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Clinical diagnosis of endometriosis: a call to action

Open AccessPublished:January 06, 2019DOI:https://doi.org/10.1016/j.ajog.2018.12.039
      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.

      Key words

      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.
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      This is nothing short of a public health emergency. CNN.
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      As daunting as this number is, it only tells part of the story, as an estimated 6 of 10 endometriosis cases are undiagnosed.
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      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.
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      The challenge of diagnosing endometriosis

      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.
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      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.
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      Several factors exacerbate this delay,
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      Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.
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      Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.
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      Diagnostic delay of endometriosis in the Netherlands.
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      Factors associated with time to endometriosis diagnosis in the United States.
      including “normalization” of symptoms and misdiagnosis.
      • Hudelist G.
      • Fritzer N.
      • Thomas A.
      • et al.
      Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.
      The presence of diagnostic delays is a worldwide phenomenon, occurring even in countries with universal healthcare.
      • Hudelist G.
      • Fritzer N.
      • Thomas A.
      • et al.
      Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.
      • Staal A.H.
      • Van Der Zanden M.
      • Nap A.W.
      Diagnostic delay of endometriosis in the Netherlands.
      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,
      • Nnoaham K.E.
      • Hummelshoj L.
      • Webster P.
      • et al.
      Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.
      erosion of the patient−physician relationship,
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      • Law C.
      • Hudson N.
      • et al.
      The social and psychological impact of endometriosis on women's lives: a critical narrative review.
      • Moradi M.
      • Parker M.
      • Sneddon A.
      • Lopez V.
      • Ellwood D.
      Impact of endometriosis on women's lives: a qualitative study.
      and development of central sensitization—a mechanism whereby persistent endometriosis-associated pain increases pain awareness, even at sites unconnected anatomically with the lesion(s).
      • Nnoaham K.E.
      • Hummelshoj L.
      • Webster P.
      • et al.
      Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.
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      Visceral hypersensitivity in endometriosis: a new target for treatment?.
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      Endometriosis alters brain electro-physiology, gene expression and increased pain sensitization, anxiety, and depression in female mice.
      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.
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      Progression of endometriosis in non-medically managed adolescents: a case series.
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      Endometriosis in adolescents is a hidden, progressive and severe disease that deserves attention, not just compassion.
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      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.
      Practice bulletin no. 114: management of endometriosis.
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      Endometriosis: diagnosis and management.
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      Consensus on current management of endometriosis.
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      Treatment of pelvic pain associated with endometriosis: a committee opinion.
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      ESHRE guideline: management of women with endometriosis.
      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.
      National Institute for Health and Care Excellence
      Endometriosis: diagnosis and management (NG73). London, United Kingdom; 2017.
      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.
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      Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients.
      Detecting endometriosis via laparoscopy relies on the visual identification of lesions, a practice that is challenged by heterogeneous lesion appearance,
      • Albee 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.
      inaccessible lesion location (particularly for deep lesions),
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      Surgery for endometriosis: beyond medical therapies.
      and interobserver variability.
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      • et al.
      Endometriosis diagnosis and staging by operating surgeon and expert review using multiple diagnostic tools: an inter-rater agreement study.
      Surgical risks associated with laparoscopy are generally low,
      • Singh S.S.
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      Surgery for endometriosis: beyond medical therapies.
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      • Yang H.
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      Treatment patterns, complications, and health care utilization among endometriosis patients undergoing a laparoscopy or a hysterectomy: a retrospective claims analysis.
      although they merit consideration, given the potential for major (albeit rare) complications
      • Chapron C.
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      Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a meta-analysis.
      and the need for re-treatment after initial laparoscopy because there is no surgical cure for endometriosis.
      • Soliman A.M.
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      • Yang H.
      • Wu E.Q.
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      Retreatment rates among endometriosis patients undergoing hysterectomy or laparoscopy.
      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.
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      Incremental direct and indirect cost burden attributed to endometriosis surgeries in the United States.

      Argument for clinical diagnosis

      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 al
      • Soliman A.M.
      • Fuldeore M.
      • Snabes M.C.
      Factors associated with time to endometriosis diagnosis in the United States.
      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 endometriosis
      Study design and populationMethod of diagnosisAssessment or parameterResults
      Endometriosis (general)
      Saha 2017
      • Saha R.
      • Marions L.
      • Tornvall P.
      Validity of self-reported endometriosis and endometriosis-related questions in a Swedish female twin cohort.
      Reported are the agreement between self-reported symptoms of endometriosis and diagnosis of endometriosis recorded in medical records


      Cross-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 2017
      • Fuldeore 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.


      Respondents 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 2016
      • Ashrafi M.
      • Sadatmahalleh S.J.
      • Akhoond M.R.
      • Talebi M.
      Evaluation of risk factors associated with endometriosis in infertile women.


