What are the current treatment options for a patient with endometriosis, considering recent studies?

Current Treatment Options for Endometriosis

Start with NSAIDs for immediate pain relief, followed by continuous combined oral contraceptives or progestins as first-line hormonal therapy, reserving GnRH agonists for refractory cases and surgery for severe disease or when medical management fails. 1

Stepwise Treatment Algorithm

First-Line Medical Management

• Begin with NSAIDs (naproxen 550 mg twice daily or ibuprofen 600-800 mg three times daily) as the most effective immediate pain relief option 1, 2
• Initiate continuous combined oral contraceptives as they are as effective as GnRH agonists for pain control while causing far fewer side effects, with benefits including low cost and widespread availability 3, 4
• Progestins are equally effective alternatives to oral contraceptives, including oral norethindrone or depot medroxyprogesterone acetate, with similar efficacy in reducing pain and lesion size 1, 2
• The U.S. Medical Eligibility Criteria classifies endometriosis as Category 1 (no restrictions) for combined hormonal contraceptive use, meaning these medications can be safely used without concern for worsening the condition 1

Second-Line Medical Management (For Refractory Cases)

• GnRH agonists for at least 3 months provide significant pain relief when first-line therapies fail, with mean pain reduction of 13.15 to 17.6 points on a 0-100 visual analog scale 1, 4
• Mandatory add-back therapy (norethindrone acetate 5 mg daily with or without low-dose estrogen) must be implemented simultaneously to prevent bone mineral loss without reducing pain relief efficacy 1, 2
• Danazol for at least 6 months shows equivalent efficacy to GnRH agonists in reducing pain, though it is less commonly used due to side effects 1

Third-Line Options

• Aromatase inhibitors are emerging as third-line treatments for refractory cases 4
• Tramadol 50-100 mg every 6 hours has shown superior efficacy to naproxen for severe endometriosis pain 2

Surgical Management

Indications for Surgery

• Surgical excision by a specialist is the definitive treatment when medical therapy is ineffective, contraindicated, or for severe endometriosis 3, 4
• Surgery provides significant pain reduction during the first 6 months following the procedure 1, 2
• Preoperative MRI pelvis is essential to map disease extent, identify deep infiltrating lesions, and plan surgical approach 3

Surgical Approach

• Laparoscopic excision is preferred over ablation or fulguration of endometriotic lesions 5
• Bowel resection should be performed when necessary to achieve complete disease removal 3
• Bladder endometriosis requires partial cystectomy with complete excision of visible disease 3

Definitive Surgery

• Hysterectomy with bilateral salpingo-oophorectomy remains the definitive approach for completed childbearing, though approximately 25% experience recurrent pelvic pain and 10% undergo additional surgery 3, 4
• Hormone replacement therapy with estrogen is not contraindicated following hysterectomy and bilateral salpingo-oophorectomy for endometriosis 1, 3

Critical Pitfalls to Avoid

• No medical therapy eradicates endometriosis lesions completely—all hormonal treatments only temporize symptoms 1, 3
• 11% to 19% of patients have no pain reduction with hormonal medications, and 25% to 34% experience recurrent pelvic pain within 12 months of discontinuing treatment 4
• Up to 44% of women experience symptom recurrence within one year after surgery, highlighting the need for ongoing management 1, 2
• Medical treatment does not improve future fertility outcomes, and hormonal suppression should not be used in women actively seeking pregnancy 1
• Pain severity correlates poorly with laparoscopic appearance but correlates with lesion depth 1, 2
• Limit ketorolac use to a maximum of 5 days due to gastrointestinal and renal risks 2

Adjunctive Non-Pharmacologic Measures

• Heat application to the abdomen or back may reduce cramping pain 2
• Acupressure on Large Intestine-4 (LI4) or Spleen-6 (SP6) points may help reduce cramping pain 2
• Aromatherapy with lavender may increase satisfaction and reduce pain or anxiety 2

Recent Evidence Highlights

• A 2025 JAMA review confirms that hormonal treatments including combined oral contraceptives, progestins, and GnRH agonists all lead to clinically significant pain reduction compared with placebo, with little difference in effectiveness among options 4
• Endometriosis is now reframed as a multisystem neuroinflammatory disorder affecting approximately 190 million women worldwide, with genetic studies identifying shared risk factors with inflammatory and chronic pain conditions 6, 7
• Diagnostic delay averages 5 to 12 years after onset of symptoms, with most women consulting 3 or more clinicians prior to diagnosis 4