Clinical diagnosis of endometriosis: a call to action
2019; Elsevier BV; Volume: 220; Issue: 4 Linguagem: Inglês
10.1016/j.ajog.2018.12.039
ISSN1097-6868
AutoresSanjay K. Agarwal, Charles Chapron, Linda C. Giudice, Marc R. Laufer, Nicholas Leyland, Stacey A. Missmer, Sukhbir S. Singh, Hugh S. Taylor,
Tópico(s)Gynecological conditions and treatments
ResumoEndometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4–11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women's healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide. Endometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4–11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women's healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide. THE PROBLEM: Endometriosis is undiagnosed in a large proportion of affected women, resulting in ongoing and progressive symptoms with associated negative impacts on health and well-being. Current practice standards, which rely primarily on laparoscopy for a definitive diagnosis before beginning therapy, frequently result in prolonged delay between symptom onset, diagnosis, and subsequent treatment.A SOLUTION: Enhanced use of clinical diagnostic techniques may reduce the delay in time to diagnosis and hence bring more rapid relief to affected patients, limit disease progression, and prevent sequelae. THE PROBLEM: Endometriosis is undiagnosed in a large proportion of affected women, resulting in ongoing and progressive symptoms with associated negative impacts on health and well-being. Current practice standards, which rely primarily on laparoscopy for a definitive diagnosis before beginning therapy, frequently result in prolonged delay between symptom onset, diagnosis, and subsequent treatment. A SOLUTION: Enhanced use of clinical diagnostic techniques may reduce the delay in time to diagnosis and hence bring more rapid relief to affected patients, limit disease progression, and prevent sequelae. Endometriosis has such wide-ranging and pervasive sequelae that it has been described as "nothing short of a public health emergency" requiring immediate action.1Hatch O. This is nothing short of a public health emergency. CNN.March 28, 2018https://www.cnn.com/2018/03/27/opinions/endometriosis-start-a-conversation-hatch-opinion/index.htmlDate accessed: April 14, 2018Google Scholar Population-based data suggest that more than 4 million reproductive-age women have diagnosed endometriosis in the United States.2Fuldeore M.J. Soliman A.M. Prevalence and symptomatic burden of diagnosed endometriosis in the United States: national estimates from a cross-sectional survey of 59,411 women.Gynecol Obstet Invest. 2017; 82: 453-461Crossref PubMed Scopus (142) Google Scholar As daunting as this number is, it only tells part of the story, as an estimated 6 of 10 endometriosis cases are undiagnosed.3Morassutto C. Monasta L. Ricci G. Barbone F. Ronfani L. Incidence and estimated prevalence of endometriosis and adenomyosis in northeast Italy: a data linkage study.PLoS One. 2016; 11: e0154227Crossref PubMed Scopus (91) Google Scholar Thus more than 6 million American women may experience repercussions of endometriosis without the benefit of understanding the cause of their symptoms or appropriate management. When discussing the patient's experience with endometriosis, pain and infertility are usually of greatest concern, as they are 2 of the disease's more common symptoms. However, the real toll is even greater: women with endometriosis experience diminished quality of life, increased incidence of depression, adverse effects on intimate relationships, limitations on participation in daily activities, reduced social activity, loss of productivity and associated income, increased risk of chronic disease, and significant direct and indirect healthcare costs.4Culley L. Law C. Hudson N. et al.The social and psychological impact of endometriosis on women's lives: a critical narrative review.Hum Reprod Update. 