{"paper_id":"87b63133-902a-4442-95d7-f3eadd16e412","body_text":"Full Terms & Conditions of access and use can be found at\nhttps://www.tandfonline.com/action/journalInformation?journalCode=igye20\nGynecological Endocrinology\nISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/igye20\nThe effect of endometriosis on sexual function as\nassessed with the Female Sexual Function Index:\nsystematic review and meta-analysis\nFaustino R. Pé\nrez-López , Lía Ornat , Gonzalo R. Pérez-Roncero , María T.\nLópez-Baena , Manuel Sánchez-Prieto & Peter Chedraui\nTo cite this article: Faustino R. Pérez-López , Lía Ornat , Gonzalo R. Pérez-Roncero , María T.\nLópez-Baena , Manuel Sánchez-Prieto & Peter Chedraui (2020): The effect of endometriosis on\nsexual function as assessed with the Female Sexual Function Index: systematic review and meta-\nanalysis, Gynecological Endocrinology, DOI: 10.1080/09513590.2020.1812570\nTo link to this article:  https://doi.org/10.1080/09513590.2020.1812570\nView supplementary material \nPublished online: 03 Sep 2020.\nSubmit your article to this journal \nArticle views: 2\nView related articles \nView Crossmark data\n\n\nARTICLE\nThe effect of endometriosis on sexual function as assessed with the Female\nSexual Function Index: systematic review and meta-analysis\nFaustino R. P /C19erez-L/C19opeza,b ,L /C19ıa Ornat b , Gonzalo R. P /C19erez-Roncero\na , Mar/C19ıaT .L /C19opez-Baenaa ,\nManuel S /C19anchez-Prietoc and Peter Chedraui d\naInstituto de Investigaci /C19on Sanitaria de Arag /C19on, Zaragoza, Spain;\nbDepartment of Obstetrics and Gynecology, University of Zaragoza Faculty of\nMedicine, Zaragoza, Spain; cDepartament of Obstetrics and Gynecology, Instituto Universitario Dexeus, Barcelona, Spain; dInstituto de\nInvestigaci/C19on e Innovaci /C19on en Salud Integral, Facultad de Ciencias M /C19edicas, Universidad Cat /C19olica de Santiago de Guayaquil, Guayaquil, Ecuador\nABSTRACT\nAim: To systematically compare sexual function between non-treated women with and without\nendometriosis.\nMethods: A systematic review was performed on PubMed/Medline, Scopus, EMBASE, Web of Science and\nCochrane Library databases searching studies that analyzed sexual function (assessed with the 19-item\nFemale Sexual Function Index [FSFI]), and dyspareunia, chronic pelvic pain and dysmenorrhea (assessed\nwith a visual analogue scale [VAS]) in women with and with endometriosis.\nResults: In 4 studies, non-treated women with endometriosis presented a higher risk of female sexual\ndysfunction (mean total FSFI score /C20 26.55; OR ¼ 2.38; 95% confidence interval [CI] ¼ 1.12, 5.04).\nAlthough mean total FSFI scores were not significantly different between women with and without endo-\nmetriosis (mean difference [MD] ¼/C0 2.15; 95% CI /C0 4.96, 0.67); all FSFI domain scores were significantly\nlower in women with endometriosis ( n ¼ 4 studies): desire (MD ¼/C0 0.43; 95% CI /C0 0.57, /C0 0.19); arousal\n(MD ¼/C0 0.66; 95% CI /C0 1.15, /C0 0.17); lubrication (MD ¼/C0 0.41; 95% CI /C0 0.79, /C0 0.02); orgasm (MD ¼\n/C0 0.40; 95% CI /C0 0.73, /C0 0.06); satisfaction (MD ¼/C0 0.45; 95% CI /C0 0.72, /C0 0.18); and pain (MD ¼/C0 1.03;\n95% CI /C0 1.34, /C0 0.72). Women with endometriosis displayed differences (more severity) in terms of VAS\nscores (2 studies) for dyspareunia (MD ¼ 1.88; 95% CI 0.38, 3.37) and chronic pelvic pain (MD ¼ 2.92;\n95% CI 1.26, 4.58); but not for dysmenorrhea.\nConclusion: Non-treated women with endometriosis displayed altered sexual function as evidenced by\nlower scores in all FSFI domains, and severity of dyspareunia and chronic pelvic pain.\nARTICLE HISTORY\nReceived 23 June 2020\nRevised 17 August 2020\nAccepted 17 August 2020\nPublished online 3 Septem-\nber 2020\nKEYWORDS\nChronic Pelvic Pain;\nDyspareunia; Endometriosis;\nFemale Sexual Dysfunction;\nFemale Sexual Function\nIndex; Visual Analogue\nScale\nIntroduction\nFemale sexual dysfunction, particularly painful sex, is a common\ncomplaint in adult women of all ages. During reproductive years,\nendometriosis is a highly prevalent gynecological disease.