Endometriosis in adolescents: Epidemiology, clinical features, and diagnosis

INTRODUCTION — Endometriosis refers to the presence of endometrial glands and stroma outside the endometrial cavity and uterine musculature. These ectopic endometrial implants are usually located in the pelvis but can occur nearly anywhere in the body. The disease can occur in adolescents and can present with pelvic pain symptoms ranging from mild to severe, including dysmenorrhea and daily pelvic pain.

This topic will provide an overview on endometriosis as it applies to adolescent patients; disease presentation and evaluation in adults is reviewed separately. (See "Endometriosis: Clinical features, evaluation, and diagnosis".)

In this topic, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. We encourage the reader to consider the specific counseling and treatment needs of transgender and gender-expansive individuals.

EPIDEMIOLOGY AND PATHOGENESIS — Much of the available information on endometriosis is based on studies of adult patients. These detailed discussions of epidemiology, pathogenesis, histology, and lesion types are presented in related content. (See "Endometriosis in adults: Pathogenesis, epidemiology, and clinical impact".)

Points specific to the adolescent population include:  

Prevalence — The prevalence of endometriosis in adolescents who present for specialist evaluation of moderate to severe pelvic pain appears to be high (60 to 75 percent) while the prevalence in the general adolescent population is not known [1,2]. Globally, it is estimated that approximately 10 percent of reproductive females of all ages have endometriosis [3]. These estimates are likely low as many patients experience a diagnostic delay of symptoms, particularly for symptoms that begin in adolescence [4]. (See 'Diagnostic delay' below.)

●Surgical confirmation – One systematic review including 15 selected studies reported visually-confirmed prevalence rates of 62 percent among all adolescents undergoing laparoscopic surgery for indications of pelvic pain or dysmenorrhea, 75 percent among adolescents with chronic pelvic pain resistant to treatment with hormonal contraceptives and/or nonsteroidal anti-inflammatory drugs (NSAIDs), and 70 percent among adolescents with dysmenorrhea [1].

●Surgery and imaging – Another systematic review reported a mean prevalence of 64 percent (range 25 to 100 percent) based on studies using both laparoscopy and imaging to diagnosis endometriosis in adolescents with pelvic pain undergoing gynecologic investigation [2].

For the general adult population, estimates vary depending upon the population studied (symptomatic or asymptomatic) and the method of diagnosis (clinical, imaging, or surgical). (See "Endometriosis in adults: Pathogenesis, epidemiology, and clinical impact", section on 'Prevalence'.)

Pathogenesis — While many theories have been proposed to explain the etiology of endometriosis, no single theory explains all cases, all the theories help to explain some aspects of the disease, and the types and frequencies of pathogenetic mechanisms may differ for adolescents and postpubertal/premenarchal endometriosis patients compared with adult patients. It is likely that the cause of endometriosis is multifactorial, with contributions from several of the proposed mechanisms.

Briefly, theories for the pathogenesis of endometriosis include retrograde menstruation, lymphatic and/or hematologic spread, coelomic metaplasia, direct transplantation, aberration of cellular immunity, and neonatal uterine bleeding. A detailed discussion of endometriosis pathogenesis is presented in related content. (See "Endometriosis in adults: Pathogenesis, epidemiology, and clinical impact", section on 'Pathogenesis'.)

IMPORTANT CLINICAL DISEASE DIFFERENCES SPECIFIC TO ADOLESCENTS

Risk factors — Certain predisposing factors make adolescents uniquely vulnerable to endometriosis and should therefore heighten suspicion of the disease. These include:

●Obstructive congenital anomalies – Obstructive congenital anomalies of the female genital tract that enhance retrograde menstrual flow, such as vaginal agenesis, imperforate hymen, and transverse vaginal septum, have been associated with an increased risk of endometriosis in the adolescent population [5-7]. In one study of 50 adolescents, endometriosis was found in approximately half of subjects undergoing surgical treatment of obstructive reproductive tract anomalies after menarche; the incidence appeared to be anomaly-specific, with the highest incidence among adolescents with cervical aplasia [8]. These findings support the implantation or retrograde menstruation theory, which suggests that endometrial tissue from the uterus is shed during menstruation and transported through the fallopian tubes, thereby gaining access to, and implanting on, pelvic structures [9].

Case reports have noted that correction of the obstructive anomaly has been associated with both regression and persistence of endometriosis [7,10]. These findings suggest that initial disease development may be related to an abundance of endometrial tissue that overwhelms the body’s ability to remove it, perhaps through immune mechanisms, and that disease persistence may result from prior or ongoing peritoneal seeding.

