Diagnosis and management of endometriosis

Catherine Allaire, Mohamed A Bedaiwy, Paul J Yong
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2023 · vol. 195(10) , pp. E363–E371 · doi:10.1503/cmaj.220637 · PMID:36918177 · PMC10120420 · W4324148429
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This paper defines endometriosis as a chronic condition of endometrial-like tissue outside the uterus causing estrogen-driven inflammation and outlines its diagnosis and management.

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This 2023 CMAJ review summarizes the epidemiology, pathophysiology, diagnosis, and management of endometriosis, drawing on human adult research, clinical guidelines, systematic reviews, and randomized trials identified via a targeted (nonsystematic) MEDLINE search. It reports that endometriosis affects about 10% of women of reproductive age, can involve superficial to deep and extrapelvic disease, has no cure, and that while surgery can provide definitive histopathology, many international guidelines now recommend a nonsurgical clinical diagnosis using symptoms, physical exam, and imaging to reduce treatment delays. The review also highlights that disease natural history is variable—progression occurs in 29%–45% of untreated patients, unchanged in 33%–42%, and regression in 22%–29%—and that persistent pain despite complete treatment may involve central sensitization or nociplastic pain. A major caveat is that the review is explicitly based on targeted nonsystematic literature searches rather than a systematic review. This paper is centrally about endometriosis — it reviews diagnosis and management across the spectrum of disease and pain mechanisms.

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Abstract

[For a first-person account of endometriosis, see www.cmaj.ca/lookup/doi/10.1503/cmaj.230215][1] KEY POINTS Endometriosis is a chronic condition defined by the presence of endometrial-like tissue outside of the uterus, which can lead to estrogen-driven inflammation. The extent of disease can be
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How