\nPersistent sexual pain related to endometriosis has been associ-\nated to biological, psychological, sexual and interpersonal factors\n[1]. Clinical symptoms of endometriosis include dysmenorrhea,\nchronic pelvic pain, dyspareunia, lumbar pain, dyschezia, dysuria\nand infertility. The prevalence of sexual dysfunction in women\nwith endometriosis is almost double as compared to those with\nother gynecological disorders [ 2]. Dyspareunia and chronic pelvic\npain negatively impact several domains of sexual function, espe-\ncially in women with deep infiltrating endometriosis (DIE) and\nrectovaginal or bowel endometriosis as compared to other forms\nof endometriosis or healthy women [ 3–5]. There are also psycho-\nlogical consequences, including mood swings, depressive and\nanxious symptoms that, at the same time, may increase pelvic\ndiscomfort [ 6–8]. The objective of this systematic review and\nmeta-analysis is to compare sexual function between non-treated\nwomen with and without endometriosis.\nMethods\nProtocol, search strategy, eligibility criteria and\nstudy selection\nThe systematic review and meta-analysis was carried out follow-\ning the principles of the PRISMA guidelines [ 9]. Formal institu-\ntional review board approval was not required, as this analysis\nconsisted of the pooling of published studies.\nA systematic literature search was conducted in PubMed-\nMedline, Scopus, EMBASE, and Web of Science databases from\ninception through March 9 2020, and without language restric-\ntions. We searched for free terms ‘endometriosis’ OR\n‘endometrioma’ OR ‘rectovaginal endometriosis ’ AND ‘sexual\nfunctioning’ OR ‘sexual dysfunction ’ OR ‘sexuality’ OR\n‘dyspareunia’ OR ‘sexual life ’. The Pubmed search strategy is\navailable in Appendix A (Supplementary Table A1). An iterative\nprocess was used to ensure that all relevant articles were\nobtained. A further manual search of bibliographic references\nwas also carried out in selected studies and in existing reviews to\nidentify potential studies that were not captured by the electronic\ndatabase searches.\nCONTACT: Faustino R. P /C19erez-L/C19opez faustino.perez@unizar.es Department of Obstetrics and Gynecology, University of Zaragoza Faculty of Medicine, Domingo\nMiral s/n, Zaragoza, 50009, Spain\nSupplemental data for this article is available online at https://doi.org/10.1080/09513590.2020.1812570.\n/C2232020 Informa UK Limited, trading as Taylor & Francis Group\nGYNECOLOGICAL ENDOCRINOLOGY\nhttps://doi.org/10.1080/09513590.2020.1812570\n\nEligible for inclusion were relevant cohort and case-control\nstudies that: (i) assessed women of reproductive age with clinical\nendometriosis and those without endometriosis who were not\nreceiving any hormonal treatment; (ii) evaluated sexual function/\ndysfunction as assessed with a validated sexual function/dysfunc-\ntion questionnaire; (iii) were in any language irrespective of age,\nrace, and date of publication; and (iv) were addressing the same\npopulation if they reported complementary information to the\nmain paper. Articles were excluded if they were narrative reviews,\nabstracts and conference proceedings, or non-human studies. All\ndisagreements regarding inclusion/exclusion were discussed and\nsolved by consensus with all authors. Meta-analyses were prede-\nfined/planned for each validated sexuality questionnaire if reported\nin at least two different populations.\nData extraction and risk of bias assessment\nA Microsoft Excel sheet was designed for data input. Two\nresearchers extracted publication details, eligibility and exclusion\ncriteria, as well as information about the study population and\ndesign, period of study, sample size and clinical characteristics of\nthe studied population. Discrepancies and controversies of\nextracted data were discussed in order to reach a consensus. Due\nto the fact that some results were reported as medians and their\n25% and 75% confidence intervals, appropriate calculations were\nperformed to obtain mean and standard deviations that served\nfor the meta-analysis [ 10].