{"paper_id":"4faf07f1-82e9-4e09-96d5-73cb5f14d48e","body_text":"Submit Manuscript | http://medcraveonline.com\nAbbrevations: ADVIA, analyzer centaur bayer; BMI, \nbody mass index; CA-125,ovarian cancer-related tumor marker, \nCA-19-9,Carbohydrate antigen 19-9, CLIA,Chemiluminescence \nimmunoassay, DHEA- S, dehydroepiandrosterone sulfate; MRI, \nmagnetic resonance imaging; PRL, prolactin\nIntroduction\nEndometriosis is a serious gynecological disease that mainly \naffects patients of childbearing age.1  Endometriosis has the character \nof an inflammatory, systemic and chronic disease, which can occur in \nup to 15 % of women. A characteristic feature is the presence of tissue \nresembling the endometrium outside the uterine cavity. The time from \nthe first symptoms to a clear diagnosis often takes more than 10 years. \nThis is because there are no specific markers for the diagnosis of \nendometriosis.2  Nevertheless, some studies indicate that some non-\nspecific markers may be used for testing, such as CA-125 or CA-19-9, \nor that certain hormone levels, such as DHEA-S values, can also be \nindicators.3,4 Endometriosis is an estrogen-dependent disease that is \nassociated with other disorders, such as fertility disorders (incidence \nup to 40 %) and sexual dysfunction (up to 50 % of patients). Some \nstudies suggest that endocrine and immune changes may be associated \nwith chronic stress, anxiety and even depression.5 The results of some \nstudies point out that patients with endometriosis, more than with other \ngynecological problems, suffer from psychopathological comorbidity \n- most often anxiety and depressive symptoms. 6 Other studies have \neven shown the possibility of an increased risk of developing not \nonly symptoms, but even depressive and anxiety disorders. 7,8 In \nthese cases, questionnaires such as the BDI or HAM-A were used, \nwhich we also used in our study, because the results of some current \nstudies are often contradictory, partly due to the use of different and \ndifferent methodologies.9 Another difference is probably the possible \noccurrence of other psychiatric comorbidities, which have not yet \nbeen diagnosed in the patients, because the main diagnosis is precisely \nendometriosis and its complications.\nThe aim of our work in patients with endometriosis was to try to \nevaluate not only the relationship between sexual functions, stress, \nanxiety and depression, but also the results of the values of stress \nhormones such as cortisol and prolactin.\nWe also added to our research the TSC-40 questionnaire, which \nwe have already used in our endometriosis research, which does \nnot only focus on PTSD, but serves to assess other possible adverse \nsituations, such as various stressful experiences or emotional and \npartner problems, which patients with endometriosis often mention. \nUsing this questionnaire, we can evaluate wider psychological \naspects, moreover, symptomatic reactions do not have to be tied only \nto a specific event.\nMaterials and methods\nStudy group and tissue specimens\nA total of 92 patients with a mean age of 30.07 (SD=6.33), age \nrange (24-46 years), were selected for our study from a total of 100 \npatients with a histologically confirmed diagnosis of endometriosis \nat the Department of Sexology of Charles University in Pilsen. The \nprospective study began in October 2018 and ended in September \n2021. The average duration of endometriosis in our patients was 9.45 \nyears (SD=2.13). The most common symptoms reported by patients \nwere dysmenorrhea (73 patients), sex pain (66 patients), orgasmic \ndisorders (45 patients), fear of sex (33 patients), mood swings (23 \npatients), partner discomfort (44 patients), depression (5 patients) \nand sleep disorders (18 patients). All 92 patients had one or more \nsymptoms of endometriosis.10\nInt Clin Pathol J. 2023;10(1):45‒48. 45\n©2023 Fiala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which \npermits unrestricted use, distribution, and build upon your work non-commercially.