Endometriosis: symptoms, diagnosis, treatment

Endometriosis is a chronic inflammatory disease in which endometrial-like tissue grows outside the uterine cavity: on the pelvic peritoneum, ovaries, uterosacral ligaments, intestines, bladder, and elsewhere. It causes pain (dysmenorrhea, chronic pelvic pain, dyspareunia), dysfunction of adjacent organs, and, in some patients, fertility issues. Because the disease is recurrent, its management is considered a "long roadmap," with changes in tactics at different stages of life. [1]

In recent years, the diagnostic approach has shifted from "laparoscopy for all" to a "reasonably noninvasive" strategy: in cases with typical clinical and imaging findings, diagnosis can be made without diagnostic laparoscopy and treatment can begin; surgery is reserved for complex cases, severe pain, deep infiltrating nodules, suspected alternative diagnoses, or with fertility as a priority. This reduces delays in care and the risk of unnecessary interventions. [2]

Treatment is multi-level. Priorities depend on the patient's goals: pain control, fertility preservation/realization now or later, and protection of vital functions (e.g., in case of bowel/ureteral damage). Modern options include continuous hormonal regimens (COCs/progestins/levonorgestrel IUDs), GnRH agonists/antagonists with "add-back therapy," targeted laparoscopic surgery, and assisted reproductive technologies. [3]

It's important to remember: endometriosis is a common cause of pain and decreased quality of life, but it's not "rarity" or a "life sentence." A clear explanation of the disease, a realistic plan, and shared decision-making can shorten the "diagnostic odyssey" that traditionally lasts years. [4]

Code according to ICD-10 and ICD-11

In ICD-10, endometriosis is coded in block N80.*: uterus (N80.0), ovary (N80.1), fallopian tube (N80.2), peritoneum (N80.3), vagina (N80.4), intestine (N80.5), skin (N80.6), other and unspecified forms (N80.8-N80.9). In case of combined localizations, several codes are indicated. This is important for statistics and routing to high-tech care. [5]

ICD-11 uses the GA10 "Endometriosis" section with localization details and the ability to further coordinate (e.g., specifying a specific organ/side). This taxonomy better reflects the clinical picture and facilitates analytical accounting. [6]

It is advisable to record the clinical diagnosis in the discharge summary, indicating the phenotype (peritoneal, ovarian "endometrioma," deep infiltrative) and ICD code, as well as, if necessary, the impact on functions (ureteral obstruction, intestinal stenosis). This increases the transparency of routing (surgery, ART). [7]

When combined with infertility, codes from the sections “female infertility” (ICD-10 N97 , ICD-11 GA31 ) are added, which is important for maintaining registries and insurance coverage. [8]

Epidemiology

According to the WHO, endometriosis affects approximately 10% of women and girls of reproductive age—approximately 190 million people worldwide. However, the true prevalence may be higher due to underreporting and diagnostic delays. The disease impacts education, work, mental health, and fertility, making it a public health concern. [9]

Up to 50% of women undergoing infertility evaluation have endometriosis (based on clinical series and tertiary centers), although causality and the degree of impact vary by phenotype and age. Medical systems note an average delay in diagnosis of years, highlighting the value of noninvasive diagnosis and early empirical treatment. [10]

The burden of the disease extends beyond pain: frequent concomitant gastrointestinal and urinary symptoms, fatigue, and anxiety/depression are also present. The lack of a "permanent cure" prioritizes long-term strategies with acceptable side effects—from continuous hormonal regimens to staged surgery when indicated. [11]

For 2024-2025, national guidelines (NICE NG73 - update) have been updated, emphasizing the role of high-quality ultrasound mapping/MRI, treatment escalation, and the patient's right to choose between equally evidence-based options. [12]

Reasons

There is no single cause: it is a multifactorial process involving retrograde menstruation, impaired immune clearance, ectopic metaplasia, stem/progenitor cells, and genetic predispositions. The inflammatory microcosm of the peritoneum is important: cytokines and prostaglandins support pain, angiogenesis, and lesion growth. [13]

