What is on the differential diagnosis for Endometriosis?

Key differentials include Pelvic inflammatory disease, Adenomyosis, Uterine fibroids, Interstitial cystitis / bladder pain syndrome, Irritable bowel syndrome, Ovarian cyst (functional, hemorrhagic), Ectopic pregnancy, Primary dysmenorrhea.

What are the high-yield PANCE pearls for Endometriosis?

Combined hormonal contraception used continuously (skipping placebo week) is more effective than cyclic dosing for endometriosis pain. Add-back therapy is required after 6 months of GnRH agonist therapy to prevent bone mineral density loss. CA-125 is NOT a screening or diagnostic test for endometriosis — it has poor sensitivity and specificity. Adolescents with severe dysmenorrhea unresponsive to NSAIDs + COCPs should be evaluated for endometriosis. Decidualization of endometriomas in pregnancy can mimic ovarian malignancy on imaging — interpret with caution.

Reproductive · PANCE / PANRE

Endometriosis

Written & clinically reviewed by Ryan Busch, PA-C · Updated July 2026 · Report an error

Ectopic endometrial-like tissue causing cyclic pelvic pain, dysmenorrhea, dyspareunia, and infertility.

Also known as: endometriosis, endometrioma, chocolate cyst, adenomyosis (related)

Overview

Estrogen-dependent inflammatory disorder defined by the presence of endometrial-like glands and stroma outside the uterine cavity — most often on the ovaries, pelvic peritoneum, and uterosacral ligaments.

Epidemiology

Affects 6-10% of reproductive-age women and up to 50% of those with infertility or chronic pelvic pain. Mean diagnostic delay 7-10 years from symptom onset.

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Risk factors

Early menarche, short cycles (<27 days), heavy/prolonged menses
Nulliparity, low BMI
First-degree relative with endometriosis (6-7x risk)
Müllerian anomalies producing outflow obstruction

Pathophysiology

Leading theory: retrograde menstruation deposits viable endometrial cells in the peritoneal cavity, where they implant and respond cyclically to ovarian estrogen. Local inflammation, neoangiogenesis, fibrosis, and aberrant nerve growth produce pain. Coelomic metaplasia and lymphatic/hematogenous spread explain extra-pelvic disease.

Clinical presentation

Symptoms

Cyclic pelvic pain that worsens with menses (secondary dysmenorrhea)
Deep dyspareunia
Dyschezia, cyclic rectal bleeding, or dysuria (depending on implant location)
Infertility (often the presenting complaint)
Chronic noncyclic pelvic pain in advanced disease

Signs / physical exam

Tender nodularity of uterosacral ligaments or cul-de-sac (best felt during menses)
Fixed, retroverted uterus from adhesions
Adnexal mass (endometrioma)
Often no findings on exam, especially with superficial disease

Classic findings

Reproductive-age woman with progressive secondary dysmenorrhea, deep dyspareunia, and infertility; ovarian 'chocolate cyst' on ultrasound.

Differential diagnosis

Pelvic inflammatory disease — Fever, cervical motion tenderness, mucopurulent discharge; positive GC/CT testing
Adenomyosis — Diffusely enlarged, boggy, tender uterus; heavy menses; MRI shows thickened junctional zone
Uterine fibroids — Bulk symptoms, heavy menses; enlarged irregular uterus; ultrasound diagnostic
Interstitial cystitis / bladder pain syndrome — Suprapubic pain with bladder filling, urinary urgency/frequency, negative urine culture
Irritable bowel syndrome — Pain with altered bowel habits, relief with defecation; Rome criteria
Ovarian cyst (functional, hemorrhagic) — Acute pain, unilateral; ultrasound shows simple or hemorrhagic cyst
Ectopic pregnancy — Positive hCG, unilateral pain, vaginal bleeding
Primary dysmenorrhea — Crampy pain with menses without identifiable pathology; responds to NSAIDs/COCPs

Diagnostic workup

Diagnostic criteria

Historically definitive diagnosis required laparoscopic visualization with histologic confirmation; current ACOG/ESHRE guidance supports clinical diagnosis and empiric treatment when imaging and history are consistent, reserving surgery for refractory cases or when histology will change management.