\nThe methodological quality of the selected studies was inde-\npendently assessed by two authors using the Newcastle –Otawa\nScale for case-controls studies [ 11]. This scale consists of three\nbroad perspectives including the selection of the study group, the\ncomparability of the groups, and the ascertainment of the pri-\nmary outcome. The maximum score can be 9 stars. Studies with\nseven star-items or more are categorized as high quality and\nthose with six star-items or less as low quality.\nData synthesis and analysis\nForest plots were planned for outcomes reported in at least two\nstudies using any validated test to assess female sexual function,\nusing DerSimonian and Laird random-effects models and the\ninverse variance method [ 12]. Associations among dichotomous\noutcomes are reported as odds ratio (OR); and for continuous\noutcomes mean differences (MDs), both with their correspond-\ning 95% confidence interval (CI). We evaluated statistical hetero-\ngeneity using the Cochrane chi square (X\n2), the I2 statistic, and\nthe between-study variance using the tau square ( s2)[ 13,14].\nI2 values of 30 –75% indicate a moderate level of heterogeneity. A\np < .1 for the chi-square defined the presence of heterogeneity;\nand a s2 > 1 defines the presence of substantial statistical hetero-\ngeneity. We planned to estimate the publication bias if there are\nat least 10 studies reporting the same outcome [ 15].\nThe Review Manager program (RevMan, version 5.3, Oxford,\nUK; The Cochrane Collaboration) was used for statis-\ntical analyses.\nResults\nSelection and characteristics of the studies\nA total of 366 records were identified through systematic data-\nbase searches and 3 through other sources ( Figure 1 ). After the\nremoval of duplicates, 314 items were screened by title, leaving\n74 for review of abstract content. Eligibility was assessed in 23\nfull text articles, leaving a total of eleven. Seven of these papers\nwere excluded, four that did not have a control group and three\nthat reported in each one data of sexual function assessed by a\ndifferent tool. There was one study using the Female Health\nOutcomes in Women questionnaires [ 2], one study with the\nMcCoy Female Sexuality Questionnaire [ 16], one study with the\nFemale Sexual Quotient [ 5], and four studies using the Female\nSexual Function Index (FSFI) [ 17]. Therefore, a total of 4 studies\nreporting results with the FSFI were included in this meta-analysis\n(Figure 1 )[ 18–21]. The general characteristics and main relevant\nclinical and socio-demographic findings of patients included in the\n4s t u d i e sa r ep r e s e n t e di nTable 1.\nThe FSFI is a 19-item self-reported instrument used to meas-\nure overall sexual function in the past 4 weeks in women who\nare sexually active and have a partner. The tool is composed of\nsix domains of sexual function each providing a score. The sum\nof all domain scores yields a total FSFI score. These domains\nare: desire (2 items, questions 1&2), arousal (4 items, questions\n3&4 and 5&6), lubrication (4 items, questions 7&8 and 9&10),\norgasm (3 items, questions 11&12&13), satisfaction (3 items,\nquestions 14&15&16), and pain (3 items, questions 17&18&19)\n[17]. A total FSFI score of /C20 26.55 was used to define women at\nhigher risk of sexual dysfunction [ 22].