What are the causes and treatment options for endometriosis?

Causes and Treatment Options for Endometriosis

Causes of Endometriosis

Endometriosis is a chronic inflammatory systemic disease characterized by the presence of endometrial-like tissue outside the uterus, primarily caused by retrograde menstruation, genetic predisposition, hormonal imbalances, and immune system dysfunction. 1, 2

The primary theories for endometriosis development include:

• Retrograde menstruation: Menstrual blood containing endometrial cells flows back through the fallopian tubes into the pelvic cavity
• Genetic factors: Family history increases risk, with multiple genetic mutations identified
• Immune system dysfunction: Failure of the immune system to clear endometrial tissue from abnormal locations
• Hormonal influences: Estrogen-dependent growth and inflammation
• Environmental factors: Exposure to certain chemicals and toxins

Risk factors include:

• Younger age at menarche
• Shorter menstrual cycle length
• Lower body mass index
• Nulliparity
• Congenital obstructive müllerian anomalies 2

Diagnostic Approaches

Diagnosis is often delayed by 5-12 years after symptom onset, with most women consulting 3 or more clinicians before diagnosis 2. Key diagnostic methods include:

1. Clinical assessment: Evaluate for dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility
2. Imaging studies:
   • Transvaginal ultrasound (TVUS): First-line imaging with 92.4% sensitivity for intestinal endometriosis
   • MRI: 92.4% sensitivity and 94.6% specificity for intestinal endometriosis
   • Transrectal ultrasound: 97% sensitivity for rectovaginal endometriosis 1
3. Laparoscopy: Definitive diagnosis requires surgical visualization of lesions 2

Treatment Algorithm

First-Line Treatment: Hormonal Therapy

Hormonal medications should be offered as first-line treatment for all symptomatic premenopausal women with endometriosis who are not currently seeking pregnancy. 1, 2

Options include:

1. Progestins:

   • Norethindrone acetate: Start at 5 mg daily and gradually increase to 15 mg daily over 6-9 weeks as needed for symptom control 1, 3
   • Depot medroxyprogesterone acetate: Effective for endometriosis-associated pain 1

2. Combined Oral Contraceptives (COCs):

   • Provide consistent hormonal suppression
   • Contraindicated in severe hypertension, complicated valvular heart disease, migraines with aura, or history of thromboembolism 1

Second-Line Treatment Options

For patients with persistent symptoms despite first-line therapy:

1. GnRH Agonists with Add-Back Therapy:

   • Minimum 3-month treatment course
   • Always use with add-back therapy to prevent bone mineral loss
   • Effective for pain relief by reducing estrogen production 1

2. GnRH Antagonists:

   • Newer oral options with fewer side effects than older therapies 4

Surgical Interventions

Consider surgery when:

• Hormonal therapies are ineffective or contraindicated
• Definitive diagnosis is needed
• Fertility restoration is desired

Options include:

1. Laparoscopic excision/ablation:

   • Improves natural fertility by removing adhesions and restoring normal pelvic anatomy
   • Be aware of recurrence rates up to 44% within one year 1

2. Hysterectomy with removal of endometriotic lesions:

   • Consider for patients who have completed childbearing with severe symptoms
   • Approximately 25% experience recurrent pelvic pain after hysterectomy
   • 10% require additional surgery 1

Fertility Management

For patients with endometriosis-related infertility:

1. Use the Endometriosis Fertility Index (EFI) to predict fertility outcomes after surgical staging 1

2. Treatment options:

   • Intrauterine insemination (IUI): Beneficial for mild-moderate endometriosis
   • In vitro fertilization (IVF): Often most effective for advanced disease 1

Adjunctive Therapies

Consider adding:

• Anti-inflammatory diet (low fat, high fiber)
• Vitamin D supplementation to reduce endometrial pain 1

Monitoring and Long-Term Management

• Regular assessment of symptom control every 3 months
• Monitor for side effects of hormonal therapy
• Be aware of recurrence rates (25-44% within 12 months of discontinuing hormonal treatment)
• Screen for associated conditions including hypertension, hypercholesterolemia, and inflammatory conditions 1

Important Considerations and Cautions

• Norethindrone acetate is contraindicated during pregnancy as it may cause fetal harm 3
• Avoid norethindrone acetate in patients with history of blood clots, stroke, or heart attack 3
• Recognize endometriosis as a systemic disease with manifestations beyond the pelvis, including effects on metabolism, systemic inflammation, and altered brain function 4