change in mental health compared to 6 \nmonths ago was assessed with an ordinal scale with the \nsame response options as for pain and TF .\nThe respondents’ current-state mental health was \nassessed using Patient-Reported Outcomes Measurement \nInformation System (PROMIS) and NIH Toolbox validated \nscales (Cella et al. 2007, Gershon et al. 2013, Hanmer et al. \n2020). The scales assessed depression, anxiety and pain \ninterference during the last 7 days and perceived stress and \nemotional support since the pandemic was announced. \nV alidated translations of some of these measures were not \navailable and thus could not be included in the survey in \nthat language. This applied to the perceived stress measure \nin German and the emotional support scale in French and \nPortuguese.\nPain catastrophising as a measure of how participants \nworry and distress about their physical pain (Crombez et al. \n2020, Petrini & Arendt-Nielsen 2020 ) was assessed using \nthe Pain Catastrophising Scale (PCS) (Cronbach’s α =  0.87) \n(Sullivan et al. 1995, Osman et al. 2000 ). This is a 13-item \nquestionnaire that used a 5-point scale ranging from 0 (not \nat all) to 4 (all the time); the total PCS score was computed \nby summing the responses to all 13 items ( Sullivan et  al. \n1995).\nPrevious diagnoses of anxiety and depression \nrequiring therapy or medication were extracted from \na question assessing comorbidities. The participants \nwere asked to tick a ‘Y es’ box if they they had received a \nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2653:4\ndiagnosis for any of those comorbidities (Supplementary \nAppendix 1. A.7).\nCOVID-19 pandemic impact\nA set of questions assessed the impact of the COVID-19 \npandemic on personal and work life (Supplementary \nAppendix 1. C.10) and access to medication or planned \nappointments/treatments for both endometriosis and \nother reported comorbidities (Supplementary Appendix 1. \nB.1–3) (Demetriou et al. 2021).\nStatistical analysis\nData were extracted and processed using the IBM SPSS \nStatistics software, Version 27. A mean score for all \nrespondents was calculated for each NRS pain scale. The \nscoring for the PROMIS and NIH Toolbox scales was \ndone using the HealthMeasures tool which produces a \nt-score value per respondent per scale. A mean of t-scores \nwas then calculated for each scale. Descriptive statistics \nwere calculated for all the variables, including mean, s.d.  \nands.e. and median, where appropriate. Frequencies and \npercentages were calculated for the effect of the pandemic \non endometriosis symptoms and mental health.\nNon-parametric tests (chi-square and Spearman’s \nbivariate correlations) were used for analyses that included \nordinal data (change in endometriosis pain, TF and mental \nhealth), while parametric statistical testing (ANOV As \nand Pearson’s bivariate correlations) was used for the \ncontinuous variables (PROMIS scales and PCS).\nA mediation analysis was employed to explore whether \nthe relationship between the reported change in mental \nhealth as a predictor and changes in pain or TF as outcomes \nwas facilitated by the following hypothesised mediators: \npain catastrophising, perceived stress or emotional \nsupport. As a sensitivity analysis, the mediation analyses \nwere repeated on the population of respondents who \nreported no alteration of their endometriosis medication \ntreatment due to the pandemic. The mediation analysis \nwas run using PROCESS on IBM SPSS Statistics software, \nVersion 27 (Hayes 2013).\nResults\nPelvic pain was reported as the most bothersome \nendometriosis symptom before the pandemic by more than \nhalf of our respondents (55.3%). For further demographic \ninformation and characteristics for our respondents, please \nrefer to Table 1.\nOverall, as a result of the COVID-19 pandemic, \napproximately half of the respondents (50.8%) reported no \nmajor life changes more than most people (of the general \npopulation), while 17.5% reported a significant decrease \nin their earnings and 14% reported that they had to work \nfor much longer hours ( Table 2). About 31.3% described \nalteration of their medications related to endometriosis \n(hormones or analgesics). Although perceived stress of the \ncohort (mean t-score =  50.2, s.d. =  8.0) was in line with the \nscore of the reference population, 12% of our respondents \nhad scores ≥60, which suggest higher than average stress \npotentially needing surveillance by a mental health \nprofessional (Scoring 2018).\nImpact of pandemic on mental health\nAbout 38.6% of the respondents reported a marked \nworsening in their mental health, while 55.4% reported \nminimal or no change and 3.7% marked improvement. \nTable 1 Summary of participants’ characteristics presented \nas mean ± s.d . or frequencies and percentages (%), where \nappropriate.