\nMeta-analysis of sexual function and dyspareunia\nThere were no significant mean differences (MD) in terms of age\n(MD ¼ 1.69 years, 95% CI /C0 0.14, 3.53; Figure 2(A) ) and total\n19-item FSFI scores (MD ¼/C0 2.15, 95% CI /C04.96, 0.67; Figure\n2(B)) when comparing women with and without endometriosis\n[18–21]. Despite finding no differences in mean total FSFI\nscores, women with endometriosis displayed a higher risk of sex-\nual dysfunction (defined as a total FSFI score /C20 26.55) [ 22]\n(OR ¼ 2.38; 95% CI 1.12, 5.04, n ¼ 3s t u d i e s ;Figure 2(C))[ 18,19,\n21]. Women with endometriosis displayed lower scores in each of\nt h eF S F Id o m a i n s :d e s i r e( M D¼/C0 0.43; 95% CI /C00.67, /C00.19,\nFigure 3(A)); arousal (MD ¼/C0 0.66; 95% CI /C01.15, /C00.17; Figure\n3(B)); lubrication (MD ¼/C0 0.41; 95% CI /C0 0\n .79, /C00.02; Figure\n3(C)); orgasm (MD ¼/C0 0.40; 95% CI /C00.73, /C00.06; Figure 3(D));\nsatisfaction (MD ¼/C0 0.45; 95% CI /C0 0.72, /C00.18; Figure 3(E)), and\npain (MD ¼/C0 1.03; 95% CI /C0 1.34, /C00.72; Figure 3(F))[ 18–21].\nIn two studies, visual analogue scale (VAS) pain scores for\ndyspareunia were significantly higher in women with endometri-\nosis (MD ¼ 1.88; 95% CI 0.38, 3.37; Figure 4(A) )[ 18,19].\nDyspareunia would had been worse if one takes into account\nthat 7 additional women with endometriosis and one without\nendometriosis in the De Graaf et al. study were unable to main-\ntain/have sexual intercourse [ 18]. Chronic pelvic pain was also\nassessed with a VAS, also showing significantly more pain sever-\nity in women with endometriosis as compared to controls (MD\n¼ 2.92; 95% CI 1.26, 4.58; Figure 4(B) )[ 18,19]. Finally, there\nwere no significant differences in terms of dysmenorrhea inten-\nsity between women with and without endometriosis as assessed\nwith the VAS (MD ¼ 1.80: 95% CI /C02.63, 6.23; Figure\n4(C))[ 18,19].\nRisk of bias\nAppendix A, Supplementary Table A2 displays the assessment of\nrisk of bias by means of the Newcastle –Otawa Scale [ 11], show-\ning a low risk of bias (score /C21 7).\n2 F. R. PÉREZ-LÓPEZ ET AL.\n\nPublication bias\nSince there were only 4 studies, we were unable to calculate pub-\nlication bias with the funnel plot and the Egger ’s test [ 15].\nDiscussion\nThe present meta-analysis found that un-treated women with\nendometriosis in their early fourth decade of life have an\nincreased risk of sexual dysfunction, dyspareunia and chronic\npelvic pain in comparison to those without endometriosis.\nDespite this, no significant differences were found in relation to\nthe severity of dysmenorrhea. Endometriosis is a chronic gyneco-\nlogical disease that causes a negative impact on physical, psycho-\nlogical and sexual aspects of life. Regarding sexuality, the impact\nof the disease has been studied in different clinical conditions,\ntreatment scenarios, associated to infertility, and general health\nand quality of life. Sexual function is severely compromised in\nwomen who smoke, have dyspareunia, severe chronic pelvic\npain, bladder syndrome, and an increased body mass index or a\nfamily history of chronic pain [ 23,24].\nSystematic reviews have analyzed sexual function or dysfunc-\ntion among women with endometriosis who had been receiving\nvarious treatments, indicating that more than half of these\nwomen suffer some type of sexual dysfunction [ 25,26]. Although\nsurgical and pharmacological treatments may improve sexual\nfunction among women with endometriosis, in some cases dis-\ncomfort during intercourse and sexual dysfunction may persist\n[27]. Despite this, to date we are not aware of any meta-analysis\nthat compares female sexual function and different forms of\ngenital pain between untreated women with and without\nendometriosis.\nAmong the few available studies, we found 4 reporting the\nassessment of sexual function with the 19-item FSFI. This ques-\ntionnaire is a useful tool for the evaluation of female sexual func-\ntion, and its total score allows us to objectively screen women\nwho are at a higher risk of sexual dysfunction [ 20, 28]. In our\nstudy, although mean total FSFI scores did not differ among\ncases and controls; significant lower scores for each of the\ndomains of the FSFI were found in women with endometriosis,\nsuggesting that endometriosis has impaired their sexuality.