2013; 19: 625-639Crossref PubMed Scopus (336) Google Scholar, 5Moradi M. Parker M. Sneddon A. Lopez V. Ellwood D. Impact of endometriosis on women's lives: a qualitative study.BMC Womens Health. 2014; 14: 123Crossref PubMed Scopus (209) Google Scholar, 6Kvaskoff M. Mu F. Terry K.L. et al.Endometriosis: a high-risk population for major chronic diseases?.Hum Reprod Update. 2015; 21: 500-516Crossref PubMed Scopus (217) Google Scholar, 7Soliman A.M. Coyne K.S. Gries K.S. Castelli-Haley J. Snabes M.C. Surrey E.S. The effect of endometriosis symptoms on absenteeism and presenteeism in the workplace and at home.J Manag Care Spec Pharm. 2017; 23: 745-754Crossref PubMed Scopus (80) Google Scholar, 8Soliman A.M. Surrey E. Bonafede M. Nelson J.K. Castelli-Haley J. Real-world evaluation of direct and indirect economic burden among endometriosis patients in the United States.Adv Ther. 2018; 35: 408-423Crossref PubMed Scopus (64) Google Scholar Moreover, emerging data indicate that endometriosis is associated with greater risk of obstetric and neonatal complications.9Harada T. Taniguchi F. Onishi K. et al.Obstetrical complications in women with endometriosis: a cohort study in Japan.PLoS One. 2016; 11: e0168476Crossref PubMed Scopus (48) Google Scholar, 10Berlac J.F. Hartwell D. Skovlund C.W. Langhoff-Roos J. Lidegaard O. Endometriosis increases the risk of obstetrical and neonatal complications.Acta Obstet Gynecol Scand. 2017; 96: 751-760Crossref PubMed Scopus (64) Google Scholar, 11Zullo F. Spagnolo E. Saccone G. et al.Endometriosis and obstetrics complications: a systematic review and meta-analysis.Fertil Steril. 2017; 108: 667-672Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar, 12Chen I. Lalani S. Xie R.H. Shen M. Singh S.S. Wen S.W. Association between surgically diagnosed endometriosis and adverse pregnancy outcomes.Fertil Steril. 2018; 109: 142-147Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar There are no pathognomonic features or biomarkers necessary and sufficient to define endometriosis. Rather, key symptoms that currently prompt surgical evaluation, such as pain and infertility, can have multiple causes. Endometriosis is typically defined by its histology: extrauterine lesions consisting of endometrial glands, endometrial stroma, and/or hemosiderin-laden macrophages. Based on location and depth, lesions are further described as superficial peritoneal lesions, ovarian endometrioma, or deep endometriosis. However, the presence of lesions does not preclude other etiologies for the patient's symptoms, and the lack of obvious lesions does not eliminate the possibility of endometriosis. Furthermore, there is poor correlation between symptoms and severity or extent of disease, as quantified by current staging systems.13Johnson N.P. Hummelshoj L. Adamson G.D. et al.World Endometriosis Society consensus on the classification of endometriosis.Hum Reprod. 2017; 32: 315-324Crossref PubMed Scopus (309) Google Scholar From a clinical perspective, endometriosis may be better defined as a menstrual cycle−dependent, chronic, inflammatory, systemic disease that commonly presents as pelvic pain. Moving from a histological to a clinical definition opens the door to a different approach to diagnosis, one that emphasizes symptoms and their origins over lesion presence or absence, and that may, in the future, be validated by specific, noninvasive disease biomarkers. Among those who ultimately receive a successful definitive diagnosis, contemporary literature describes delays from symptom onset to diagnosis ranging from 4 to 11 years.5Moradi M. Parker M. Sneddon A. Lopez V. Ellwood D. Impact of endometriosis on women's lives: a qualitative study.BMC Womens Health. 