Options for the treatment of patients with symptomatic endometriosis are hormonal therapies that suppress ovulation and menstruation, surgical treatment or a combination of both. 35 Diet and lifestyle modifications may also be helpful but have not been well studied. 36 Diets that target concurrent conditions such as irritable bowel syndrome and painful bladder syndrome have more evidence supporting their usefulness. 37 , 38 Nonspecialist health care providers should feel empowered to diagnose endometriosis and start management ( Figure 2 ). Nonsteroidal anti-inflammatory drugs may be a helpful first-line treatment for symptoms of dysmenorrhea, but no evidence suggests that they improve nonmenstrual symptoms. 39 Many hormonal options can be used to treat endometriosis; all have a comparable efficacy of 60%–80%, and are recommended by clinical practice guidelines ( Table 2 ). 26 , 27 , 35 However, they have variable costs and adverse effects. 40 The goal of hormonal therapy is to suppress the menstrual cycle, create amenorrhea and, preferably, stop ovulation if that process is painful. Hormonal therapies are contraceptive and, therefore, are not appropriate for patients who are trying to conceive. Nonhormonal medical therapies that target inflammatory or angiogenic pathways are being explored, but none are currently available. 40 Hormonal therapies for endometriosis Nausea, spotting, headache, mood changes, breast discomfort Acne, spotting, mood changes, headache, weight gain, breast discomfort Spotting, headaches, breast discomfort, functional ovarian cysts May need to be replaced sooner for pain control May not suppress ovulation pain reliably Hot flushes, headache, depression, decreased BMD and vaginal dryness Adverse effects minimized with add-back hormone replacement therapy Hot flushes, headache, depression, decreased BMD and vaginal dryness Adverse effects minimized with add-back hormone replacement therapy Hot flushes, decrease BMD and headaches Used in combination with other medication Note: BMD = bone mineral density, GnRH = gonadotropin-releasing hormone. Hormonal suppression can be achieved with combined estrogen–progestin contraceptives (cyclic or continuous, with the latter being more effective) or progestin-only medications (oral or injectable medications, subcutaneous implants or intrauterine devices). Evidence supports their effectiveness for endometriosis symptoms, and current guidelines consider all these as acceptable first-line options. Two systematic reviews and a Cochrane review (including 5 randomized controlled trials [RCTs]) have concluded that treatment with combined hormonal contraceptives reduces endometriosis-associated pain — including dysmenorrhea, noncyclic pelvic pain and dyspareunia — and improves quality of life, compared with placebo. However, these reviews also noted that the studies were of low quality, with a high risk of bias and short follow-up duration (3–11 mo). 41 – 43 The efficacy of various progestogens was evaluated in a Cochrane review and a systematic review focused on dienogest. 44 , 45 They found that continuous progestogens are effective for the treatment of endometriosis-associated pain, with variable adverse effects and no evidence that 1 oral progestogen is more efficacious than another. In a systematic review comparing the levonorgestrel-releasing intrauterine system with gonadotropin-releasing hormone (GnRH) agonists, which included 5 RCTs, both were comparable in relieving endometriosis-associated pain. 46 Patient-centredness should underpin choice of treatment and discussions should include information on individual risk factors and patient preferences. Several treatments may need to be tried before one is found that provides good cycle suppression with acceptable adverse effects. Once a successful first-line treatment is found, it can be continued for many years. Second-line therapies include GnRH agonists and antagonists, as well as aromatase inhibitors. Use of GnRH agonists and, at higher doses, GnRH antagonists requires add-back hormone replacement therapy to counteract the menopausal adverse effects of severe hypoestrogenism. Use of oral danazol, a synthetic androgen, is no longer supported, given its adverse effects. Second-line treatment options are usually started by a gynecologist, most often when endometriosis is confirmed by imaging or surgery. Long-term use of second-line agents is sometimes required and, therefore, ongoing administration may be provided by the primary care provider. The available hormonal therapies, their adverse effects and relative costs are listed in Table 2 . Surgical treatment is offered when drug therapies are contraindicated (such as for patients who are trying to conceive), are not tolerated or have failed to provide adequate relief. A minimally invasive approach with complete treatment of the disease is considered best practice by most international guidelines. 26 , 27 , 35 Some patients may choose surgery as their first option after counselling about its benefits (including fertility benefits, which are affected by factors such as age) and its risks and limitations, including recurrence of disease and persistence of pain from other causes. 26 , 27 , 35 In patients for whom endometriosis has led to ureteric or bowel obstruction, surgery may be the only management option. If surgical management is pursued, endometriosis is usually staged according to the revised American Society for Reproductive Medicine (ASRM) classification system as minimal, mild, moderate or severe (Stages I–IV). This staging system reflects extent of disease and anatomic distortion, and correlates with surgical complexity, but is poorly correlated to severity of pain and fertility. 10 The Endometriosis Fertility Index, a tool that combines patient history, revised ASRM staging and anatomic state of the adnexae at the end of surgery, has been shown to be reliable in predicting the likelihood of conceiving without in vitro fertilization after surgery. 47 In the context of infertility, surgery for treatment of superficial peritoneal endometriosis or endometriomas may improve the chance of natural conception, but must be balanced with other options such as assisted reproductive technologies. 26 A Cochrane systematic review concluded that surgery was effective for pain symptoms but included only 3 small RCTs with follow-up of 6–12 months. 48 Other systematic reviews have shown a persistence or recurrence rate of 22% at 2 years and of 40%–50% at 5 years after surgery. 49 Treating patients with hormonal management postoperatively may decrease the rate and speed of recurrence of pain symptoms. 50 Because of the complexity and higher risks associated with surgery for patients with deep endometriosis, detection of deep endometriosis on imaging allows for improved surgical planning and timely referral to specialized surgeons or centres of expertise. Unfortunately, access to such care is limited in some regions of Canada. Laparoscopic hysterectomy, with or without removal of 1 or both ovaries, may also be an option for select patients — such as those who have ongoing dysmenorrhea or heavy menstrual bleeding, adenomyosis or recurrence of disease and who have no desire for future fertility — after appropriate counselling of benefits and risks. Hysterectomy with concurrent treatment of endometriosis has better pain outcomes than conservative surgery alone, but it is still not curative. 51 Removal of both ovaries causes premature surgical menopause with potential adverse effects on bone and heart health (as compliance with hormone replacement therapy is low) and provides only marginal additional benefit for pain over hysterectomy alone. 52 Some patients may not respond to medical or surgical management and may develop persistent pelvic pain that may reflect central sensitization or nociplastic pain, with accompanying chronic overlapping pain conditions. In patients with complex pain, a multidisciplinary plan of care that follows chronic pelvic pain guidelines is most likely to lead to improved quality of life. This may include pain education, pelvic physiotherapy, psychological interventions (such as cognitive behavioural therapy, acceptance and commitment therapy or mindfulness-based therapy) and targeted interventions for other pain contributors. 24 , 53 , 54 A multidisciplinary, multimodal, patient-centred approach has been recognized as best practice for chronic pain conditions. Primary care providers often play a central role in coordinating this care or referring the patient to a specialized clinic, where available. 25 , 55