      Retrospective 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 2016
      • Apostolopoulos N.V.
      • Alexandraki K.I.
      • Gorry A.
      • Coker A.
      Association between chronic pelvic pain symptoms and the presence of endometriosis.


      Prospective, observational study of women who underwent laparoscopy for chronic pelvic pain (N = 144)
      Laparoscopically visualized endometriosisNoncyclical painEndometriosis, 62.5%; no endometriosis, 70.8%; p = 0.48
      DysmenorrheaEndometriosis, 79.1%; no endometriosis, 87.5%; p = 0.37
      DyspareuniaEndometriosis, 25.0%; no endometriosis, 33.3%; p = 0.46
      DyscheziaEndometriosis, 25.0%; no endometriosis, 20.8%; p = 0.69
      Schliep 2015
      • Schliep K.C.
      • Mumford S.L.
      • Peterson C.M.
      • et al.
      Pain typology and incident endometriosis.


      Operative 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 = 0.04
      Cyclic pelvic painEndometriosis, 49.5%; other, 31.0%; normal pelvis, 33.1%; p < 0.001
      Vaginal pain with intercourseEndometriosis, 54.7%; other, 41.5%; normal pelvis, 32.4%; p < 0.001
      Deep pain with intercourseEndometriosis, 53.2%; other, 38.1%; normal pelvis, 30.9%; p < 0.001
      Burning vaginal pain after intercourseEndometriosis, 33.2%; other, 22.5%; normal pelvis, 22.1%; p = 0.03
      Pain just before menstrual periodEndometriosis, 75.3%; other, 61.9%; normal pelvis, 66.2%; p = 0.03
      Level of cramps with periodEndometriosis, 91.1%; other, 85.0%; normal pelvis, 79.4%; p = 0.01
      Pain after period is overEndometriosis, 38.4%; other, 26.5%; normal pelvis, 38.2%; p = 0.04
      Pain at ovulation (mid-cycle)Endometriosis, 67.4%; other, 49.0%; normal pelvis, 52.2%; p = 0.001
      DysuriaEndometriosis, 22.6%; other, 19.1%; normal pelvis, 11.0%; p = 0.03
      DyscheziaEndometriosis, 44.2%; other, 32.7%; normal pelvis, 25.7%; p = 0.002
      Heitman 2014
      • Heitmann 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.


      Retrospective 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 2013
      • Peterson 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.
      Data are adjusted odds ratios


      ENDO 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 2012
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.


      Prospective, 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 2011
      • Paulson J.D.
      • Paulson J.N.
      Anterior vaginal wall tenderness (AVWT) as a physical symptom in chronic pelvic pain.


      Prospective 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 2011
      • Droz J.
      • Howard F.M.
      Use of the Short-Form McGill Pain Questionnaire as a diagnostic tool in women with chronic pelvic pain.


      Retrospective 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, 38%; NPV, 77%
      ShootingSensitivity, 70%; specificity, 43%; PPV, 37%; NPV, 75%
      Punishing/cruelSensitivity, 49%; specificity, 65%; PPV, 40%; NPV, 72%
      SplittingSensitivity, 36%; specificity, 77%; PPV, 43%; NPV, 71%
      Paulson 2009
      • Paulson J.D.
      Correlation of anterior vaginal wall pain with endometriosis in infertile patients.


      Prospective study of consecutive women with unexplained infertility (N = 55)
      Laparoscopically or histologically confirmed endometriosisAnterior vaginal wall tendernessSensitivity, 84%; specificity, 75%; PPV, 86%; NPV, 69%
      Meuleman 2009
      • Meuleman C.
      • Vandenabeele B.
      • Fieuws S.
      • Spiessens C.
      • Timmerman D.
      • D'hooghe T.
      High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners.


      Retrospective case series comprising infertile women with regular cycles and no prior endometriosis diagnosis (N = 221)
      Histologically verified endometriosisPelvic painSensitivity, 59%; specificity, 56%; PPV, 54%; NPV, 57%
      Pelvic pain and type of infertility, age, and duration of infertilitySensitivity, 65%; specificity, 73%
      Hudelist 2009
      • Hudelist G.
      • Oberwinkler K.H.
      • Singer C.F.
      • et al.
      Combination of transvaginal sonography and clinical examination for preoperative diagnosis of pelvic endometriosis.
      Ranges reflect different values based on anatomic locations of the endometriotic lesions


      Prospective study of consecutive women with symptoms of endometriosis (N = 200)
      Histologically verified endometriosisVaginal examinationSensitivity, 23-88%; specificity, 89–100%; PPV, 65–100%; NPV, 85–99%; accuracy, 86–99%
      Vaginal examination and TVSSensitivity, 67–100%; specificity, 86–100%; PPV, 50–100%;NPV, 93–100%; accuracy, 86–100%
      Flores 2008
      • Flores I.
      • Abreu S.
      • Abac S.
      • Fourquet J.
      • Laboy J.
      • Rios-Bedoya C.
      Self-reported prevalence of endometriosis and its symptoms among Puerto Rican women.


