What Is Endometriosis? Causes, Symptoms, and Treatments

What exactly is endometriosis?

Endometriosis is defined by the presence of endometrial-like glands and stroma outside the uterine cavity. Lesions most often appear on the ovaries, fallopian tubes, peritoneum, and rectovaginal septum. They respond to cyclical hormonal signals, bleed locally, and provoke an inflammatory response that can produce adhesions, scarring, and nerve involvement. The World Health Organization classifies endometriosis as a major cause of pelvic pain and infertility that affects women and girls of reproductive age globally, though exact prevalence figures should be checked against the current WHO fact sheet since global estimates are periodically revised. WHO fact sheet

Endometriosis is not the same disease as adenomyosis (endometrial tissue within the uterine muscle wall) or fibroids (benign smooth-muscle tumors of the uterus), though symptoms can overlap and a patient can have more than one condition at once.

Ectopic lesions share molecular features with the eutopic endometrium but are not identical to it. A growing body of laboratory and translational work has focused on the local biology of superficial peritoneal lesions specifically, including their capacity to generate estrogen and inflammatory signaling in situ rather than depending solely on ovarian estrogen. A recent narrative review of superficial peritoneal endometriosis summarizes this shift toward functional and molecular characterization of lesions beyond what surgical inspection alone can show (Superficial Peritoneal Endometriosis Beyond Surgical Diagnosis, 2026). This is an evolving research area rather than an established diagnostic standard, and it does not change how the disease is diagnosed or staged today.

Disease is generally grouped by location and depth: superficial peritoneal disease (the most common form), ovarian endometriomas (cystic lesions filled with old blood, sometimes called "chocolate cysts"), and deep infiltrating endometriosis (DIE), which extends more than a few millimeters below the peritoneal surface and can involve the bowel, bladder, or ureters. DIE is generally associated with the most severe symptoms and the most complex surgery.

What causes endometriosis?

No single mechanism fully explains why endometriosis develops. The leading and most widely taught explanation is retrograde menstruation: menstrual tissue flows backward through the fallopian tubes and implants on pelvic surfaces. Because retrograde flow occurs in most menstruating women but only a minority develop endometriosis, researchers believe defective immune clearance of this tissue, genetic susceptibility, and hormonal factors also have to be involved. Reported differences in natural killer cell and macrophage activity in the peritoneal fluid of affected women are commonly cited in this context, though exact figures vary across studies and should be checked against the primary literature rather than treated as fixed.

Genome-wide association studies have identified multiple genetic risk loci linked to endometriosis, with signals near genes involved in cell adhesion and estrogen metabolism, and family history is a recognized risk factor. Epigenetic silencing of progesterone receptor signaling is a frequently replicated laboratory finding that may help explain the progesterone resistance seen in lesion tissue. Estrogen itself is central to the disease: lesions can express aromatase and generate estrogen locally, which can sustain lesion activity even when systemic estrogen is suppressed, and this local estrogen production is one reason treatment that lowers circulating estrogen does not always fully control disease activity.

Additional theories, including stem-cell origin and coelomic metaplasia, have been proposed to explain rarer presentations, such as endometriosis reported in men on long-term estrogen therapy or in adolescents before menarche. These remain research explanations rather than established mechanisms.

What are the symptoms?

Symptoms vary widely, and some people with confirmed endometriosis have no symptoms at all. When present, symptoms generally fall into three groups.

Pelvic pain. Painful periods (dysmenorrhea) are the most frequently reported symptom and often begin before bleeding starts and outlast it. Deep pain during intercourse (dyspareunia) is common, particularly with disease involving the uterosacral ligaments. Chronic pelvic pain lasting more than six months, independent of the menstrual cycle, is also frequently reported. Pain on defecation or urination suggests possible bowel or bladder involvement, and cyclic rectal bleeding or blood in the urine is uncommon but is a more specific sign of bowel or bladder DIE and warrants prompt evaluation.

Fertility-related concerns. Endometriosis is commonly identified during infertility evaluations. Proposed mechanisms include pelvic adhesions distorting normal anatomy, oxidative stress affecting oocyte quality, altered endometrial receptivity, and, in more severe disease, tubal obstruction.

Non-gynecologic symptoms. Fatigue, bloating, nausea, and mood changes are commonly reported but often go unrecognized as endometriosis-related. Bowel symptoms that track with the menstrual cycle are frequently mistaken for irritable bowel syndrome, which is one contributor to diagnostic delay. Exact rates of these symptoms vary widely between studies and populations, so specific percentages should be treated as approximate rather than fixed.

How is endometriosis diagnosed?

Diagnosis combines clinical suspicion, imaging, and, when treatment decisions require certainty, surgical confirmation.

History and exam. A detailed menstrual and pain history is the starting point. Tenderness on pelvic exam or a fixed, retroverted uterus can support suspicion, but a normal exam does not rule out the disease.