\nPsychological hallmarks of endometriosis with \nemphasis on sexual dysfunction, stress, anxiety and \ndepressive symptoms\nVolume 10 Issue 1 - 2023\nLudek Fiala,1,2 Jiri Lenz,3,4 Zdenek Adamik,5 \nRachel Sajdlova,1 Daniela Kestlerova,1 Vaclav \nVetvicka6 \n1Department of Sexology, Charles University, Czech Republic\n2Department of Psychiatry, Charles University Prague, Czech \nRepublic\n3Department of Pathology, Czech Republic\n4University of Veterinary and Pharmaceutical Sciences Brno, \nCzech Republic\n5Faculty of Humanities, Czech Republic\n6Department of Pathology, University of Louisville, USA\nCorrespondence: Vaclav Vetvicka, Department of Pathology, \nUniversity of Louisville, USA, Email \nReceived: June 12, 2023 | Published: June 30, 2023\nAbstract\nEndometriosis is associated with gynecological disorders and infertility. More than 50 % \nof women report that they suffer from sexual dysfunctions, the most significant of which \nis pain, which can subsequently be associated with stress, anxiety, depression and partner \ndiscomfort. In our study, we focused on evaluating these symptoms. A total of 92 patients \nwith endometriosis were included in the study. Clinical examinations were focused on \nbiochemical analysis of cortisol and prolactin, as important hormones that can respond to \nstress, anxiety and depressive symptoms. At the same time, sexual function, stress, anxiety \nand depressive symptoms were psychometrically evaluated in these patients.  Positive \ncorrelations were found between psychosocial trauma/stress and results from the sexual \nfunction questionnaire (R=0.30). Furthermore, positive correlations were evaluated between \nthe results of Beck’s questionnaire for assessing depression and prolactin (R=0.39) and \nalso between the results of Beck’s questionnaire for assessing depression and the anxiety \ntest (R=0.33). We also found a high correlation between prolactin and anxiety (R=0.86). \nAll results were confirmed by the Mann-Whitney test. These results represent important \nfindings regarding the relationship of certain stress hormones, with sexual dysfunction and \nsymptoms related to stress, anxiety and depression in women with endometriosis, which are \nstill receiving little attention within endometriosis.\nKeywords: anxiety, depression, endometriosis, sexual function, psychology\nInternational Clinical Pathology Journal\nResearch Article\n Open Access\n\n\nPsychological hallmarks of endometriosis with emphasis on sexual dysfunction, stress, anxiety and \ndepressive symptoms\n46\nCopyright:\n©2023 Fiala et al.\nCitation: Fiala L, Lenz J, Adamik Z, et al. Psychological hallmarks of endometriosis with emphasis on sexual dysfunction, stress, anxiety and depressive \nsymptoms. Int Clin Pathol J. 2023;10(1):45‒48. DOI: 10.15406/icpjl.2023.10.00218\nThe exclusion criteria were: pregnancy, cancer, hormonal or \nmetabolic disorders such as obesity, diabetes mellitus, as well as \npsychiatric disorders - psychosis, schizophrenia, bipolar disorder \nand psychiatrist-diagnosed anxiety and depressive disorder, as well \nas diagnosed PTSD, which could affect the results of psychometric \nmeasurements. The revised American Society for Reproductive \nMedicine (rASRM) score was used to classify endometriosis. 11 \nEndometriosis was diagnosed by histological examination. \nHistological diagnosis of endometriosis was based on the presence of \nendometriotic glands and stroma.12\nAll patients underwent an initial gynecological examination, \nfollowing up on previous gynecological findings, as well as basic \nbiochemical tests to rule out other diseases. On the second to fourth \nday of the cycle, prolactin (PRL) and cortisol were obtained from \nperipheral blood. The gynecological examination was supplemented \nby a detailed ultrasound examination. Laparoscopic examination was \nperformed in 89 patients with subsequent confirmation of histological \nfindings, laparotomy examination was performed in 3 patients. MRI \nof the gynecological area of the small pelvis was performed in 6 \npatients.13\nNeuroendocrinological markers\nTo evaluate the correlations, we primarily focused on the results of \ncortisol and prolactin as the stress hormones. For their evaluation, 2 \nml of blood serum were collected in a special vacuum gel separation \ntube according to routine procedures at the Institute of Biochemistry \nat Charles University in Pilsen. The sample transport time was 20 \nminutes. Blood samples were transported in a refrigerator at 4°C to \nthe Central Laboratory in Pilsen and were evaluated using routine \nlaboratory laboratory tests.