2014; 14: 123Crossref PubMed Scopus (209) Google Scholar, 14Nnoaham K.E. Hummelshoj L. Webster P. et al.Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.Fertil Steril. 2011; 96: 366-373Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar, 15Hudelist G. Fritzer N. Thomas A. et al.Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.Hum Reprod. 2012; 27: 3412-3416Crossref PubMed Scopus (242) Google Scholar, 16Fourquet J. Sinaii N. Stratton P. et al.Characteristics of women with endometriosis from the USA and Puerto Rico.J Endometr Pelvic Pain Disord. 2015; 7: 129-135Crossref PubMed Scopus (12) Google Scholar, 17Staal A.H. Van Der Zanden M. Nap A.W. Diagnostic delay of endometriosis in the Netherlands.Gynecol Obstet Invest. 2016; 81: 321-324Crossref PubMed Scopus (70) Google Scholar, 18Soliman A.M. Fuldeore M. Snabes M.C. Factors associated with time to endometriosis diagnosis in the United States.J Womens Health (Larchmt). 2017; 26: 788-797Crossref PubMed Scopus (54) Google Scholar Several factors exacerbate this delay,14Nnoaham K.E. Hummelshoj L. Webster P. et al.Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.Fertil Steril. 2011; 96: 366-373Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar, 15Hudelist G. Fritzer N. Thomas A. et al.Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.Hum Reprod. 2012; 27: 3412-3416Crossref PubMed Scopus (242) Google Scholar, 17Staal A.H. Van Der Zanden M. Nap A.W. Diagnostic delay of endometriosis in the Netherlands.Gynecol Obstet Invest. 2016; 81: 321-324Crossref PubMed Scopus (70) Google Scholar, 18Soliman A.M. Fuldeore M. Snabes M.C. Factors associated with time to endometriosis diagnosis in the United States.J Womens Health (Larchmt). 2017; 26: 788-797Crossref PubMed Scopus (54) Google Scholar including "normalization" of symptoms and misdiagnosis.15Hudelist G. Fritzer N. Thomas A. et al.Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.Hum Reprod. 2012; 27: 3412-3416Crossref PubMed Scopus (242) Google Scholar The presence of diagnostic delays is a worldwide phenomenon, occurring even in countries with universal healthcare.15Hudelist G. Fritzer N. Thomas A. et al.Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.Hum Reprod. 2012; 27: 3412-3416Crossref PubMed Scopus (242) Google Scholar, 17Staal A.H. Van Der Zanden M. Nap A.W. Diagnostic delay of endometriosis in the Netherlands.Gynecol Obstet Invest. 2016; 81: 321-324Crossref PubMed Scopus (70) Google Scholar Consequences of the delay in diagnosis are experienced by patients in multiple ways, including persistent symptoms and a commensurate detrimental impact on quality of life,14Nnoaham K.E. Hummelshoj L. Webster P. et al.Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.Fertil Steril. 2011; 96: 366-373Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar erosion of the patient−physician relationship,4Culley L. Law C. Hudson N. et al.The social and psychological impact of endometriosis on women's lives: a critical narrative review.Hum Reprod Update. 2013; 19: 625-639Crossref PubMed Scopus (336) Google Scholar, 5Moradi M. Parker M. Sneddon A. Lopez V. Ellwood D. Impact of endometriosis on women's lives: a qualitative study.BMC Womens Health. 2014; 14: 123Crossref PubMed Scopus (209) Google Scholar and development of central sensitization—a mechanism whereby persistent endometriosis-associated pain increases pain awareness, even at sites unconnected anatomically with the lesion(s).14Nnoaham K.E. Hummelshoj L. Webster P. et al.Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.Fertil Steril. 2011; 96: 366-373Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar, 19Issa B. Onon T.S. Agrawal A. et al.Visceral hypersensitivity in endometriosis: a new target for treatment?.Gut. 2012; 61: 367-372Crossref PubMed Scopus (59) Google Scholar, 20As-Sanie S. Harris R.E. Harte S.E. Tu F.F. Neshewat G. Clauw D.J. Increased pressure pain sensitivity in women with chronic pelvic pain.Obstet Gynecol. 