●Family history – Some adolescents may have a genetic predisposition to developing endometriosis. Although the etiology of endometriosis remains poorly understood, it is estimated that it has a heritability of 50 percent, with 26 percent due to common genetic variants [11]. Patients with a first-degree relative with confirmed endometriosis have a seven times greater risk of having endometriosis compared with the general population [12]. In a genome-wide association study meta-analysis including 60,674 cases of endometriosis, 42 loci with 49 distinct signals were identified in association with endometriosis [13]. Adolescents with affected family members may experience a similar and earlier age at onset of symptoms as well [14]. Genetic studies have demonstrated familial clustering of the disease with likely polygenic or multifactorial inheritance [15].

●Early life risk factors – Studies have postulated secondhand smoke during childhood [16] and sexual and physical abuse in early life [17] are associated with increased risk of endometriosis. Dietary exposures in adolescence, such as dairy intake, may impact the risk of subsequent endometriosis [18]. Earlier age at menarche and a shorter cycle length have also been associated with a greater incidence of endometriosis, thus prompting investigators to include these parameters in a self-report questionnaire to identify adolescents at risk of developing endometriosis [19]. However, early life and adolescent interventions to reduce risk of endometriosis remain understudied and causality cannot be inferred from the above studies.

Diagnostic delay — Diagnostic delay (ie, the time from symptom onset to diagnosis) is commonly experienced by patients with endometriosis and often worse for adolescents, who may see multiple doctors and experience multi-year delays before diagnosis [20]. Diagnostic delays of four to nine years have been reported for adolescent patients [4,21,22]. Younger age at symptom onset is associated with longer delay [23]. Normalization of dysmenorrhea by clinicians and patients may be a contributing factor.

Additional factors that may contribute to diagnostic delay include:

●Patient – Patient factors include reluctance to discuss pain because of embarrassment, fear of stigmatization, and/or lack of endometriosis knowledge [24-26].

●Clinician – Clinician factors include lack of disease knowledge specific to adolescents, particularly for younger patients; reluctance to perform physical examination and/or surgery; and subtle appearance of endometriosis lesions in adolescents [24,27]. Additionally, symptoms of endometriosis may overlap with or be attributed to other conditions, such as irritable bowel syndrome or primary dysmenorrhea [28].

Potential screening questions — For endometriosis, early identification of the disease facilitates treatment, which may prevent or slow disease progression [29], decrease adverse long-term effects of the disease (eg, chronic pain, endometriomas, infertility), and, thus, improve patient quality of life. Screening questionnaires have been developed with the goal of identifying at-risk patients more quickly [19,30]. Questionnaires are able to discriminate adult patients at high or low risk of endometriosis [30], but data specific to questionnaires for adolescents are lacking. In the absence of validated questionnaires, a thorough history is used to identify patients at risk for endometriosis. (See 'History' below.)

CLINICAL FEATURES

Age distribution — Endometriosis occurs in adolescents of all ages, including some preteens. Although it had been assumed that endometriosis can present only after many years of menstruation, this is incorrect; symptomatic cases have been documented prior to menarche in girls who have started breast development and in others shortly after menarche [5,31,32]. Two-thirds of adults with endometriosis report that their symptoms started before age 20, and approximately 20 percent developed pain before age 15 [4]. These early manifestations suggest that there are likely other contributing mechanisms to endometriosis and not simply years of retrograde menstruation.

Presenting symptoms — Pelvic pain is the most common presenting symptom of endometriosis in adolescents (table 1) [27]. (See "Endometriosis: Clinical features, evaluation, and diagnosis", section on 'Clinical features'.)  

●Pelvic pain – Pelvic pain is the most common presenting symptom in adolescents [33]. Pain can present as both dysmenorrhea and/or nonmenstrual pelvic pain, be cyclic and/or noncyclic, and occur alone and/or with other symptoms (eg, nausea, heavy menstrual bleeding, gastrointestinal [GI] symptoms) [21,33]. Pain onset may be gradual or acute and begin at any point during adolescence. Coexisting pain syndromes are common.

•Cyclicity of pain – While both dysmenorrhea and noncyclic pain occur frequently, noncyclic pain may actually be more common (64 percent noncyclic versus 58 percent dysmenorrhea in one observational study [33]) and may be the main presenting symptom in nearly 30 percent of patients [34].

•Comparison with adult patients – Compared with patients diagnosed as adults, adolescent patients more commonly present with a combination of pain symptoms and less commonly present with infertility or endometriomas [33,35].

