What is the first‑line treatment for a reproductive‑aged woman with symptomatic endometriosis?

First-Line Treatment for Symptomatic Endometriosis in Reproductive-Aged Women

For a reproductive-aged woman with symptomatic endometriosis, start with NSAIDs for immediate pain relief, followed by combined oral contraceptives or progestins as first-line hormonal therapy. 1, 2, 3

Initial Pain Management

• NSAIDs should be initiated immediately for endometriosis-related pain at appropriate doses (naproxen 550 mg twice daily or ibuprofen 600-800 mg three times daily). 1, 3
• NSAIDs provide rapid symptomatic relief while hormonal therapy takes effect. 1, 2

First-Line Hormonal Therapy

Combined oral contraceptives and progestins are equally effective first-line options with superior safety profiles compared to more costly regimens. 1, 3

Combined Oral Contraceptives

• Continuous oral contraceptive pills are as effective as GnRH agonists for pain control while causing far fewer side effects. 1
• Benefits include low cost, minimal side effects, and widespread availability. 1
• In network meta-analysis (n=1680,15 trials), hormonal treatments including combined oral contraceptives led to clinically significant pain reduction compared with placebo, with mean differences ranging between 13.15 and 17.6 points on 0-100 visual analog scale. 4

Progestins

• Progestins demonstrate similar efficacy to oral contraceptives in reducing pain and lesion size. 1
• Options include dienogest, norethindrone acetate (NETA), or depot medroxyprogesterone acetate (MPA) for long-term treatment. 3, 5
• Acne occurs in fewer than 10% of women treated with dienogest 2 mg. 1

When First-Line Therapy Fails

Second-Line Options

• GnRH agonists for at least 3 months provide significant pain relief when first-line therapies fail. 1, 2, 3
• Add-back therapy is mandatory with long-term GnRH agonist use to prevent bone mineral loss without reducing pain relief efficacy. 1, 2, 3
• Danazol for at least 6 months shows equivalent efficacy to GnRH agonists in reducing pain. 1, 2

Surgical Intervention

• Surgery should be considered when medical treatment is ineffective, contraindicated, or for severe endometriosis. 1, 2, 3
• Surgical excision by a specialist is the definitive treatment, while medical therapies effectively temporize symptoms but cannot eradicate the disease. 1, 3
• Up to 44% of women experience symptom recurrence within one year after surgery, highlighting the importance of ongoing management. 1, 2, 3

Critical Pitfalls to Avoid

• No medical therapy completely eradicates endometriotic lesions—treatment is suppressive, not curative. 2, 3
• 11% to 19% of individuals with endometriosis have no pain reduction with hormonal medications. 4
• 25% to 34% experience recurrent pelvic pain within 12 months of discontinuing hormonal treatment. 4
• Medical treatment does not improve future fertility outcomes, and hormonal suppression should not be used in women actively seeking pregnancy. 1, 3
• Long-term GnRH agonist use without add-back therapy causes significant bone mineral loss. 2, 3
• Pain severity correlates poorly with laparoscopic appearance but correlates with lesion depth. 1, 3

Special Considerations

• For women not seeking immediate pregnancy, hormonal suppression is appropriate first-line therapy. 4
• For women desiring fertility, surgical excision by a specialist is the definitive treatment, followed by assisted reproduction techniques if necessary. 3
• Approximately 25% of patients who undergo hysterectomy for endometriosis experience recurrent pelvic pain and 10% undergo additional surgery. 4