2013; 122: 1047-1055Crossref PubMed Scopus (87) Google Scholar, 21Li T. Mamillapalli R. Ding S. et al.Endometriosis alters brain electro-physiology, gene expression and increased pain sensitization, anxiety, and depression in female mice.Biol Reprod. 2018; 99: 349-359Crossref PubMed Scopus (44) Google Scholar Moreover, although the evidence is limited, failure of timely diagnosis and adequate endometriosis management may foster disease progression and adhesion formation that may compromise fertility and increase the risk of central sensitization and chronic pelvic pain.22Unger C.A. Laufer M.R. Progression of endometriosis in non-medically managed adolescents: a case series.J Pediatr Adolesc Gynecol. 2011; 24: e21-e23Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 23Brosens I. Gordts S. Benagiano G. Endometriosis in adolescents is a hidden, progressive and severe disease that deserves attention, not just compassion.Hum Reprod. 2013; 28: 2026-2031Crossref PubMed Scopus (101) Google Scholar, 24Coxon L. Horne A.W. Vincent K. Pathophysiology of endometriosis-associated pain: a review of pelvic and central nervous system mechanisms.Best Pract Res Clin Obstet Gynaecol. 2018; 51: 53-67Crossref PubMed Scopus (65) Google Scholar The current diagnostic paradigm, endorsed by professional societies, requires laparoscopy with or without histologic verification as the gold standard, although many societies endorse the treatment of symptoms before obtaining a definitive surgical diagnosis.25Practice bulletin no. 114: management of endometriosis.Obstet Gynecol. 2010; 116: 223-236Crossref PubMed Scopus (226) Google Scholar, 26Leyland N. Casper R. Laberge P. Singh S.S. Society of Obstetricians and Gynaecologists of Canada Endometriosis: diagnosis and management.J Obstet Gynaecol Can. 2010; 32: S1-S32Abstract Full Text PDF PubMed Scopus (244) Google Scholar, 27Johnson N.P. Hummelshoj L. World Endometriosis Society Montpellier ConsortiumConsensus on current management of endometriosis.Hum Reprod. 2013; 28: 1552-1568Crossref PubMed Scopus (371) Google Scholar, 28Practice Committee of the American Society for Reproductive Medicine Treatment of pelvic pain associated with endometriosis: a committee opinion.Fertil Steril. 2014; 101: 927-935Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, 29Dunselman G.A. Vermeulen N. Becker C. et al.ESHRE guideline: management of women with endometriosis.Hum Reprod. 2014; 29: 400-412Crossref PubMed Scopus (1417) Google Scholar Notably, the 2017 National Institute for Health and Care Excellence guidelines reflect a philosophical shift, presenting empiric therapy prior to laparoscopy in the diagnostic and treatment algorithm unless fertility is a priority.30National Institute for Health and Care ExcellenceEndometriosis: diagnosis and management (NG73). London, United Kingdom; 2017.http://nice.org.uk/guidance/ng73Date accessed: May 18, 2018Google Scholar Although the merits of laparoscopy and its role in disease management should not be minimized, its accuracy, risks, and cost-effectiveness warrant reevaluation. The poor correlation between reported symptoms and extent of disease found at laparoscopy further illustrates the limitations of surgical disease assessment.31Vercellini P. Fedele L. Aimi G. Pietropaolo G. Consonni D. Crosignani P.G. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients.Hum Reprod. 2007; 22: 266-271Crossref PubMed Scopus (327) Google Scholar Detecting endometriosis via laparoscopy relies on the visual identification of lesions, a practice that is challenged by heterogeneous lesion appearance,32Albee Jr., R.B. Sinervo K. Fisher D.T. Laparoscopic excision of lesions suggestive of endometriosis or otherwise atypical in appearance: relationship between visual findings and final histologic diagnosis.J Minim Invasive Gynecol. 