\nPRL measurement\nBlood for PRL testing was routinely collected and transported \nto the faculty laboratory under standard conditions. Collection \ntook place two hours after awakening of patients and samples were \nmeasured by chemiluminescence immunoassay (CLIA). Normal PRL \nlevels ranged from 3 to 25g/l. The average PRL value in the examined \nwomen was 23.48g/l (SD=13.01).\nCortisol\nCortisol samples were taken in the morning, preferably between \n07:00 and 09:00 hours and then between 13:00 and 15:00hours, to \nminimize daily cortisol fluctuations. Subsequently, the serum cortisol \nlevel was determined in a biochemical laboratory according to normal \nanalytical procedures. 14 Serum cortisol levels were identified by \nchemiluminescent immunoassay (CLIA) using an ADVIA analyzer \n(Centaur Bayer). The intra- and interassay scattering coefficients \nwere 2.9 and 12.2 %, respectively. The cortisol value normally ranges \nfrom 118-618nmol/l. Our patients had mean values   of 289.87nmol/l \n(SD=182.91).\nPsychometric measurements\nThe female sexual distress scale-revised (FSDS-R)\nThe FSDS-R questionnaire is used in connection with the \nexamination of sexual function. It was revised in 2005 and evaluates \nthe issues over the last 30 days on a scale of: never 0, rare 1, sometimes \n2, frequently 3, always 4. It contains 13 questions. A score ≥11 \nindicates FSD (Female Sexual Dysfunction).15 The average values   of \nthe questionnaire in the examined group were 28.68 (SD=5.90).\nTrauma symptoms checklist (TSC-40)\nThe TSC-40 uses 40 questions, which are evaluated on a Likert four-\npoint scale. The total score is from 0 to 120. Using the questionnaire, \nthe symptoms of stress associated with traumatic experiences are \nevaluated in the examined patients. This is a highly reliable test.16  For \na total of 92 patients, TSC-40 values   were statistically processed with \na mean value of 24.42 (SD=12.54).\nBeck depression inventory-II  (BDI-II)\nThis is a questionnaire that contains a self-assessment scale of the \nseverity of depression. It consists of 21 items (these are also individual \nsymptoms and negative thoughts occurring to varying degrees in \ndepressed individuals).17 The mean value of this questionnaire was 7.5 \nin patients (SD=3.36). \nHamilton rating scale for anxiety- HAM-A \nHAM-A is one of the important assessment scales that can be used \nto measure the severity of anxiety symptoms in research conditions. \nThe scale consists of 14 items and each is defined by a series of \nsymptoms and measures mental and somatic anxiety. Each item is \nrated on a scale from 0 (not present) to 4 (severe), with a total score \nrange of 0-56.18\nHAM-A had a mean value of 20.00 in patients (SD=11.01). \nThe completion of the FSDS-R, TSC-40 and BDI-II questionnaires \nwas supervised by a sexologist, and the HAM-A questionnaire was \nadministered by a psychologist with the patients.\nStatistical analysis\nStatistical evaluation of all psychometric measurements included \ndescriptive statistics and Spearman’s correlation coefficients. The \nstatistical results were subsequently confirmed by the Mann-Whitney \ntest. This test is also called the Mann-Whitney-Wilcoxon test (MWW \nrank-sum test). It is a non-parametric test of the null hypothesis \nfor randomly selected values   of x and y from two sets. 19 Statistical \nmethods were evaluated using Statistica software version 12.\nResults\nIn the mutual statistical assessment, positive correlations were \nfound between the results of the Beck scale questionnaire for assessing \nthe severity of depression (BDI-II) and PRL (R=0.39), then confirmed \nby Mann-Whitney test (z-score is 5.98019, P value is <0.00001, \nresult is significant at P<0.05). Furthermore, the correlation between \nBDI-II and HAM-A (R=0.33), confirmed by the Mann-Whitney test \n(z-score is -8.55827, P value is <0.00001, the result is significant at \nP<0.05) (Figure 1). Positive correlations were found between TSC-40 \nand FSDS-R (R=0.30), confirmed by Mann-Whitney test (z-score is \n3.89503, the value of P is 0.0001, the result is significant at P <0.05).  \nWe also found a high correlation between PRL and HAM-A (R=0.86). \nDiscussion\nEndometriosis is one of the most common causes of female pelvic \npain, which can manifest as dyspareunia, but also as dysmenorrhea, \novulation pain or dysuria and dyschezia. According to research, it \nseems that the level of pain may not depend on the size of the extent \nof endometriosis. This suggests that psychological factors may \nbe involved in the nature of the pain, which may have significant \nnegative effects on their mental health, quality of life, women may be \nlimited in social activities, and it also affects their partner relationship \nand sex life.\n\nPsychological hallmarks of endometriosis with emphasis on sexual dysfunction, stress, anxiety and \ndepressive symptoms\n47\nCopyright:\n©2023 Fiala et al.\nCitation: Fiala L, Lenz J, Adamik Z, et al. Psychological hallmarks of endometriosis with emphasis on sexual dysfunction, stress, anxiety and depressive \nsymptoms. Int Clin Pathol J. 2023;10(1):45‒48. DOI: 10.15406/icpjl.2023.10.00218\nFigure 1 Relationship of BDI-II score with HAM-A score and PRL level.\nSignificant Spearman correlations between depression (BDI-II) and PRL level \n(R=0.39) and between depression (BDI-II) and anxiety (HAM-A) (R=0.33) \nobserved in patients with endometriosis are illustrated.\nIn addition to pain, individual patients may experience other types \nof symptoms, such as anxiety, fear, and depression, as well as signs of \nsexual dysfunction, such as reduced desire, satisfaction, or orgasmic \nsymptoms. Sexual dysfunction usually accompanies up to 50 % of \npatients with endometriosis.20\nThese symptoms subsequently negatively affect the nature of \npain experienced by women with endometriosis. In addition, the \nsubsequent development of sexual dysfunction can also occur in \nthe partners of women with endometriosis, especially those who are \nintensely aware of their problems.\nTherefore, it is necessary to focus not only on the treatment of \nendometriosis foci, but also on the psychogenic part of this serious \ndisease. A better knowledge of understanding these relationships can \nhelp to positively influence these symptoms subsequently.\nThe results of this study are consistent with the hypothesis \nof possible relationships between stress, anxiety, depression and \nneuroendocrine markers in patients with endometriosis. 21 We found \nsignificant relationships confirmed by the Spearman correlation \nbetween the results of the FSDS-R score, which indicates sexual \ndysfunction, and the TSC-40 questionnaire, which describes \npsychosocial trauma and stress, as well as positive study results \nbetween the BECK-II, which describes depressive symptoms, and \nthe results of the HAM- questionnaire A, which captures different \nstates of anxiety and levels of PRL. Cortisol levels did not show any \npositive correlation. One of the possible reasons why there was a \ncorrelation only with prolatin and not also with cortisol is the fact that \nthe possible influence of fat mass in patients (BMI) is mentioned in \nthe professional literature, which leads to different results. However, \nno one has studied this effect in detail. BMI was not determined for \nthe patients in our study.22\nConclusion\nIn conclusion, limited research suggests that women with \nendometriosis are at risk of psychosocial or psychiatric disorders. 23 \nIt remains to be determined whether these problems are caused by \nendometriosis associated with chronic gynecological pain or also by \nother factors.24 Women diagnosed with the symptoms of endometriosis \nshould also be examined for psychosocial and psychiatric disorders \nat the same time. In this regard, it is important not to underestimate \nthe psychological assessment of those patients who are at risk of \ndeveloping symptoms of anxiety and depression and to provide \nthem with appropriate psychological support. 25 It is necessary to \nemphasize the importance of a multidisciplinary approach not only \nin the diagnosis, but subsequently in the treatment of women with \nendometriosis.\nAcknowledgments\nNone.\nConflicts of interest\nThe authors state that there are no conflicts of interest regarding \nthe publication of this article.\nFunding\nNone.\nReferences\n1. Králíčková M, Fiala L, Losan P, et al. Altered immunity in endometriosis: \nwhat came first? Immunol Invest. 2018;47:569–582. \n2. Moradi M, Parker M, Sneddon A, et al. Impact of endometriosis on \nwomen’s lives: a qualitative study. BMC Womens Health. 