Triggering and maintaining factors may include early menarche, shortened cycles, heavy menstruation, family history, anatomical features (e.g., obstructive defects), and surgical implantation of cells (scar after cesarean section). However, the presence of factors does not mean the inevitability of the disease. [14]

Certain phenotypes (deep infiltrating endometriosis - DIE) exhibit different biology: invasive growth into ligaments/intestinal wall, a neurogenic component of pain, and a tendency toward fibrosis. This influences the choice of method (specialized surgery versus long-term medical suppression). [15]

The hormonal dependence of the foci (estrogen-dependent growth) explains the effectiveness of regimens that reduce ovarian estrogen production (GnRH antagonists/agonists, progestins, COCs) and local activity (LNG IUD). [16]

Risk factors

Non-modifiable factors include a family history of the disease in first-degree relatives, early menarche, short cycles, and some developmental defects (obstructions) and, possibly, genetic variants associated with inflammatory pathways. These factors increase the risk "background." [17]

Modifiable/comorbid conditions: High body mass index is not a direct cause, but is associated with increased pain and decreased tolerance to therapy; chronic stress and sleep disturbances worsen pain perception. Lifestyle modification is part of the plan, although it does not replace specific treatment. [18]

Reproductive history factors (none pregnancies, shortened cycles, heavy menstrual periods) increase the total estrogen exposure. Certain surgeries (cesarean sections) are associated with a rare form of scar endometriosis. [19]

Coexisting diseases (adenomyosis, irritable bowel syndrome, migraine) can increase symptoms and require a multidisciplinary approach. [20]

Pathogenesis

The lesions contain glandular-stromal structures reminiscent of the endometrium, but actively interact with nerve endings and immune cells. The release of prostaglandins, interleukins, and growth factors creates a "vicious cycle" of pain and inflammation. This explains the effectiveness of NSAIDs and hormonal suppression. [21]

Endometriomas ("chocolate cysts") on the ovaries are the result of repeated superficial hemorrhages with hemosiderin deposition and capsular fibrosis. They can reduce ovarian reserve; during surgery, it is important to carefully remove the capsule while preserving ovarian tissue. [22]

Deep infiltrating endometriosis is characterized by penetration of >5 mm into underlying tissues (ligaments, bowel/ureteral wall). It is more often associated with neuronal remodeling and severe nociceptive/neuropathic pain, requiring experienced surgery and/or long-term drug suppression. [23]

Even after radical surgery, the disease can recur, so ESHRE emphasizes that a “life cycle” plan with possible changes in options is more realistic than the goal of “cure forever.” [24]

Symptoms

The "big four" symptoms are painful menstruation, chronic pelvic pain, pain during intercourse, and pain during defecation/urination (especially during menstruation). Intensity does not always correlate with the rASRM stage; the focus is on complaints and impact on life. [25]

Extraintestinal symptoms are common: nausea/bloating, fatigue, lower back pain, radiating to the thigh. In case of intestinal involvement - cyclic hematochezia/constipation; in case of ureteral involvement - silent obstruction with risk of hydronephrosis (screening is important). [26]

The relationship with fertility is variable: some women achieve pregnancy spontaneously, while others require ART; the older the age and the more pronounced the phenotype (endometriomas/HIE), the more likely the need for escalation. [27]

Diagnostic delays are associated with pain normalization ("it happens to everyone"), lack of awareness, and lack of resources. Educating patients and primary care physicians is key to earlier intervention. [28]

Forms and stages

There are three clinical forms: peritoneal endometriosis (superficial lesions), ovarian (endometriomas), and deep infiltrating endometriosis (DIE). These forms are often combined with each other and with adenomyosis. The choice of imaging and treatment depends on the form. [29]