●Coexisting symptoms – Individuals with symptom onset during adolescence more frequently report having pain in combination with heavy menstrual bleeding, premenstrual spotting, and systemic symptoms (including nausea/stomach upset or dizziness/headache during menses) than those with symptom onset as adults [21].

•Bowel and bladder symptoms – Other reported symptoms include bowel dysfunction (eg, rectal pain, constipation, painful defecation that may be cyclic, rectal bleeding, irritable bowel syndrome) and bladder dysfunction (eg, dysuria, urgency, nocturia, hematuria) [16,20,28]. Adolescents may report pain with urination during menses and menstrual pain that gets worse or better with bowel movements [33].

•Comorbid pain conditions – In one study of 620 adolescents with endometriosis, 25 percent reported one additional pain condition and 60 percent reported two or more additional pain conditions, as compared with 37 and 22 percent of control patients, respectively [33]. Similarly, an earlier study found comorbid pain syndromes in 56 percent of patients with documented endometriosis [36]. A different study reported sexually active adolescents with endometriosis were more likely to experience dyspareunia, including pain that persisted in the 24 hours after intercourse, than their peers without endometriosis [33,37].

Associated diagnoses — Several other disease entities have been associated with endometriosis [36]. Observational studies have reported a higher than expected rate of autoimmune diagnoses compared with the general population [38-43]. Studies using genetic correlation analyses have suggested that endometriosis may share genetic pathways with migraine, uterine fibroids, subtypes of ovarian cancer, melanoma, asthma, GI reflux disease, osteoarthritis, and depression [13,44]. The underlying mechanisms behind these associations are not yet known and causality cannot be assumed. However, given these associations, we ask patients being evaluated for endometriosis about other concomitant medical diagnoses.

Alarm findings — Adolescents with endometriosis may seek care at an emergency department due to the severity or refractory nature of their abdominal or pelvic pain symptoms. Any adolescent with unstable vital signs should be promptly evaluated to exclude other diagnoses such as ovarian torsion or a ruptured ectopic pregnancy. An adolescent with persistent pain at home despite typical pain relief measures and additional symptoms such as new asymmetric pain or nausea/vomiting may also warrant seeking emergent care for a pelvic pain evaluation.  

Disease progression — The natural history of endometriosis in adolescents is poorly understood as there is a lack of longitudinal data across the reproductive lifespan and very little information published on adolescents treated surgically but without postoperative hormonal therapy [45]. In a case series of adolescents who underwent second laparoscopy after noncontinuation of postsurgical medical therapy, the patients had clear progression of their disease, with two patients progressing from stage 1 disease to stage 4 disease over 5 to 10 years [46]. Several studies have also noted more advanced-stage endometriosis in older adolescents within their cohorts [47,48].

INITIAL EVALUATION — Evaluation of adolescent patients with pelvic pain is similar to that for adults, with the addition of several age-specific considerations. (See "Endometriosis: Clinical features, evaluation, and diagnosis" and "Chronic pelvic pain in adult females: Evaluation".)

History — Specific questions to identify patients with potential endometriosis are presented in the table (table 2). The patient's family may contribute to the history, but the history, including sexual activity, should be taken privately when appropriate. A full discussion of a gynecologic history is presented in related content. (See "The gynecologic history and pelvic examination", section on 'Gynecologic history'.)

●Pain characteristics and functional impact

•Characteristics – We ask about the location, timing of onset, cyclicity, and quality of the pain, as well as associated symptoms, such as nausea or changes in bowel and bladder habits. Asking the patient to keep a diary can help document the frequency and character of pain; determine whether the pain is cyclic and/or acyclic; and identify associated symptoms, such as changes in bowel or bladder function (table 2).

•Impact on function – In our experience, symptoms that negatively impact function raise greater concern for endometriosis. We ask if the symptoms impair the patient’s ability to attend school, work, and/or extracurricular activities; cause the patient to avoid activities; or prompt the patient to seek urgent or emergency care.  

●Other pain syndromes – Screening for coexisting pain generators is critical. We ask about symptoms that may suggest other pain conditions, such as painful bladder syndrome; irritable bowel syndrome; headache, including migraine; and chronic pain syndromes (eg, vulvar pain of unknown etiology, fibromyalgia) [36].

●Symptom overlap – We ask about gastrointestinal (GI) and/or urologic symptoms because patients with endometriosis often have symptoms that impact a combination of organ systems. The degree of severity and relative bother of the symptoms help guide specialty referral. (See 'When to refer to a specialist' below.)

