{"paper_id":"fb7e59e4-2f69-459a-af64-7461c8e753b6","body_text":"A PubMed search was performed for English-language articles using the MeSH term  endometriosis  to identify systematic reviews, meta-analyses, clinical trials, observational studies, and practice guidelines published between January 1, 1999, and December 30, 2024. The search yielded 1656 articles. Additional narrative reviews were selected by the authors based on their knowledge of the literature. A total of 99 studies were included, consisting of 37 systematic reviews or meta-analyses, 4 clinical trials, 31 observational studies, 9 practice guidelines or consensus statements, and 18 narrative reviews.\nEndometriosis is typically diagnosed in individuals in their early 30s, 3  despite average symptom onset in adolescence to the early 20s. 3 , 10  Although a 10% prevalence of endometriosis among reproductive-age women in the general population is often stated, 2  a systematic review of 69 observational studies reported that prevalence varies widely, depending on geographic location, setting (general or specialist clinic, hospital data and insurance claims), symptoms, age, and diagnosis method (symptoms, ultrasound, surgery). 2  Endometriosis is observed (primarily via laparoscopy) in 28.1% (95% CI, 26.9%–29.4%), as reported in a meta-analysis of 11 observational studies, of women presenting with chronic pelvic pain and 24.8% (95% CI, 23.9%–25.8%), as reported in a meta-analysis of 17 observational studies, of women presenting with infertility. 2  In a systematic review of 27 cross-sectional, case-control, and cohort studies from the US and Europe, women with endometriosis-associated pelvic pain reported significantly reduced health-related quality of life, and impaired mental health, sexual function, and work productivity compared with women without endometriosis. 5\nRisk factors for endometriosis include obstructive müllerian anomaly (uterine anomaly causing blockage of menstrual outflow), which is associated with a 47% prevalence of endometriosis (95% CI, 36%–58%). 11  Other risk factors, based on prospective cohort studies and meta-analyses of cohort and case-control studies, include onset of menarche before age 12 years, 12  menstrual cycle intervals fewer than 28 days, 13  lower body mass index, 14  and nulliparity. 15  Twin studies estimate heritability of endometriosis at approximately 50%, 16 , 17  but no single genes have been associated with most familial cases. A family history of endometriosis is also a risk factor (for sisters, relative risk, 5.2; 95% CI, 3.4–7.2), 18  which is partially attributable to genetic heritability as well as increased awareness and access to care.\nEndometriosis is categorized into 4 subtypes: superficial peritoneal, deep, ovarian (endometriomas), and extrapelvic endometriosis ( Figure 1 ). Subtypes may occur alone or in combination and are important to distinguish because they may affect the diagnostic and treatment approach.  Superficial peritoneal endometriosis  lesions occur on the peritoneal surface of serosa of abdominal or pelvic viscera.  Deep endometriosis  lesions penetrate the pelvic peritoneal surface (eg, uterosacral ligaments) or infiltrate the muscularis propria of pelvic visceral organs such as the bowel or urinary tract (bladder or ureter).  Ovarian endometriomas  are cysts within the ovary lined by endometrial glands and stroma.  Extrapelvic endometriosis  refers to lesions outside of the pelvis, which have been reported in nearly every organ system, including the diaphragm, thoracic cavity, abdominal wall, and brain. 20  The prevalence of endometriosis subtypes in the general population is unknown. Available data are from series of surgical cases and vary widely depending on factors such as age, clinical setting (eg, community hospital vs endometriosis referral center), and presurgical symptoms.\nThe pathogenesis of endometriosis involves sex-steroid and inflammatory processes. Retrograde efflux of endometrial cells through the fallopian tubes into the pelvis during menstruation is widely accepted as a contributor to the origin of lesions within the abdominal-pelvic cavity. Lymphatic or vascular metastasis have also been proposed and cannot be excluded as a cause of extrapelvic lesions. 21 – 23  Endometriosis lesions are dependent on estradiol-mediated mechanisms that promote cellular proliferation and adhesion, localized fibrosis and inflammation, immune dysregulation, and coordinated nerve and blood vessel ingrowth. 