{"paper_id":"48c054e4-fa70-48ad-9737-69344300675d","body_text":"Endometriosis is a gynecological disease characterized by the presence of endometrial\ntissue (composed of glands and stroma) outside the uterine cavity ( Giudice, 2010 ;  Zondervan  et al. , 2020 ;  Taylor  et al. , 2021 ). Endometriosis affects about 10%\nof adolescents and women of reproductive age worldwide ( Giudice, 2010 ;  Fuldeore &\nSoliman, 2017 ;  Zondervan  et\nal. , 2020 ;  Taylor  et\nal. , 2021 ). Endometriosis has traditionally been associated\nwith two main symptoms: pelvic pain (particularly during menstrual bleeding, known\nas dysmenorrhea) and infertility ( Giudice,\n2010 ;  Zondervan  et al. ,\n2020 ;  Taylor  et al. ,\n2021 ;  Ottolina  et al. ,\n2024 ).\nAdenomyosis develops when endometrial tissue grows within the uterine wall\n(myometrium) ( Levy  et al. ,\n2013 ;  Upson & Missmer, 2020 ).\nThe true prevalence of adenomyosis is unknown. Adenomyosis was found in\nhistopathological findings of hysterectomies in studies ranging from 8.8% to 61.5%\n( Upson & Missmer, 2020 ). Abnormal\nuterine bleeding, dysmenorrhea, and infertility are common symptoms in patients with\nadenomyosis ( Levy  et al. ,\n2013 ). Interestingly, numerous studies have found a strong association\nbetween adenomyosis and endometriosis ( Leyendecker\n et al. , 2015 ).\nEndometriosis and adenomyosis negatively impact women’s quality of life.\nEndometriosis has been associated with an increase in disruptions in the academic,\nwork, and social lives of young women ( Gupta\n et al. , 2021 ;  Bell\n et al. , 2023 ). Consequently, endometriosis causes\nlarge economic losses in Australia, with an estimated annual cost of roughly $16,970\nto $20,898 per woman per year, with most of the expenses attributable to absence\nfrom work ( Armour  et al. ,\n2019 ;  Bell  et al. ,\n2023 ). The economic burden in the United States is estimated to be\n$78-$119 billion per year ( Simoens  et\nal. , 2012 ;  Ellis  et\nal. , 2022 ). Endometriosis has comparable direct and indirect\ncosts with other chronic diseases, such as heart disease and diabetes mellitus\n( Simoens  et al. , 2012 ;\n Armour  et al. , 2019 ).\nThe diagnosis of endometriosis and adenomyosis remains a major challenge for general\npractitioners and reproductive medicine specialists. According to studies, the\ninterval between the first clinical manifestations and the diagnosis of\nendometriosis can take up to 12 years, particularly in young women ( Hadfield  et al. , 1996 ;  Arruda  et al. , 2003 ;  Husby  et al. , 2003 ). The\n“normalization,” nonspecificity, and multiplicity of endometriosis symptoms, as well\nas the lack of specific biomarkers and variation in the intensity of symptoms, make\nendometriosis and adenomyosis clinical diagnosis challenging ( Zondervan  et al. , 2020 ). Dysmenorrhea (62.2%),\nchronic pelvic pain (56.8%), deep dyspareunia (54.7%), cyclical intestinal\ncomplaints (48.3%), infertility (39.8%), and cyclical urinary complaints (11.7%)\nwere the most commonly reported symptoms among a group of Brazilian women who\nunderwent laparoscopy with histological confirmation of endometriosis ( Bellelis  et al. , 2010 ).\nThe worsening of quality of life, increased risk of mental disorders, disease\nprogression with the intensification of symptoms, development of central\nsensitization of pelvic pain, and erosion of the physician-patient relationship are\nsome of the consequences of endometriosis diagnosis and treatment delays ( Zondervan  et al. , 2020 ).\nFurthermore, the absence of adequate clinical-surgical management and reproductive\nplanning for women with undiagnosed endometriosis can have serious reproductive\nconsequences, including accelerated loss of ovarian reserve, infertility, and the\nneed for assisted reproductive technology to achieve pregnancy ( Tanbo & Fedorcsak, 2017 ;  Bonavina & Taylor, 2022 ).