\nCharacteristics Values\nAge 33.2 ± 7.9\nWork status before the pandemic\n Working in a paid job, as a full-time employee \nor worker\n2632 (56.3)\n Working in a paid job, as a part-time employee \nor worker\n801 (17.1)\n Self-employed 483 (10.3)\n Not in paid work force 758 (16.2)\nHighest level of education\n Primary/grade school 23 (0.5)\n Lower secondary/middle school or upper \nsecondary/high school\n109 (13.2)\n Post-secondary, not university/some college \nor vocational school\n1184 (25.2)\n University 1866 (39.8)\n Postgraduate 998 (21.3)\nLiving situation \n Alone 546 (11.6)\n Flatmates/roommates/friends 189 (4)\n Parents/family partner, no children 770 (16.4)\n Partner, no children 1904 (40.5)\n Partner and children 1050 (22.3)\n Children, no other adults 129 (2.7)\n Other – please describe 118 (2.5)\nGeographical region of residence\n Europe 3201 (67.9)\n North America 701 (14.9)\n Latin America and the Carribean 430 (9.1)\n Asia 21 (0.4)\n Oceania 249 (5.3)\n Africa 19 (0.4)\nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2663:4\nA sensitivity analysis was undertaken to explore whether \na pre-existing diagnosis of anxiety or depression disorder \nwas associated with the reported change in mental \nhealth. A greater percentage of participants with a \ndiagnosis reported a marked worsening of mental health, \nwhile a greater percentage of respondents without a \ndiagnosis reported minimal worsening, with no change \nor improvement in their mental health (significant chi-\nsquare test: χ2(6) =  342.83, P < 0.001, Cramer’s V =  0.279, N \nof diagnosis =  1831). However, in both groups, more than \n30% of the respondents reported a marked worsening of \ntheir mental health (Fig. 1A).\nAdditionally, we explored whether other factors \nassociated with an individual’s experience of the pandemic \nmay have impacted on their mental health. There was \nno significant correlation between pandemic-associated \nmajor life changes and reported change in mental health \n(r =  0.005, P = 0.073) nor for perceived stress (r =  0.019, \nP = 0.408). Participants who worried that endometriosis \nmade them vulnerable to COVID-19 and those who \nreported being at high risk for COVID did experience \ngreater worsening of mental health, but these relationships \nwere weak (r =  0.149, P < 0.001 and r =  0.087 , P < 0.001, \nrespectively).\nImpact of pandemic on endometriosis-\nassociated symptomatology\nAbout 39.3% of the respondents reported a marked \nworsening of their endometriosis-associated pain, while \n54.1% reported minimal or no change and only 3.8% \nmarked improvement ( Fig. 1B ). Similarly, 49.9% of the \nrespondents reported marked worsening of their TF , while \n43.3% had minimal or no worsening and 4.3% had minimal \nimprovement (Fig. 1C). Findings followed a similar pattern \nwhen analysed by geographical region, ranging from \n27.3% to 51.2% for reported marked worsening in pain and \nfrom 33.3% to 57% for reported marked worsening in TF \n(Supplementary Table 1). When asked about changes in \ntheir bleeding pattern, 59.2% of the respondents reported \nTable 2 Summary of altered medications, altered planned treatments, mental health diagnosis and COVID-19 impact, presented \nas frequencies and percentages (%).\nFrequency Percent (%)\nAltered medication and planned treatments 3663 78.4\nAltered medication treatment 1476 31.3\nAltered planned treatment 3151 66.8\nMental health diagnosis 1831 38.8\nCOVID-19 impact\n Had symptoms of COVID-19 753 16\n Had a positive test for COVID-19 79 1.7\n Been admitted to hospital because of COVID-19 18 0.4\n Has anyone you live with had symptoms of COVID-19 591 12.6\n Has anyone you live with had a positive test for COVID-19 67 1.4\n Has someone close to you (family or friend) died because of COVID-19 381 8.1\n Are you considered ‘vulnerable’/at high risk from COVID-19 990 21.1\n Live with someone considered ‘vulnerable’/at high risk from COVID-19 1162 24.7\n Worry that endometriosis makes you more vulnerable to COVID-19 2534 53.9 \nCOVID-19 pandemic impact on major life changes\n No, nothing more than for most people 2397 50.8\n I have lost my job 352 7.5\n I have had to work much longer hours 662 14\n I have had a significant decrease in my earnings 824 17.5\n I cannot run my business 239 5.1\n I have had to move out of my home 132 2.8\n My relationship with my partner has fallen apart 241 5.1\n I have had to postpone/cancel my wedding 115 2.4\nMost important/bothersome before the pandemic\n Pelvic pain 2602 55.3\n Heavy and/or irregular bleeding 395 8.4\n Fatigue 293 6.2\n Bowel problems 403 8.6\n Urinary/bladder problems 109 2.3\n Pain during or after sex 263 5.6\n Infertility/difficulty getting pregnant 410 8.7\nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2673:4\nno change, while 17.4% reported increased or more \nfrequent bleeding and 15.2% reported decreased or less \nbleeding during the pandemic.