21 – 23  However, pathophysiological changes extend beyond the lesions and include altered immune and progesterone responsiveness of the uterine endometrium and increased inflammation and angiogenesis in the mesothelial cells of the pelvic peritoneum ( Figure 2 ).\nThe mechanisms by which endometriosis causes pelvic pain and/or infertility are multifactorial and not fully understood. Pain due to endometriosis can be caused by a combination of nociceptive, neuropathic, and nociplastic mechanisms ( Figure 2 ). 27 \n Nociceptive  pain is caused by direct activation of peripheral nociceptors (sensory receptors for noxious stimuli) and is likely due to localized inflammation surrounding lesions.  Neuropathic  pain may be due to peripheral sensitization and/or direct nerve fiber invasion by lesions, which may increase with surgical injury.  Nociplastic  pain (pain from altered pain perception in the central nervous system) manifests as widespread body pain, fatigue, memory difficulties, and poor sleep and is associated with systemic inflammation from immunoreactive white blood cells. 28  Endometriosis may affect fertility through multiple pathways, including impaired ovarian function, adhesions causing tubal blockage, and dysfunction of uterine endometrium. 23\nThe most common presenting symptom is pelvic pain, including dysmenorrhea (painful menses), nonmenstrual pelvic pain, and deep dyspareunia (pain with deep vaginal penetration;  Box ). In a cross-sectional study of self-reported survey data from 940 women with surgically confirmed endometriosis, 89.3% reported at least 1 pelvic pain symptom, including 78.7% with dysmenorrhea, 69.4% with non-menstrual pelvic pain, and 44.9% with deep dyspareunia. 3  This study also reported dyschezia (painful bowel movements) in 27.0%, infertility in 26.2%, ovarian cysts in 19.5%, and dysuria in 9.9%; 2% were asymptomatic. 3  In less than 1% of patients, deep endometriosis can cause bowel obstruction, hydroureter, hematochezia, and/or hematuria; these signs and symptoms should raise the suspicion for deep endometriosis. 29 , 30  The intensity of pelvic pain in patients with endometriosis varies, does not correlate with number, location, or subtype of lesions (except deep disease in the posterior cul-de-sac correlates with dyspareunia) but typically increases during menses. 31 , 32  Similar to patients with other chronic pain conditions, 28  patients with endometriosis are more likely than women without endometriosis to report moderate to severe fatigue in the absence of anemia (50.7% vs 22.4%), 4  sleep disturbances (29.2% vs 12.5%), and mood disorders (67% vs 51.2% cumulative incidence over 12.5 years). 33\nSymptoms of extrapelvic endometriosis reflect the location of the lesions and, similar to other endometriosis subtypes, typically worsen during menses. 20  For example, thoracic endometriosis can cause catamenial (symptoms that recur during menses) pneumothorax, hemoptysis, and/or shoulder pain during menses. Abdominal wall endometriosis is associated with cyclic pain in a palpable subcutaneous nodule. Umbilical skin lesions can bleed during menses.\nAfter menopause, patients with endometriosis typically have resolution of symptoms due to decline in estrogen levels. However, symptoms of endometriosis can persist or present for the first time in menopause, particularly among women who use hormone replacement therapy, although the frequency of incident and prevalent symptoms in menopause is unknown. 34\nThe World Endometriosis Research Foundation 24  and Society of Obstetricians and Gynecologists of Canada 25  provide recommendations on the physical examination of patients with suspected endometriosis using a trauma-informed framework, which minimizes distress, supports autonomy, and builds trust ( Figure 3 ). Although a pelvic examination cannot identify superficial peritoneal lesions, it may identify ovarian endometriomas and signs of deep endometriosis and can evaluate for other causes of pelvic pain such as pelvic floor myalgia (tenderness with vaginal palpation of pelvic floor muscles). Several pelvic examination findings suggest deep endometriosis or ovarian endometriomas. In patients with surgically confirmed deep endometriosis, 67% to 95% had palpable thickening, nodularity, or tenderness of the posterior cul-de-sac and/or decreased uterine mobility, and 75% to 90% had a palpable ovarian mass on pelvic examination prior to surgery. 