Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

Endometriosis is a disease characterized by the presence of functional endometrial tissue outside the uterine cavity. The most commonly affected sites are the ovaries, broad ligaments, and the surrounding pelvic structures. Endometriosis can also affect distant sites such as the lungs, ureters, and CNS. The exact pathogenesis of endometriosis has not been established, although several theories have been put forth. The Sampson theory of retrograde menstruation, the coelomic metaplasia theory, and the lymphatic and vascular dissemination theory offer possible explanations for the mechanisms of implantation and invasion of endometrial tissue outside the uterine cavity. Endometriosis is a cause of dysmenorrhea and dyspareunia; accordingly, it must be differentiated from other conditions presenting with similar symptoms such as adenomyosis, pelvic inflammatory disease, pelvic congestion syndrome, and submucosal uterine fibroids. The goal of medical therapy is pain management and the reduction of the endometrial implant size. Therapeutic options include GnRH agonists and danazol. Surgical therapy is reserved for patients with severe forms of the disease or who fail to improve with standard medical therapy.

In the early 19th century, endometriosis was described as adenomyomas. In the 1920s, endometriosis was differentiated from adenomyosis and a detailed description of the disease was given by Cullen and Sampson. Sampson proposed the theory of retrograde menstruation as the pathogenesis of the disease.

Endometriosis is classified into four stages of severity based on the revised American Society for Reproductive Medicine scoring system. The staging is based on the distribution of the lesions and the presence of adhesions.

The exact pathogenesis of endometriosis is not clear and several theories have made an attempt to describe its pathogenesis. The Sampson theory of retrograde menstruation, the coelomic metaplasia theory, and the lymphatic and vascular dissemination theory explain the implantation and invasion of endometrial tissue outside the uterine cavity. Immunologic factors and genetic factors are also thought to play a role in the pathogenesis of endometriosis.

The exact cause of endometriosis is unknown; the disease is thought to be multifactorial in origin.

Endometriosis is a cause of dysmenorrhea and dyspareunia. Endometriosis must be differentiated from other conditions presenting with similar symptoms such as adenomyosis, pelvic inflammatory disease, pelvic congestion syndrome, and submucosal uterine fibroids.

Endometriosis affects approximately around 11% of the female population in the reproductive age group. Endometriosis is more common among Caucasians than among African Americans. The disease accounts for the majority of patients with chronic pelvic pain and infertility.

The risk factors predisposing women to the development of endometriosis include early age at menarche, nulliparity, positive family history, and the presence of congenital cervical stenosis or obstructive lesions in the uterovaginal tract.

Standard screening for endometriosis is not recommended.

Endometriosis is a condition affecting females in the reproductive age group. It has a wide spectrum of presentations. It can be asymptomatic, present with premenstrual spotting and cyclic abdominal pain, present with infertility or chronic pelvic pain, or present as deep endometriosis with dyspareunia, dyschezia, and cyclic rectal bleeding. Complications of endometriosis include infertility, fibrosis, chocolate cyst, and, rarely, effects on other organs such as the lungs.

Endometriosis is a condition affecting women in the reproductive age group. The patients with endometriosis may have positive family history, presence of congenital cervical stenosis or obstructive lesions in the uterovaginal tract The presenting features include cyclical abdominal pain, dysmenorrhea, pain with passing stools, and pain with intercourse.

Examination findings on digital vaginal examination and speculum examination include a fixed retroverted uterus, palpable nodularity of the uterosacral ligaments, and cul-de-sac with narrowing of the posterior fornix.

Laboratory findings associated with endometriosis include features of iron deficiency anemia and increased levels of cancer antigen-125 and interleukin 1.

There are no specific EKG findings associated with endometriosis.

On chest X-ray, chest endometriosis is characterized by small bubbles at the level of the right diaphragm associated with pneumothorax.

CT of endometriosis is not the most sensitive noninvasive method for the diagnosis; MRI is more useful. On CT scans, endometriosis shows catamenial pneumothorax, hemothorax, and lung nodules.