\nFurther analysis on the effect of treatment alterations \non the changes in symptoms revealed a significant effect \nbetween respondents that reported an alteration of their \ncurrent treatments and those who did not both for pain \n(χ2(6) =  244.6, P = 0.000) and TF ( χ2(6) =  164.7 , P = 0.000). \nBoth these effects were moderate, as evidenced by the \nCramer’s V values (pain: Cramer’s V =  0.235 and TF: \nCramer’s V =  0.192). A greater percentage of respondents \nwith alterations in their treatments or medications \nreported a marked worsening of pain and TF , while a greater \npercentage of the respondents that had no alteration to \ntheir current treatment or medication reported minimal \nworsening, no change or improvement of their pain and \nTF . However, of those who did not have a medication \nalteration, we still found that 24.8% had a marked \nworsening of their pain and 39.9% had marked worsening \nof their TF . Of the responders who reported alterations to \ntheir current treatment or medication, 47.2% also reported \nalterations to their bleeding pattern.\nRelationship between reported changes in mental \nhealth and endometriosis symptoms\nSpearman’s correlation analyses revealed a significant \npositive relationship between changes in mental health \nand changes in pain (r =  0.33, P < 0.001) and TF (r =  0.48, \nP < 0.001).\nRelationship between reported changes in \nendometriosis symptoms and other factors related to \nthe pandemic\nNo significant effects were found in the correlations \nbetween perceived stress and changes in pain or TF \n(Spearman’s correlation P > 0.05). Similarly, there was no \nrelationship between major life changes associated to the \nCOVID-19 pandemic and reported changes in pain or TF \n(r =  0.008, P = 0.624 and r =  –0.018, P = 0.263 respectively). \nThose participants who worried about endometriosis \nmaking them vulnerable to COVID-19 or who were at \nhigh risk for another reason did report an increased pain \nand TF; however, the effect sizes were small for all these \nrelationships (r =  0.046–0.126).\nRelationship between psychological measures and \ncurrent pain intensity\nThere were no significant correlations between absolute \nlevels of anxiety, depression, perceived stress and the \nintensity of any of the pain symptoms (Spearman’s \ncorrelations P > 0.05).\nInteraction between changes in mental health and \nendometriosis symptoms via pain catastrophising, \nemotional support and perceived stress\nA mediation analysis on the relationship between change \nin mental health and change in pain explained by PCS \nrevealed a weak significant effect (B =  0.071, lower limit \nof confidence interval (LLCI) =  0.060, upper limit of \nconfidence interval (ULCI) =  0.082) of PCS as a mediator \n(Fig. 2A). A similarly significant but weak effect (B =  0.050, \nLLCI =  0.040, ULCI =  0.060) was also found for the \nrelationship between change in mental health and change \nin TF mediated by PCS (Fig. 2B).\nFigure 1 (A) Change in mental health for all responders (medium grey), \nresponders with pre-existing anxiety and or depression diagnosis (light \ngrey) and responders without pre-existing diagnosis (dark grey) presented \nas percentages (%) (N = 4381). (B and C) Change in (B) pain and (C) fatigue \nfor all responders (medium grey), responders with alterations to their \nendometriosis medication (light grey) and responders without alterations \nto their endometriosis medication (dark grey) presented as percentages \n(%) (N = 4343).\nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2683:4\nAs a sensitivity analysis, the above mediation analyses \nwere repeated on the sample of respondents who had no \nalterations in their medication. The results showed that the \nfirst mediation between the change in mental health and \nchange in pain had a weak but significant effect (B =  0.058, \nLLCI =  0.046, ULCI =  0.070) of PCS. Results of the second \nmediation revealed a similar result of a weak significant \neffect (B =  0.050, LLCI =  0.038, ULCI =  0.062) of PCS on the \nrelationship between the change in mental health and the \nchange in TF .\nFurther mediation analyses exploring the relationship \nbetween change in mental health and change in \nendometriosis symptoms explained by perceived stress and \nemotional support as mediators revealed no significant \neffects of either mediator (perceived stress: pain: B =  0.00, \nLLCI =  –0.01 1, ULCI= 0.01 1 and TF: B =  0.00, LLCI =  –0.015, \nULCI =  0.014; emotional support: pain: B =  0.00, \nLLCI =  –0.001, ULCI =  0.002 and TF: B =  0.00, LLCI =  -0.001, \nULCI= 0.01 1).\nWhen the mediation analyses were repeated on \nthe respondents who reported no alterations to their \nmedications due to the pandemic, the results remained not \nsignificant (perceived stress: pain: B =  0.00, LLCI =  –0.002, \nULCI =  0.003 and TF: B =  –0.0004, LLCI= –0.003, ULCI= \n0.002; emotional support: pain: B: –0.003, LLCI =  –0.003, \nULCI =  0.002 and TF: B =  0.00, LLCI =  –0.001, ULCI =  0.003).