      Respondents to a self-administered questionnaire (N = 1285)
      Self-reported surgically confirmed endometriosisDysmenorrheaCases, 82.5%; general population, 59.3%; p < 0.001
      Severe dysmenorrheaCases, 65.9%; general population, 52.9%; p = NS
      DyspareuniaCases, 52.0%; general population, 20.0%; p < 0.001
      Problems conceivingCases, 70.6%; general population, 25.2%; p < 0.001
      Chronic pelvic painCases, 80.0%; general population, 22.9%; p < 0.001
      Ballard 2008
      • Ballard K.D.
      • Seaman H.E.
      • De Vries C.S.
      • Wright J.T.
      Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study—part 1.
      Shown here are symptoms and signs with an odds ratio for predicting endometriosis of 5.0 or greater


      National case-control study comprising women with endometriosis (n = 5540) and matched controls (n = 21,239)
      Diagnostic or procedural codes consistent with endometriosis recorded in a nationwide general practice databaseDysmenorrheaOR, 9.8 (95% CI, 8.8–10.9)
      Pelvic painOR, 13.5 (95% CI, 11.7–15.7)
      DyspareuniaOR, 9.4 (95% CI, 8.0–11.1)
      Abdominal painOR, 5.9 (95% CI, 5.5–6.4)
      MenorrhagiaOR, 5.0 (95% CI, 4.6–5.5)
      Intermenstrual painOR, 6.9 (95% CI, 4.7–10.2)
      Infertility/subfertilityOR, 6.2 (95% CI, 5.4–7.1)
      Pelvic inflammatory diseaseOR, 6.4 (95% CI, 5.6–7.4)
      Ovarian cystsOR, 12.2 (95% CI, 9.9–15.0)
      Ovary painOR, 9.1 (95% CI, 3.2–26.0)
      Endometriosis (stages III and IV)
      Peterson 2013
      • Peterson 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.
      Data are adjusted odds ratios


      ENDO Study—prospective, matched exposure cohort study comprising women undergoing pelvic surgery (n = 495)
      Surgically visualized endometriosis (operative cohort)History of infertilityOR, 4.74 (95% CI, 2.57–8.75)
      DysmenorrheaOR, 3.43 (95% CI, 1.02–11.5)
      Pelvic painOR, 1.60 (95% CI, 0.89–2.87)
      Pelvic pain (surgical indication)OR, 4.47 (95% CI, 2.39–8.38)
      Nnoaham 2012
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.


      Prospective, observational study of symptomatic women with scheduled laparoscopy (N = 1396)
      Laparoscopically visualized endometriosisModel comprising multiple factors (eg, dyschezia, ovarian cyst, infertility, cycle length, GI/bladder symptoms, race, etc)Sensitivity, 71%; specificity, 85%
      Model with ultrasoundSensitivity, 82%; specificity, 76%
      Endometriosis and other peri-ovarian dhesions
      Marasinghe 2014
      • Marasinghe J.P.
      • Senanayake H.
      • Saravanabhava N.
      • Arambepola C.
      • Condous G.
      • Greenwood P.
      History, pelvic examination findings and mobility of ovaries as a sonographic marker to detect pelvic adhesions with fixed ovaries.


      Prospective, observational study comprising women evaluated for infertility and/or chronic pelvic pain (N = 110)
      Laparoscopically visualized endometriosisDyspareuniaSensitivity, 46%; specificity, 77%; PPV, 52%; NPV, 73%; accuracy, 47%
      DysmenorrheaSensitivity, 76%; specificity, 70%; PPV, 57%; NPV, 84%; accuracy, 71%
      Dyspareunia and dysmenorrheaSensitivity, 78%; specificity, 64%; PPV, 54%; NPV, 85%; accuracy, 68%
      Vaginal examinationSensitivity, 73%; specificity, 88%; PPV, 77%; NPV, 86%; accuracy, 83%
      Dyspareunia, dysmenorrhea, and vaginal examinationSensitivity, 84%; specificity, 62%; PPV, 54%; NPV, 88%; accuracy, 69%
      Fixed ovaries on TVSSensitivity, 78%; specificity, 94%; PPV, 88%; NPV, 89%; accuracy, 88%
      Dyspareunia, dysmenorrhea, vaginal examination and fixed ovariesSensitivity, 92%; specificity, 61%; PPV, 56%; NPV, 93%; accuracy, 71%
      Deep endometriosis
      Perello 2017
      • Perello M.
      • Martinez-Zamora M.A.
      • Torres X.
      • et al.
      Markers of deep infiltrating endometriosis in patients with ovarian endometrioma: a predictive model.