2008; 15: 32-37Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar inaccessible lesion location (particularly for deep lesions),33Singh S.S. Suen M.W. Surgery for endometriosis: beyond medical therapies.Fertil Steril. 2017; 107: 549-554Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar and interobserver variability.34Schliep K.C. Chen Z. Stanford J.B. et al.Endometriosis diagnosis and staging by operating surgeon and expert review using multiple diagnostic tools: an inter-rater agreement study.Br J Obstet Gynecol. 2017; 124: 220-229Crossref Scopus (20) Google Scholar Surgical risks associated with laparoscopy are generally low,33Singh S.S. Suen M.W. Surgery for endometriosis: beyond medical therapies.Fertil Steril. 2017; 107: 549-554Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 35Surrey E.S. Soliman A.M. Yang H. Du E.X. Su B. Treatment patterns, complications, and health care utilization among endometriosis patients undergoing a laparoscopy or a hysterectomy: a retrospective claims analysis.Adv Ther. 2017; 34: 2436-2451Crossref PubMed Scopus (18) Google Scholar although they merit consideration, given the potential for major (albeit rare) complications36Chapron C. Fauconnier A. Goffinet F. Breart G. Dubuisson J.B. Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a meta-analysis.Hum Reprod. 2002; 17: 1334-1342Crossref PubMed Scopus (168) Google Scholar and the need for re-treatment after initial laparoscopy because there is no surgical cure for endometriosis.37Soliman A.M. Du E.X. Yang H. Wu E.Q. Haley J.C. Retreatment rates among endometriosis patients undergoing hysterectomy or laparoscopy.J Womens Health (Larchmt). 2017; 26: 644-654Crossref PubMed Scopus (15) Google Scholar From a pragmatic perspective, evaluation of laparoscopy for endometriosis diagnosis and management must include a discussion of costs, which are substantially higher compared with nonsurgical approaches.38Soliman A.M. Taylor H.S. Bonafede M. Nelson J.K. Castelli-Haley J. Incremental direct and indirect cost burden attributed to endometriosis surgeries in the United States.Fertil Steril. 2017; 107: 1181-1190Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Reliance on laparoscopy for endometriosis diagnosis supports the viewpoint that the presence of identifiable lesions in the pelvis is the central tenet of endometriosis, rather than approaching endometriosis as a menstrual cycle−dependent, chronic, inflammatory, systemic disease that often presents as pelvic pain. By shifting the paradigm to the patient rather than the lesion, the path to clinical diagnosis has the potential to be more inclusive with reduced diagnostic delay. Indeed, Soliman et al18Soliman A.M. Fuldeore M. Snabes M.C. Factors associated with time to endometriosis diagnosis in the United States.J Womens Health (Larchmt). 2017; 26: 788-797Crossref PubMed Scopus (54) Google Scholar reported diagnosing endometriosis by nonsurgical methods shortened the mean time from first consultation to diagnosis compared with surgical diagnosis. This shift, however, requires clinical diagnostic methodologies that accurately identify endometriosis. To that end, we have compiled data on the accuracy of clinical assessments for diagnosing endometriosis (Table 1). Notably, these studies were highly heterogeneous, which precluded performance of a meaningful meta-analysis.Table 1Predictive value of signs, symptoms, and clinical findings for diagnosing endometriosisStudy design and populationMethod of diagnosisAssessment or parameterResultsEndometriosis (general)Saha 201747Saha R. Marions L. Tornvall P. Validity of self-reported endometriosis and endometriosis-related questions in a Swedish female twin cohort.Fertil Steril. 