\nDiscussion\nMain findings\nIn this study, we found that the early stages the \nCOVID-19 pandemic were perceived by people with \nendometriosis as having a negative impact on mental \nhealth and endometriosis symptoms, with almost 40% \nreporting a marked worsening of their mental health and \nendometriosis-associated pain and approximately half \nreporting a marked worsening of their TF . Additionally, \napproximately a third of respondents described a change in \ntheir bleeding pattern. Reports of worsening of symptoms \nwere not limited to those who reported changing their \nmedication due to the pandemic measures nor those with \na pre-existing mental health diagnosis; this was seen in \nresponses from all regions of the world.\nReported changes in mental health were \nsignificantly correlated with reported changes in pain \nand TF . Interestingly, reported changes in endometriosis \nsymptoms had no significant association with perceived \nstress. Increased pain catastrophising appears to play a \nrole in mediating the relationships between mental health \nand pain and TF; however, this was not the case for either \nperceived stress or perceived emotional support.\nStrengths and limitations\nThe major strength of this study is the large sample size, \ncollected over a relatively short time-period. This was \ncrucial to capture the responses of the participants during \nthe first wave of the pandemic when similar measures were \ntaken across countries, and the COVID-19 pandemic was \nstill a novel stressful event for most people without the \nlockdown/pandemic fatigue that it is currently associated \nwith. Respondents resided in 70 different countries, \nincluding regions usually overlooked or under-represented \nin similar studies (Rogers et al. 2009). Moreover, we captured \na wide age range and varied socio-economic backgrounds, \nalthough our study did require people to have access to the \ninternet and be able to complete an online study.\nHowever, the study design meant we had no access to \nhealthcare records to confirm the endometriosis diagnosis. \nWe aimed to mitigate against this, by questioning how the \nendometriosis diagnosis had been made and including only \nrespondents who reported a surgical or imaging diagnosis. \nFurthermore, effect sizes were small and therefore results \nshould be interpreted with caution; however, they can be \nindicative of the associations between changes in clinical \nsymptoms and the COVID-19 pandemic as a stressful event.\nFigure 2 Model for mediation analyses for the relationship between \nchanges in mental health and (A) pain and (B) fatigue mediated by PCS.\nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2693:4\nAdditionally, our sample may not fully reflect the \nbackground population of people with endometriosis, \nfocusing instead on those who follow support groups or \nresearchers online or those who actively visited these sites \nduring the pandemic perhaps because they felt the need for \nadditional support. Importantly, there was no possibility of \nperforming a face-to-face study or recruiting directly from \nclinic cohorts at this time as most benign gynaecology \nservices were paused. Finally, as this is a cross-sectional \nonline study, our data were derived from patients’ reports \nof changes in their endometriosis symptoms and quality of \nlife which could have biased our results. However, fatigue is \na subjective experience; therefore, the reported changes by \nthe respondents still provide valuable information.\nInterpretation\nRelatively early in the pandemic, concerns were being \nexpressed about the potential for a pandemic-related \nincrease in chronic pain ( Clauw et al. 2020). Of the three \npotential mechanisms discussed, two may be particularly \nrelevant to our study: (i) worsening of chronic pain \nsecondary to an exacerbation of pre-existing pain-\nassociated physical or psychological factors and (ii) new-\nonset chronic pain triggered by exacerbation of other \nrisk factors. Thus, it is plausible that some of the reported \nworsening of pain we saw in our cohort is correlated with \nincreased disease activity either due to an inability to \nobtain hormonal therapies that normally keep the disease \nsuppressed or due to altered endogenous hormone activity. \nHowever, we do not believe that altered hormone therapies \nis the sole factor as we excluded people who described a \ncomplete change in hormone therapy when compared \nto that 6 months ago and less than a third of our cohort \nreported having to change/stop medications including \nhormonal therapies. Moreover, even from those who \nreported no change in any medication, approximately \na quarter reported worsening pain. Many people with \nendometriosis will describe a flare in their symptoms with \neither regular or unscheduled bleeding and over 40% \nof our cohort reported a change in the bleeding pattern. \nBoth physiological and psychological stress can disrupt the \nactivity of the hypothalamic–pituitary–ovarian axis, and \nstudies have shown that during the pandemic both elite \nathletes ( McNamara & Harris Rachel 2020 ) and women \nwith a confirmed diagnosis of COVID-19 ( Li et  al. 2021) \nhave experienced changes in their cycle. Other factors \nsuch as deteriorating mental health, poor sleep, reduced \nability/desire to undertake physical activity or stress are \nalso likely to be playing a role. It is interesting to consider \nwhether these factors may also have contributed to the \ndevelopment of pain in those in whom this was not the \npredominant symptom previously (~40% of our cohort). \nWe are certainly increasingly aware that there is little \nrelationship between pain symptoms and extent/location \nof endometriosis as visualised at laparoscopy ( Vercellini \net  al. 1996 ) and that the factors contributing to pain in \nassociation with endometriosis are complex ( Stratton & \nBerkley 201 1, Coxon et al. 2018).