      Retrospective analysis of consecutive women with ovarian endometrioma who underwent surgery (N = 178)
      Histologically verified endometriosisModel including previous pregnancy, history of surgery for endometriosis, endometriosis-associated pelvic pain scoreSensitivity, 80%; specificity, 84%
      Lafay Pillet 2014
      • Lafay Pillet M.C.
      • Huchon C.
      • Santulli P.
      • Borghese B.
      • Chapron C.
      • Fauconnier A.
      A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma.
      Lafay Pillet et al18 evaluated combining multiple signs, symptoms, and findings to predict the presence of deep endometriosis. Presented here are the individual measures included in the final model.


      Prospective, single-center study of women with a histological diagnosis of endometriosis (N = 211)
      Histologically verified endometriosisInfertility (primary or secondary)Sensitivity, 51%; specificity, 73%; OR, 1.5; p = 0.003
      Duration of pain >24 moSensitivity, 62%; specificity, 81%; OR, 7.1; p < 0.001
      VAS deep dyspareunia >5Sensitivity, 69%; specificity, 59%; OR, 3.2; p = 0.007
      VAS GI symptoms ≥5Sensitivity, 75%; specificity, 76%; OR, 9.3; p < 0.001
      Severe dysmenorrheaSensitivity, 55%; specificity, 75%; OR, 3.5; p < 0.001
      Hudelist 2011
      • Hudelist G.
      • Ballard K.
      • English J.
      • et al.
      Transvaginal sonography vs. clinical examination in the preoperative diagnosis of deep infiltrating endometriosis.
      Ranges reflect different values based on anatomic locations of the endometriotic lesions


      Prospective study of premenopausal women with suspected endometriosis (N = 129)
      Histologically verified endometriosisVaginal examinationSensitivity, 25–78%; specificity, 80–100%; PPV, 43–100%; NPV, 84–98%; accuracy, 73–98%
      TVSSensitivity, 50–96%; specificity, 96–100%; PPV, 50–100%; NPV, 90–99%; accuracy, 90–99%
      Bazot 2009
      • Bazot M.
      • Lafont C.
      • Rouzier R.
      • Roseau G.
      • Thomassin-Naggara I.
      • Darai E.
      Diagnostic accuracy of physical examination, transvaginal sonography, rectal endoscopic sonography, and magnetic resonance imaging to diagnose deep infiltrating endometriosis.
      Ranges reflect different values based on anatomic locations of the endometriotic lesions


      Retrospective, longitudinal study of consecutive women with clinical evidence of endometriosis (N = 92)
      Laparoscopically visualized endometriosisVaginal examinationSensitivity, 18–74%; specificity, 72–96%; PPV, 40–97%; NPV, 24–90%; accuracy, 54–87%
      TVSSensitivity, 9–94%; specificity, 67–100%; PPV, 50–100%; NPV, 25–89%; accuracy, 77–96%
      Rectal endoscopic sonographySensitivity, 7–89%; specificity, 44–100%; PPV, 33–100%; NPV, 9–90%; accuracy, 48–90%
      MRISensitivity, 55–87%; specificity, 86–99%; PPV, 73–99%; NPV, 38–94%; accuracy, 84–94%
      To identify relevant studies, a search of the MEDLINE database was performed using the following search terms: endometriosis AND (pain OR cycle OR infertility OR “physical exam” OR “physical examination” OR “pelvic exam” OR “pelvic examination”) AND (specificity OR sensitivity OR accuracy). Articles were limited to clinical studies published in English from 2008 through March 2018. Additional studies identified via citations in associated manuscripts were added if applicable.
      ENDO, Endometriosis: Natural History, Diagnosis, and Outcomes Study; GI, gastrointestinal; HR, hazard ratio; MPQ, McGill Pain Questionnaire; MRI, magnetic resonance imaging; NPV, negative predictive value; PPV, positive predictive value; TVS, transvaginal sonography; VAS, visual analogue scale.
      Agarwal. Clinical diagnosis of endometriosis. Am J Obstet Gynecol 2019.
      a Reported are the agreement between self-reported symptoms of endometriosis and diagnosis of endometriosis recorded in medical records
      b Data are adjusted odds ratios
      c Ranges reflect different values based on anatomic locations of the endometriotic lesions
      d Shown here are symptoms and signs with an odds ratio for predicting endometriosis of 5.0 or greater
      e Lafay Pillet et al
      • Soliman A.M.
      • Fuldeore M.
      • Snabes M.C.
      Factors associated with time to endometriosis diagnosis in the United States.
      evaluated combining multiple signs, symptoms, and findings to predict the presence of deep endometriosis. Presented here are the individual measures included in the final model.