35  Patients with suspected lesions in the vagina, umbilicus, or within abdominal surgical scars should be referred to a gynecologist for possible biopsy of these lesions ( Figure 1  and  Box ).\nMultiple international guidelines 25 , 36 – 39  recommend transvaginal pelvic ultrasound as the initial diagnostic test for patients with pelvic pain and/or suspected endometriosis. A 2016 Cochrane review reported that, compared with surgical visualization, transvaginal ultrasound had high sensitivity (93%, 95% CI, 87%–99%) and specificity (96%, 95% CI, 92%–99%) for ovarian endometriomas (8 studies, n = 765), moderate sensitivity for deep endometriosis (79%, 95% CI, 69%–89%, 9 studies, n = 934), but low sensitivity for superficial peritoneal lesions (65%, 95% CI, 27%–100%). 40  In 2024, the Society of Radiologists in Ultrasound published a consensus on augmented pelvic ultrasound to improve the diagnosis of deep endometriosis. 41  This technique—supported by the European Society of Human Reproduction and Embryology, 39  the Society of Obstetricians and Gynecologists of Canada, 25  and the National Institute for Health and Care Excellence guidelines 38 —is not widely used in the US. Unlike routine transvaginal ultrasound, augmented pelvic ultrasound includes evaluation of the relative position of the ovaries (eg, “kissing ovaries” suggests deep endometriosis) and dynamic uterine sliding (absence of uterine slide against the rectosigmoid suggests adhesions and deep endometriosis). In a prospective observational study of 273 patients undergoing laparoscopic surgery, augmented pelvic ultrasound had a sensitivity of 88.4% (95% CI, 83.2%–92.4%) and specificity of 78.8% (95% CI, 67.0%–87.9%) for detecting deep endometriosis. 42\nMagnetic resonance imaging (MRI) enables evaluation of other pelvic organs, features of ovarian malignancy when ultrasound is inconclusive, and it can diagnose extrapelvic endometriosis. 43  A systematic review (14 observational studies, n = 1577) reported that MRI using an endometriosis-specific protocol interpreted by experienced radiologists had a sensitivity of 91% to 93.5% and a specificity of 86% to 87.5% for deep and ovarian endometriosis compared with laparoscopy or other forms of imaging. 44  Because no imaging modality has 100% sensitivity, absence of findings on imaging does not exclude the diagnosis of endometriosis.\nHistological confirmation is considered the criterion standard for diagnosing endometriosis, which requires visualization (usually by laparoscopy) to biopsy lesions in the abdomen and pelvis. However, multiple society guidelines 25 , 36 – 39  recommend making a presumed diagnosis based on symptoms, supported by physical examination findings and pelvic imaging with ultrasound and/or MRI ( Figures 3  and  4 ), although no validated diagnostic criteria exist. Additionally, no diagnostic blood or molecular markers for endometriosis have been validated in clinical populations. 45  This shift in diagnostic approach reflects awareness that requiring surgery for diagnosis may delay treatment. Moreover, surgery is not always accessible, and empirical hormonal treatment offers comparable overall efficacy to surgical removal of lesions.\nEndometriosis is a chronic condition without medical or surgical cure. Current treatments include nonopioid analgesics, hormonal medications, surgery, and adjunct therapies, such as pelvic floor physical therapy. Treatment focuses on managing pain and reducing recurrence, using individualized strategies based on patient preference and fertility goals, which may change over time.\nHormonal treatment should be offered to symptomatic women with clinically suspected endometriosis who do not wish to conceive immediately. Multiple guidelines 25 , 38 , 39  advise that clinicians should not prescribe medical treatments or surgically remove lesions in asymptomatic individuals but should inform patients about the incidental findings. Exceptions include asymptomatic patients with large ovarian endometriomas or deep lesions causing hydronephrosis (see below).\nGuidelines state that patients may be offered nonsteroidal anti-inflammatory drugs (NSAIDs) for endometriosis-associated pain; NSAIDs can be used alone or in combination with hormonal treatments. 