The rASRM scale (stages I-IV) is used to describe prevalence; it is convenient but correlates poorly with pain. For DIE, more "topographical" classifications and structured ultrasound/MR mapping reports (reflecting involvement of the intestine, urinary tract, ligaments, and vaginal vaults) are used. [30]

NICE and ESHRE emphasise that staging does not equal symptom severity; the aim is a personalised combination of treatments to control pain/function or address fertility. [31]

A separate phenotype - extrapelvic endometriosis (scar of the anterior abdominal wall, diaphragm, pleura) - is rare and requires collaboration with specialized surgeons and radiologists. [32]

Complications and consequences

Without treatment, pain may worsen, adhesions may form, ovarian reserve may decrease (especially with endometriomas), and functional complications of the intestines/urinary tract (including ureteral obstruction) may occur. Psychosocial burden (anxiety, depression, decreased performance) is no less significant. [33]

The risk of malignant transformation is low, but somewhat increased for some histotypes of ovarian cancer (endometrioid, clear cell) against the background of endometriomas; preventive surgeries are not recommended for everyone - the decision is made individually, taking into account age, plans, and family risk. [34]

Surgical complications depend on the extent of the procedure (especially with bowel resection/ureterolysis). Therefore, DIE procedures should be performed in experienced centers with a multidisciplinary team (gynecologist, colorectal/urological surgeon, radiologist). [35]

Relapse is a characteristic of the disease; its risk is reduced by maintenance hormonal regimens after surgery (if there are no plans to become pregnant) and high-quality primary surgery with complete treatment of lesions as indicated. [36]

Diagnostics

Diagnosis is based on clinical evaluation (pain, cycle, sexual/bowel/urinary function history) and targeted imaging. The current standard is to perform expert-level transvaginal ultrasound with mapping of DIE zones (rectovaginal septum, vaults, retrocervical region, sigmoid colon, bladder) and a search for endometriomas. Bowel preparation, if necessary, improves accuracy for rectosigmoid lesions. [37]

Pelvic MRI is a problem solver and preoperative planning tool: it is indicated for equivocal/negative ultrasound in symptomatic patients, for suspected DIE, ureteral/intestinal involvement, and for structured reporting prior to multidisciplinary surgery. The 2025 ESUR consensus update recommends standardized protocols and reporting. [38]

Diagnostic laparoscopy is no longer the "mandatory gold standard" for diagnosis. It is performed when surgical treatment is planned, in cases of refractory pain, discrepancy between clinical and imaging findings, or when biopsy of questionable lesions is required. When indicated, its diagnostic value remains high. [39]

Laboratory tests (CA-125, etc.) are not diagnostic; their use is limited (e.g., dynamics in individual patients). The main role is the clinical imaging route with a clear goal setting (pain/function/fertility). [40]

Differential diagnosis

Chronic pelvic pain has many causes. Endometriosis is primarily distinguished from adenomyosis (diffuse thickening/"granularity" of the myometrium on ultrasound/MRI), irritable bowel syndrome, inflammatory bowel disease, cystitis/interstitial cystalgia, and myofascial pelvic floor pain. These conditions often coexist, and in such cases, a combination of treatments is used. [41]

Endometriomas must be differentiated from other ovarian cysts (functional, dermoid, and tumors); typical ultrasound features (fine particle size, absence of papillary growths) and MR patterns (T1 hyperintensity with T2 shading) are helpful. If in doubt, targeted surgical verification is recommended. [42]

Intestinal DIE is differentiated from diverticulitis, tumors, and inflammatory strictures; MR enterography/pelvic MRI and colorectal consultation are helpful. Ureteral involvement is differentiated from urolithiasis and other strictures (renal ultrasound/CT urography, if indicated). [43]

If the pain is severe and the visualization is “clear,” the diagnosis is reconsidered: there may be dominant myofascial/neuropathic pain, endometriosis outside the visual field (diaphragm), or other rare causes; in such cases, a decision is made whether diagnostic laparoscopy is justified. [44]

Treatment

1) Education and non-pharmacological support. Explanation of the nature of the disease, pain/cycle diary, NSAIDs as needed, sleep/stress management, physical activity, pelvic floor physiotherapy, sexual rehabilitation. These measures reduce pain and increase tolerance to the main treatment. [45]

2) Hormonal suppression (first line for pain).