       Symptoms

      Pelvic pain, although common among women with endometriosis, is insufficient alone as an indicator of endometriosis, as it can be associated with several gynecologic (and nongynecologic) conditions.
      • Meuleman C.
      • Vandenabeele B.
      • Fieuws S.
      • Spiessens C.
      • Timmerman D.
      • D'hooghe T.
      High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners.
      However, pelvic pain that is described as chronic, cyclic, and persistent or progressive (ie, worsening over time) increases the likelihood of an association with endometriosis.
      • Fuldeore 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.
      • Schliep K.C.
      • Mumford S.L.
      • Peterson C.M.
      • et al.
      Pain typology and incident endometriosis.
      • Peterson 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.
      Pain is typically initially menstrual (dysmenorrhea), but may progress to include nonmenstrual pelvic pain, which is prevalent among women with diagnosed endometriosis.
      • Divasta A.D.
      • Vitonis A.F.
      • Laufer M.R.
      • Missmer S.A.
      Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood.
      When asked about their experiences living with endometriosis, participants in the qualitative study by Moradi et al
      • Moradi M.
      • Parker M.
      • Sneddon A.
      • Lopez V.
      • Ellwood D.
      Impact of endometriosis on women's lives: a qualitative study.
      universally described their pain as “severe and progressive during menstrual and nonmenstrual phases.” Women with endometriosis are more likely to report dyspareunia, dyschezia, and dysuria than unaffected women.
      • Fuldeore 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.
      • Schliep K.C.
      • Mumford S.L.
      • Peterson C.M.
      • et al.
      Pain typology and incident endometriosis.
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.
      • Flores I.
      • Abreu S.
      • Abac S.
      • Fourquet J.
      • Laboy J.
      • Rios-Bedoya C.
      Self-reported prevalence of endometriosis and its symptoms among Puerto Rican women.
      • Ballard K.D.
      • Seaman H.E.
      • De Vries C.S.
      • Wright J.T.
      Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study—part 1.
      • Lafay Pillet M.C.
      • Huchon C.
      • Santulli P.
      • Borghese B.
      • Chapron C.
      • Fauconnier A.
      A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma.
      Although the sensitivity of dyspareunia is generally low,
      • Saha R.
      • Marions L.
      • Tornvall P.
      Validity of self-reported endometriosis and endometriosis-related questions in a Swedish female twin cohort.
      • Heitmann 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.
      • Marasinghe J.P.
      • Senanayake H.
      • Saravanabhava N.
      • Arambepola C.
      • Condous G.
      • Greenwood P.
      History, pelvic examination findings and mobility of ovaries as a sonographic marker to detect pelvic adhesions with fixed ovaries.
      indicating that its presence is not specific to endometriosis, deep dyspareunia is associated with deep endometriosis.
      • Lafay Pillet M.C.
      • Huchon C.
      • Santulli P.
      • Borghese B.
      • Chapron C.
      • Fauconnier A.
      A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma.
      Response of pain to treatment may be another indicator of endometriosis. Although nonsteroidal anti-inflammatory drugs (NSAIDs) effectively treat primary dysmenorrhea, pain reduction with these agents may be insufficient in women with endometriosis.
      • Leyland N.
      • Casper R.
      • Laberge P.
      • Singh S.S.
      • Society of Obstetricians and Gynaecologists of Canada
      Endometriosis: diagnosis and management.
      • Practice Committee of the American Society for Reproductive Medicine
      Treatment of pelvic pain associated with endometriosis: a committee opinion.
      However, caution is indicated before dismissing NSAID-responsive pain as simply dysmenorrhea; early symptoms of endometriosis may be responsive to these agents, and we should not miss an opportunity to treat the disease before the development of serious sequelae.

       Patient and family history

      History of infertility is strongly associated with endometriosis, although this may be skewed due to more thorough evaluation of women with infertility increasing the chances of successful diagnosis.
      • Fuldeore 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.
      • Peterson 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.
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.
      • Flores I.
      • Abreu S.
      • Abac S.
      • Fourquet J.
      • Laboy J.
      • Rios-Bedoya C.
      Self-reported prevalence of endometriosis and its symptoms among Puerto Rican women.
      • Ballard K.D.
      • Seaman H.E.
      • De Vries C.S.
      • Wright J.T.
      Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study—part 1.
      • Lafay Pillet M.C.
      • Huchon C.
      • Santulli P.
      • Borghese B.
      • Chapron C.
      • Fauconnier A.
      A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma.
      • Saha R.
      • Marions L.
      • Tornvall P.
      Validity of self-reported endometriosis and endometriosis-related questions in a Swedish female twin cohort.
      Other factors associated with a greater likelihood of successful endometriosis diagnosis are family history of the disease,
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.
      • Ashrafi M.
      • Sadatmahalleh S.J.
      • Akhoond M.R.
      • Talebi M.
      Evaluation of risk factors associated with endometriosis in infertile women.
      previous pelvic surgery,
      • Ashrafi M.
      • Sadatmahalleh S.J.
      • Akhoond M.R.
      • Talebi M.
      Evaluation of risk factors associated with endometriosis in infertile women.
      and a history of benign ovarian cysts and/or ovarian pain.
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.
      • Ballard K.D.
      • Seaman H.E.
      • De Vries C.S.
      • Wright J.T.
      Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study—part 1.