36 – 39 , 46  However, a 2017 Cochrane review found insufficient evidence that NSAIDs reduce pain in endometriosis, with only 1 low-quality trial of 24 participants. 47\nRandomized trials have not evaluated the efficacy of opioid analgesics for treating endometriosis-associated pelvic pain. Due to risk of dependency, opioids are not recommended.\nHormonal treatment, which can be initiated in the primary care setting, is first-line treatment recommended by international guidelines. 36 – 39 , 46  All hormonal treatments target sex steroid-dependent pathophysiology of endometriosis by suppressing ovarian activity and creating a hypoestrogenic environment, which can lead to regression of endometriosis lesions. 48  First-line hormonal treatment includes combined estrogen-progestin contraceptives or progestogens, second-line hormonal treatment includes gonadotropin-releasing hormone (GnRH) agonists and antagonists, and third-line hormonal treatment includes aromatase inhibitors ( Table ). Approximately 25% to 34% of women with endometriosis experience recurrent pelvic pain within 12 months of discontinuing hormonal therapy, 54  and incidence of pain recurrence is likely higher with longer duration of time off hormonal therapy. Despite similar efficacy of hormonal medications, individual responses vary, often necessitating trials of different medications within and across classes to achieve optimal symptom control and minimize adverse effects such as breakthrough bleeding.\nGuidelines recommend combined estrogen-progestin contraceptives (typically containing 20 μg-30 μg ethinyl estradiol) and progestin-only medications such as norethindrone acetate as first-line treatment due to their low cost and few adverse effects. A network meta-analysis of 1680 women from 15 RCTs reported that all hormonal treatments led to a similar clinically significant pain reduction measured usinga0 to 100 visual analog scale (minimum clinically important difference, 10 points). 38  Compared with placebo, combined oral contraceptives reduced pelvic pain by a mean difference of 15.1 (95% CI, −20.8 to −9.3); oral progestogens, 12.6 (95% CI, −15.3 to −9.8); progestogens delivered via intrauterine device (52 mg levonorgestrel system), 17.7 (95% CI, −25.5 to −9.8); intramuscular progestogens, 13.2 (95% CI, −16.2 to −10.1); and intramuscular GnRH agonists (leuprolide acetate), 15.7 (95% CI, −21.3 to −10.1). However, a systematic review of 58 studies (38 RCTs, 16 prospective, 4 retrospective cohort studies) with 11 881 participants reported that 11% to 19% of women experienced no pain reduction with hormonal therapy and 5% to 59% still had some pain at the end of the study period despite hormone use. 54\nGuidelines recommend continuous use of a combined estrogen-progestin contraceptive (omitting the hormone-free interval) over cyclic use with the goal of achieving amenorrhea. 39  In a prospective cohort study of 293 women with endometriosis, continuous hormonal suppression was associated with lower frequency of dysmenorrhea (9.4% vs 20.9%,  P  = .02) and nonmenstrual pelvic pain (9.4% vs 23.9%,  P  = .006) when compared with cyclic use. 49  Improvement in pelvic pain should be assessed approximately 3 months after starting oral contraceptives. When hormonal suppression is initiated by primary care clinicians, referral to a gynecologist should be considered if pain persists or adverse effects such as breakthrough bleeding or mood changes are intolerable.\nGnRH agonists and antagonists, such as leuprolide and elagolix, are second-line therapy due to their high cost and adverse effects of decreased bone mineral density and vasomotor symptoms, which limit their long-term use. 38 , 39 , 46  GnRH agonists and antagonists are typically prescribed by gynecologists, usually after surgical confirmation of endometriosis and removal of lesions, particularly in adolescents. 