What causes endometriosis?

Causes of Endometriosis

Endometriosis is caused by a multifactorial etiology including genetic factors with epigenetic influences, environmental exposures, retrograde menstruation, inflammation, and hormone dysregulation that together lead to the development of endometrial-like tissue outside the uterus. 1

Retrograde Menstruation: The Primary Mechanism

• Retrograde menstruation plays a major role in the pathophysiology of endometriosis, explaining the asymmetric distribution of lesions that predominate in the posterior compartment of the pelvis and on the left side 2
• Factors that increase menstrual reflux significantly increase the risk of endometriosis, including:
  • Early menarche
  • Short menstrual cycles
  • Abnormal uterine bleeding
  • Congenital obstructive müllerian anomalies (e.g., obstructed hemivagina) 3

Genetic Factors

• Approximately 50% of endometriosis risk is attributable to genetic factors 4
• The risk of developing endometriosis for a first-degree relative is five times higher than in the general population 2
• Unlike single-gene disorders, endometriosis involves multiple genetic variants with small individual effects that collectively increase risk 4
• Recent research has identified somatic mutations in endometriotic lesions, some of which are present in the eutopic endometrium, particularly in epithelial cells 4

Inflammatory and Hormonal Mechanisms

• Endometriosis should be defined as an inflammatory disease process 1
• Key hormonal characteristics include:
  • Estrogen-dependence
  • Progesterone resistance 1
• Inflammation and biosteroid hormone synthesis are the main mechanisms promoting implantation and growth of endometriotic lesions 2

Pain Mechanisms

• Pain associated with endometriosis involves multiple mechanisms:
  • Nociception (direct tissue damage)
  • Hyperalgia (increased sensitivity to pain)
  • Central sensitization (nervous system amplification of pain signals) 2
• The location of pain often correlates with the location of lesions (e.g., dyspareunia with lesions in specific areas, digestive symptoms with bowel involvement) 2

Environmental Factors

• Environmental factors likely account for approximately 50% of endometriosis risk 4
• The role of environmental factors, particularly endocrine disruptors, is plausible but not conclusively demonstrated 2

Relationship to Infertility

Endometriosis-associated infertility can be explained by several mechanisms:

• Pelvic inflammation disrupting natural fertilization
• Ovarian factors affecting oocyte quality and/or quantity
• Uterine factors disrupting implantation 2

Disease Progression

• Literature does not support consistent progression of endometriosis over time in terms of lesion volume or number 2
• The risk of acute complications like digestive occlusion or kidney function loss appears to be exceptional in monitored patients 2

Important Clinical Considerations

• Endometriosis affects approximately 10% of women during their reproductive years 5, 3
• Diagnosis is often delayed by 5-12 years after symptom onset, with most women consulting 3 or more clinicians before diagnosis 3
• While definitive diagnosis requires surgical visualization of lesions, a clinical diagnosis can often be made based on symptoms, physical examination, and imaging 5

Potential Complications

• There is an epidemiological association between endometriosis and rare subtypes of ovarian cancer (endometrioid and clear cell carcinomas), though the relative risk is moderate (around 1.3) and a causal relationship has not been established 2
• The low incidence of endometriosis-associated ovarian cancer does not warrant specific screening or risk-reducing strategies 2

Understanding the complex etiology of endometriosis is crucial for developing effective diagnostic approaches and treatment strategies that address the underlying mechanisms of this challenging condition.