       Menstrual cycle characteristics

      In a recent cross-sectional survey of approximately 50,000 women, several menstrual cycle characteristics were more prevalent among women with vs without diagnosed endometriosis, including heavy menstrual bleeding, excessive/irregular bleeding, passing clots, and irregular menstrual periods. Premenstrual spotting also correlates with endometriosis in infertile women.
      • Heitmann 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.
      • Ashrafi M.
      • Sadatmahalleh S.J.
      • Akhoond M.R.
      • Talebi M.
      Evaluation of risk factors associated with endometriosis in infertile women.
      Although these disorders are common in women with endometriosis, most of these women have regular cycles without abnormal bleeding.

       Physical examination

      Data from comparative studies suggest that findings on physical examination can identify endometriosis with high accuracy.
      • Hudelist G.
      • Oberwinkler K.H.
      • Singer C.F.
      • et al.
      Combination of transvaginal sonography and clinical examination for preoperative diagnosis of pelvic endometriosis.
      • Hudelist G.
      • Ballard K.
      • English J.
      • et al.
      Transvaginal sonography vs. clinical examination in the preoperative diagnosis of deep infiltrating endometriosis.
      • Bazot M.
      • Lafont C.
      • Rouzier R.
      • Roseau G.
      • Thomassin-Naggara I.
      • Darai E.
      Diagnostic accuracy of physical examination, transvaginal sonography, rectal endoscopic sonography, and magnetic resonance imaging to diagnose deep infiltrating endometriosis.
      For example, using defined criteria for a positive bimanual pelvic examination (ie, palpable nodularity, stiffened and/or thickened pelvic anatomy, especially the uterosacral ligaments, vagina, rectovaginal space, pouch of Douglas, adnexa, rectosigmoid, or posterior wall of the urinary bladder), Hudelist et al
      • Hudelist G.
      • Oberwinkler K.H.
      • Singer C.F.
      • et al.
      Combination of transvaginal sonography and clinical examination for preoperative diagnosis of pelvic endometriosis.
      reported endometriosis diagnosis accuracy of 86–99%, depending on anatomic location. Diagnostic acumen of pelvic examination is lower for deep endometriosis,
      • Hudelist G.
      • Ballard K.
      • English J.
      • et al.
      Transvaginal sonography vs. clinical examination in the preoperative diagnosis of deep infiltrating endometriosis.
      • Bazot M.
      • Lafont C.
      • Rouzier R.
      • Roseau G.
      • Thomassin-Naggara I.
      • Darai E.
      Diagnostic accuracy of physical examination, transvaginal sonography, rectal endoscopic sonography, and magnetic resonance imaging to diagnose deep infiltrating endometriosis.
      although examination during menses improves detection.
      • Leyland N.
      • Casper R.
      • Laberge P.
      • Singh S.S.
      • Society of Obstetricians and Gynaecologists of Canada
      Endometriosis: diagnosis and management.
      Anterior vaginal wall tenderness has low sensitivity for detecting endometriosis in women with chronic pelvic pain,
      • Paulson J.D.
      • Paulson J.N.
      Anterior vaginal wall tenderness (AVWT) as a physical symptom in chronic pelvic pain.
      but demonstrates prognostic value for endometriosis among women with unexplained infertility.
      • Paulson J.D.
      Correlation of anterior vaginal wall pain with endometriosis in infertile patients.
      A caveat to bimanual examination is that it may not be feasible for non−sexually active adolescents/young adults and may not identify early-stage, superficial disease.

       Combination assessments

      The ability to identify endometriosis nonsurgically is enhanced when multiple factors are combined. Ballard et al
      • Ballard K.D.
      • Seaman H.E.
      • De Vries C.S.
      • Wright J.T.
      Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study—part 1.
      reported that the likelihood of endometriosis increased with the number of symptoms present, from an odds ratio of 5.0 with 1 symptom to 84.7 for 7 or more symptoms. Several investigators have used this approach to develop models for predicting endometriosis.
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.
      • Lafay Pillet M.C.
      • Huchon C.
      • Santulli P.
      • Borghese B.
      • Chapron C.
      • Fauconnier A.
      A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma.
      • Perello M.
      • Martinez-Zamora M.A.
      • Torres X.
      • et al.
      Markers of deep infiltrating endometriosis in patients with ovarian endometrioma: a predictive model.
      Using data from a prospective, multinational study, Nnoaham et al
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.
      created a model combining symptoms and patient history with ultrasound findings that predicted revised American Society for Reproductive Medicine (rASRM) stage III and IV endometriosis with good accuracy. The authors suggest that such screening tools could reduce “diagnostic delay, high investigation costs, and personal suffering associated with endometriosis.”
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.