10 , 39  To counteract adverse menopausal effects of GnRH medications, current guidelines 25 , 36 , 38 , 39  recommend coadministration of hormonal replacement therapy with combined estrogen-progestin or norethindrone acetate, known as add-back therapy. A meta-analysis (13 RCTs, 945 participants) reported that add-back therapy led to a clinically meaningful reduction in loss of bone mineral density in the lumbar spine compared with GnRH monotherapy (weighted mean difference, −0.03 g/cm 2 ; 95% CI, −0.05 to −0.02) without reduced efficacy in treating pelvic pain. 55\nIn contrast to injectable GnRH agonists, GnRH antagonists are oral medications, have rapid onset of action, and quick return of menses once discontinued (eg, median time to resumption of menses is 31 days for relugolix combination therapy 51 ). There are 2 US Food and Drug Administration (FDA)–approved medications: elagolix (low dose, 150 mg once daily; high dose, 200 mg twice daily) and relugolix combination therapy ( Table ). In replicate randomized clinical trials, 872 and 817 women were randomized in each study, and 653 and 632 completed the trial. At 6 months for both studies, those taking elagolix were more likely than those taking placebo to have a clinically significant reduction in dysmenorrhea: 42.1% and 46.2% in the low-dose groups; 75.3% and 76.9% in the high-dose groups; and 23.1% and 25.4% in the placebo groups and similarly have a clinically significant reduction in and nonmenstrual pelvic pain: 45.7% and 51.6% in the low-dose groups; 62.1% and 62.2% in the high-dose groups; and 34.9% and 40.6% in the placebo groups ( P  < .001 for all comparisons). 50  Similarly, in replicate clinical trials assessing relugolix, 638 and 623 women were randomized. In both studies 75% in the relugolix group had clinically significant improvement in dysmenorrhea vs 27% and 30% in the placebo groups, respectively; 59% in the first study and 66% in the second study had significant improvement in nonmenstrual pelvic pain vs 40% and 43% in the placebo groups, respectively ( P  < .001 for all comparisons), 51  with sustained efficacy and tolerability at 2 years. 52\nAromatase inhibitors are not currently FDA-approved for endometriosis treatment but can be considered as third-line hormonal therapy for patients who do not improve with first-line and second-line hormonal treatments, based on low-quality evidence. 53\nInternational guidelines recommend offering surgery as an option for endometriosis-associated pain if medical treatment is contraindicated, ineffective, or has unacceptable adverse effects. 36 – 39 , 46  Surgery should be considered for patients with ovarian endometriomas of any size that have features concerning for malignancy or are large (>5 cm), due to low likelihood of resolution with hormone treatment and risk of ovarian torsion. Based on expert opinion, surgical removal of endometriosis lesions should be performed for deep endometriosis causing hematuria, hematochezia, or obstructive conditions of the urinary or intestinal tract. Evidence supporting the effectiveness of surgery is limited to observational and small randomized studies with follow-up periods of 1 year, often not including or differentiating between endometriosis subtypes. 23 , 56  In a systematic review of studies of women who underwent surgical removal of endometriosis lesions without postoperative hormone treatment (9 RCTs, 9 prospective, 7 retrospective cohort studies, n = 2652), persistent pain and adverse events such as hemorrhage or fever were reported in 25.0% and 8.1% of women, respectively, at a median follow-up of 24 months. 57\nSurgical efficacy in improving pain varies by endometriosis subtype. Evidence supporting efficacy of laparoscopic surgical removal of superficial peritoneal lesions for pain relief is limited. 58  High-quality evidence comparing efficacy of excision vs ablation (eg, via CO 2  laser) of superficial endometrial lesions is lacking; practice reflects surgeon preference. 59\nFor ovarian endometriomas, RCTs have not been performed comparing surgery with no treatment for pain relief. A 2024 Cochrane review of 9 RCTs (n = 578) reported that ovarian cystectomy was associated with reduced dysmenorrhea and cyst recurrence compared with cyst drainage and ablation (dysmenorrhea, 19.5% vs 49.3%; n = 140;  P  < .001; cyst recurrence, 9.1% vs 36.9%; n = 264;  P  < .001). 60  However, ovarian cystectomy may harm fertility, as shown by a 38% reduction in postoperative anti-Müllerian hormone levels, a biomarker of ovarian reserve (meta-analysis of 8 studies, n = 237; weighted average preoperative hormone levels, 3.0 ng/mL). 