●Shared medical diagnoses – As endometriosis appears to share genetic pathways with other diseases and pain syndromes [13,44], we ask patients being evaluated for endometriosis if they have been diagnosed with other pain conditions, migraine or tension headaches, asthma, and autoimmune conditions such as lupus.

●Mental health – As with any chronic pain condition, mental health screening should also be considered as there is an increased risk of anxiety and depression in adolescents with symptoms of persistent pelvic pain [49]. (See "Chronic pelvic pain in adult females: Evaluation", section on 'Psychosocial assessment'.)

●Family history – A family history should be obtained. Patients with a first-degree relative with confirmed endometriosis have a seven times greater risk of having endometriosis compared with the general population [12]. First-degree relatives with a history of pelvic pain and/or infertility are also considered as contributing to the patient's risk of endometriosis, even if they have not been formally evaluated for endometriosis.

●Exposure to abuse – Given the association between history of abuse and chronic pelvic pain, which is the main symptom of endometriosis in adolescents, we screen all patients for such exposures [50,51]. The evaluation for endometriosis continues regardless of screening findings; endometriosis itself has not been associated with childhood abuse [52].

●Quality of life – Endometriosis impacts all aspects of life. Thus, we ask about school and/or work absenteeism as well as decreased engagement in activities, exercise, sleep, and/or relationships [20,53,54].

Physical examination — Physical examination is performed to identify potential causes of the patient's symptoms and exclude abnormalities such as pelvic mass (eg, uterine fibroid, ovarian cyst) and obstructive anomaly of the reproductive tract. However, physical examination alone is unlikely to diagnose endometriosis in the adolescent since most cases of endometriosis in this population are superficial diseases that cannot be detected by physical examination.

●Shared decision-making – The approach to abdominopelvic examination is influenced by the patient's age, preferences, and prior experience (eg, tampon use, prior pelvic examination, sexual activity). The patient may accept visual inspection, bimanual examination, speculum examination, or a combination. We reassure patients that omitting a pelvic examination is not a barrier to further evaluation, diagnosis, and treatment of endometriosis. Sonographic examination can be performed to augment (or in place of) a limited physical examination and identify/exclude causes of abdominopelvic pain other than endometriosis. (See 'Imaging' below.)

●Examination components – We perform the components of the pelvic examination that are acceptable to the patient and likely to yield diagnostic information. Components that we consider for adolescent patients being evaluated for endometriosis include:

•Abdominal examination – The abdomen is evaluated for tenderness, pattern of tenderness if present (diffuse or focal), masses, hernias, and prior surgical incisions.

-Evaluation for abdominal wall myofascial pain and trigger points should be performed and is described elsewhere. (See "Chronic pelvic pain in adult females: Evaluation", section on 'Back, abdomen, and extremities'.).

-Evidence of a reticulated pattern of hyperpigmentation (erythema ab igne) would suggest chronic exposure to heat for pain relief (eg, heating pad, hot water bottle). (See "Acquired hyperpigmentation disorders", section on 'Erythema ab igne'.)

•Visual inspection – Visual inspection of the vulva, urethra, and vaginal introitus can confirm a patent vaginal outlet, exclude an imperforate hymen (eg, congenital), and exclude vulvar and/or urethral diseases that may be contributing to symptoms; for example:

-Evidence of a bulging, often blue-tinged, obstruction at the vagina in a premenarchal adolescent typically diagnoses an imperforate hymen. (See "Congenital anomalies of the hymen and vagina".)

-Other obstructive anomalies, such as agenesis of the lower vagina or transverse vaginal septum, may not be easily appreciated via visual inspection alone. If a patent introitus is not visible with visualization, including gentle downward traction of the labia, a small q-tip can be inserted to assess for patency.

-Patients who have undergone female genital cutting may have an obstructed vaginal outlet. (See "Female genital cutting".)

•Bimanual and/or speculum examination – We do not typically perform bimanual or speculum examinations on adolescents, particularly those who have not had vaginal intercourse or used tampons. These examinations are generally low yield, uncomfortable, stressful, and often do not add information that cannot be obtained from imaging studies (eg, pelvic ultrasound). (See 'Imaging' below.)

We offer bimanual and speculum examinations when we believe it will add value to the diagnostic process and is acceptable to the patient.

-Bimanual – We asses for adnexal enlargement (eg, from endometrioma) and uterosacral nodularity, although both are relatively uncommon in adolescents [55]. Additionally, we assess for pelvic floor tenderness; patients with evidence of pelvic floor myalgia may benefit from targeted treatment, including pelvic floor physical therapy. (See "Myofascial pelvic pain syndrome in females: Clinical manifestations and diagnosis".)