\nThe visualization (often by laparoscopy) of endometriotic lesions, whether confirmed\nby histology or not, remains the gold standard for diagnosing endometriosis. The use\nof imaging tests (ultrasound or magnetic resonance imaging) is also recommended for\nnonsurgical assessment of suspected endometriosis cases ( Becker  et al. , 2022 ). Ideally, patients\nsuspected of having endometriosis should be referred for imaging or surgical\nevaluation ( Becker  et al. ,\n2022 ;  Ottolina  et al. ,\n2024 ). Self-reporting tools based on patient complaints have been\nproposed to identify women with suspected endometriosis symptoms to reduce\ndiagnostic delay and support early endometriosis treatment ( Surrey  et al. , 2017 ;  Fauconnier  et al. , 2021 ;  Chapron  et al. , 2022 ).\nThis study aims to assess the prevalence of self-reported symptoms of endometriosis\nand adenomyosis among Brazilian university students and identify potential\npredictors of these diseases.\n\nThis is a cross-sectional study conducted between January and October 2023. The study\npopulation consisted of Brazilian female students from the University of Fortaleza\n(UNIFOR), a private university in Fortaleza, Ceara, in the northeast of Brazil. This\nstudy was reported in accordance with The Strengthening the Reporting of\nObservational Studies in Epidemiology (STROBE) Statement. Non-Brazilians, those\nunder the age of 18 years, those unable to communicate in Portuguese, and those who\nrefused to participate in the study were excluded. Eligible participants were asked\nto participate in the study using an internal communication platform and social\nnetworking application (WhatsApp Messenger). Those who wanted to participate used a\nGoogle Form link to access the online questionnaire. An online questionnaire link\nwas accessible for completion between August 1 and September 30, 2023.\nThe electronic instrument was developed using the Menstrual Disorder of Teenagers\nQuestionnaire ( Parker  et al. ,\n2010 ). A pilot study was conducted to test the validity and\nreliability of the questionnaire. After that, it was revised based on\nparticipant feedback and test-retest results. The final questionnaire comprised\n27 items divided into three sections: general information, menstrual cycles, and\nsymptoms related to the period ( Table\n1 ).\nEnglish version of the questionnaire used in the study.\nParticipants were asked to provide their age, weight, height, age at first\nperiod, course enrolled, number of years at university, history of gynecological\ndiseases (endometriosis, adenomyosis, uterine fibroid, polycystic ovary\nsyndrome, endometrial polyp, and other diseases), and use of a contraceptive\nmethod (combined pill, hormonal intrauterine device, copper/silver intrauterine\ndevice, combined injectable, progesterone injection, male condom, female condom,\ncontraceptive implant, minipill, or other methods).\nThe occurrence of periods and the characteristics of menstrual cycles were\nassessed with the questions listed in  Table\n1  (section 2). The period pattern (regularity, duration, and\nintensity of flow), the presence of dysmenorrhea (intensity, pattern,\nprogression, and use of medication), interference with sexual practice, and\ndaily activities, including missing classes, were asked of participants.\nParticipants were asked about the occurrence of the following symptoms associated\nwith the period: nausea, vomiting, bloating (swollen tummy), diarrhea,\nconstipation, heartburn/reflux, changes in appetite, aching down the legs,\npelvic pain, lower back pain, pain when urinating, pain when full bladder, blood\nin urine, urgency to urinate, pain when evacuating, blood in feces, discharge\nvaginal, irritability, anxiety, and depression.\nData were input into an Excel 2020 spreadsheet (Microsoft Corp., Redmond,\nWashington), and descriptive statistics for survey responses were deduced.\nParticipants were divided into two groups based on whether they self-reported\nhaving endometriosis and/or adenomyosis, known as ENDO/ADENO and NO ENDO/ADENO.