• Continuous COCs (or cyclical depending on tolerance).
• Progestins (dienogest, medroxyprogesterone, norethisterone).
• LNG IUS - local suppression and relief of menorrhagia/dysmenorrhea.

The method is chosen based on contraindications and preferences; it is stopped if conception is a priority. [46]

3) GnRH agonists/antagonists with “add-back”.

• GnRH agonists are effective but require an "add-back" (estrogen + low-dose progestin) to protect bones/side effects.
• Oral GnRH antagonists (elagolix, relugolix combination, linzagolix) provide dose-dependent estradiol suppression and a manageable tolerability profile; they are used with an "add-on" for long-term pain control. In 2025, NICE recommended linzagolix for some patients in England; relugolix combination was previously approved. These options are not suitable if the goal is pregnancy "now." [47]

4) Surgery. Indications: refractory pain despite optimal drug therapy, DIE with organ dysfunction (intestine/ureter), doubt about the diagnosis/onco-vigilance, priority for immediate fertility in the case of endometriomas/adhesions. The goal is complete excision of visible lesions with restoration of anatomy, while sparing the ovarian reserve as much as possible. For endometrioma, cytoreductive cystectomy of the capsule (rather than coagulation) is preferable, performed carefully. DIE is performed in multidisciplinary centers. [48]

5) Fertility. In the absence of spontaneous pregnancy and/or associated factors, ART (IVF/ICSI) is considered. Prior to IVF, tubal sanitation is recommended for hydrosalpinx; for endometriomas >3-4 cm, the decision on surgery is individualized (balance between decreased reserves and access to follicles/infection prevention). NICE 2024 and ESHRE recommend avoiding delays in women of advanced reproductive age. [49]

6) What's new? The 2024-2025 International Consensus Guidelines on Ultrasound/MRI mapping standardize noninvasive diagnostics of DIE, and the 2024 ACR update emphasizes the benefits of bowel preparation before TV-ultrasound for suspected rectosigmoid lesions. The role of oral GnRH antagonists is expanding; studies of combined non-pharmacological programs (physiotherapy + psychoeducation) as an adjunct to treatment are active. [50]

Prevention

There is no specific primary prevention for the disease, but the overall burden can be reduced through early recognition of symptoms, empirical initiation of therapy for typical presentations, training in pain self-management, and removing barriers to specialized imaging and referral to an expert center. This reduces "lost years" and the risk of severe forms. [51]

Secondary prevention of recurrence: maintenance hormonal regimens after surgery (if conception is not the goal), control of comorbid pain (myofascial, neuralgia), warm physical activity, sleep, and stress management. An individualized monitoring plan with "alarm signals" (symptoms of ureteral and intestinal obstruction) is a mandatory part of the discharge summary. [52]

Forecast

Most patients achieve clinically significant pain control with hormonal therapy or after appropriate surgery followed by suppression. The fertility prognosis varies: in mild cases, spontaneous pregnancy is possible, while in cases with associated factors or age, early escalation to ART is more often necessary. [53]

Endometriosis is a "marathon" disease, not a "sprint" one: remissions and relapses alternate. The best long-term results come from a partnership between the patient and the team, timely adjustments to the treatment plan (medications ↔ surgery ↔ ART), and the use of imaging/reporting standards for accurate planning. [54]

Table 1. ICD codes for endometriosis

System	Code	Meaning
ICD-10	N80.0-N80.9	Endometriosis of various localizations (uterus, ovaries, tubes, peritoneum, etc.)
ICD-11	GA10.*	Endometriosis (with details by organ and side)

Table 2. Which visualization is “best” when?