-Speculum – Speculum examination allows for visualization of the vagina and cervix, exclusion of congenital anomalies that could contribute to symptoms (eg, vaginal septum, duplicate structures), and testing for sexually transmitted infections (STIs).

(See "Congenital anomalies of the hymen and vagina".)

(See "Benign cervical lesions and congenital anomalies of the cervix".)

(See "Sexually transmitted infections: Issues specific to adolescents".)

•Rectal examination – We do not perform rectal examinations for the purpose of diagnosing endometriosis. A rectal examination may be helpful if there is concern for an obstructive anomaly based on the history and the patient is unable to tolerate, or declines, a bimanual examination. On rectal examination, an obstructed vagina may be felt as a bulge superior to the rectum; the location of the bulge informs the likely level of obstruction in the vagina.

Discussion of the gynecologic examination and examination of adult patients suspected of having endometriosis are presented in related content.

●(See "The gynecologic history and pelvic examination", section on 'Pelvic examination'.)

●(See "Endometriosis: Clinical features, evaluation, and diagnosis", section on 'Physical examination'.)

Laboratory — There are no specific laboratory tests that have been validated as noninvasive diagnostic tests for endometriosis in adolescents. However, laboratory studies are considered as needed to exclude other causes of pain.

●Tests to consider – While we do not reflexively order all tests below, these tests are commonly ordered as indicated by the patient's history and physical examination findings.

•Urinalysis and urine culture to exclude urinary tract sources of pain (eg, urinary tract infection, stone). (See "Acute simple cystitis in adult and adolescent females".)

•Pregnancy test to exclude the possibility of ectopic pregnancy. (See "Ectopic pregnancy: Clinical manifestations and diagnosis".)

•Tests for STIs (eg, gonorrhea, chlamydia, trichomoniasis), when appropriate. (See "Sexually transmitted infections: Issues specific to adolescents".)

•Complete blood count and erythrocyte sedimentation rate, which may suggest the presence of an acute or chronic inflammatory process but are not typically elevated by endometriosis (unless there is superimposed infection or ruptured cyst). These tests should be considered if history (eg, fever) and physical examination findings raise concern for an infectious etiology of pelvic pain such as acute appendicitis, pelvic inflammatory disease, or infected endometrioma. A complete blood count is helpful to assess for pain due to blood loss such as a ruptured ovarian cyst.

●Test to avoid – Cancer antigen 125 (CA 125) is most commonly used as a biomarker for ovarian cancer but can be elevated in other conditions, including endometriosis. A serum CA 125 level is not a useful screening or diagnostic test due to its low sensitivity and specificity; thus, it should not be used to diagnose or rule out endometriosis in any age group (table 3). It has been used occasionally to follow the progress of disease in patients who have histologically or visually confirmed endometriosis at surgery [56], but we prefer to rely on the patient's report of self-specific symptoms (which is typically pain) to follow endometriosis; thus, we do not use CA 125 in clinical management. (See "Endometriosis in adults: Pathogenesis, epidemiology, and clinical impact".)

Imaging — Adolescent endometriosis is not typically identified with imaging studies because superficial peritoneal lesions are the most common form of endometriosis in adolescents, and these are not visualized on imaging studies. This is a contrast from adult patients, in whom ovarian endometriomas and deeply infiltrative endometriosis are more common and ultrasound and magnetic resonance imaging (MRI) can identify these lesions, which are signs of more advanced disease. However, imaging may be helpful to exclude other potential diagnoses, such as ovarian cyst, tumor, or a reproductive tract anomaly, in adolescent patients. It is important to note that normal imaging results do not exclude the diagnosis of endometriosis in adolescents and adults.

The authors typically obtain imaging for patients with acyclic or asymmetric pelvic pain (to exclude structural causes of pain, such as an ovarian cyst) or for patients with worsening and/or progressive dysmenorrhea (to exclude a possible obstructive anomaly). Additionally, imaging is often performed for patients whose symptoms do not respond to empiric therapy for primary dysmenorrhea (eg, nonsteroidal anti-inflammatory drugs [NSAIDs] or hormonal treatment). Imaging is also obtained before the decision to pursue laparoscopy for diagnostic and/or therapeutic management of endometriosis to ensure no unanticipated cause of pain is present prior to the risks of anesthesia.  

●Ultrasound – When imaging is desired, ultrasound is typically the first-line modality because it visualizes the uterus and adnexa, is commonly available and low cost, and avoids ionizing radiation. (See "Overview of ultrasound examination in obstetrics and gynecology", section on 'Gynecologic sonography'.)