\nThe variables extracted from the electronic instrument were compared between the\ntwo groups (ENDO/ADENO  vs . NO ENDO/ADENO). Continuous variables\nwere compared using unpaired Student’s  t  test, and categorical\nvariables were compared using the Fisher’s exact test or χ 2 \ntest in the SPSS™ (SPSS Statistical Software V.22.0, IBM Corp., Armonk,\nNew York). Adjusted multivariate analysis was performed using binary logistic\nregression and included the following independent variables: visual analog scale\n(VAS) dysmenorrhea ( > 8), worsening of dysmenorrhea,\nmissing class during the period, dyspareunia, and dysuria.  p \nvalues of less than 0.05 were considered statistically significant. Informed\nconsent was included on the welcome page of the survey. The study was approved\nby the Research Ethics Committee of the UNIFOR (CAAE: 69273423.6.0000.5052).\n\nOne hundred and forty women agreed to participate in the study. Four (2.9%) students\nself-reported adenomyosis alone, 26 (18.6%) students self-reported endometriosis\nalone, and two (1.4%) students self-reported an associated diagnosis of\nendometriosis and adenomyosis. Thus, study participants were divided into two\ngroups: ENDO/ADENO (32 students) and NO-ENDO/ADENO (108 students).\nThe demographic characteristics of the study participants are shown in  Table 2 . The mean age of the participants was\n22.4±5.2yr (ranging from 18 to 48yr), and there was no difference between\ngroups ( p =0.069). The means of weight, height, and body mass index\nwere 62.5±11.8kg, 1.61±0.1m, and 23.9±4.3, respectively.\nSixty-seven percent (n=94/140) of participants were normal weight, 2.1% (n=3/140)\nwere underweight, 22.1% (n=31/140) were overweight, and 8.6% (n=12/140) were obese.\nAnthropometric markers were similar between the two groups.\nDemographic characteristics of participants.\nThe mean age at menarche of the participants was 11.8±1.4 yr (ranging from 9\nto 17yr), with no difference between groups ( p =0.252). The use of\ncontraceptive methods was self-reported by 58.6% (n=82/140) of participants and was\ncomparable between groups ( p =0.183). The mean of years spent at\nuniversity one course was 2.2±1.3yr, with no difference between groups\n( p =0.718). A quarter of the women in both groups and the total\nnumber of participants were medical students ( Table\n2 ).\nThe frequency of gynecological diseases and menstrual cycle characteristics of the\nparticipants were summarized in  Table 3 .\nStudents in the ENDO/ADENO group self-reported a lower presence of menstrual\nbleeding (called period), 65.6% ( n =21/32)  versus \n91.7% (n=99/108), respectively ( p <0.001). However, the\nregularity of the period was comparable between groups ( p =0.052).\nThere was no difference between the duration and intensity (heavy menstrual bleeding\nand menstrual bleeding with clots) of the period between the groups.\nFrequency of gynecological diseases and characteristics of menstrual\ncycle.\nThe mean of the visual analog scale (VAS) dysmenorrhea was higher in the ENDO/ADENO\ngroup (7.5±2.5  vs . 5.7±2.2,\n p <0.001). Participants in the ENDO/ADENO group also had a higher\npercentage of severe dysmenorrhea (VAS≥8) (62.5% [n=20/32]\n vs . 19.4% [n=21/108],  p <0.001).\nDysmenorrhea worsening over the last 12 months was significantly more common among\nstudents in the ENDO/ADENO group than the NO ENDO/ ADENO group (81.3% [n=26/32]\n vs . 32.4% [n=35/108],  p <0.001). However,\nthere was no difference in the need for medicine to control dysmenorrhea between\ngroups. Participants in the ENDO/ADENO group reported missing classes more\nfrequently during the periods (53.1% [n=17/32]  vs . 25% [n=27/108],\n p <0.001).\nThe frequency of symptoms self-reported by study participants is presented in  Table 4 . The occurrence of most symptoms was\ncomparable between the two groups. Only dyspareunia (50% [n=16/32]\n vs . 17.6% [ n =19/108],\n p <0.001) and dysuria (31.25 [n=10/32]  vs . 11.1%\n[n=12/108],  p =0.005) were significantly more common among students\nin the ENDO/ADENO group.\nFrequency of gynecological diseases and characteristics of menstrual\ncycle.