Labs

Pregnancy test, urinalysis, GC/CT (exclude PID/ectopic)
CA-125 may be elevated but is nonspecific — not used for diagnosis

Imaging

Transvaginal ultrasound — first-line; identifies endometriomas (homogeneous low-level echoes, 'ground glass' appearance) and deep infiltrating disease
MRI — for surgical planning, deep infiltrating endometriosis, or extra-pelvic disease
Empiric medical therapy may be initiated without surgical confirmation if clinical picture is consistent

Diagnostic algorithm

flowchart TD
  A[Cyclic pelvic pain<br/>± dysmenorrhea, dyspareunia, infertility] --> B[Pelvic exam + TVUS<br/>Rule out PID, pregnancy]
  B --> C{Endometrioma<br/>or deep disease?}
  C -->|Yes| D[Consider MRI<br/>Surgical referral]
  C -->|No| E[Empiric trial:<br/>NSAIDs + COCP]
  E --> F{Symptoms<br/>controlled?}
  F -->|Yes| G[Continue therapy<br/>± switch to continuous COCP]
  F -->|No| H[Progestin or<br/>levonorgestrel IUD]
  H --> I{Refractory?}
  I -->|Yes| J[GnRH agonist/antagonist<br/>+ add-back]
  I -->|Still refractory| K[Laparoscopic excision]
  K --> L[Definitive surgery<br/>if childbearing complete]

Stepwise approach to suspected endometriosis — empiric medical therapy precedes surgery in most cases.

Treatment

First-line

NSAIDs — ibuprofen, naproxen — for pain
Combined hormonal contraception (COCP, patch, ring) — continuous or cyclic; first-line hormonal therapy
Progestins — norethindrone acetate, medroxyprogesterone, dienogest, levonorgestrel IUD

Surgical

Laparoscopic excision or ablation of implants — for pain refractory to medical therapy or infertility
Cystectomy for endometriomas >3-4 cm (excision preferred over drainage to reduce recurrence)
Definitive: hysterectomy with bilateral salpingo-oophorectomy — reserved for severe refractory disease in women with completed childbearing

Infertility

Surgical excision of endometriomas/adhesions can improve fertility in stage I-II
IVF for advanced disease or persistent infertility — hormonal suppression NOT used (suppresses ovulation)

Second-line / adjunct

GnRH agonists — leuprolide, goserelin, nafarelin — induce hypoestrogenic state; require add-back therapy (low-dose estrogen + progestin or norethindrone 5 mg) after 6 months to prevent bone loss
GnRH antagonists — elagolix (oral, partial estrogen suppression, dose-dependent), relugolix combination (relugolix/estradiol/norethindrone)
Aromatase inhibitors — letrozole, anastrozole — refractory cases, often combined with progestin or COCP

Complications

Infertility (impaired oocyte quality, tubal scarring, distorted anatomy)
Chronic pelvic pain with central sensitization
Ovarian endometrioma rupture, torsion
Bowel/bladder obstruction from deep infiltrating disease
Slightly increased risk of clear cell and endometrioid ovarian cancers

PANCE pearls

Combined hormonal contraception used continuously (skipping placebo week) is more effective than cyclic dosing for endometriosis pain.
Add-back therapy is required after 6 months of GnRH agonist therapy to prevent bone mineral density loss.
CA-125 is NOT a screening or diagnostic test for endometriosis — it has poor sensitivity and specificity.
Adolescents with severe dysmenorrhea unresponsive to NSAIDs + COCPs should be evaluated for endometriosis.
Decidualization of endometriomas in pregnancy can mimic ovarian malignancy on imaging — interpret with caution.

References

ACOG PB 114 — ACOG Practice Bulletin No. 114: Management of Endometriosis (reaffirmed)
ESHRE 2022 — ESHRE Guideline: Endometriosis (Becker et al., Hum Reprod Open 2022)
ASRM 2014 — Treatment of Pelvic Pain Associated with Endometriosis: ASRM Committee Opinion

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