What is the first‑line treatment for endometriosis in a reproductive‑age woman presenting with dysmenorrhea, chronic pelvic pain, or infertility?

First-Line Treatment for Endometriosis

NSAIDs combined with hormonal suppression using combined oral contraceptives or progestins are the first-line treatment for endometriosis in reproductive-age women presenting with dysmenorrhea, chronic pelvic pain, or infertility who are not actively trying to conceive. 1, 2, 3

Immediate Pain Management

• Start NSAIDs immediately (naproxen 550 mg twice daily or ibuprofen 600-800 mg three times daily) for acute pain relief as the initial intervention. 1, 2
• NSAIDs provide immediate symptomatic relief while hormonal therapy takes effect and should be used at appropriate scheduled doses rather than as-needed. 1

First-Line Hormonal Therapy

Combined oral contraceptives (COCs) or progestins are equally effective first-line hormonal options and should be initiated concurrently with NSAIDs:

• Combined oral contraceptives are Category 1 (no restrictions) for women with endometriosis and provide effective pain relief equivalent to more costly regimens with superior safety profiles. 1, 2
• COCs can be used continuously (skipping placebo weeks) to maintain amenorrhea and suppress endometriotic tissue. 4
• Progestins (oral or depot medroxyprogesterone acetate) demonstrate similar efficacy to COCs in reducing pain and lesion size. 1, 2
• For endometriosis specifically, norethindrone acetate can be initiated at 5 mg daily for two weeks, then increased by 2.5 mg every two weeks until reaching 15 mg daily, maintained for 6-9 months. 5

Key Clinical Considerations

• No medical therapy eradicates endometriosis lesions completely—all hormonal treatments suppress disease activity but do not cure the condition. 1, 2
• Pain severity correlates poorly with laparoscopic appearance but does correlate with depth of infiltration. 1
• 11-19% of patients experience no pain reduction with hormonal medications, and 25-34% have recurrent pain within 12 months of discontinuing treatment. 3

When to Escalate Beyond First-Line Therapy

Refer to gynecology or escalate to second-line therapy if:

• Symptoms persist after 3-6 months of first-line hormonal therapy. 1
• Patient cannot tolerate or has contraindications to COCs or progestins. 3
• Severe disease is suspected based on examination or imaging findings. 1

Second-Line Options (When First-Line Fails)

• GnRH agonists (leuprolide 3.75 mg IM monthly or 11.25 mg every 3 months) for at least 3 months provide the most robust pain relief for refractory cases. 1, 2
• Mandatory add-back therapy with norethindrone acetate 5 mg daily (with or without low-dose estrogen) must be prescribed simultaneously to prevent bone mineral loss without reducing analgesic efficacy. 1, 2

Surgical Considerations

• Surgery should be considered when medical treatment is ineffective, contraindicated, or for severe endometriosis with deep infiltrating disease. 1, 4
• Surgical excision by a specialist provides significant pain reduction in the first 6 months, but 44% experience symptom recurrence within one year. 1, 2
• Laparoscopic visualization and excision remain the gold standard for definitive diagnosis and treatment of advanced disease. 3

Critical Pitfalls to Avoid

• Do not delay hormonal therapy waiting for surgical confirmation—empiric treatment based on clinical diagnosis is appropriate and recommended. 1, 3
• Do not use hormonal suppression in women actively seeking pregnancy, as medical treatment does not improve future fertility outcomes. 1
• Do not rely on CA-125 for diagnosis, as it has limited utility particularly in mild or minimal disease. 1
• The average diagnostic delay is 5-12 years, so maintain high clinical suspicion in women with characteristic pain patterns: secondary dysmenorrhea beginning before menstrual onset, deep dyspareunia worsening during menses, and sacral backache coinciding with menstruation. 1, 3