Imaging. Transvaginal ultrasound performed by an experienced sonographer can detect ovarian endometriomas with good accuracy, though it is much less reliable for superficial peritoneal disease. MRI with bowel preparation can add useful detail for suspected deep infiltrating disease, particularly involving the bowel or bladder. Reported sensitivity and specificity figures for both modalities vary by study population and operator experience; specific percentages in older literature should be confirmed against current radiology guidance rather than quoted as universal.

Blood tests. CA-125 is often elevated in endometriosis but lacks the sensitivity and specificity needed for screening or diagnosis on its own, especially in earlier-stage disease. It is not recommended as a standalone diagnostic tool. Research into blood- and tissue-based molecular markers, including circulating DNA and epigenetic signatures, is ongoing but has not reached routine clinical use. Early proof-of-concept work on enzymatic approaches to circulating DNA in endometriosis illustrates the kind of investigational research underway, distinct from any approved diagnostic or treatment (DNase I therapy proof-of-concept study, 2026).

Surgical diagnosis. Laparoscopy with biopsy and histological confirmation remains the definitive diagnostic standard. Current European Society of Human Reproduction and Embryology (ESHRE) guidance emphasizes confirming the diagnosis histologically before committing a patient to long-term medical treatment planned around a presumed diagnosis; readers should consult the current published ESHRE guideline directly for the exact wording and any updates, since guideline language is periodically revised.

One important, if uncommon, diagnostic pitfall: endometriosis can occasionally present atypically, including with unusual complications such as recurrent hemorrhagic ascites, which can be mistaken for other intra-abdominal conditions. A recent case report describes this presentation and underscores why unexplained recurrent ascites in a woman of reproductive age should prompt consideration of endometriosis alongside more common causes (case report, 2026). This is a rare presentation, not a typical one, and should not be generalized to most patients.

The core, quotable summary: endometriosis is a chronic, estrogen-responsive condition in which endometrial-like tissue grows outside the uterus and drives pelvic pain and, in a substantial subset of patients, infertility; imaging can raise or support suspicion, but laparoscopy with histology remains the diagnostic reference standard, and no blood test currently replaces it.

How is endometriosis staged, and does stage predict symptoms?

The ASRM revised classification assigns a score based on lesion type, size, location, and adhesions, placing disease into four stages:

Stage correlates only loosely with pain severity: a patient with minimal (Stage I) disease can have severe pain, and a patient with severe (Stage IV) disease can have little pain. Stage correlates somewhat better with fertility outcomes. The ENZIAN classification is used alongside ASRM staging specifically to map deep infiltrating lesions in more surgical detail.

Should you try medication or surgery first?

This is the decision most patients actually face, and the honest answer is that it depends on the goal.

If pain control without imminent pregnancy plans is the goal, medical therapy is generally tried first because it is less invasive and can be started without surgery.

• Combined hormonal contraceptives (pills, patch, or ring) are typically first-line. They suppress ovulation and create a hormonal environment that tends to reduce menstrual pain; continuous dosing without a placebo interval is often better tolerated for symptom control than cyclic dosing.
• Progestin-only options, including the levonorgestrel intrauterine system, oral progestins, and injectable depot medroxyprogesterone, can also reduce pain. Dienogest, a progestin used in some markets specifically for endometriosis, has a reasonably strong trial base in the specific literature, including comparisons against GnRH agonist therapy; exact response rates from any single trial should be verified against the primary publication rather than repeated as fixed statistics.
• GnRH agonists (leuprolide, nafarelin, goserelin) suppress estrogen to very low, postmenopausal-range levels and can produce strong pain responses, but they carry hypoestrogenic side effects, including bone density loss, which is why use without "add-back" hormone therapy is generally limited to a defined treatment window rather than indefinite use. Add-back therapy (typically a progestin, sometimes with low-dose estrogen) is used to protect bone while preserving pain control.
• GnRH antagonists taken orally, including elagolix and combination products pairing an antagonist with low-dose estradiol and a progestin, offer a faster onset and offset of hormonal suppression than injectable agonists. Elagolix received FDA approval for endometriosis-associated pain in 2018, and a once-daily combination product received FDA approval in 2022; current prescribing information and any label updates should be confirmed on the FDA's website before individualizing treatment.
• Aromatase inhibitors, usually paired with a progestin or contraceptive, are generally reserved for pain that has not responded to the options above, given their own estrogen-suppression side effects and the need for bone health monitoring.

All hormonal therapies for endometriosis are suppressive rather than curative, and none are appropriate while a patient is actively trying to conceive, since most work by preventing ovulation or otherwise altering the hormonal environment needed for pregnancy.

If fertility is the near-term priority, or pain is refractory to medical therapy, or imaging shows an endometrioma or suspected deep infiltrating disease, surgical evaluation becomes more central to the decision.