61\nFor deep endometriosis, surgical removal may reduce endometriosis-associated pain and improve quality of life. 39  Endometriosis lesions can be excised from most locations. However, resection near or involving the ureter, bowel, or thorax carries increased risk, warranting interdisciplinary care with colorectal, urological, and/or thoracic surgeons. A multicenter prospective cohort study (n = 4721) reported that laparoscopic excision of deep rectovaginal endometriosis was associated with a reduction in menstrual pain 24 months postoperatively. 62  Menstrual pain, measured usinga0 to 10 numeric scale, decreased from a preoperative median of 9 (95% CI, 9–9) to a postoperative score of 5 (95% CI, 4–6), noncyclical pelvic pain from 6 (95% CI, 6–6) to 3 (95% CI, 2–3), deep dyspareunia from 6 (95% CI, 5–6) to 2 (95% CI, 1–2), and cyclical dyschezia from 6 (95% CI, 6–6) to 2 (95% CI, 1–3;  P  < .001 for all comparisons; minimum clinically important difference, 4). 63  Complications occurred in 7%, with hemorrhage and conversion to laparotomy occurring in less than 1% of patients, 62  supporting the recommendation that experienced surgeons perform deep endometriosis removal. 37 – 39 , 64\nAsystematic review of 25 studies (9 RCTs, 8 prospective cohort studies, 7 retrospective studies, and 1 longitudinal unmatched study; n = 2652; median follow-up, 24 months) of surgical outcomes without postoperative hormone treatment reported recurrent pain in 15.8% of patients following surgical removal of lesions. 57  A meta-analysis of 11 RCTs and 3 prospective cohort studies (n = 1766) reported postoperative hormonal suppression was associated with reduced endometriosis recurrence at a median follow-up of 18 months based on symptoms or imaging (10.7% vs 26.4%, relative risk, 0.41; 95% CI, 0.26 to 0.65). 65  Based on a meta-analysis of 6 RCTs and 1 prospective cohort study (n = 652), postoperative hormonal suppression was associated with lower pain scores (standard mean difference, −0.49 [small effect], 95% CI, −0.91 to −0.07) compared with no treatment or placebo. 65\nGuidelines recommend offering hysterectomy to women with endometriosis who are not interested in pursuing pregnancy and have treatment-resistant pain, ie, pain despite hormonal suppression and surgical removal of lesions. 36 – 39 , 46  However, the quality of evidence for hysterectomy for pain management is low given a lack of randomized trials, short follow-up, and inconsistent outcome definitions. 66 , 67  A Canadian retrospective cohort study of 4489 individuals who underwent hysterectomy for endometriosis reported a 10.5% reoperation rate (most commonly, oophorectomy and adhesiolysis) within 10 years. 67\nAlthough not specifically studied in endometriosis, there is evidence that hysterectomy with and without oophorectomy is associated with increased incidence of cardiovascular, metabolic, and mental health disorders, which should be discussed with patients prior to surgery. 68 – 70 Thus, guidelines recommend offering hysterectomy with excision of endometriosis lesions only to women with persistent pain that reduces quality of life, who do not desire future fertility, and have not responded to other treatments. 36 – 39 , 46  Given the risks of surgical menopause and insufficient evidence for pain improvement, ovarian conservation is preferred if the ovaries are normal and there is no known genetic risk of ovarian cancer (eg,  BRCA1 ). 71 , 72\nGuidelines advise that clinicians discuss nonmedical therapies that may enhance quality of life, 39  such as pelvic floor physical therapy, 73  pain-focused psychological interventions, 74 – 76  pain education, 77  exercise, 78  dietary modification such as antioxidant use, 79  and acupuncture. 80  Patient education is recommended to help women understand their condition and make informed decisions about treatment. 77 , 81  However, guidelines do not provide recommendations about specific adjunct treatments due to limited evidence in patients with endometriosis.\nGuidelines advise against prescribing hormonal suppression, such as with combined hormonal contraceptives, progestins, or GnRH agonists or antagonists, for women with endometriosis for the sole purpose of enhancing future fertility, including for those planning pregnancy after endometriosis surgery because there is no evidence supporting their efficacy in either situation. 39\nModerate-quality evidence from a meta-analysis of 3 RCTs with 528 participants suggests laparoscopic treatment (ablation or excision) of superficial peritoneal endometriosis increases viable intrauterine pregnancy rates compared with diagnostic laparoscopy alone (302 vs 186 viable pregnancies per 1000 persons, odds ratio, 1.89; 95% CI, 1.25–2.86). 