MRI is useful for the assessment of the anatomical locations and severity of the disease. The typical appearance of endometriosis includes a characteristic hyperintensity on T1-weighted images and a hypointensity on T2-weighted images.

Abdominal ultrasound is useful to differentiate endometriosis from other cystic lesions of female reproductive system. The endometrial lesions have increased vascularity and will demonstrate increased Doppler flow. Transvaginal ultrasound is more sensitive than abdominal ultrasound.

There are no associated other imaging findings with endometriosis.

Diagnostic laparoscopy is the gold standard to assess the severity and extent of the disease.

The primary goal of medical therapy is pain management and regression of the endometrial lesions. NSAIDS are useful for pain management. There are many therapeutic options available to reduce the size of endometrial lesions. Gonadotrophin releasing hormone agonists and danazol are widely used. Continuous oral contraceptive pill (OCP) use is also helpful in patients with mild to moderate endometriosis.

Patients with failed medical therapy and patients with stage 3 or stage 4 disease are candidates for surgical therapy. Laser and excision are done for isolated lesions, while total hysterectomy is reserved for patients with extensive disease.

There are no primary preventive measures for endometriosis.

There are no secondary preventive measures for endometriosis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

Endometriosis was described in the early 19th century as adenomyoma. In the late 19th century, Sampson proposed the theory of retrograde menstruation as the pathogenesis of the endometriosis. In the 1920s, endometriosis was differentiated from adenomyosis and a detailed description of the disease was given by Cullen and Sampson.

• In the early 19th century, Rokitansky described the presence of functional endometrial tissue outside of the uterine cavity in patients with ovarian and endometrial cancers.^[1]
• In the late 19th century, Sampson was the first to describe the response of the endometrium to hormonal changes and proposed the theory of retrograde menstruation as a cause of endometriosis.^[1]
• In the 1920’s, Cullen was the first to describe the histological features of the endometrium in a patient with abdominal endometriosis and named the disease as adenomyoma.^[1]
• In the 1920’s, endometriosis was differentiated from adenomyosis and Rokitansky described a case series of 23 cases with the chocolate cyst of the ovary.^[1]
• In 1973, Acosta described the rate of surgical success based on the site and severity of endometriosis.^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2] Aravind Kuchkuntla, M.B.B.S[3]

Endometriosis is classified into four stages of severity based on the revised American Society for Reproductive Medicine scoring system. The staging is based on the distribution of the lesions and the presence of adhesions.

• Stage I:
  • Minimal disease
  • Lesions isolated and limited to the pelvis
  • No adhesions present
• Stage II:
  • Mild endometriosis lesions are superficial with size less than 5 cm on aggregate
  • Lesions scattered on the peritoneum and ovaries
  • No significant adhesions present
• Stage III:
  • Moderate disease characterized by the presence of multiple implants
  • Includes both superficial and deeply invasive lesions
  • Peritubal and periovarian adhesions may be evident
• Stage IV:
  • Severe disease characterized by multiple superficial and deep implants
  • Large ovarian endometriomas
  • Dense adhesions present

Endometriosis is classified based on anatomical phenotype (subtype) rather than disease stage. It is categorized into four subtypes:

• Superficial peritoneal endometriosis
• Deep endometriosis
• Ovarian endometriomas
• Extrapelvic endometriosis

Subtypes may occur alone or in combination and are clinically important because they influence diagnostic evaluation and treatment approach.

The prevalence of individual subtypes in the general population is unknown.

Superficial peritoneal endometriosis consists of lesions located on the peritoneal surface or serosa of abdominal or pelvic viscera.

Lesions may vary in appearance and may be blue, brown, red, white, or clear.

Superficial peritoneal lesions are often difficult to detect with imaging. Transvaginal ultrasound has low sensitivity for superficial peritoneal disease (65%, 95% CI, 27%–100%).^[2]

Deep endometriosis refers to lesions that penetrate beneath the peritoneal surface or infiltrate the muscularis propria of pelvic organs such as the bowel, bladder, or ureter.