       Additional considerations

      Imaging can be a useful adjunct to clinical diagnostic measures, and transvaginal ultrasound improves accuracy when used adjunctively with symptoms, patient history, and/or physical findings.
      • Nnoaham K.E.
      • Hummelshoj L.
      • Kennedy S.H.
      • Jenkinson C.
      • Zondervan K.T.
      World Endometriosis Research Foundation Women's Health Symptom Survey Consortium
      Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.
      • Marasinghe J.P.
      • Senanayake H.
      • Saravanabhava N.
      • Arambepola C.
      • Condous G.
      • Greenwood P.
      History, pelvic examination findings and mobility of ovaries as a sonographic marker to detect pelvic adhesions with fixed ovaries.
      • Hudelist G.
      • Oberwinkler K.H.
      • Singer C.F.
      • et al.
      Combination of transvaginal sonography and clinical examination for preoperative diagnosis of pelvic endometriosis.
      Ultrasound is particularly sensitive for detecting ovarian endometriomas and deep endometriosis.
      Practice bulletin no. 114: management of endometriosis.
      • Nisenblat V.
      • Bossuyt P.M.
      • Farquhar C.
      • Johnson N.
      • Hull M.L.
      Imaging modalities for the non-invasive diagnosis of endometriosis.
      • Turocy J.M.
      • Benacerraf B.R.
      Transvaginal sonography in the diagnosis of deep infiltrating endometriosis: a review.
      Indeed, a Cochrane meta-analysis found that transvaginal ultrasound approaches the sensitivity and specificity needed to replace surgery for endometrioma detection.
      • Nisenblat V.
      • Bossuyt P.M.
      • Farquhar C.
      • Johnson N.
      • Hull M.L.
      Imaging modalities for the non-invasive diagnosis of endometriosis.
      The International Deep Endometriosis Analysis (IDEA) group consensus statement on systematic sonographic evaluation of the pelvis in women with suspected endometriosis provides standards for improved imaging.
      • Guerriero S.
      • Condous G.
      • Van Den Bosch T.
      • et al.
      Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.
      Traditional routine transvaginal ultrasound may be limited to endometrioma diagnosis; however, “expert-guided” imaging, as outlined by the IDEA group, will help improve clinical assessment across endometriosis manifestations. Nonetheless, not all endometriosis will be visualized by imaging, and imaging cannot be used to rule out endometriosis.
      Magnetic resonance imaging is a noninvasive option; however, it is expensive, not universally available, and lacks sensitivity, and is therefore infrequently used for endometriosis diagnosis. Although many are currently being studied, as yet, no noninvasive or minimally invasive biomarker has been established to diagnose endometriosis.
      • Cho S.
      • Mutlu L.
      • Grechukhina O.
      • Taylor H.S.
      Circulating microRNAs as potential biomarkers for endometriosis.
      • Fassbender A.
      • Burney R.O.
      • O D.F.
      • D'hooghe T.
      • Giudice L.
      Update on biomarkers for the detection of endometriosis.
      • Cosar E.
      • Mamillapalli R.
      • Ersoy G.S.
      • Cho S.
      • Seifer B.
      • Taylor H.S.
      Serum microRNAs as diagnostic markers of endometriosis: a comprehensive array-based analysis.
      Much of what is known about endometriosis comes from surgically diagnosed adults. Increased research into endometriosis among surgically diagnosed adolescents and prospective studies of those with suggestive signs and symptoms will help to better identify hallmarks of disease onset and risk factors for disease progression and treatment prognosis. Although a detailed review of endometriosis in adolescents is beyond the scope of this discussion, it is noteworthy that endometriosis occurs in adolescents and that patients who are younger at the time of symptom onset experience longer diagnostic delays than older patients.
      • Staal A.H.
      • Van Der Zanden M.
      • Nap A.W.
      Diagnostic delay of endometriosis in the Netherlands.
      • Soliman A.M.
      • Fuldeore M.
      • Snabes M.C.
      Factors associated with time to endometriosis diagnosis in the United States.
      This delay is attributed to prolonged time before seeking treatment and a longer interval between first clinical consultation and referral or diagnosis. It is important that clinicians evaluate symptoms that merit suspicion in adolescents as seriously as in adults.
      • Divasta A.D.
      • Vitonis A.F.
      • Laufer M.R.
      • Missmer S.A.
      Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood.