•Transvaginal – For patients who accept a vaginal approach, transvaginal pelvic ultrasound is preferred because the proximity of the transducer to the uterus and adnexa provides optimal visualization.

•Transabdominal – Transabdominal ultrasound is a reasonable alternative for patients who decline a vaginal approach. The abdominal approach minimizes discomfort, particularly for patients who have not experienced prior vaginal penetration (eg, by a tampon, finger, or penetrative sex) but the imaging may be less clear.

•Transperineal – If available, transperineal ultrasound can evaluate for vaginal or lower uterine abnormalities without the need for vaginal placement of the probe.

●Magnetic resonance imaging (MRI) – MRI is typically performed to further define an abnormality suspected by ultrasound or if the ultrasound is not adequate (eg, patient with obesity who requires abdominal imaging) but the clinical suspicion for pathology is high. Severe endometriosis phenotypes, including ovarian endometrioma and deep infiltrating endometriosis, have been readily identified via MRI in adolescents, typically after 18 years of age [57]. However, MRI should not be used as a first-line imaging test because of its expense and poor sensitivity for detecting superficial peritoneal lesions, which are the most common form of endometriosis in adolescents [58-60]. (See "Endometriosis: Clinical features, evaluation, and diagnosis", section on 'Modalities'.)

●Computed tomography (CT) – CT is generally not helpful in diagnosing endometriosis because of low test sensitivity. Additionally, CT exposes the patient to ionizing radiation. However, CT performed for other indications may identify an endometrioma, which is diagnostic.

DIAGNOSIS

Definitive diagnosis — Endometriosis is definitively diagnosed when ectopic endometrial tissue is confirmed on tissue biopsy (ie, endometrial tissue located outside the endometrium or myometrium) [61]. Tissue biopsy is typically obtained during laparoscopic surgery. Additional findings may include endometriosis lesions and/or endometrioma. However, given the potential morbidity of surgery, presumptive clinical diagnosis is reasonable in some patients. (See 'Role of presumptive clinical diagnosis' below.)

Disease staging — Surgical staging is performed at the time of laparoscopy. The revised American Society for Reproductive Medicine (ASRM) scoring system is commonly used, although there are other classification and descriptive systems [61-64]. Staging is the same for adolescent and adult patients, and is described in detail in related content. (See "Endometriosis: Clinical features, evaluation, and diagnosis", section on 'Surgical staging of disease'.)

Role of presumptive clinical diagnosis — While surgery allows definitive tissue diagnosis of endometriosis, a presumptive clinical diagnosis can be made based on the adolescent's symptoms, history, examination findings, and clinical findings. The benefit of presumptive diagnosis is earlier start of treatment without the need for surgery, and its inherent risks. This approach may be desirable for adolescents who may not want surgery or if the risks of surgery outweigh the benefits, and is consistent with professional society guidelines, including those published by the American College of Obstetricians and Gynecologists (ACOG) and the European Society of Human Reproduction and Embryology (ESHRE) [27,65,66].

For example, a clinical diagnosis should be considered in the adolescent who has pain with cyclic oral contraceptives and warrants treatment with continuous use of oral contraceptives for complete menstrual suppression. Despite the benefits of assigning a clinical diagnosis, it is important to educate patients on its limitations and that it is not always accurate. Surgery remains a valuable intervention when medical therapy does not provide adequate symptom relief. Not all patients with pelvic pain have endometriosis confirmed at surgery, but treatment strategies for the management of pelvic pain remain similar in many ways.

DIFFERENTIAL DIAGNOSIS — For adolescents, the differential diagnosis of endometriosis focuses on common causes of acute and/or chronic pain in this population (table 4).The etiology and evaluation of chronic pain in this population are discussed in detail separately. (See "Chronic abdominal pain in children and adolescents: Approach to the evaluation", section on 'Etiology'.)

We consider the following entities for adolescent patients being evaluated for endometriosis. Patients whose symptoms are predominantly from one organ symptom may benefit from referral to a specialist. (See 'When to refer to a specialist' below.)

●Gynecologic – Both acute and chronic pain may be a result of pregnancy (intrauterine or ectopic), sexually transmitted infection (STI) and/or pelvic inflammatory disease, müllerian abnormalities with outflow obstruction, ovarian cysts and masses, and ovarian torsion (more typically severe acute pain). Specific tests diagnose pregnancy and STI. Imaging, typically with ultrasound, can evaluate for uterine anomalies and adnexal pathology.