These lesions commonly involve the uterosacral ligaments and rectosigmoid colon and may present as nodular lesions with associated fibrosis and adhesions.

Pain severity does not generally correlate with lesion number, location, or subtype; however, deep disease in the posterior cul-de-sac correlates with dyspareunia.^[3][4]

Transvaginal ultrasound has moderate sensitivity for detecting deep endometriosis (79%, 95% CI, 69%–89%).^[2]

Magnetic resonance imaging using an endometriosis-specific protocol has reported sensitivity of 91%–93.5% and specificity of 86%–87.5% for deep and ovarian endometriosis when compared with laparoscopy or other imaging modalities.^[5]

Ovarian endometriomas are cystic lesions within the ovary lined by endometrial glands and stroma. They characteristically contain dark, blood-stained fluid and are sometimes referred to as “chocolate cysts.”

Transvaginal ultrasound has high diagnostic accuracy for ovarian endometriomas, with sensitivity of 93% (95% CI, 87%–99%) and specificity of 96% (95% CI, 92%–99%).^[2]

MRI similarly demonstrates high sensitivity (91%–93.5%) and specificity (86%–87.5%) for ovarian endometriosis.^[5]

Extrapelvic endometriosis refers to lesions occurring outside of the pelvis. Lesions have been reported in nearly every organ system, including:

• Diaphragm
• Thoracic cavity
• Abdominal wall
• Brain^[6]

Clinical manifestations depend on lesion location and may include catamenial pneumothorax, hemoptysis, shoulder pain during menses, or cyclic pain in abdominal wall nodules.^[6]

Although classification by subtype assists in determining imaging strategy and surgical planning, lesion subtype does not reliably predict pain severity. With the exception of deep posterior cul-de-sac disease and dyspareunia, pain intensity does not correlate with lesion number, location, or subtype.^[3][4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2] Aravind Kuchkuntla, M.B.B.S[3]

The exact pathogenesis of endometriosis is not clear; several theories have been set forth. The Sampson theory of retrograde menstruation, the coelomic metaplasia theory, and the lymphatic and vascular dissemination theory explain the implantation and invasion of the endometrial tissue outside the uterine cavity. Immunologic factors and genetic factors are also thought to play a role in the pathogenesis of endometriosis.

The exact pathogenesis of endometriosis remains incompletely understood. Several mechanisms have been proposed to explain the presence of viable, hormonally responsive <u>endometrial tissue</u> outside the uterine cavity.^{[1][2][3][4][5]}

Sampson’s theory proposes that viable endometrial tissue passes in a retrograde fashion through the fallopian tubes into the peritoneal cavity during menstruation, where it implants onto pelvic structures and organs.^[1]

Clinical observations supporting this theory include the increased risk of endometriosis in patients with cervical stenosis and congenital outflow obstruction, conditions that increase retrograde menstrual efflux and facilitate peritoneal implantation.

However, retrograde menstruation alone does not fully explain the occurrence of endometriosis in premenarcheal girls or rare cases identified in newborns.^[6]

Endometrial cells may also disseminate via lymphatic or hematogenous pathways, which may account for lesions identified at distant or extrapelvic sites.

Experimental evidence suggests that endometrial stem cells from the basalis layer and bone marrow–derived stem cells may migrate via retrograde, lymphatic, or hematogenous routes, contributing to the development of ectopic lesions.

The mere presence of endometrial cells outside the uterine cavity does not constitute endometriosis. Translocated cells must adhere to surrounding tissues, evade immune surveillance, survive, and respond to estrogen stimulation.

Factors facilitating implantation and survival include:

• Endometrial stromal cells, which are essential for tissue adhesion
• Resistance of ectopic cells to cell-mediated immunity
• Increased proliferative capacity
• Increased aromatase expression leading to elevated local estrogen concentrations
• Aberrant integrin expression enhancing attachment and invasion

Endometrial glandular cells contribute to tissue invasion.^[7]

Degradation of the extracellular matrix due to increased proteolytic activity allows invasion and establishment of lesions. Matrix metalloproteinases and plasmin facilitate extracellular matrix breakdown and lesion expansion.