\nAlterations of sexual function in women with endometriosis are\nnot only related to the disease per se and its stage, yet also to\nother factors such as anxiety, depression, sleep problems, exces-\nsive body weight and less physical activity [ 29].\nWomen with endometriosis may have severe chronic pelvic\npain, dysmenorrhea, dischezia, and urinary symptoms. We found\nsignificant higher mean dyspareunia VAS scores in women with\nFull text excluded\n(n = 7):\n• No control group \n(n = 4)\n Studies repor/g415ng with\na tool other than the\nFSFI (n = 3)\nIden/g415fica/g415onScreeningEligibilityIncluded\nFull-text ar/g415cles assessed \nfor eligibility\n(n = 11)\nRecords a/g332er screening \nby /g415tle \n(n = 74)\nRecords a/g332er screening \nby abstract\n(n = 23)\nStudies included in the \nquan/g415ta/g415ve synthesis\n( n = 4)\nStudies included in the \nqualita/g415ve synthesis\n(n = 4)\nRecords a/g332er removing \nduplicates \n(n = 314)\nRecords iden/g415fied \nthrough other sources\n(n = 3)\nRecords iden/g415fied through \ndatabase searching\n(n = 366)\nFigure 1. Flowchart of study selection.\nGYNECOLOGICAL ENDOCRINOLOGY 3\n\nTable 1. Characteristics of the included studies assessing sexual function with the Female Sexual Function Index in women with and without endometriosis.\nAuthor;\nDate\nStudy location; Period. Aim of\nthe study Exclusion criteria Study design and participants Main findings\nDe Graaf\n2016 [ 18]\nMaastricht, The Netherlands;\nJune 2011 to December\n2012. Aim: to compare pain\nsymptoms; medical history;\naspects of mental\nfunctioning; sexual\nfunctioning and quality of\nlife between women with\nendometriosis and a\ncontrol group aged 18 to\n42 years who had sexual\nrelationship for at least\nthree months duration.\nExclusion criteria: hysterectomy, being pregnant,\nbreastfeeding or to have given birth in the\npast three months, have severe comorbidity\nsuch as Crohn ’s disease, type 1 diabetes or\nmalignancies, and were on medication not\nrelated to endometriosis that could influence\non sexual functioning such as anxiolytic and\nantipsychotic medication. Women who\nunderwent surgery in the inclusion period\nwere enrolled at least three months\nafter surgery.\nCross-sectional study. Study population: 83 women with\nendometriosis established by means of laparoscopy\nor open surgery using the known visual aspects of\nthe disease. Women had a median age of 25.4 [19.3-\n30.9]. Patients with a strong suspicion of the\ndiagnosis of endometriosis based on symptoms in\ncombination with a positive pelvic clinical\nexamination, ultrasound or MRI were also included.\nControl group: 40 women attending the outpatient\nclinic due to issues related with contraception.\nDyspareunia and depressive symptoms were\nassociated to impaired sexual functioning in\nwomen with endometriosis, whereas sexual\nfunctioning in their male partners was not\naffected. The majority of the participants\nwere enrolled in a tertiary care center. This\nhas led to an over-presentation of women\nneeding tertiary care, and this could have\nalso led to an over-presentation of\ntheir symptoms.\nEvangelista\n2014 [ 19]\nRio de Janeiro, Brazil; July to\nDecember 2011. Aim: to\nassess sexual function in\nwomen with deep\ninfiltrative endometriosis as\ncompared to women\nrecruited in a family\nplanning clinic.\nPatients whose cognitive abilities were\ninsufficient to comprehend and interpret the\nquestionnaire were excluded; as well as\nthose with debilitating chronic illnesses\n(diabetes mellitus, hypertension, lupus,\nthyroid disease, etc.) and those who had not\nengaged in penetrative vaginal intercourse\nduring the month preceding the\nstudy enrollment.