What is the recommended diagnostic work‑up and step‑wise treatment for endometriosis in a reproductive‑age woman presenting with dysmenorrhea, chronic pelvic pain, dyspareunia, or unexplained infertility?

Endometriosis: Diagnostic Work-up and Step-wise Treatment

Diagnostic Approach

Endometriosis is a clinical diagnosis that does not require surgical confirmation before initiating treatment—begin with symptom assessment and transvaginal ultrasound as first-line imaging. 1, 2

Clinical Presentation to Identify

• Pain patterns: Dysmenorrhea (often starting before menstrual onset), deep dyspareunia (worse during menses), dyschezia, dysuria, or chronic pelvic pain 1, 2
• Infertility: Present in approximately 50% of patients with endometriosis 1, 2
• Physical examination findings: Nodularity, fixed retroverted uterus, or tender uterosacral ligaments—though normal examination does not exclude diagnosis 1, 2

Imaging Algorithm

Step 1: Standard transvaginal ultrasound (TVUS) as initial imaging modality 1, 2

Step 2: If TVUS is inconclusive or deep disease is suspected:

• Expanded protocol TVUS (requires specialized training, includes uterosacral ligament evaluation, rectosigmoid assessment, dynamic sliding maneuvers, and bowel preparation) 2
• OR MRI pelvis without IV contrast (90.3% sensitivity and 91% specificity for deep pelvic endometriosis) 1, 2

Step 3: MRI with IV contrast is highly recommended when differentiating endometriomas from ovarian malignancies 1, 2

Critical Diagnostic Pitfalls to Avoid

• Do not use CT pelvis—it has no role in standard endometriosis diagnosis 1, 2
• Do not rely on CA-125—it has no clinical utility for diagnosis and should not be used 1
• Do not assume negative imaging excludes endometriosis—superficial peritoneal disease is poorly detected by all imaging modalities 2
• Do not delay treatment waiting for laparoscopy—surgical confirmation is no longer required before initiating empiric treatment 1, 2

Step-wise Treatment Algorithm

For Women NOT Currently Seeking Pregnancy

First-Line: Hormonal Therapy 1, 3, 4

Start with progestins OR combined oral contraceptives as first-line treatment due to favorable safety profile, tolerability, and cost-effectiveness 1, 3

• Progestins reduce the size of endometriotic lesions 3
• Hormonal treatments (combined oral contraceptives, progestins, GnRH agonists) lead to clinically significant pain reduction with mean differences of 13.15-17.6 points on 0-100 visual analog scale compared to placebo 4
• Continue hormonal therapy as long as symptoms persist and fertility is not immediately desired 1, 3
• Monitor clinically every 6 months to assess treatment response and side effects 1

Important caveat: 11-19% of patients have no pain reduction with hormonal medications, and 25-34% experience recurrent pelvic pain within 12 months of discontinuing treatment 4

Second-Line: GnRH Agonists or Antagonists 1, 3

• Consider if first-line therapies are ineffective, poorly tolerated, or contraindicated 1, 3
• Use GnRH agonists for at least 3 months with add-back therapy to reduce bone mineral loss without reducing pain relief efficacy 1, 3
• Danazol for at least 6 months is equally effective to GnRH agonists for pain relief 1, 3

Third-Line: Surgical Intervention 1, 4

• Consider when hormonal therapies are ineffective or contraindicated 1, 4
• Surgery is associated with significant pain reduction during the first 6 months following the procedure 1, 3
• Critical limitation: Up to 44% of women experience symptom recurrence within one year after surgery 1, 3
• For rectosigmoid bowel lesions, surgical options include shaving, discoid resection, or segmental resection based on preoperative imaging 1
• Complete r-ASRM classification, Enzian classification, and Endometriosis Fertility Index (EFI) for women undergoing surgery 1

Hysterectomy Considerations:

• May be considered when initial treatments are ineffective 4
• Approximately 25% of patients who undergo hysterectomy experience recurrent pelvic pain and 10% undergo additional surgery 4

For Women Seeking Pregnancy

Medical suppression does not benefit fertility and should not be used for this indication alone 5

• Surgery is probably efficacious for all stages of disease when fertility is the goal 5
• Controlled ovarian hyperstimulation with intrauterine insemination is recommended in early-stage and surgically corrected endometriosis when pelvic anatomy is normal 5
• In vitro fertilization is treatment of choice in advanced cases, with success potentially augmented by prolonged GnRH analog treatment 5

Long-term Monitoring and Associated Risks

• Women with endometriosis have increased cardiovascular risk, including stroke (HR 1.34,95% CI 1.10-1.62) 1
• Endometriosis is associated with recurrent pregnancy loss, which may warrant pre-conception treatment 1
• Patients with ovarian endometriosis are at higher risk for developing ovarian carcinomas, including endometrioid and clear cell carcinomas 6