Reproductive · PANCE / PANRE

Endometriosis

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 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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Question 1ReproductiveMedium
A 30-year-old woman has 2 years of worsening dysmenorrhea and deep dyspareunia. Transvaginal ultrasound shows bilateral ovarian cysts with homogeneous low-level internal echoes (chocolate cysts), and diagnostic laparoscopy confirms endometriosis. Which of the following is the most appropriate first-line medical therapy?
  • ALeuprolide GnRH agonist therapy
  • BCombined oral contraceptives
  • CDanazol androgenic steroid therapy
  • DNaproxen NSAID monotherapy
Reveal answer & full explanation
Correct answer: B — Combined oral contraceptives
  • ALeuprolide GnRH agonist therapy
  • BCombined oral contraceptives✓
  • CDanazol androgenic steroid therapy
  • DNaproxen NSAID monotherapy

Why Combined oral contraceptives is correct

  • Combined oral contraceptive pills (OCPs) and progestins are first-line medical therapy for endometriosis-associated pain and suppress cyclic endometrial stimulation
  • They are well tolerated for long-term use, are inexpensive, and provide contraception in a patient who is not currently seeking pregnancy
  • Per current ACOG and ESHRE guidance, combined hormonal contraceptives or progestins are the recommended initial hormonal therapy after confirmed or presumed endometriosis
  • Definitive surgery (hysterectomy with bilateral salpingo-oophorectomy) is reserved for severe disease after childbearing is complete, not initial therapy

Why the others are wrong

  • Leuprolide GnRH agonist therapy — a GnRH agonist reserved for pain refractory to first-line hormonal therapy and requiring add-back therapy to limit hypoestrogenic side effects and bone loss; right class, wrong step.
  • Danazol androgenic steroid therapy — an androgenic agent that is effective but now rarely used because of hirsutism, weight gain, and other androgenic effects; an outdated buzzword answer, not current first-line.
  • Naproxen NSAID monotherapy — an NSAID that relieves dysmenorrhea pain but does not suppress the underlying disease, so it is an adjunct rather than definitive medical therapy; anchoring on the pain symptom.
Question 2ReproductiveMedium
A 29-year-old woman presents with a 3-year history of progressively worsening dysmenorrhea, deep dyspareunia, and chronic pelvic pain. She has been unable to conceive after 18 months of unprotected intercourse. Pelvic exam reveals tender uterosacral nodularity and a fixed, retroverted uterus. Transvaginal ultrasound shows a 4-cm right ovarian cyst with homogeneous low-level internal echoes. Empiric NSAIDs and combined oral contraceptives have provided only partial relief. Which of the following is the most appropriate test to establish a definitive diagnosis?
  • ALaparoscopy with biopsy
  • BSerum CA-125 assay
  • CEndometrial biopsy
  • DPelvic MRI with contrast
Reveal answer & full explanation
Correct answer: A — Laparoscopy with biopsy
  • ALaparoscopy with biopsy✓
  • BSerum CA-125 assay
  • CEndometrial biopsy
  • DPelvic MRI with contrast

Why laparoscopy with biopsy is correct

  • Definitive diagnosis of endometriosis requires direct visualization of endometriotic implants at laparoscopy with histologic confirmation by biopsy.
  • Laparoscopy also allows simultaneous staging and surgical treatment: excision or ablation of lesions and lysis of adhesions.
  • This patient has classic clinical and imaging features of endometriosis: cyclic pelvic pain, deep dyspareunia, infertility, uterosacral nodularity, and an ovarian endometrioma on ultrasound.

Why the others are wrong

  • Serum CA-125 assay — may be elevated in endometriosis but is nonspecific (also elevated in PID, ovarian cancer, fibroids, pregnancy) and lacks sensitivity for mild disease; not diagnostic.
  • Endometrial biopsy — samples the eutopic lining of the uterine cavity, which is normal in endometriosis; the implants sit on peritoneum, ovaries, and uterosacral ligaments, so this samples the wrong compartment.
  • Pelvic MRI with contrast — helpful for mapping deep infiltrating endometriosis preoperatively but does not provide tissue diagnosis.

Additional high-yield points

  • Clinical and imaging findings often suggest endometriosis and may justify empiric medical therapy, but the formal diagnosis still rests on laparoscopic visualization with biopsy.
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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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Commonly confused with

vs Uterine Fibroids

Related Reproductive diagnoses

Polycystic Ovary Syndrome (PCOS)Uterine Fibroids (Leiomyoma)Abnormal Uterine BleedingPrimary AmenorrheaSecondary AmenorrheaMenopausePelvic Inflammatory Disease (PID)Bacterial VaginosisCandidal VulvovaginitisTrichomoniasisCervical Cancer and HPVEndometrial CancerOvarian CancerBreast Cancer

Differentials & related conditions

Irritable Bowel Syndrome (IBS)Ectopic Pregnancy

Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.