\nCross-sectional, prospective study. Study population: 57\nwomen with DIE and chronic pelvic pain (aged 18 to\n45), current sexual activity (onset of sexual activity at\nleast 1 year prior to study enrollment). DIE diagnosis\nwas based on pelvic pain and/or infertility associated\nwith at least two of the following: detection of a\nhardened nodule in the vesico-uterine or\nrectouterine pouch on vaginal and/or rectal\nexamination; transvaginal ultrasound or MRI findings\nconsistent with infiltrating endometriosis in the\npelvis; and surgical visualization or histopathological\nconfirmation of endometriosis.\nControl group: 38 women (aged 18 and 45), sexually\nactive, with onset of vaginal intercourse at least 1\nyear prior to study enrollment, no severe\ndysmenorrhea (visual analog scale score <8), no\nclinical evidence of endometriosis, and with a normal\ngynecological examination.\nThere was no significant difference in total FSFI\nscores, and also the desire, arousal and\norgasm domains of the tool. However, there\nwas a significant difference between the two\ngroups in the pain domain. Both conclusions\ndid not change after controlling for potential\nconfounders.\nGhajarzadeh\n2014 [ 20]\nTehran, Iran; January 2013 to\nAugust 2013. Aim: to\nevaluate sexual function in\nIranian women with\nendometriosis in\ncomparison with\nhealthy controls.\nNot stated. Cross-sectional study. Study population: 44 women with\nlaparoscopically diagnosed endometriosis (mean age\n33.1 ± 6.8 years); BMI ¼ kg/m2 25.9 ± 5.4. The most\ncommon clinical symptoms were dysmenorrhea (77.2\n%), dyspareunia (47.7 %), pelvic pain (27.2 %) and\npain during defecation (25 %).\nControl group: 80 healthy women from patient ’s\nfamilies and hospital staff, aged 33.5 ± 7.1 years; BMI\n¼ 25.9 ± 5.4 kg/m\n2.\nFSFI total and three domain scores (arousal,\norgasm and pain) were significantly different\nbetween patients and controls. Education\nlevel and BMI were significantly different in\npatients with and without sexual dysfunction.\nBMI was the independent predictor for total\nFSFI score in both case and control groups.\nMelis\n2015 [ 21]\nCagliari, Italy; January 2010 to\nJune 2011. Aim: to assess\nsexual function, quality of\nlife, and perceived body\nimage among women with\ndeep endometriosis as\ncompared to\nhealthy women.\nPatients affected by vaginismus or vulvodynia\nwithout deep nodule tenderness. Women\nwith any hormonal or antidepressant\ntreatment during the study or during the\nmonth before the study. Most participants\nwere patients who were sent after surgical\ndiagnosis by other hospitals without any\nhormonal treatment. Patients with any\nchronic disease were excluded. Volunteers\nwere healthy women consecutively recruited\namong those coming for a\nregional screening.\nCross sectional study. Endometriosis population: 41\nwomen with deep endometriosis after clinical,\nbiochemical, ultrasonography, MRI evaluation who\nwere not taking any hormonal or antidepressant\ntreatment during the study or the prior month.\nMean age was 31.5 ± 6.4 years. A washout period of\n2 months was prescribed for 2 patients under\nestroprogestin/progestin treatment.\nControl group: 40 women without endometriosis\n(mean age 30.4 ± 5.1 years).\nDeep endometriosis has a significant impact on\nsexuality and body image. Women with\nendometriosis showed a greater intensity of\npain during and after penetration. Moreover,\nsignificant differences were detected in\nsexual function between the women with\nand without endometriosis regarding the\nFSFI ‘desire’ domain. The differences in the\ndomains of arousal, lubrication, orgasm, and\nsatisfaction were not statistically significant.\nBMI: body mass index; DIE: deep infiltrative endometriosis; FSFI: Female Sexual Function Index; MRI: magnetic resonance imaging.\n4 F. R. PÉREZ-LÓPEZ ET AL.\n\nendometriosis in comparison to the controls. It is important to\nmention that 7 women with endometriosis and one without in\nthe De Graaf et at.