2014;14:123. \n3. Fiala L, Bob P, Raboch J. Oncological markers CA-125, CA 19-9 and \nendometriosis. Medicine. 2018;97:e13759. \n4. Simitsidellis I, Saunders PTK, Gibson DA. Androgens and endometrium: \nNew insights and new targets. Mol Cell Endocrinol. 2018;465:48–60. \n5. Králíčková M, Vetvicka V , Fiala L, et al. The search for biomarkers in \nendometriosis: a long and windy road. Reprod Sci. 2022;29:1667–1673.\n6. Pope CJ, Sharma V , Sharma S, et al. A systematic review of the \nassociation between psychiatric disturbances and endometriosis. J \nObstet Gynaecol Can. 2015;37:1006–1015.\n7. Gambadauro P, Carli V , Hadlaczky G. Depressive symptoms among \nwomen with endometriosis: a systematic review and meta-analysis. Am \nJ Obstet Gynecol. 2019;220:230–241. \n8. Sepulcri Rde P, do Amaral VF. Depressive symptoms, anxiety, and \nquality of life in women with pelvic endometriosis. Eur J Obstet \nGynecol Reprod Biol. 2009;142:53–56.\n9. Friedl F, Riedl D, Fessler S, et al. Impact of endometriosis on quality \nof life, anxiety, and depression: an Austrian perspective. Arch Gynecol \nObstet. 2015;292:1393–1399.\n10. Taylor HS, Kotlyar AM, Flores V A. Endometriosis is a chronic \nsystemic disease: clinical challenges and novel innovations. Lancet. \n2021;397:839–852. \n11. Lee SY , Koo YJ, Lee DH. Classification of endometriosis. Yeungnam \nUniv J Med. 2021;38:10–18. \n12. Lenz J, Chvatal R, Fiala L, et al. Comparative immunohistochemical \nstudy of deep infiltrating endometriosis, lymph node endometriosis and \natypical ovarian endometriosis including description of a perineural \ninvasion. Biomed Pap Med Fac Univ Palacky Olomouc . 2021;165:69–\n79. \n13. Ito TE, Abi Khalil ED, Taffel M, et al. Magnetic resonance imaging \ncorrelation to intraoperative findings of deeply infiltrative endometriosis. \nFertil Steril. 2017;107:e11–e12. \n14. Hannibal KE, Bishop MD. Chronic stress, cortisol dysfunction, and \npain: a psychoneuroendocrine rationale for stress management in pain \nrehabilitation. Phys Ther. 2014;94:1816–1825.\n\n\nPsychological hallmarks of endometriosis with emphasis on sexual dysfunction, stress, anxiety and \ndepressive symptoms\n48\nCopyright:\n©2023 Fiala et al.\nCitation: Fiala L, Lenz J, Adamik Z, et al. Psychological hallmarks of endometriosis with emphasis on sexual dysfunction, stress, anxiety and depressive \nsymptoms. Int Clin Pathol J. 2023;10(1):45‒48. DOI: 10.15406/icpjl.2023.10.00218\n15. Derogatis L, Clayton A, Lewis-D’Agostino D, et al.Validation of the \nfemale sexual distress scale-revised for assessing distress in women with \nhypoactive sexual desire disorder. J Sex Med. 2008;5:357–364. \n16. Briere J. Dissociative symptoms and trauma exposure: specificity, \naffect dysregulation, and posttraumatic stress. J Nervous Mental Dis . \n2006;194:78–82. \n17. Beck AT, Steer RA, Ball R, et al. Comparison of beck depression \ninventories -IA and -II in psychiatric outpatients. J Pers Assess . \n1996;67:588–597. \n18. Thompson E. Hamilton rating scale for anxiety (HAM-A). Occup Med \n(Lond). 2015;65:601.\n19. Perme MP, Manevski D. Confidence intervals for the Mann-Whitney \ntest. Stat Methods Med Res. 2019;28:3755–3768. \n20. Fiala L, Lenz J, Bob P. Effect of psychosocial trauma and stress on \nsexual dysfunction in women with endo metriosis. Medicine (Baltimore). \n2021;100:e26836. \n21. Laganà AS, La Rosa VL, Rapisarda AMC, et al. Anxiety and depression \nin patients with endometriosis: impact and management challenges. Int \nJ Womens Health. 2017;9:323–330. \n22. Roelfsema F, Pijl H. Phase difference between serum prolactin and \ncortisol rhythms is related to body mass index in humans. J Clin  \nEndocrinol Metab. 2012;97:E2293–E2296.\n23. Brasil DL, Montagna E, Trevisan CM, et al. Psychological stress levels \nin women with endometriosis: systematic review and meta-analysis of \nobservational studies. Minerva Med. 2020;111:90–102. \n24. Ruoff GE. Depression in the patient with chronic pain. J Fam Pract . \n1996;43(6 Suppl):S25–33; discussion S34.\n25. Basson R, Gilks T. Women’s sexual dysfunction associated with \npsychiatric disorders and their treatment. Womens Health (Lond).  \n2018;14:1745506518762664.","source_license":"CC0","license_restricted":false}