The eutopic endometrium proliferates in response to estrogen. Estrogen production depends on aromatase activity, which catalyzes the conversion of ovarian androstenedione into estrone.^[8]

Ectopic endometrial tissue demonstrates increased aromatase expression, resulting in elevated local estrogen levels and enhanced proliferation.

Additionally, endometriotic tissue exhibits progesterone resistance, impairing normal regulation of estrogen-driven proliferation. Progesterone resistance contributes to persistent lesion growth and survival.

Reduction of excess estrogen stimulation and correction of progesterone resistance form the basis of medical therapy.

Pathophysiological changes extend beyond the ectopic lesions themselves. Endometriosis is associated with immune dysregulation and increased inflammatory activity within the pelvic environment.^[9][10][11]

Alterations include:

• Increased inflammation and angiogenesis within mesothelial cells of the pelvic peritoneum
• Recruitment of immune cells
• Sustained production of proinflammatory cytokines
• Altered immune responsiveness within the uterine endometrium

These immune abnormalities contribute to lesion persistence and chronic inflammation.^[9][10][11]

Endometriosis lesions demonstrate coordinated neurogenesis and neovascularization.^[9][10][11]

New nerve fiber growth toward lesions and new blood vessel formation support lesion survival and contribute to pain generation.

The interaction between inflammatory mediators, immune cells, and sensory nerves sustains a self-perpetuating inflammatory microenvironment.

Pelvic pain in endometriosis is multifactorial and may involve a combination of nociceptive, neuropathic, and nociplastic mechanisms.^[12][13]

Nociceptive pain results from activation of peripheral nociceptors due to localized inflammation surrounding lesions.^[12]

Lesions release proinflammatory cytokines and pain mediators that stimulate and amplify nociceptive signaling.

Neuropathic pain may result from:

• Peripheral sensitization
• Direct nerve fiber infiltration by lesions
• Injury to nerves during surgical intervention^[12]

Lesions may rarely involve nerves such as the pudendal, obturator, or sciatic nerve.^[12]

Pelvic organ cross-sensitization may occur when neuronal activity in one pelvic organ sensitizes adjacent organs through shared spinal pathways.^[12]

---

Nociplastic pain refers to altered pain processing within the central nervous system.^[12][13]

It manifests as:

• Widespread body pain
• Fatigue
• Memory difficulties
• Sleep disturbances^[13]

Immune activation surrounding lesions may alter systemic immune signaling, contributing to central sensitization within the spinal cord and brain.^[12][13]

This leads to:

• Amplification of ascending pain signals
• Loss of descending pain inhibition
• Generalized sensory hypersensitivity

Nociplastic pain may explain why:

• Lesion number and subtype are weakly associated with pain severity^[14][15]
• Surgical removal of lesions does not alleviate pain in all patients
• Pain may recur without evidence of recurrent lesions^[12][13]

Compromised function of the hypothalamic-pituitary axis and sympathetic-adrenal medullary systems may further amplify immune dysregulation and pain signaling.^[12][13]

Endometriosis may impair fertility through multiple mechanisms, including:

• Impaired ovarian function
• Adhesions causing tubal obstruction
• Dysfunction of the uterine endometrium^[11]

These mechanisms reflect both structural distortion and molecular alterations in the reproductive environment.

Endometriosis most commonly affects dependent areas of the pelvis, with the ovaries being the most frequent site.^[16]

Other commonly affected sites include:

• Pelvic peritoneum lining the uterus
• Posterior cul-de-sac
• Round and broad ligaments of the uterus
• Lymph nodes

Less common sites include:

• Cervix^[17]
• Vagina
• Vulva
• Rectosigmoid^[18]
• Anterior abdominal wall^[19]
• Surgical scars^[20]
• Urinary bladder
• Kidney^[21]
• Lungs
• Urinary tract

Genetic predisposition contributes to disease susceptibility. Polymorphisms in genes involved in cell-mediated immunity and aromatase activity have been described in women with endometriosis.^[22][23]

Polymorphisms in genes encoding <cytokines and toll-like receptors have also been associated with increased risk.