•(See "Chronic pelvic pain in nonpregnant adult females: Causes".)

•(See "Chronic pelvic pain in adult females: Evaluation".)

●Gastrointestinal – Acute gastrointestinal (GI) pain may reflect appendicitis, bowel hernia, and/or irritable bowel syndrome. Common causes of chronic GI pain include inflammatory or irritable bowel disease (eg, Crohn disease), food allergy (eg, celiac disease), and constipation.

•(See "Causes of acute abdominal pain in children and adolescents".)

•(See "Chronic abdominal pain in children and adolescents: Approach to the evaluation".)

●Urologic – Urologic sources of pain can include infection (eg, cystitis), bladder pain syndrome (ie, interstitial cystitis), urethral diverticulum, kidney stones, and vesicoureteral reflux.

•(See "Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents".)

•(See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis".)

•(See "Kidney stones in children: Clinical features and diagnosis".)

•(See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

●Neurologic – Abdominal migraine can cause intermittent recurring abdominal pain. (See "Types of migraine and related syndromes in children", section on 'Abdominal migraine'.)

●Musculoskeletal – Pelvic floor myalgia can coexist with endometriosis or be independent and can be identified during the pelvic examination. (See "Myofascial pelvic pain syndrome in females: Clinical manifestations and diagnosis".)

WHEN TO REFER TO A SPECIALIST — Patients with endometriosis often have overlapping symptoms, which can make it difficult to determine if the cause is gynecologic, gastrointestinal (GI), urologic, or a combination. As evidence-based guidelines are lacking, we suggest the following approach:

●Gynecology – Gynecologic evaluation is always warranted for young patients with moderate to severe pain that is primarily cyclic or is substantially worse with menstrual periods or pain that significantly interferes with function. Referral to a gynecologist may be helpful if pelvic imaging is abnormal or the adolescent's symptoms do not improve with a trial of hormonal contraceptives and they need further management for persistent or worsening symptoms. In addition, a gynecologic evaluation may be the best first option for adolescents with pain and a family history of endometriosis and/or infertility given that family history is an established risk factor for the disease. (See 'Risk factors' above.)

●Gastroenterology – While menses-associated GI symptoms, such as bloating, constipation, or pain with bowel movements, commonly occur in patients with endometriosis, GI-specific diseases, such as Crohn disease, do not typically have a cyclic relationship to menstrual cycles. However, the overlap of symptoms can make distinguishing the etiology challenging. Patients with symptoms suggestive of irritable bowel syndrome should be screened [28]. Individuals with noncyclic and GI-predominant symptoms may benefit from early GI consultation. Patients who report blood in their stool always warrant GI evaluation, regardless of whether it is cyclic, intermittent, or repetitive in nature. (See "Chronic abdominal pain in children and adolescents: Approach to the evaluation".)

●Urology – Patients with hematuria, other significant bladder symptoms (eg, urinary frequency, urgency, incontinence), or bladder pain are referred to a urologist. Bladder pain syndrome, or interstitial cystitis, is common in patients with endometriosis.

•(See "Chronic pelvic pain in nonpregnant adult females: Causes", section on 'Urinary tract'.)

•(See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis".)

UNIQUE POPULATIONS

●Patients with endometrioma and/or deep infiltrating disease – While most adolescents with endometriosis have superficial disease, deep infiltrating endometriosis and ovarian endometriomas are less common but possible. A retrospective review of 270 patients aged 12 to 20 years referred for gynecologic ultrasound reported ovarian endometriomas in 22 patients (11 percent) and deep infiltrating endometriosis in 10 (3.7 percent) [67]. A study of 86 patients age ≤22 years who underwent surgery for endometriosis identified advanced stage endometriosis in 20 patients (23 percent); findings included ovarian endometrioma (14 patients), rectovaginal nodule (1 patient), and diaphragmatic and pulmonary endometriosis (1 patient) [47].  

Advanced-stage endometriosis more commonly presents as endometriomas in adolescents and typically at an older age than those with early-stage disease [47]. Adolescents with endometriomas may experience more frequent pain than patients of other age groups [68].