\nThe interdependency of physical and mental health is \nincreasingly being considered in health research and policy \n(HM Government Department of Health 201 1, Naylor et al. \n2012). In keeping with this, there has been a greater focus \non mental health in people with endometriosis over the \nrecent years. Endometriosis appears to increase the risk for \nmental health disorders, although the mechanisms remain \nunclear and could include aspects of endometriosis itself \n(e.g. inflammation) as well as wider factors (e.g. chronic \npain and infertility) ( Pope et al. 2015, Laganà et al. 2017). \nOur findings are in line with the literature suggesting high \ncomorbidity between endometriosis and common mental \nhealth disorders ( Sepulcri & do Amaral 2009 , Facchin \net  al. 2017): 38.8% of the participants had a pre-existing \ndiagnosis of anxiety and/or depression requiring therapy \nor medication. As in the general population, it is likely that \nmany more individuals experienced clinically significant \nsymptoms but were undiagnosed ( Williams et  al. 2017). \nThose with a pre-existing diagnosis were more likely to \ndescribe a marked worsening of their mental health in the \nearly stages of the pandemic.\nAs we expected, there was a close relationship between \nchanges in mental health and in pain and TF . Generally, \nthese relationships are considered bidirectional with, for \nexample, a worsening of pain impacting negatively on \nmood and a deteriorating mood amplifying the experience \nof pain ( Hooten 2016 ). Our data, being cross-sectional, \ncan tell us nothing about directionality. However, given \nthat in the population as a whole mental health was seen \nto deteriorate from early on in the pandemic ( Brooks et al. \n2020, Di Giuseppe et  al. 2020 , Kujawa et  al. 2020 ) and \ndisease activity is likely to have stayed stable for many, we \nhypothesise that a change in mental health status is likely \nto be a driver for pain and fatigue for a proportion of our \ncohort. It is interesting that pain catastrophising but not \nperceived stress or emotional support appears to play a role \nin mediating the relationships between worsening mental \nhealth and increased pain and TF . Pain catastrophising is \nincreasingly being identified as a predictor of poor response \nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2703:4\nto treatment and exacerbation of symptoms across a range \nof chronic pain conditions ( Severeijns et  al. 2001, Martin \net  al. 2 011) and thus should be a focus of future research \nin endometriosis. It is plausible that sleep disturbance \ncould be a factor relating to the change in all the measures \nassessed, and recent evidence has shown a negative impact \nof the pandemic on sleep and a subsequent worsening \nof mental health ( Villadsen et  al. 2021 ). Unfortunately, \na measure of sleep was not obtained at the present study, \nin order to keep the questionnaire shorter and reduce the \nparticipant’s burden.\nConclusion\nOur study demonstrates the impact the COVID-19 pandemic \nhas had on the physical and mental health of people with \nendometriosis. Whilst our data specifically apply to the \nimpact of the early stages of the pandemic, we believe these \nfindings have applicability beyond this period. We are \nincreasingly aware of the need to manage endometriosis \nas a chronic condition with a relapsing remitting course \nand symptoms that are variable, unpredictable and difficult \nto manage ( Zondervan et al. 2018). Stressful events (either \nrepeated/prolonged minor stressors or single major life \nevents) are common, and the data presented here would \nsupport the idea that stressful events can exacerbate mental \nill health, fatigue and endometriosis-associated pain. \nOur findings highlight the potentially important role for \npsychological approaches in the management of physical \nsymptoms: approaches such as cognitive behavioural \ntherapy which can reduce pain catastrophising and increase \ncoping skills may well positively impact on pain and fatigue \nin addition to improving mental health symptoms (Schütze \net al. 2018). Identifying those most vulnerable to the adverse \neffects of stress, including individuals with undiagnosed \nmental health conditions, would allow interventions to be \nselected most effectively.