Who

If a patient has symptoms and signs of deep endometriosis or investigations reveal an endometrioma, they should be referred for assessment by a gynecologist, who will likely order further imaging with pelvic magnetic resonance imaging or advanced transvaginal ultrasonography. Depending on the wait times for specialist consultation or imaging, it may be appropriate to seek both at the same time and start first-line medical therapy. Patients with suspected superficial peritoneal endometriosis who do not respond to, have contraindications to or decline first-line medical management options, and those who are actively trying to conceive or have infertility, would also benefit from gynecologic assessment and management ( Figure 1 ).

What

The natural history of the disease was observed using laparoscopy, repeated at 6–12 months, among patients enrolled in the untreated arms of 2 randomized trials that evaluated surgical treatment of patients with minimal to moderate disease. Endometriosis progressed in 29%–45% of patients, was unchanged in 33%–42% of patients and regressed in 22%–29% of patients. 18 , 19 This information changed the long-held belief that endometriosis is always progressive. Most patients report that their symptoms started in adolescence and improve at menopause, although some patients continue to have pain after menopause. 20 The improvement at menopause is likely owing to lack of estrogen stimulation. Although current medical and surgical therapies are not curative, they provide considerable symptom relief for many patients. However, some people with endometriosis develop a more complex, persistent pain problem despite complete treatment, which may be secondary to central sensitization or nociplastic pain, recently defined by the International Association for the Study of Pain as “pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.” 21 Mechanisms of central sensitization in endometriosis include a reduction in descending modulation of peripheral signals (gate theory) and cross-sensitization that gives rise to symptoms in visceral and somatic structures (via viscero–visceral and viscero–somatic cross-talk in the spinal cord). 22 The development of central sensitization may account for the evolution of cyclical pain to chronic pelvic pain and the development of other chronic pain conditions. In 2015, the National Institutes of Health recognized the entity of chronic overlapping pain conditions as a cluster of chronic pain conditions that often co-exist, occur predominantly in women, and likely share common immune, neural and endocrine mechanisms. 23 Endometriosis was one of these conditions, along with commonly co-existing conditions, such as vulvodynia, irritable bowel syndrome and painful bladder syndrome. Other chronic overlapping pain conditions are chronic migraine, chronic low back pain, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia and temperomandibular disorders. 23 Patients who do not respond, or have only a short-term response, to endometriosis-targeted treatments and who have concurrent pain conditions may have developed a central sensitization or nociplastic pain process. 24 , 25 Evidence suggests that early treatment of endometriosis and associated pain may decrease the risk of development of chronic pain, which further supports the importance of early assessment and intervention. 22

Conclusion

Endometriosis is a common and complex condition that can cause considerable distress and can lead to the development of chronic pelvic pain, infertility or end-organ damage. Early recognition and diagnosis are key to providing timely treatment. Primary care providers can make a clinical diagnosis of endometriosis and start first-line medical management. Referral to a gynecologist for second-line hormonal therapy or surgery is important, when indicated. Hormonal or surgical treatments can provide symptom relief and are part of a long-term management plan for this chronic condition. Multidisciplinary care may be required to address complex persistent pain.

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Condition tags

endometriosischronic_pelvic_pain

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Female Female Female Female Humans Humans Humans Humans Pelvic Pain Pelvic Pain Pelvic Pain Pelvic Pain

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