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

Pathophysiological Mechanisms

Endometriosis is best understood as an inflammatory disease process with key hormonal characteristics including estrogen-dependence and progesterone resistance. The development of this condition involves several interrelated mechanisms:

1. Retrograde Menstruation

   • Menstrual blood containing endometrial cells flows backward through the fallopian tubes into the pelvic cavity
   • These displaced endometrial cells implant and grow on pelvic organs

2. Genetic Factors

   • Strong hereditary component with multiple candidate genes involved 2
   • Genetic variants affect susceptibility to the disease
   • Family history increases risk significantly

3. Epigenetic Modifications

   • Aberrant DNA methylation patterns and histone modifications 3
   • Differential expression of DNA methyltransferases and histone deacetylators
   • Non-coding microRNAs show altered expression in endometriotic lesions

4. Hormonal Dysregulation

   • Estrogen-dependent growth of lesions 4
   • Progesterone resistance in endometriotic tissue
   • Aberrant expression of estrogen-metabolizing enzymes
   • Increased local estradiol formation in endometriotic lesions

5. Immune System Dysfunction

   • Impaired immune surveillance allows endometrial cells to implant outside the uterus
   • Chronic inflammatory response to ectopic endometrial tissue

6. Environmental Factors

   • Exposure to environmental toxins may influence disease development
   • Dioxins and other endocrine-disrupting chemicals have been implicated

Clinical Implications

Understanding the causes of endometriosis has important clinical implications:

• Endometriosis affects approximately 10% of women during their reproductive years 1, 5
• The condition is associated with debilitating pelvic pain in 90% of cases and infertility in 26% 5
• Diagnosis is often delayed by 5-12 years after symptom onset 5
• Women with endometriosis have an increased risk of cardiovascular disease, including stroke 6

Cardiovascular Risk Considerations

Recent evidence indicates that endometriosis increases stroke risk by 16-34% 6. This association appears to be mediated through:

• Higher risk of hypertension and elevated cholesterol in endometriosis patients 6
• Chronic inflammatory state
• Potential effects of treatments (hysterectomy/oophorectomy and hormone therapy) 6

Young individuals with endometriosis may benefit from enhanced cardiovascular risk assessment and prevention strategies, as the diagnosis typically occurs during reproductive years 6.

Clinical Pearls and Pitfalls

• Pearl: Early identification of endometriosis allows for timely intervention that may reduce long-term complications including pain, infertility, and cardiovascular risk.
• Pitfall: Assuming that endometriosis is solely a reproductive disorder overlooks its systemic inflammatory nature and associated cardiovascular risks.
• Pearl: A family history of endometriosis should raise clinical suspicion in women presenting with pelvic pain or infertility.
• Pitfall: Normal physical examination and imaging do not exclude the diagnosis of endometriosis 5.

The multifactorial nature of endometriosis underscores the importance of a comprehensive approach to both diagnosis and management, recognizing it as a chronic inflammatory condition with systemic implications beyond reproductive health.