Situation	Preferred method	For what
Suspected endometrioma/basic mapping	Expert TV ultrasound	Fast access, high accuracy for ovaries and many DIE areas
Suspected intestinal/ureteral DIE, surgical plan	MRI of the pelvis (HIE protocol)	Topographic map for the surgical team
Negative/questionable ultrasound with persistent symptoms	MRI as a "problem solver"	Exclude "hidden" lesions, adenomyosis
Preoperative standardization	Structured Report (US/MRI)	A common language with surgeons

Table 3. Drug therapy for pain: "ladder"

Step	Options	Comments
1	NSAIDs, continuous COCs	First line in case of typical picture, especially before further examination
2	Progestins/LNG IUD	An alternative to COCs, good for menorrhagia
3	GnRH agonists/antagonists + "add-back"	For refractory pain; manage side effects
4	Combined pain programs	Physiotherapy, psychoeducation, CBT/ACT as an adjunct

Table 4. Surgery: selection guidelines

Scenario	What to do	Why
Refractory pain, confirmed foci	Laparoscopic excision	The best chance for relief is with proper selection.
Endometrioma >3-4 cm (individually)	Ovarian-sparing capsule cystectomy	Less relapse than with coagulation; monitor AMH
DIE of the intestine/ureter	Multidisciplinary surgery	Safety and completeness of correction
No effect, priority is pregnancy	Early escalation to ART	Avoid wasting time/reserves

Table 5. Red flags requiring expedited route

Sign	Possible problem	Actions
Pain + dysuria/hematuria in cycle	Bladder/ureteral lesion	Kidney ultrasound, MRI, urologist, don't delay
Cyclic hematochezia/stool obstruction	intestinal HIE	MRI/Colo-consultation
A drop in AMH, large endometriomas in women 35+	Risk of loss of reserve	Reproductive specialist, discussion of ART/cryotherapy
Persistent pain with "pure" visualization	Alternative causes	Revision of diagnosis, pain management

Table 6. Fertility in endometriosis: quick reference points

Situation	Tactics
<35 years, mild forms, tubes are passable	6-12 months of attempts; if unsuccessful, AI/IVF depending on age
35-38 years or combined factors	Faster to ART (≤6 months waiting)
Endometrioma, low reserve	Individual: ART vs. sparing surgery; oocyte cryopreservation is discussed
After surgery and no plans to get pregnant	Maintenance hormone therapy to prevent relapse

FAQ

• Is it possible to make a diagnosis without laparoscopy?

Yes. With typical symptoms and characteristic findings on expert ultrasound/MRI, a diagnosis can be made without diagnostic laparoscopy and treatment can be initiated. Surgery is indicated in complex cases, when therapy is ineffective, fertility is a priority, or when the diagnosis is in doubt. [55]

• Which pills work best?

First-line treatments include continuous COCs or progestins/LNG-IUDs. For refractory pain, agonists or modern oral GnRH antagonists with add-back therapy are used; the choice depends on the goals and tolerability. These medications are not suitable if you are actively planning a pregnancy. [56]

• Should all endometriomas be removed before IVF?

Not always. The decision is individualized, taking into account cyst size, age, fertility reserve (AMH/AFH), infection risks, and access to follicles. Any intervention on the ovary can reduce the fertility reserve, so many patients prefer to proceed directly to ART. [57]

• Will surgery provide a “permanent cure”?

Surgery can significantly reduce pain and improve quality of life, but endometriosis is a chronic disease with a risk of recurrence. The best results come from a combination of high-quality surgery and subsequent hormonal suppression (if conception is not the goal). [58]

• Are there any new drugs?

Yes. The use of oral GnRH antagonists (elagolix, relugolix combination, linzagolix) is increasing. In 2025, NICE recommended linzagolix for some patients; relugolix combination was previously approved. Discuss whether this is appropriate for your situation. [59]