[ 18] study were unable to maintain sexual\nintercourse due to their history of extreme dyspareunia; hence it\ncan be presumed that this outcome would be even worse (higher\nVAS score) if more studies and/or cases were available. Previous\npublications have reported that women with endometriosis who\nreceive endocrine treatments achieve significant relief of their\ndyspareunia while increasing their total FSFI scores (better sexual\nfunction); although in some cases sexual function is not com-\npletely restored [ 30,31].\nChronic pelvic pain is a complex problem observed in women\nduring their reproductive years. In this sense, endometriosis is a\ncommon cause, but symptoms are not constant and may vary\namong populations and throughout time, in fact decreasing or\ndisappearing after menopause. In the present meta-analysis, we\nalso found information regarding chronic pelvic pain, assessed\nwith the VAS, in 2 of the 4 selected FSFI studies. Analysis found\nsignificant differences in terms of more intense chronic pelvic\npain in women with endometriosis as compared to those without\nthe disease. It seems that endometriosis alters peritoneal homeo-\nstasis and induces the production of pro-inflammatory and\nangiogenic cytokines [ 32]. Pelvic pain due to DIE may also be\nrelated to compression or infiltration of endometriotic implants\nin the sub-peritoneal space [ 33]. Endometriotic lesions are pre-\nsent in some 30 to 40% of women subject to laparoscopy due to\nchronic pelvic pain [ 34]. However, a 25% of cases can be asymp-\ntomatic which may be related to different factors with no clear\nor consistent patterns found [ 35]. Chronic pelvic pain may also\nbe related to psychological dysfunction, anxiety and depression,\ndecreased levels of self-compassion and emotional regulation, a\nhistory of sexual abuse, previous surgery, and urinary or digest-\nive alterations [ 36–38].\nThe present meta-analysis found no significant differences in\nterms of VAS scores for dysmenorrhea. Dysmenorrhea may be\nassociated to chronic pelvic and also non-pelvic causes. A recent\nmeta-analysis pointed out that women with dysmenorrhea have\na higher risk of chronic pelvic pain as compared to those with-\nout dysmenorrhea [ 39]. On the other hand, dyspareunia and dys-\nmenorrhea are less intense in women who only have ovarian\nendometriosis in comparison to other locations [ 40]. In fact, as\nassessed with different tools, the extension and pain due to endo-\nmetriosis are not consistently related.\nLimitations\nThe principal limitation of our meta-analysis is the availability of\nfew studies with only four publications directly comparing sexual\nfunction assessed with the FSFI among un-treated women with\nand without endometriosis. Unfortunately, three studies had to\nbe excluded due to the fact that each one used a different tool\nFigure 2. Forest plots comparing women with and without endometriosis according to mean difference of age expressed as years (A), mean difference in total\nFemale Sexual Function Index score (B), and risk of female sexual dysfunction (odds ratio) according to the FSFI cutoff of /C20 26.55 (C).\nGYNECOLOGICAL ENDOCRINOLOGY 5\n\n[2, 5, 16]. These other tools may provide complementary infor-\nmation not found with the FSFI. Sexual life and expectations\nmay change with age and the presence of endometriosis [ 41].\nWomen of our meta-analysis (with and without endometriosis)\nwere in their early thirties; hence one should bear in mind that\nother age groups may have different sexual function characteristics.\nA n o t h e rl i m i t a t i o no fo u rm e t a - a n a l y s i si st h a tc o n t r o l sw e r e\nwomen without endometriosis who attended gynecological consul-\ntations for routine checkup, and although having a similar age and\nbeing free of symptoms, they were not subjected to any diagnostic\nlaparoscopic procedure specific for women with endometriosis.\nHowever this approach would have been unethical.