A positive family history of endometriosis in a first-degree relative is associated with approximately a six-fold increased risk of developing the disease.

Endometriosis is associated with an increased risk of developing ovarian cancer.^[24][25]

The gross appearance of lesions depends on location, duration, menstrual cycle phase, and degree of fibrosis.

On laparoscopy, pelvic endometriosis may appear as raised, dark, non-hemorrhagic lesions. Lesions may also appear brown, black, white, yellow, pink, or clear depending on vascularity and hemorrhagic content.

Ovarian endometriosis may present as a cyst containing dark, thick, hemolyzed blood, commonly referred to as a “chocolate cyst.”

Advanced disease may result in fibrosis and pelvic adhesions visible during laparoscopy.

Histologic examination demonstrates the presence of endometrial glandular epithelium and endometrial stromal cells within ectopic sites.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2]

The exact cause of endometriosis remains incompletely understood. Current evidence suggests that endometriosis results from a combination of retrograde menstruation, genetic predisposition, hormonal influences, and immune dysregulation.

Retrograde efflux of endometrial cells through the fallopian tubes into the pelvic cavity during menstruation is widely accepted as a contributor to the origin of endometriosis lesions within the abdominal–pelvic cavity.^[1][2][3]

Lymphatic or vascular dissemination has also been proposed and cannot be excluded as a mechanism contributing to extrapelvic lesions.^[1][2][3]

However, retrograde menstruation alone does not fully explain why only a subset of individuals develop clinically significant disease.

Twin studies estimate the heritability of endometriosis to be approximately 50%.^[4][5]

A family history of endometriosis is a significant risk factor. Among sisters of affected individuals, the relative risk is 5.2 (95% CI, 3.4–7.2).^[6]

Although heritability appears substantial, no single gene has been identified as responsible for the majority of familial cases.^[4][5][6]

Earlier onset of menstruation is associated with increased risk.

Menarche before age 12 years is associated with increased risk of endometriosis.^[7]

This may increase cumulative lifetime exposure to retrograde menstrual efflux.

Shorter menstrual cycles (<28 days) are associated with increased risk.^[8]

More frequent menses may increase the frequency of retrograde efflux and implantation events.

Lower body mass index has been associated with increased risk of endometriosis.^[9]

The mechanism underlying this association remains unclear but may involve hormonal or inflammatory factors.

Nulliparity is associated with increased risk of endometriosis.^[10]

The protective mechanism of pregnancy may involve prolonged anovulation and suppression of menstruation.

Obstructive Müllerian anomalies are strongly associated with endometriosis.

In individuals with uterine anomalies causing blockage of menstrual outflow, the prevalence of endometriosis is reported as 47% (95% CI, 36%–58%).^[11]

Obstruction likely increases retrograde menstrual efflux and promotes implantation of endometrial tissue within the pelvis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2] Aravind Kuchkuntla, M.B.B.S[3]

Endometriosis commonly presents with dysmenorrhea, nonmenstrual pelvic pain, and deep dyspareunia. It must be differentiated from other gynecologic and nongynecologic conditions that present with pelvic pain, dyspareunia, dysmenorrhea, or abnormal uterine bleeding.

Importantly:

• Pain severity does not reliably correlate with lesion burden, number, or subtype (except deep posterior cul-de-sac disease, which correlates with dyspareunia).^[1][2]
• Normal imaging does not exclude endometriosis
• Response to hormonal therapy does not confirm the diagnosis

Endometriosis may present with:

• Dysmenorrhea
• Deep dyspareunia
• Chronic pelvic pain
• Infertility
• Dyschezia
• Dysuria
• Abnormal uterine bleeding

Differential diagnosis should consider both gynecologic and nongynecologic causes.