●Gender-diverse individuals – Symptoms of endometriosis may also present in gender-diverse adolescents, including those on testosterone therapy, and can exacerbate gender dysphoria. In one case series, endometriosis was laparoscopically diagnosed in transmasculine adolescents with pelvic pain, even while receiving testosterone therapy for gender affirmation [69].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Endometriosis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●The Basics (see "Patient education: Endometriosis (The Basics)")

●Beyond the Basics topics (see "Patient education: Endometriosis (Beyond the Basics)")

In addition, information and patient education specific to adolescent endometriosis is available through the Center for Young Women's Health at Boston Children's Hospital, including:

●Endometriosis: General information

●Endometriosis: Frequently asked questions (FAQs)

●Endometriosis: Coping with pain

●Endometriosis: Continuous hormonal pills (OCPs)

●Endometriosis: Hormonal treatment overview

●Endometriosis: Symptom quiz

SUMMARY AND RECOMMENDATIONS

●Epidemiology and pathogenesis – The prevalence of endometriosis is high in adolescents who present for evaluation of moderate to severe pelvic pain (60 to 75 percent), but the prevalence in the general adolescent population is not known. The etiology of endometriosis appears to be multifactorial; proposed mechanisms include retrograde menstruation, lymphatic and/or hematologic spread, coelomic metaplasia, direct transplantation, aberration of cellular immunity, and neonatal uterine bleeding. (See 'Epidemiology and pathogenesis' above.)

●Disease differences specific to adolescent patients

•Risk factors – Predisposing factors that make adolescents uniquely vulnerable to endometriosis, and should therefore heighten suspicion of the disease, include obstructive congenital anomalies of the reproductive tract and family history of the disease. Patients with a first-degree relative with confirmed endometriosis have a seven times greater risk of having endometriosis compared with the general population. (See 'Risk factors' above.)

•Diagnostic delay – Years-long delays in diagnosing endometriosis are common; delays of six to nine years have been reported for adolescent patients. Younger age at symptom onset appears to be associated with longer delay. Normalization of dysmenorrhea by clinicians and patients may be a contributing factor. (See 'Diagnostic delay' above.)

●Clinical features

•Timing of symptom onset – Symptomatic endometriosis commonly begins within a few years following menarche, but can occur before menarche in rare cases. (See 'Age distribution' above.)

•Common symptoms and associated diagnoses – Pelvic pain is the most common presenting symptom; pain is often both acyclic and cyclic pain. Other common co-occurring symptoms include bowel dysfunction (eg, rectal pain, constipation, painful defecation) and bladder symptoms (eg, dysuria, urgency, nocturia). (See 'Presenting symptoms' above.)

•Alarm findings – Adolescents with endometriosis may seek care at emergency departments because of the severity or refractory nature of their abdominal or pelvic pain. Any adolescent with unstable vital signs should be promptly evaluated to exclude other diagnoses such as ovarian torsion or a ruptured ectopic pregnancy. (See 'Alarm findings' above.)

●Initial evaluation – Evaluation of adolescent patients with pelvic pain is similar to that for adults, with the addition of several age-specific considerations. Initial evaluation consists of a history and physical examination, pain diary, tailored laboratory evaluation (eg, pregnancy test, complete blood count, erythrocyte sedimentation rate, urinalysis, urine culture, testing for gonorrhea and chlamydia), and ultrasonography to exclude other anatomic causes. However, a vaginal or bimanual pelvic examination should not be considered a requirement for evaluation of adolescent pelvic pain. (See 'Initial evaluation' above.)

●Diagnosis

•Definitive diagnosis and disease staging – Endometriosis is definitively diagnosed with tissue biopsy that confirms ectopic endometrial tissue (ie, tissue located outside the endometrium or myometrium). Laparoscopic surgery is the usual modality for tissue biopsy and surgical staging. Staging is generally done using the revised American Society for Reproductive Medicine (ASRM) scoring system, but others are available.

-(See 'Definitive diagnosis' above.)

-(See 'Disease staging' above.)

•Presumptive clinical diagnosis – A presumptive clinical diagnosis of endometriosis can be made in adolescents with dysmenorrhea and/or acyclic pelvic pain who are not candidates for, or prefer to avoid, surgery, and in whom other causes of pain have been reasonably excluded. Presumptive symptom-based diagnosis can facilitate earlier intervention and medical and/or surgical treatment. (See 'Role of presumptive clinical diagnosis' above.)

●Differential diagnosis – The differential diagnosis of endometriosis includes other common causes of acute and/or chronic pain in adolescents, with a focus on gynecologic, gastrointestinal (GI), and urologic etiologies (table 4). (See 'Differential diagnosis' above.)

●When to refer – Patients with endometriosis often have overlapping symptoms. Gynecologic evaluation is warranted for young patients with pain that is primarily cyclic or is substantially worse with menstrual periods. We refer patients with significant bowel and/or urinary symptoms for gastroenterology and/or urology evaluations. (See 'When to refer to a specialist' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Marc R Laufer, MD, who contributed to earlier versions of this topic review.