2017; 107: 174-178Abstract Full Text Full Text PDF PubMed Scopus (19) Google ScholaraReported are the agreement between self-reported symptoms of endometriosis and diagnosis of endometriosis recorded in medical recordsCross-sectional survey of a Swedish twin cohort (N = 26,898)Endometriosis diagnosis listed in electronic medical recordSevere dysmenorrheaSensitivity, 58%; specificity, 70%Chronic pelvic painSensitivity, 25%; specificity, 89%DyspareuniaSensitivity, 16%; specificity, 96%InfertilitySensitivity, 28%; specificity, 93%Oral pill as contraceptiveSensitivity, 16%; specificity, 80%Fuldeore 20172Fuldeore M.J. Soliman A.M. Prevalence and symptomatic burden of diagnosed endometriosis in the United States: national estimates from a cross-sectional survey of 59,411 women.Gynecol Obstet Invest. 2017; 82: 453-461Crossref PubMed Scopus (142) Google ScholarRespondents to an online, cross-sectional survey (N = 48,020)Self-report (replying in the affirmative that a doctor had previously told the subject that she has or is suspected of having endometriosis)Menstrual pelvic pain/crampingOR, 1.6 (95% CI, 1.4–1.8)Nonmenstrual pelvic pain/crampingOR, 4.1 (95% CI, 3.6–4.6)DyspareuniaOR, 3.1 (95% CI, 2.8–3.5)Heavy menstrual bleedingOR, 1.5 (95% CI, 1.3–1.7)Excessive or irregular bleedingOR, 2.1 (95% CI, 1.8–2.4)Passage of clotsOR, 1.8 (95% CI, 1.6–2.0)Irregular menstrual periods (timing/duration)OR, 1.5 (95% CI, 1.3–1.7)Constipation/bloating/diarrheaOR, 1.9 (95% CI, 1.7–2.2)Fatigue/weariness/anemiaOR, 2.2 (95% CI, 2.0–2.5)InfertilityOR, 3.6 (95% CI, 3.0–4.4)Ashrafi 201650Ashrafi M. Sadatmahalleh S.J. Akhoond M.R. Talebi M. Evaluation of risk factors associated with endometriosis in infertile women.Int J Fertil Steril. 2016; 10: 11-21PubMed Google ScholarRetrospective case-control study involving women who underwent laparoscopy for infertility evaluation (341 with endometriosis; 332 with a normal pelvis)Laparoscopically visualized endometriosisFamily history of endometriosisOR, 2.7 (95% CI, 1.06–7.1)History of galactorrheaOR, 1.8 (95% CI, 1.1–3.05)History of pelvic surgeryOR, 14.5 (95% CI, 6.1–34.2)DysmenorrheaOR, 1.8 (95% CI, 1.1–2.8)Pelvic painOR, 4.1 (95% CI, 2.4–6.8)DyspareuniaOR, 1.6 (95% CI, 1.09–2.4)Premenstrual spottingOR, 2.2 (95% CI, 1.3–3.6)FatigueOR, 2.6 (95% CI, 1.3–5.1)Apostolopoulos 201664Apostolopoulos N.V. Alexandraki K.I. Gorry A. Coker A. Association between chronic pelvic pain symptoms and the presence of endometriosis.Arch Gynecol Obstet. 2016; 293: 439-445Crossref PubMed Scopus (32) Google ScholarProspective, observational study of women who underwent laparoscopy for chronic pelvic pain (N = 144)Laparoscopically visualized endometriosisNoncyclical painEndometriosis, 62.5%; no endometriosis, 70.8%; p = 0.48DysmenorrheaEndometriosis, 79.1%; no endometriosis, 87.5%; p = 0.37DyspareuniaEndometriosis, 25.0%; no endometriosis, 33.3%; p = 0.46DyscheziaEndometriosis, 25.0%; no endometriosis, 20.8%; p = 0.69Schliep 201540Schliep K.C. Mumford S.L. Peterson C.M. et al.Pain typology and incident endometriosis.Hum Reprod. 2015; 30: 2427-2438Crossref PubMed Scopus (82) Google ScholarOperative cohort from the ENDO study—women without a history of surgically confirmed endometriosis who underwent laparoscopy or laparotomy (N = 473)Surgically visualized endometriosisChronic pelvic painEndometriosis, 44.2%; other, 39.0%; normal pelvis, 30.2%; p = 0.04Cyclic pelvic painEndometriosis, 49.5%; other, 31.0%; normal pelvis, 33.1%; p < 0.001Vaginal pain with intercourseEndometriosis, 54.7%; other, 41.5%; normal pelvis, 32.4%; p < 0.001Deep pain with intercourseEndometriosis, 53.2%; other, 38.1%; normal pelvis, 30.9%; p < 0.001Burning vaginal pain after intercourseEndometriosis, 33.2%; other, 22.5%; normal pelvis, 22.1%; p = 0.03Pain just before menstrual