	Clinical Features	Physical Examination	Diagnostic Findings
Endometriosis	Dysmenorrhea Deep Dyspareunia Nonmenstrual pelvic pain Infertility Dyzchezia (cyclic) Symptoms worse during menses Common in women between 25 to 35 years	Nodularity in posterior fornix Adnexal masses (endometrioma) Fixed retroverted uterus Decreased uterine mobility Tenderness of posterior cul-de-sac Lateral displacement of cervix	Transvaginal ultrasound has high sensitivity for ovarian endometriomas, moderate sensitivity for deep infiltrating disease, and low sensitivity for superficial peritoneal lesions.[3] Magnetic resonance imaging improves detection of deep and ovarian disease.[4] CA-125 may be elevated but is nonspecific.   Absence of imaging findings does not exclude endometriosis.   Laparoscopic visualization with histologic confirmation is diagnostic. Features Suggesting Deep Infiltrating Endometriosis: • Cyclic hematochezia   • Hematuria during menses   • Severe dyschezia   • Bowel obstruction   • Hydroureter   These findings should raise suspicion for deep endometriosis.[5][6]
Adenomyosis[7]	Heavy menstrual bleeding Dysmenorrhea Common in women 40–50 years	Diffusely enlarged, tender uterus	Asymmetric thickening of the myometrium on MRI
Submucous uterine leiomyomas[8]	Menorrhagia Pelvic pressure Infertility Peak age 25–44	Enlarged irregular mobile uterus	Transvaginal ultrasound shows myomas
Pelvic inflammatory disease[9]	History of sexually transmitted infection Multiple sexual partners Fever Acute pelvic pain	Cervical motion tenderness Uterine/adnexal tenderness Purulent discharge	Positive nucleic acid amplification tests for Chlamydia trachomatis and N. gonorrhea Gram negative diplococci on gram stain
Pelvic congestion syndrome[10]	Chronic pelvic heaviness Deep dyspareunia Post-coital pain Pain worse after prolonged standing Pain worse at the end of the day	Bimanual tenderness	Pelvic varicosities on ultrasound with reduced blood flow

These conditions frequently mimic endometriosis:

	Clinical Features
Irritable Bowel Syndrome	Altered bowel frequency Abdominal pain Symptoms may worsen during menses
Bladder Pain Syndrome / Interstitial Cystitis	Urinary urgency Frequency Nocturia Normal urinalysis
Pelvic Floor Myofascial Pain	Pain worsened by activity Pelvic floor muscle tenderness Trigger points on examination

In young women presenting with acute severe lower abdominal pain, the following conditions should be considered:

Disease	Findings
Ectopic pregnancy[11]	Missed menses Positive pregnancy test Ultrasound shows empty uterus ± adnexal mass
Appendicitis[12]	Right lower quadrant pain Nausea/vomiting Ultrasound sensitivity 75–90%
Rupturedovarian cyst[13]	Sudden onset pain May follow trauma Ultrasound diagnostic
Ovarian cyst torsion[14]	Acute unilateral lower quadrant pain Nausea/vomiting Tender adnexal mass Ultrasound diagnostic
Hemorrhagic ovarian cyst[14]	Localized abdominal pain Nausea/vomiting Possible hypovolemia Ultrasound diagnostic
Acute cystitis[15][16]	Urinary frequency Urgency Dysuria Suprapubic pain
Endometriosis[14]	Cyclic pelvic pain Worsening during menses Deep dyspareunia Laparoscopic visualization confirms diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2] Aravind Kuchkuntla, M.B.B.S[3]

Endometriosis affects approximately 11,000 per 100,000 females of reproductive age. Endometriosis affects approximately 1 in 10 individuals of reproductive age.^[1] Endometriosis is more common in the Caucasian population than the African American population. Endometriosis accounts for the majority of patients with chronic pelvic pain and infertility.