\nSupplementary materials\nThis is linked to the online version of the paper at https ://do i.org /10.1 530/\nR AF-22 -0028 .\nDeclaration of interest\nThe authors declare that the research was conducted in the absence of \nany commercial or financial relationships that could be construed as a \npotential conflict of interest. Completed ICMJE disclosure of interest forms \nfor each author are available.\nFunding\nFunding for the study was provided by internal funding resources at the \nUniversity of Oxford.\nAuthor contribution statement\nK V conceived the study. E C, C L, C B, A I, B M, M K, K G, E E, E F, K Z and \nK V designed the study including translations. L D, R S, C B, A I, B M and \nM K analysed the data. L D and K V drafted the manuscript. All authors \ncontributed to revising the manuscript.\nAcknowledgements\nWe would like to thank the following groups for advertising the study \nand publishing the link to the online survey on their websites and \nsocial media resources: Endometriosis.org; Endometriosis Association \nof Ireland; Endometriosis Research Center; Q Endo; EndoActive \nAustralia and New Zealand; Endometriosis Australia; The Endometriosis \nNetwork; Endometriosis NZ; Trinidad and Tobago Endometriosis \nAssociation; EndoFrance; EndoHome; ENDOmind; Endometriose-\nVereinigung Deutschland, Associação Portuguesa de Apoio à Mulheres \ncom Endometriose, Endometriosis and me, Associação Brasileira de \nEndometriose e Ginecologia Minimamente Invasiva; EndoMadrid and \nEndoEuskadi.\nReferences\nBrooks SK, Webster RK, Smith LE, Woodland L, Wessely S, \nGreenberg N & Rubin GJ  2020 The psychological impact of \nquarantine and how to reduce it: rapid review of the evidence. Lancet \n395 912–920. (https://doi.org/10.1016/S0140-6736(20)30460-8)\nCarbone MG, Campo G, Papaleo E, Marazziti D & Maremmani I  \n2021 The importance of a multi-disciplinary approach to the \nendometriotic patients: the relationship between endometriosis and \npsychic vulnerability. Journal of Clinical Medicine 10 1616. (https://doi.\norg/10.3390/jcm10081616)\nCella D, Y ount S, Rothrock N, Gershon R, Cook K, Reeve B, \nAder D, Fries JF, Bruce B, Rose M, et al. 2007 The patient-reported \noutcomes measurement information system (PROMIS): progress of an \nNIH roadmap cooperative group during its first two years. Medical Care \n45 S3–S1 1. (available at: https ://jo urnal s.lww .com/ lww-m edica lcare \n/Full text/ 2007 / 05001 /The_ Patie nt_Re porte d_Out comes _Meas ureme \nnt.2. aspx). (https://doi.org/10.1097 /01.mlr.0000258615.42478.55)\nClauw DJ, Häuser W, Cohen SP & Fitzcharles M  2020 Considering \nthe potential for an increase in chronic pain following the COVID-\n19 pandemic. Pain 161 1694–1697. (https://doi.org/10.1097 /j.\npain.0000000000001950)\nCoxon L, Horne A W & Vincent K  2018 Pathophysiology of \nendometriosis-associated pain: a review of pelvic and central nervous \nsystem mechanisms. Best Practice and Research: Clinical Obstetrics and \nGynaecology 51 53–67. (https://doi.org/10.1016/j.bpobgyn.2018.01.014)\nCrombez G, De Paepe AL, V eirman E, Eccleston C, V erleysen G & \nV an Ryckeghem DML 2020 Let’s talk about pain catastrophizing \nmeasures: an item content analysis. PeerJ 8 e8643. (https://doi.\norg/10.7717 /peerj.8643)\nDemetriou L, Cox E, Lunde CE, Becker CM, Invitti AL, Martínez-\nBurgo B, Kvaskoff M, Garbutt K, Evans E, Fox E, et al. 2021 The \nglobal impact of COVID-19 on the care of people with endometriosis. \nFrontiers in Global Women’s Health 2 662732. (https://doi.org/10.3389/\nfgwh.2021.662732)\nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2713:4\nDenny E & Mann CH  2007 Endometriosis-associated dyspareunia: the \nimpact on women’s lives. Journal of Family Planning and Reproductive \nHealth Care 33 189–193. (https://doi.org/10.1783/1471 18907781004831)\nDi Giuseppe M, Zilcha-Mano S, Prout TA, Perry JC, Orrù G & \nConversano C  2020 Psychological impact of coronavirus disease \n2019 among italians during the first week of lockdown. Frontiers in \nPsychiatry 11 576597. (https://doi.org/10.3389/fpsyt.2020.576597)\nDworkin RH, T urk DC, Farrar JT, Haythornthwaite JA, \nJensen MP , Katz NP , Kerns RD, Stucki G, Allen RR, Bellamy N, \net al. 2005 Core outcome measures for chronic pain clinical \ntrials: IMMPACT recommendations. Pain 113 9–19. (https://doi.\norg/10.1016/j.pain.2004.09.012)\nFacchin F, Barbara G, Dridi D, Alberico D, Buggio L, \nSomigliana E, Saita E & V ercellini P  2017 Mental health in \nwomen with endometriosis: searching for predictors of psychological \ndistress. Human Reproduction 32 1855–1861. (https://doi.org/10.1093/\nhumrep/dex249)\nGershon RC, Wagster MV, Hendrie HC, Fox NA, Cook KF & \nNowinski CJ  2013 NIH toolbox for assessment of neurological and \nbehavioral function. Neurology 80 (Supplement 3) S2–S6. (https://doi.