periodEndometriosis, 75.3%; other, 61.9%; normal pelvis, 66.2%; p = 0.03Level of cramps with periodEndometriosis, 91.1%; other, 85.0%; normal pelvis, 79.4%; p = 0.01Pain after period is overEndometriosis, 38.4%; other, 26.5%; normal pelvis, 38.2%; p = 0.04Pain at ovulation (mid-cycle)Endometriosis, 67.4%; other, 49.0%; normal pelvis, 52.2%; p = 0.001DysuriaEndometriosis, 22.6%; other, 19.1%; normal pelvis, 11.0%; p = 0.03DyscheziaEndometriosis, 44.2%; other, 32.7%; normal pelvis, 25.7%; p = 0.002Heitman 201448Heitmann R.J. Langan K.L. Huang R.R. Chow G.E. Burney R.O. Premenstrual spotting of ≥2 days is strongly associated with histologically confirmed endometriosis in women with infertility.Am J Obstet Gynecol. 2014; 211: 358Abstract Full Text Full Text PDF PubMed Scopus (13) Google ScholarRetrospective cohort of consecutive women with or without pelvic pain who were evaluated for infertility (N = 80)Histologically verified endometriosisPremenstrual spotting for ≥2 daysSensitivity, 76%; specificity, 90%; PPV, 96%; NPV, 74%; accuracy, 81%DysmenorrheaSensitivity, 87%; specificity, 63%; PPV, 75%; NPV, 79%; accuracy, 76%DyspareuniaSensitivity, 38%; specificity, 83%; PPV, 74%; NPV, 51%; accuracy, 58%Peterson 201341Peterson C.M. Johnstone E.B. Hammoud A.O. et al.Risk factors associated with endometriosis: importance of study population for characterizing disease in the ENDO Study.Am J Obstet Gynecol. 2013; 208: 451Abstract Full Text Full Text PDF PubMed Scopus (77) Google ScholarbData are adjusted odds ratiosENDO Study—Prospective, matched-exposure cohort study comprising women undergoing pelvic surgery (n = 495) and a matched cohort (n = 131)Surgically visualized endometriosis (operative cohort)Pelvic MRI-diagnosed endometriosis (matched cohort)History of infertilityOR, 2.43 (95% CI, 1.57–3.76) [operative]; 7.91 (1.69–37.2) [matched]DysmenorrheaOR, 2.46 (95% CI, 1.28–4.72) [operative]; 1.41 (0.28–7.14) [matched]Pelvic painOR, 1.39 (95% CI, 0.95–2.04) [operative]; 0.76 (0.09–6.54) [matched]Pelvic pain (surgical indication)OR, 3.67 (95% CI, 2.44–5.50) [operative]Nnoaham 201243Nnoaham K.E. Hummelshoj L. Kennedy S.H. Jenkinson C. Zondervan K.T. World Endometriosis Research Foundation Women's Health Symptom Survey ConsortiumDeveloping symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.Fertil Steril. 2012; 98: 692-701Abstract Full Text Full Text PDF PubMed Scopus (74) Google ScholarProspective, observational study of symptomatic women with scheduled laparoscopy (N = 1396)Laparoscopically visualized endometriosisModel comprising multiple factors (eg, dysmenorrhea, dyschezia, nonmenstrual pelvic pain, ovarian cyst, family history, race, etc)Sensitivity, 85%; specificity, 44%Model and ultrasoundSensitivity, 58%; specificity, 89%Paulson 201154Paulson J.D. Paulson J.N. Anterior vaginal wall tenderness (AVWT) as a physical symptom in chronic pelvic pain.JSLS. 2011; 15: 6-9Crossref PubMed Scopus (8) Google ScholarProspective cohort of women with chronic pelvic pain (N = 284)Laparoscopically or histologically confirmed endometriosisAnterior vaginal wall tenderness (endometriosis and other pathology)Sensitivity, 93%Anterior vaginal wall tenderness (endometriosis only)Sensitivity, 17%Droz 201165Droz J. Howard F.M. Use of the Short-Form McGill Pain Questionnaire as a diagnostic tool in women with chronic pelvic pain.J Minim Invasive Gynecol. 2011; 18: 211-217Abstract Full Text Full Text PDF PubMed Scopus (24) Google ScholarRetrospective cohort of women evaluated for chronic pelvic pain (N = 331)Histologically verified endometriosisShort-form MPQ pain descriptor:CrampingSensitivity, 92%; specificity, 33%; PPV, 40%, NPV, 89%SickeningSensitivity, 73%; specificity, 46%; PPV, 40%; NPV, 78%Tiring/exhaustingSensitivity, 77%; specificity, 38%; PPV
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