More recent global estimates suggest that the prevalence of endometriosis among women aged 15–49 years is 7% (95% uncertainty interval, 6.0%–8.0%).^[1]

Among individuals undergoing laparoscopy for chronic pelvic pain, endometriosis is identified in approximately 33% to 50% of cases.^[2][3]

Among individuals with infertility, endometriosis is identified in approximately 20% to 50% of cases.^[4]

• Epidemiological data for endometriosis is scarce due to the following reasons:^[5]
  • Endometriosis includes a wide spectrum of symptoms and pathologic findings.
  • Endometriosis is asymptomatic in the early stages and a diagnosis is usually made for the first time as a part of infertility work up.
  • True prevalence may be underestimated due to prolonged diagnostic delay and reliance on surgical confirmation for definitive diagnosis.^[6]

• Worldwide, the prevalence of endometriosis is approximately 11,000 per 100,000 females in reproductive age group.^[7]
• Endometriosis accounts for 33,000 per 100,000 cases with chronic pelvic pain and 17,000 per 100,000 cases with infertility.^[8]
• In population-based analyses, the estimated prevalence among women aged 15–49 years is 7% (95% uncertainty interval, 6.0%–8.0%).^[1]
• Among individuals evaluated surgically for chronic pelvic pain, prevalence estimates range from 33% to 50%.^[2][3]
• Among individuals with infertility, endometriosis is present in approximately 20% to 50% of cases.^[4]
• Endometriosis is also a common finding among adolescents undergoing surgical evaluation for chronic pelvic pain^[2][3]
• Endometriosis may also be incidentally identified during surgical procedures performed for other indications.^[2][3]

• The mean time from symptom onset to diagnosis is approximately 7 years.^[6]
• Diagnostic delay may result from normalization of menstrual pain, symptom overlap with other conditions, and limited access to specialized care.

• Endometriosis is more common in the Caucasian population than the African American population.^[5]

• Endometriosis primarily affects women in the reproductive age group (usually between 15 and 45 years of age).  
• The peak age of diagnosis is between 25 and 35 years.  
• Although most commonly diagnosed in adults, endometriosis has been reported in adolescents and in individuals with obstructive Müllerian anomalies.^[9]

• Endometriosis is a condition that affects females.

• Twin studies estimate the heritability of endometriosis to be approximately 50%.^[10][11]
• Among sisters of affected individuals, the relative risk of endometriosis is 5.2 (95% CI, 3.4–7.2).^[12]
• Although familial clustering is observed, no single gene accounts for the majority of cases.

• Early menarche (before age 12 years) is associated with increased risk of endometriosis.^[13]
• Short menstrual cycle length (<28 days) is associated with increased risk.^[14]
• Lower body mass index has been associated with increased risk.^[15]
• Nulliparity is associated with increased risk of endometriosis.^[16]
• Among individuals with obstructive Müllerian anomalies, the prevalence of endometriosis is 47% (95% CI, 36%–58%).^[9]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2] Aravind Kuchkuntla, M.B.B.S[3]

Risk factors predisposing women to the development of endometriosis include early age at menarche, nulliparity, positive family history, and the presence of congenital cervical stenosis or obstructive lesions in the uterovaginal tract. Additional epidemiologic risk factors include short menstrual cycle length, lower body mass index, and obstructive Müllerian anomalies.^[1][2]

Twin studies estimate the heritability of endometriosis to be approximately 50%.^[3]

The risk factors predisposing women to develop endometriosis include the following:^[4][5]

• Presence of cervical stenosis and other congenital outflow obstructions (leads to the retrograde efflux of the menstrual fluid into the fallopian tubes and peritoneal cavity); among individuals with obstructive Müllerian anomalies, the prevalence of endometriosis is 47% (95% CI, 36%–58%).^[1]
• Caffeine or alcohol use
• First-degree family relative with endometriosis (relative risk among sisters 5.2; 95% CI, 3.4–7.2).^[6][7]
• Nulliparity (associated with increased risk; pregnancy may be protective due to prolonged anovulation).^[8]
• Menarche before 12 years of age (associated with increased risk).^[2]
• Short menstrual cycle length (<28 days), associated with increased risk.^[9]
• Lower body mass index (associated with increased risk).^[10]
• Tall stature
• Genetic susceptibility with estimated heritability of approximately 50%.^[11]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2] Aravind Kuchkuntla, M.B.B.S[3]

There are no screening recommendations for endometriosis.