\nBinary logistic regression was performed to verify whether missing classes, severe\ndysmenorrhea, worsening in the last 12 months, dyspareunia, and dysuria are\npredictive symptoms of endometriosis ( Table\n5 ). The statistical model that include dysmenorrhea worsening over the\nprevious 12 months was significant ( χ 2 [1]=34.7;\n p <0.001,  R 2  Negelkerke=0.334).\nDysmenorrhea worsening was the only predictor of endometriosis in university female\nstudents (odds ratio=5.73; 95% confidence interval, 1.91- 17.22,\n p =0.002;  Table 5 ).\nBinary logistic regression-based on symptoms self-reported by university\nstudents.\n\nAccording to studies, the prevalence of endometriosis remains poorly known, ranging\nfrom 2% to 10% in the general population, but can reach 50% in infertile women\n( Eskenazi & Warner, 1997 ;  Meuleman  et al. , 2009 ;  Zondervan  et al. , 2020 ). In\naddition, the prevalence of endometriosis in different age groups and based on the\nintensity of symptoms, particularly pelvic pain, remains unknown. Our study found a\n21.4% prevalence of endometriosis associated or not with adenomyosis, which is\nhigher than the general population prevalence but comparable with earlier studies\nwith young women or those who self-reported severe dysmenorrhea ( Ragab  et al. , 2015 ;  Zannoni  et al. , 2024 ). In our\nsample, the prevalence of adenomyosis associated or not with endometriosis (4.2%,\n6/140) was low compared with previous studies, which ranged from 1% to 70% ( Struble  et al. , 2016 ;  Zannoni  et al. , 2024 ;  Exacoustos  et al. , 2022 ). This\ndiscrepancy in adenomyosis prevalence reported in the literature is attributable to\ndifferent diagnostic criteria, different patient populations, differences in tissue\nsample sizes, and possible bias in histopathological analysis ( Struble  et al. , 2016 ).\nEndometriosis is a risk factor for women who complain (cyclical and noncyclical) of\ndysmenorrhea, deep dyspareunia, dysuria, dyschezia, painful rectal bleeding or\nhematuria, shoulder tip pain, catamenial pneumothorax, cyclical\ncough/hemoptysis/chest pain, cyclical scar swelling and pain, fatigue, and\ninfertility ( Becker  et al. ,\n2022 ;  Mitchell  et al. ,\n2024 ). Dysmenorrhea is a common complaint among young women, affecting up\nto 90% of adolescents ( Klein & Litt,\n1981 ;  Andersch & Milsom, 1982 ;\n Hillen  et al. , 1999 ;\n Banikarim  et al. , 2000 ;\n Martire  et al. , 2023 ;\n Oliveira  et al. , 2024 ).\nHowever, studies suggest that around 14%-23% of adolescents suffer from severe\ndysmenorrhea ( Klein & Litt, 1981 ;  Fisher  et al. , 1989 ;  Teperi & Rimpelä, 1989 ;  Wilson & Keye, 1989 ;  Martire  et al. , 2023 ). Studies show that about\n47%-73% of adolescents with severe dysmenorrhea are diagnosed with endometriosis\n( Bullock  et al. , 1974 ;\n Reese  et al. , 1996 ;\n Martire  et al. , 2023 ).\nThus, the results in our study are consistent with previous studies. Several studies\nhave already described the relationship between the presence and severity of\ndysmenorrhea and the occurrence of endometriosis ( Porpora  et al. , 1999 ;  Calhaz-Jorge  et al. , 2004 ;  Van Niekerk  et al. , 2022 ;  El-Hadad  et al. , 2023 ).\nPorpora  et al.  (1999) \nobserved a correlation between the total pain score and deep endometriosis on the\nuterosacral ligaments, peritoneal adhesions, and extent of adnexal adhesions. The\nauthors proposed that the presence and severity of dysmenorrhea are predictors of\nendometriosis ( Porpora  et al. ,\n1999 ). Recently,  El-Hadad  et\nal.  (2023)  also noted that dysmenorrhea is a predictor of\nendometriosis, particularly with onset >3 yr after menarche. Other studies have\nalso suggested that dysmenorrhea may be a predictor of endometriosis/adenomyosis\n( Peterson  et al. , 2013 ;\n Heitmann  et al. , 2014 ;\n Ashrafi  et al. , 2016 ;\n Fuldeore & Soliman, 2017 ;  Saha  et al. , 2017 ). In our\nstudy, dysmenorrhea was more severe in the endometriosis/adenomyosis group; however,\ndysmenorrhea was not considered a good predictor after multivariate analysis.