\nFigure 3. Forest plots comparing (mean difference) women with and without endometriosis according to scores obtained for each FSFI domain: desire (A), arousal\n(B), lubrication (C), orgasm (D), satisfaction (E), and pain (F).\n6 F. R. PÉREZ-LÓPEZ ET AL.\n\nOur meta-analysis of dyspareunia showed a significant trend\nfor higher severity scores in women with endometriosis as com-\npared to controls. Studies with larger samples have reported a\nhigher prevalence of dyspareunia in women with endometriosis,\nalthough this symptom may also be unrelated to the disease\n[42,43]. Several studies have reported that dyspareunia is highly\nfrequent in women with DIE who also present voiding altera-\ntions and psychological distress [ 25, 44,45]. Despite this, other\ncauses of painful sex in women with endometriosis include\ndepression or psychological stress [ 46]. Future studies should\ncombine the assessment of dyspareunia along with the use of\ntools that evaluate depressive/anxiety symptoms, and emotional\nand sexual function.\nStrengths\nThe first strength of our study is that it meta-analyzed data using\nthe FSFI. This tool has been widely used to assess female sexual\nfunction, and its components, in quite different circumstances,\ndiseases and populations throughout nearly two decades [ 47,48].\nSecondly, we analyzed cases and controls that had a similar age,\nallowing equal comparisons in terms of social and sexual behav-\nior. Despite these strengths, there is a need for studies performed\nin younger women in order to: i) assess the negative impact that\nthe disease has over sexuality; and ii) once identified those with\npotential sexual dysfunction, evaluate overtime the impact of the\ndisease or interventions.\nConclusion\nEndometriosis is not a homogeneous disease in its anatomical\ncharacteristics and clinical symptoms. The meta-analyzed infor-\nmation could not identify these involved factors and also could\nnot speculate about the types and extension of endometriosis\ndue to the small number of included studies. In this sense, one\nshould mention that higher rates of dyspareunia and chronic\npain in women with endometriosis do not predict their sexual\ndistress; with metacognitive beliefs having more influence on\nsexual distress than pain per se [49]. Despite the existence of pre-\nvious systematic reviews, this is the first meta-analysis that\nobjectively assesses female sexual dysfunction (and different\nforms of pelvic pain) in un-treated women with endometriosis\nusing the FSFI that evaluates standardized components\nof sexuality.\nAcknowledgements\nThe authors thank Prof. Stefano Angione, from the University of\nCagliari (Italy), for providing complementary information about the\npaper by Melis et al. [ 21], included in the meta-analysis. The authors\nalso thank Ms. M. Salas Valero for her assistance with the study.\nDisclosure statement\nThe authors report no conflicts of interest and are alone responsible\nfor the content and the writing of the article.\nFigure 4. Forest plots comparing (mean difference) women with and without endometriosis according to VAS scores obtained for: dyspareunia (A), chronic pelvic\npain (B), and dysmenorrhea (C).\nGYNECOLOGICAL ENDOCRINOLOGY 7\n\nORCID\nFaustino R. P /C19erez-L/C19opez http://orcid.org/0000-0002-2801-416X\nL/C19ıa Ornat http://orcid.org/0000-0001-9056-2143\nGonzalo R. P /C19erez-Roncero http://orcid.org/0000-0001-8137-4837\nMar/C19ıaT .L /C19opez-Baena http://orcid.org/0000-0002-9890-8003\nManuel S /C19anchez-Prieto http://orcid.org/0000-0001-7366-0446\nPeter Chedraui http://orcid.org/0000-0002-1556-3979\nReferences\n[1] Aerts L, Grangier L, Dallenbach P, et al. Understanding sexual pain\nin endometriosis. Minerva Ginecol. 2019;71(3):224 –234.\n[2] Di Donato N, Montanari G, Benfenati A, et al. Sexual function in\nwomen undergoing surgery for deep infiltrating endometriosis: a\ncomparison with healthy women. 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