There are currently no recommended population-based screening strategies for endometriosis. Diagnosis is symptom-driven and confirmed through clinical evaluation and, when necessary, surgical visualization.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Joseph Nasr, M.D.[2] Aravind Kuchkuntla, M.B.B.S[3]

Endometriosis affects females in the reproductive age group. Endometriosis has a wide spectrum of presentations. It can be asymptomatic, present with premenstrual spotting and cyclical abdominal pain, present with infertility or chronic pelvic pain, or present as deep endometriosis with dyspareunia, dyschezia, and cyclical rectal bleeding. Complications of endometriosis include infertility, fibrosis, chocolate cyst, and rarely, other organs such as the lungs can be affected.

Endometriosis is a chronic, estrogen-dependent inflammatory disease.^[1]

The mean time from symptom onset to diagnosis is approximately 7 years.^[2]

Pain severity does not reliably correlate with lesion number, location, or subtype (except deep posterior cul-de-sac disease, which correlates with dyspareunia).^[3][4]

Endometriosis is a condition affecting females in the reproductive age group. Endometriosis has a wide spectrum of presentations; it may be asymptomatic or present with premenstrual spotting and cyclical abdominal pain. Endometriosis may also present with infertility or chronic pelvic pain, or as deep endometriosis presenting with dyspareunia, dyschezia, and cyclical rectal bleeding. The progression of the disease, if left untreated, is variable. It can progress to a severe disease or regress or remain the same. Severe disease is called deep endometriosis. It presents with chronic pelvic pain, infertility, and other complications due to the extensive fibrosis of the pelvic structures.^[5][6]

Lesion progression is associated with localized fibrosis, angiogenesis, and coordinated nerve and blood vessel ingrowth, which contribute to structural distortion and chronic pain.^[7][8]

Endometriosis demonstrates a heterogeneous clinical course. Some individuals experience stable symptoms, while others develop progressive deep infiltrating disease involving the bowel, bladder, or ureter.^[7]

In less than 1% of patients, deep endometriosis may result in bowel obstruction, hydroureter, hematochezia, or hematuria.^[9][10]

Pain associated with endometriosis may involve nociceptive, neuropathic, and nociplastic mechanisms.^[11][12]

Central sensitization may develop, leading to amplification of pain signals, widespread body pain, fatigue, sleep disturbance, and cognitive symptoms.^[11][12]

Pain may persist despite hormonal suppression or surgical excision of lesions.^[11][12]

The major complication of endometriosis is infertility; Endometriosis is identified in approximately 20% to 50% of individuals with infertility.^[13]

Infertility may result from impaired ovarian function, adhesions causing tubal obstruction, and dysfunction of the uterine endometrium.^[8]

Common Complications

Common complications of endometriosis include:^[14][15]

• Internal abdominal organ scarring
• Adhesions
• Pelvic cysts
• Chocolate cysts
• Ruptured cyst
• Endometriosis is also associated with chronic overlapping pain conditions, including irritable bowel syndrome, bladder pain syndrome, and pelvic floor myalgia.^[11][12]

Less Common Complications

Less common complications of endometriosis include:

• Bowel obstruction  
• Ureteral obstruction or hydroureter  
• Hematochezia  
• Hematuria  
• Thoracic endometriosis presenting with catamenial pneumothorax or hemoptysis^[16]

Endometriosis is associated with an increased risk of ovarian cancer.^[17][18][19]

Prognosis of endometriosis varies with medical therapy. The majority of patients improve with medical therapy, but symptoms may recur in 30-40% of patients after the completion of treatment.^[20]

Pain improvement following surgical excision is variable, and symptom recurrence may occur even in the absence of visible recurrent lesions.^[11][12]

Endometriosis is a chronic condition, and long-term management may be required.