\norg/10.1212/WNL.0b013e3182872e5f)\nHanmer J, Jensen RE, Rothrock N  & HealthMeasures Team 2020 A \nreporting checklist for HealthMeasures’ patient-reported outcomes: \nASCQ-Me, Neuro-QoL, NIH Toolbox, and PROMIS. Journal of Patient-\nReported Outcomes 4 21. (https://doi.org/10.1 186/s41687-020-0176-4)\nHansen KE, Kesmodel US, Baldursson EB, Schultz R & Forman A  \n2013 The influence of endometriosis-related symptoms on work \nlife and work ability: a study of Danish endometriosis patients \nin employment. European Journal of Obstetrics, Gynecology, and \nReproductive Biology 169 331–339. (https://doi.org/10.1016/j.\nejogrb.2013.03.008)\nHayes AF 2013 Mediation, moderation, and conditional process analysis. \nIn Introduction to Mediation, Moderation, and Conditional Process \nAnalysis: A Regression-Based Approach edn, vol. 1, p. 20. New Y ork: \nGuilford Publications.\nHM Government Department of Health 201 1 No Health Without Mental \nHealth: Outcomes Strategy for People of All Ages, pp. 1–100. Department \nof Health, Her Majesty’s Government. (available at: (https ://as sets. \npubli shing .serv ice.g ov.uk /gove rnmen t/upl oads/ syste m/upl oads/ attac \nhment _data /file /1382 53/dh _1240 58.pd f)\nHooten WM 2016 Chronic pain and mental health disorders: \nshared neural mechanisms, epidemiology, and treatment. \nMayo Clinic Proceedings 91 955–970. (https://doi.org/10.1016/j.\nmayocp.2016.04.029)\nKarcioglu O, T opacoglu H, Dikme O & Dikme O  2018 A systematic \nreview of the pain scales in adults: which to use? American Journal \nof Emergency Medicine 36 707–714. (https://doi.org/10.1016/j.\najem.2018.01.008)\nKujawa A, Green H, Compas BE, Dickey L & Pegg S  2020 Exposure to \nCOVID‐19 pandemic stress: associations with depression and anxiety \nin emerging adults in the United States. Depression and Anxiety 37 \n1280–1288. (https://doi.org/10.1002/da.23109)\nLaganà AS, La Rosa VL, Rapisarda AMC, V alenti G, Sapia F, \nChiofalo B, Rossetti D, Ban Frangež H, Vrta čnik Bokal E \n& Vitale SG  2017 Anxiety and depression in patients with \nendometriosis: impact and management challenges. International \nJournal of Women’s Health: Dove Press 9 323–330. (https://doi.\norg/10.2147 /IJWH.S1 19729)\nLi K, Chen G, Hou H, Liao Q, Chen J, Bai H, Lee S, Wang C, Li H, \nCheng L, et al. 2021 Analysis of sex hormones and menstruation in \nCOVID-19 women of child-bearing age. Reproductive Biomedicine Online \n42 260–267. (https://doi.org/10.1016/j.rbmo.2020.09.020)\nLubián-López DM, Moya-Bejarano D, Butrón-Hinojo CA, Marín-\nSánchez P , Blasco-Alonso M, Jiménez-López JS, Villegas-\nMuñoz E & González-Mesa E  2021 Measuring resilience in women \nwith endometriosis. Journal of Clinical Medicine 10 5942. (https://doi.\norg/10.3390/jcm10245942)\nMartin CE, Johnson E, Wechter ME, Leserman J & Zolnoun DA  \n201 1 Catastrophizing: a predictor of persistent pain among women \nwith endometriosis at 1 year. Human Reproduction 26 3078–3084. \n(https://doi.org/10.1093/humrep/der292)\nMcNamara A & Harris Rachel MC  2020 Menstrual cycle change during \nCOVID-19. Sharing some early results. British Journal of Sports Medicine. \n(available at: https ://bl ogs.b mj.co m/bjs m/202 0/1 1/ 20/me nstru al-cy \ncle-c hange -duri ng-co vid-1 9/)\nMorotti M, Vincent K & Becker CM  2017 Mechanisms of pain \nin endometriosis. European Journal of Obstetrics, Gynecology, \nand Reproductive Biology 209 8–13. (https://doi.org/10.1016/j.\nejogrb.2016.07.497)\nNaylor C, Parsonage M, McDaid D, Knapp M, Fossey M & \nGalea A  2012 Long-T erm Conditions and Mental Health: The Cost of \nCo-morbidities. The King’s Fund.\nNnoaham KE, Hummelshoj L, Webster P , d’Hooghe T, de Cicco \nNardone F, de Cicco Nardone C, Jenkinson C, Kennedy SH, \nZondervan KT  & World Endometriosis Research Foundation Global \nStudy of Women’s Health consortium 201 1 Impact of endometriosis \non quality of life and work productivity: a multicenter study across \nten countries. Fertility and Sterility 96 366.e8–373.e8. (https://doi.\norg/10.1016/j.fertnstert.201 1.05.090)\nNorheim KB, Jonsson G & Omdal R  201 1 Biological mechanisms of \nchronic fatigue. Rheumatology 50 1009–1018. (https://doi.org/10.1093/\nrheumatology/keq454)\nOsman A, Barrios FX, Gutierrez PM, Kopper BA, Merrifield T \n& Grittmann L  2000 The pain catastrophizing scale: further \npsychometric evaluation with adult samples. Journal of Behavioral \nMedicine 23 351–365. (https://doi.org/10.1023/a:1005548801037)\nPetrelluzzi KFS, Garcia MC, Petta CA, Grassi-Kassisse DM & \nSpadari-Bratfisch RC  2008 Salivary cortisol concentrations, \nstress and quality of life in women with endometriosis \nand chronic pelvic pain. Stress 11 390–397. (https://doi.\norg/10.1080/10253890701840610)\nPetrini L & Arendt-Nielsen L  2020 Understanding pain \ncatastrophizing: putting pieces together. Frontiers in Psychology 11 \n3450. (https://doi.org/10.3389/fpsyg.2020.603420)\nPope CJ, Sharma V, Sharma S & Mazmanian D  2015 A systematic \nreview of the association between psychiatric disturbances and \nendometriosis. Journal of Obstetrics and Gynaecology Canada 37 \n1006–1015. (https://doi.org/10.1016/s1701-2163(16)30050-0)\nQuiñones M, Urrutia R, T orres-Reverón A, Vincent K & Flores I  \n2015 Anxiety, coping skills and hypothalamus-pituitary-adrenal (HPA) \naxis in patients with endometriosis. Journal of Reproductive Biology and \nHealth 3 2. (https://doi.org/10.7243/2054-0841-3-2)\nRamin-Wright A, Kohl Schwartz AS, Geraedts K, Rauchfuss M, \nWölfler MM, Haeberlin F, von Orelli S, Eberhard M, \nImthurn B, Imesch P , et al. 2018 Fatigue – a symptom in \nendometriosis. Human Reproduction 33 1459–1465.