      Implementing clinical diagnosis

      Clinical diagnosis is already applied in clinical practice, albeit inconsistently and without standardization.
      • Fuldeore 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.
      • Soliman A.M.
      • Fuldeore M.
      • Snabes M.C.
      Factors associated with time to endometriosis diagnosis in the United States.
      In an effort to provide a unified, practical approach to clinically diagnosing endometriosis, we have developed an algorithm informed by evidence in the literature and clinical experience (Figure 1). The proposed algorithm uses techniques readily available to most practitioners and allows clinicians to initiate treatment without delay or invasive procedures. For each step, we identify findings that are consistent with endometriosis and those suggesting a possible alternative diagnosis. In general, persistent and/or worsening cyclic or constant pelvic pain, particularly in the presence of other endometriosis-associated symptoms, patient history, and findings on physical examination, suggest endometriosis. When these findings are unclear, imaging with transvaginal ultrasound is a widely available and low-cost option.
      Figure thumbnail gr1
      Figure 1Algorithm for a clinical diagnosis of endometriosis
      Agarwal. Clinical diagnosis of endometriosis. Am J Obstet Gynecol 2019.
      This algorithm does not diminish the value of laparoscopy as a treatment option in those for whom medical therapy is insufficient, nor does it minimize laparoscopy as a diagnostic tool when clinical signs are uncertain or suggest nonendometriosis pathology (eg, other benign or malignant ovarian neoplasms). Rather, the algorithm is intended to make the diagnosis of endometriosis more accessible, reducing the negative impact of undiagnosed and untreated endometriosis on women’s lives. Practitioners should feel empowered to clinically diagnose this disease early and without an invasive procedure. Although the ramifications of early diagnosis and treatment have not been studied, the potential exists to relieve pain, to avoid central sensitization and pain persistence, to prevent infertility, and to change the trajectory of patients’ lives. It is increasingly recognized that chronic diseases such as endometriosis generate cumulative life-course impairment through limitations imposed on life choices, including education, career, and family.
      • Moradi M.
      • Parker M.
      • Sneddon A.
      • Lopez V.
      • Ellwood D.
      Impact of endometriosis on women's lives: a qualitative study.
      • Bhatti Z.
      • Salek M.
      • Finlay A.
      Chronic diseases influence major life changing decisions: a new domain in quality of life research.
      Overall patient health may also be improved by addressing the psychosocial and physical manifestations often found in conjunction with endometriosis, such as persistent pelvic pain, depression, anxiety, fatigue, bloating/weight gain, gastrointestinal issues, and sexual dysfunction.
      • Fuldeore 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.
      • Culley L.
      • Law C.
      • Hudson N.
      • et al.
      The social and psychological impact of endometriosis on women's lives: a critical narrative review.
      • Moradi M.
      • Parker M.
      • Sneddon A.
      • Lopez V.
      • Ellwood D.
      Impact of endometriosis on women's lives: a qualitative study.
      • Ashrafi M.
      • Sadatmahalleh S.J.
      • Akhoond M.R.
      • Talebi M.
      Evaluation of risk factors associated with endometriosis in infertile women.
      Now is the time to change the paradigm of the diagnosis of endometriosis by increasing speed and validity, leading to improved access to effective early treatment.

      Acknowledgments

      Medical writing support for development of this manuscript, funded by AbbVie , Inc., was provided by Crystal Murcia, PhD, and Lamara D. Shrode, PhD, CMPP, of JB Ashtin.

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      Linked Article

      • Years of unjustified hypoestrogenism, fear, and stress will not improve the management of chronic pelvic pain!
        American Journal of Obstetrics & GynecologyVol. 221Issue 2
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          Agarwal et al1 should be congratulated for emphasizing that patients with severe chronic pelvic pain should be managed actively. Indeed, years of inadequate treatment, with the assumption that this pain is normal, is deeply frustrating for these patients. Chronic pain may have significant negative impact on a patient’s quality of life, resulting in central sensitization, loss of self-confidence and trust in physicians, and making long-term management more difficult.
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        American Journal of Obstetrics & GynecologyVol. 221Issue 2
        • Preview
          Thank you for your letter entitled “Years of unjustified hypoestrogenism, fear, and stress will not improve the management of chronic pelvic pain!” The goal of our manuscript entitled “Clinical diagnosis of endometriosis: a call to action” 1 was to highlight the current unacceptable delay in diagnosis and to encourage a focus on pain, functioning, and quality of life, with or without a previous surgical diagnosis endometriosis. We agree with your statement “Even minimally invasive surgery is too invasive to manage minimal endometriosis, which is not always progressive and may heal during medical treatment or even spontaneously.”
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