\nProgressive dysmenorrhea is a clinical manifestation common to endometriosis and\nadenomyosis ( Struble  et al. ,\n2016 ;  Zondervan  et al. ,\n2020 ;  Becker  et al. ,\n2022 ). It occurs when the intensity and duration of pain during periods\nincreases over time. Few studies found that increased dysmenorrhea severity was a\ngood predictor of endometriosis ( Forman  et\nal. , 1993 ;  Eskenazi\n et al. , 2001 ;  Hsu\n et al. , 2010 ). In our study, dysmenorrhea worsening\nin the last 12 months was a good predictor of endometriosis.\nOther predictive symptoms for endometriosis have also been studied ( Heitmann  et al. , 2014 ;  Ashrafi  et al. , 2016 ;  Kayani  et al. , 2016 ;  Fuldeore & Soliman, 2017 ;  Van Niekerk  et al. , 2022 ). In\nour study, dyspareunia and dysuria were more common in students who self-reported\nhaving endometriosis and/or adenomyosis. However, multivariate analysis indicates\nthat this complaint does not predict endometriosis/adenomyosis. Although dyspareunia\nand dysuria are more common among women with endometriosis, they are not specific\nsymptoms of endometriosis/ adenomyosis ( Agarwal\n et al. , 2019 ;  Becker\n et al. , 2022 ).\nEndometriosis/adenomyosis is often the cause of life disruptions ( Zondervan  et al. , 2020 ;  Gupta  et al. , 2021 ;  Becker  et al. , 2022 ).  Gupta  et al.  (2021)  found that\nundergraduate students with endometriosis symptoms have a high level of life\ndisruption (88% any disruption, 82.7% social, 58.8% academic, and 34.4% work). A\nlarge Australian study of over 4,000 young women aged 13-25yr found that more than a\nthird of students had missed at least one class due to menstrual symptoms in the\nlast three menstrual cycles. In addition to the loss of academic activities, around\n70% of students reported difficulties concentrating during menstrual bleeding ( Armour  et al. , 2020 ). In our\nstudy, students with endometriosis/adenomyosis missed twice as many classes as\nstudents who did not self-report an endometriosis/adenomyosis diagnosis.\nThis study has several strengths. First, it identified the prevalence of\nendometriosis/adenomyosis in university students in northeastern Brazil, a\npopulation that has not yet been studied. Second, it identified the pattern of\nendometriosis/adenomyosis symptoms in young women, contributing to a better\nunderstanding of this gynecological disease. Third, the study found that\nworsening dysmenorrhea may be a predictor of endometriosis/adenomyosis in young\nwomen. Consequently, our results may contribute to reducing delays in diagnosing\nendometriosis/adenomyosis and reducing complications in the medium and long\nterm.\nOne important limitation is the study design, which was a cross-sectional study\nwith questionnaires completed individually by participants. Another limitation\nis the absence of radiologic studies or surgery to confirm the participant’s\nself-reported diagnosis. However, the questionnaire was based on a previously\nvalidated instrument in the literature. In our cross-sectional study, one\nlimitation is that the number of participants was slightly below the recommended\nsample size calculated to ensure sufficient statistical power and\nrepresentativeness. This limitation may reduce the precision of our estimates.\nWith a smaller sample size, the variability within the data is less likely to\nrepresent the diversity present in the entire population, thus increasing the\nmargin of error and potentially leading to biased results. Additionally, we\nhighlight the need for external validation of our results. External validation\nis crucial to confirm that the observed associations are not unique to our\nsample and can be generalized to broader populations.\n\nThe assessment of symptoms related to the menstrual cycle can be used as a screening\ntool for patients at risk of endometriosis/adenomyosis. The progressive worsening of\ndysmenorrhea in the last 12 months was a predictor of endometriosis/adenomyosis\ndiagnosis.","source_license":"public-domain-us","license_restricted":false}