\nRogers PA W, D’Hooghe TM, Fazleabas A, Gargett CE, \nGiudice LC, Montgomery GW, Rombauts L, Salamonsen LA \n& Zondervan KT  2009 Priorities for endometriosis \nresearch: recommendations from an international consensus \nworkshop. Reproductive Sciences 16 335–346. (https://doi.\norg/10.1 177 /1933719108330568)\nSchütze R, Rees C, Smith A, Slater H, Campbell JM & O’Sullivan P  \n2018 How can we best reduce pain catastrophizing in adults with \nchronic noncancer pain? A systematic review and meta-analysis. Journal \nof Pain 19 233–256. (https://doi.org/10.1016/j.jpain.2017.09.010)\nScoring NIHT 2018 Interpretation Guide for the IPad (2016). NIH Toolbox \nand PROMIS IPad Apps.\nSepulcri Rde P & do Amaral VF  2009 Depressive symptoms, anxiety, \nand quality of life in women with pelvic endometriosis. European \nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/\n\n\nL Demetriou et al.\n2723:4\nJournal of Obstetrics, Gynecology, and Reproductive Biology 142 53–56. \n(https://doi.org/10.1016/j.ejogrb.2008.09.003)\nSevereijns R, Vlaeyen JW, van den Hout MA & Weber WE  2001 Pain \ncatastrophizing predicts pain intensity, disability, and psychological \ndistress independent of the level of physical impairment. Clinical \nJournal of Pain 17 165–172. (https://doi.org/10.1097 /00002508-\n200106000-00009)\nStratton P & Berkley KJ  201 1 Chronic pelvic pain and endometriosis: \ntranslational evidence of the relationship and implications. Human \nReproduction Update 17 327–346. (https://doi.org/10.1093/humupd/\ndmq050)\nSullivan MJL, Bishop SR & Pivik J  1995 The pain catastrophizing scale: \ndevelopment and validation.’ Psychological Assessment 7 524–532. \n(https://doi.org/10.1037 /1040-3590.7.4.524)\nV ercellini P , Trespidi L, De Giorgi O, Cortesi I, Parazzini F & \nCrosignani PG  1996 Endometriosis and pelvic pain: relation to \ndisease stage and localization. Fertility and Sterility 65 299–304. \n(https://doi.org/10.1016/S0015-0282(16)58089-3)\nVilladsen A, Patalay P & Bann D  2021 Mental health in relation \nto changes in sleep, exercise, alcohol and diet during the COVID-\n19 pandemic: examination of five UK cohort studies. In medRxiv. \nCold Spring Harbor Laboratory Press. (https://doi.org/10.1017 /\nS0033291721004657)\nVitale SG, La Rosa VL, Rapisarda AMC & Laganà AS  2017 Impact of \nendometriosis on quality of life and psychological well-being. Journal \nof Psychosomatic Obstetrics and Gynaecology 38 317–319. (https://doi.org\n/10.1080/0167482X.2016.1244185)\nVitonis AF, Vincent K, Rahmioglu N, Fassbender A, Buck \nLouis GM, Hummelshoj L, Giudice LC, Stratton P , \nAdamson GD, Becker CM, et al. 2014 World Endometriosis \nResearch Foundation Endometriosis Phenome and biobanking \nharmonization project: II. Clinical and covariate phenotype data \ncollection in endometriosis research. Fertility and Sterility 102  \n1223–1232. (https://doi.org/10.1016/j.fertnstert.2014.07.1244)\nWilliams SZ, Chung GS & Muennig PA  2017 Undiagnosed depression: \na community diagnosis. SSM: Population Health 3 633–638. (https://\ndoi.org/10.1016/j.ssmph.2017.07.012)\nWilliamson A & Hoggart B  2005 Pain: a review of three commonly used \npain rating scales. Journal of Clinical Nursing 14 798–804. (https://doi.\norg/10.1 1 1 1/j.1365-2702.2005.01 121.x)\nWorld Health Organization 2020 No title. (available at: https ://ww w.who \n.int/ direc tor-g enera l/spe eches /deta il/wh o-dir ector -gene ral-s -open \ning-r emark s-at- the-m edia- briefi  ng-o n-cov id-19 ---1 1 -marc h-202 0). \nAccessed on 29 June 2022.\nY alçın Bahat P , Kaya C, Selçuki NFT, Polat İ, Usta T & Oral E  \n2020 The COVID‐19 pandemic and patients with endometriosis: \na survey‐based study conducted in Turkey. International Journal of \nGynaecology and Obstetrics 151 249–252. (https://doi.org/10.1002/\nijgo.13339)\nZondervan KT, Becker CM, Koga K, Missmer SA, T aylor RN & \nViganò P  2018 Endometriosis. Nature Reviews: Disease Primers 4 9. \n(https://doi.org/10.1038/s41572-018-0008-5)\nReceived 6 March 2022\nReceived in final form 24 July 2022\nAccepted 22 September 2022\nThis work is licensed under a Creative Commons \nAttribution-NonCommercial 4.0 International \nLicense.\nhttps://doi.org/10.1530/RAF-22-0028\nhttps://raf.bioscientifica.com © 2022 The authors\n Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/28/2026 02:22:35PM\nvia Open Access. This work is licensed under a Creative Commons\nAttribution-NonCommercial 4.0 International License.\nhttps://creativecommons.org/licenses/by-nc/4.0/","source_license":"CC0","license_restricted":false}