• Laparoscopic excision (cutting lesions out with margins) is generally preferred over ablation (burning the surface) when feasible, because excision allows histological confirmation and can remove deeper disease that ablation may miss.
• For ovarian endometriomas, cystectomy (removing the cyst wall) is generally preferred over drainage alone because recurrence is more common after drainage. Cystectomy itself is not risk-free: it can reduce ovarian reserve by removing some functional ovarian tissue alongside the cyst wall, which matters for patients concerned about future fertility and should be discussed explicitly before surgery.
• Deep infiltrating disease involving bowel, bladder, or ureter requires more complex surgery, ideally performed at a center experienced with this specific surgery, because complication rates, including bowel-related complications, are meaningfully higher than for superficial disease.
• Hysterectomy with removal of both ovaries offers the lowest reported recurrence risk and is an option for patients who have completed childbearing and have severe, treatment-resistant disease. It is not a guarantee against recurrence, since residual pelvic or distant lesions can remain active.

Endometriosis and fertility: what actually changes the plan

For patients with mild to moderate disease, surgical treatment of lesions has been associated with improved spontaneous pregnancy rates compared with diagnostic laparoscopy alone in trial evidence from decades ago; the general direction of benefit for earlier-stage disease is well established in the literature, though exact percentage improvements from any single older trial should be checked against the original publication before being quoted to a patient. Evidence for surgical benefit in more advanced (Stage III to IV) disease is less consistent, and IVF is often considered preferentially in that setting, particularly when ovarian reserve is already reduced or prior surgery has not led to pregnancy.

A fertility-sequencing decision framework

This framework is a starting point for the conversation with a reproductive endocrinologist or gynecologic surgeon, not a substitute for individualized evaluation. It should be applied only after imaging and, where relevant, surgical staging have clarified disease severity.

The unifying decision rule: the closer a patient is to age- or reserve-related fertility urgency, or the more advanced the disease, the less time should be spent on staged conservative approaches before involving a fertility specialist directly.

Long-term health associations

Endometriosis has been associated in observational research with a higher risk of cardiovascular disease events, a two- to threefold higher relative risk of certain ovarian cancer subtypes (clear-cell and endometrioid), and higher rates of depression and anxiety compared with women without the condition. These are population-level associations from cohort and registry studies, not proof that endometriosis directly causes each outcome in every individual, and absolute risks for something like ovarian cancer remain low even with the relative increase. Current ASRM and ESHRE guidance does not recommend routine cancer surveillance beyond standard gynecologic care based on an endometriosis diagnosis alone, though new or suspicious imaging findings always warrant prompt evaluation. Given the documented mental health association, integrated pain management that includes psychological support is a reasonable and evidence-consistent adjunct, not an alternative to medical or surgical treatment.

What happens after treatment, and when should you seek care again?

Endometriosis is a chronic disease, and symptom recurrence after surgery is common, particularly without adjuvant hormonal suppression. Post-operative use of hormonal therapy, such as the levonorgestrel IUS or continuous contraceptive dosing, is associated with a lower recurrence risk, and current ESHRE guidance generally supports a period of post-operative hormonal treatment to reduce recurrence, though the exact recommended duration should be checked against the current published guideline rather than assumed.

Reasonable ongoing monitoring includes periodic pelvic examination, ultrasound follow-up for patients with a history of endometriomas, and ovarian reserve testing if fertility is a concern. Pain that returns or fails to respond to second-line medical therapy warrants repeat imaging and specialist reassessment rather than repeated trials of the same medication. Sudden, severe abdominal pain, heavy bleeding, fever, or signs of bowel obstruction are not typical chronic endometriosis symptoms and warrant urgent, same-day medical evaluation rather than a routine follow-up appointment.

What is established, what is plausible, and what is not established

Established: Endometriosis is a chronic, estrogen-responsive condition confirmed by histology at laparoscopy; it is a recognized cause of pelvic pain and is commonly found during infertility evaluation; hormonal suppression and surgical excision each reduce pain for many patients; surgical treatment of mild to moderate disease has trial evidence supporting improved spontaneous pregnancy rates; post-operative hormonal suppression reduces (but does not eliminate) recurrence.

Plausible but not fully settled: The precise magnitude of surgical benefit for advanced-stage infertility; the clinical utility of emerging molecular and circulating-DNA markers for diagnosis or monitoring; optimal duration of post-operative hormonal suppression; whether dietary interventions meaningfully change disease progression rather than symptom perception.

Not established: Any blood test as a standalone replacement for surgical diagnosis; a cure for the underlying disease process; routine cancer screening specifically because of an endometriosis diagnosis; individualized dosing or treatment selection without a clinician who has reviewed a patient's imaging, symptoms, and fertility goals directly.