What medications are used to treat endometriosis pain?

Medications for Endometriosis Pain Management

For endometriosis-associated pain, hormonal therapies are the first-line treatment, with progestin-only options showing superior efficacy and safety profiles for most patients. 1

First-Line Treatment Options

Progestin-Only Options

• Norethindrone acetate: Initial daily dosage of 5 mg for two weeks, with increases of 2.5 mg every two weeks until reaching 15 mg daily. Treatment can be maintained for 6-9 months or until breakthrough bleeding requires temporary cessation 2
• Levonorgestrel-releasing IUD (LNG-IUD): Recommended as a first-line option, especially for patients with contraindications to estrogen 1
• Depot medroxyprogesterone acetate: Effective for pain relief with approximately 75% of patients experiencing amenorrhea 1
• Dienogest: Effective with reduced side effects compared to other options 1

Combined Hormonal Contraceptives (CHCs)

• Standard starting dose: 30-35 μg ethinyl estradiol with levonorgestrel or norgestimate
• Continuous regimen preferred for better symptom control
• Best for patients without contraindications to estrogen 1
• Consider lower doses of ethinyl estradiol to minimize potential stroke risk 1

Second-Line Treatment Options

GnRH Agonists and Antagonists

• Consider when first-line treatments are ineffective
• Effective for pain relief but can cause bone mineral loss 1, 3
• Network meta-analysis shows clinically significant pain reduction compared to placebo 3

NSAIDs

• Often used as adjunctive therapy with hormonal treatments
• Limited evidence for effectiveness specifically for endometriosis pain 4
• Very low-quality evidence shows no clear benefit of naproxen over placebo for pain relief in women with endometriosis 4

Third-Line Treatment Options

Aromatase Inhibitors

• Consider when first and second-line treatments fail 3
• May be particularly useful for refractory cases

Treatment Algorithm

1. Initial Assessment:

   • Evaluate symptom severity, fertility desires, and comorbidities
   • Check for contraindications to estrogen (age >35 years, tobacco use, hypertension, migraine with aura)

2. First-Line Treatment:

   • For patients WITHOUT contraindications to estrogen:
     • Combined hormonal contraceptives in continuous regimen
   • For patients WITH contraindications to estrogen:
     • Progestin-only options (LNG-IUD, norethindrone acetate, depot medroxyprogesterone acetate, or dienogest)

3. Evaluate Response After 3-6 Months:

   • If inadequate response, consider:
     • Alternative first-line option
     • Second-line treatment (GnRH agonists/antagonists)
     • Surgical evaluation

4. Surgical Options:

   • Consider laparoscopic excision/ablation of endometriotic lesions if medical therapy fails
   • Hysterectomy with removal of endometriotic lesions may be considered for patients who have completed childbearing and have severe symptoms unresponsive to other treatments

Important Considerations

• Treatment Duration: Long-term therapy is often necessary as symptoms frequently recur after treatment cessation (25-34% of patients experience recurrent pain within 12 months of discontinuing hormonal treatment) 1, 3

• Side Effects:

  • Hormonal therapies: Amenorrhea, breakthrough bleeding, weight gain, and mood changes 1
  • GnRH agonists: Hypoestrogenic side effects including hot flushes and bone mineral loss 5

• Treatment Limitations:

  • 11-19% of individuals have no pain reduction with hormonal medications 3
  • Approximately 25% of patients who undergo hysterectomy experience recurrent pelvic pain 3
  • Suppressive medical therapy alone does not improve fertility rates 1

• Monitoring:

  • Monitor blood pressure at follow-up visits for CHC users
  • Evaluate treatment response after 3-6 months 1

By following this evidence-based approach to medication selection, most patients with endometriosis-associated pain can achieve significant symptom relief, with approximately two-thirds of symptomatic patients being managed satisfactorily for many years using existing safe and effective medications 6.