58  However, data on live birth rates are lacking. No RCTs have been published assessing fertility outcomes after surgery for ovarian or deep endometriosis.\nGuidelines, based on meta-analyses of observational studies, 39  state that assisted reproductive technology such as in vitro fertilization can be used for endometriosis-associated infertility. 26 , 82  Surgery to remove endometriosis lesions for the sole purpose of improving fertility prior to assisted reproductive technology is not recommended because the potential benefits are unclear. 26\nCare of patients may be challenging due to the nonspecific and varying symptoms associated with endometriosis. Pain severity does not correlate with subtype of endometriosis lesions, 31 , 32  and hormone response does not confirm the diagnosis because pelvic pain of other etiologies, such as primary dysmenorrhea and adenomyosis, also improves with hormone treatment. 83  Furthermore, medications and surgery for endometriosis lesions do not consistently alleviate pain and nearly 50% of patients with a history of endometriosis who undergo a hysterectomy for recurrent pelvic pain do not have evidence of recurrent endometriosis lesions. 84\nUntreated neuropathic and nociplastic pain likely contribute to pain associated with endometriosis, and patients with endometriosis commonly have other painful conditions. For example, 25% of women with endometriosis have at least 1 coexisting pain disorder such as migraine headache, irritable bowel syndrome, interstitial cystitis, or fibromyalgia. 85 – 87  Although no clinical trials have assessed treating nociplastic pain in patients with endometriosis, those with higher levels of nociplastic pain report greater pain intensity 88  and are less likely to report pain improvement when undergoing hysterectomy 89  or surgical removal of lesions. 90  Therefore, interdisciplinary care including a gynecologist, physiotherapist, and psychologist should be encouraged. 91  Repeated surgeries should be avoided whenever possible because there are no high-quality studies that demonstrate benefit.\nPatients with endometriosis have an increased lifetime risk of ovarian cancer compared with an incidence of approximately 1.1% among all women. 92  A meta-analysis of 24 studies (7 case-control, 14 retrospective, and 3 prospective cohort studies) reported a 93% greater risk of a diagnosis of any type of ovarian cancer among patients with endometriosis. 93  Five meta-analyzed studies confirmed a 3.4-fold and a 2.3-fold greater risk of clear cell and endometrioid cancer subtypes, respectively, among patients with endometriosis compared with those without endometriosis. 93  A recent study reported risk ranging from 4-fold to 19-fold by cancer subtypes among women with endometriosis. 94  However, when accounting for detection bias, the risk estimate corrected to 1.71, consistent with the 24 study meta-analysis. 95  Prophylactic bilateral salpingo-oophorectomy to reduce ovarian cancer risk in patients with normal-appearing ovaries is not recommended by guidelines, 39  given the low absolute rate of ovarian cancer and evidence of adverse consequences of surgical menopause. 72  Individuals with endometriosis are also at increased risk of autoimmune conditions (eg, systemic lupus erythematosus and rheumatoid arthritis 96 ), cerebrovascular conditions including myocardial infarction 97  and stroke, 98  and long COVID. 99\nThis review has several limitations. First, some guideline recommendations are based on low-quality studies. Second, there is heterogeneity in endometriosis subtypes that most studies do not assess. Third, some studies may have been missed.\n\nEndometriosis is a common cause of pelvic pain affecting approximately 10% of reproductive-age women. Hormonal suppression including combined estrogen-progestin contraceptives or progestins is the first-line treatment in women who are not seeking immediate pregnancy. Surgical removal of endometriosis lesions may be performed if hormonal therapies are ineffective or contraindicated, and hysterectomy may be considered if medical treatments and surgical removal of lesions do not relieve symptoms. Treatment should be based on patient preference, symptom severity, and fertility goals, which may change over the life course.","source_license":"CC0","license_restricted":false}