What medication can I give a reproductive‑age woman with pelvic pain possibly due to endometriosis to treat the pain and help determine if it is endometriosis?

Empiric Treatment for Suspected Endometriosis Pain

Start with NSAIDs as first-line therapy, followed by continuous oral contraceptives or progestins as second-line treatment—this approach provides both pain relief and serves as a diagnostic trial, since response to hormonal suppression supports the diagnosis of endometriosis even without surgical confirmation. 1

First-Line: NSAIDs for Immediate Pain Control

• Begin with NSAIDs at appropriate therapeutic doses (naproxen 550 mg twice daily or ibuprofen 600-800 mg three times daily) as the initial approach for immediate pain relief 1, 2
• NSAIDs are widely used and recommended by the American Academy of Family Physicians, though evidence for their specific efficacy in endometriosis pain is limited 1, 3
• If using ketorolac for severe pain, limit to maximum 5 days due to gastrointestinal and renal risks 1

Second-Line: Hormonal Suppression as Both Treatment and Diagnostic Trial

Oral Contraceptives (Preferred Initial Hormonal Option)

• Prescribe combined oral contraceptives used continuously (without placebo weeks) as the most cost-effective hormonal option 1, 3
• Oral contraceptives provide effective pain relief compared to placebo and may be equivalent to more costly regimens 1
• In network meta-analysis, hormonal treatments including oral contraceptives led to clinically significant pain reduction with mean differences of 13.15-17.6 points on a 0-100 visual analog scale 2

Progestins (Equally Effective Alternative)

• Consider oral progestins or depot medroxyprogesterone acetate as effective alternatives with similar efficacy to oral contraceptives 1
• For suspected rectovaginal or deep infiltrating endometriosis, norethisterone acetate at low dosage should be preferred 3

Interpreting the Therapeutic Trial

Response Supports Endometriosis Diagnosis

• Improvement with hormonal suppression strongly suggests endometriosis, even without laparoscopic confirmation 1
• The depth of endometriosis lesions correlates with severity of pain, though pain has little relationship to the type of lesions seen by laparoscopy 4
• Pain from endometriosis typically presents as secondary dysmenorrhea (commencing before menses), deep dyspareunia (exaggerated during menses), or sacral backache with menses 4

Non-Response Requires Escalation

• 11-19% of individuals with endometriosis have no pain reduction with hormonal medications, so lack of response does not definitively rule out endometriosis 2
• If first-line hormonal therapies fail after an adequate trial (typically 3 months), consider escalation to GnRH agonists 1, 2

Third-Line: GnRH Agonists for Refractory Cases

• GnRH agonists for at least 3 months provide the most robust pain relief and are appropriate for chronic pelvic pain even without surgical confirmation 1
• Leuprolide 3.75 mg intramuscularly monthly or 11.25 mg every 3 months are standard dosing regimens 1
• Always prescribe add-back therapy simultaneously (norethindrone acetate 5 mg daily with or without low-dose estrogen) to prevent bone mineral loss without reducing pain relief efficacy 4, 1
• GnRH agonists and danazol for at least 6 months appear equally effective for pain relief 4

Critical Pitfalls to Avoid

• No medical therapy eradicates endometriosis lesions—all treatments provide only symptomatic relief through hormonal suppression 4, 1, 2
• 25-34% experience recurrent pelvic pain within 12 months of discontinuing hormonal treatment, so long-term maintenance therapy is often necessary 2
• Normal physical examination and imaging do not exclude endometriosis diagnosis 2
• Diagnosis is often delayed 5-12 years after symptom onset, with most women consulting 3 or more clinicians before diagnosis 2

When to Consider Surgical Referral

• Refer to gynecology if medical therapy fails after adequate trials or if symptoms are severe and debilitating 1
• Surgery provides significant pain reduction in the first 6 months, though 44% experience recurrence within one year 4, 1
• Definitive diagnosis requires surgical visualization of lesions, though clinical diagnosis based on symptoms and therapeutic response is acceptable for initiating treatment 2