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The genetic-epigenetic theory

Endometriosis is a benign tumor and requires genetic and epigenetic (G-E) modifications of the cell

  • The original cell is not important can be endometrium, or stem cells, or even bone marrow cells
  • We are born with some G-E defects which is our predisposition
  • During life we acquire more defects: above a threshold endometriosis starts
 

Pathophysiology of endometriosis
The driving motors  are

  • pollution
  • oxidative stress
    • of blood from  retrograde menstruation
    • infection

Observations on endometriosis

The G-E theory for the first time permits to explain ALL observations made on endometriosis including the clonality of lesions.

the endometriotic disease theory

This theory is an update of the endometriotic disease theory of 1999.

The Sampson theory

Sampson Theory
This theory is no longer valid since not compatible with all observations of endometriosis such as endometriosis in man, and the clonal aspect of endometriosis.

In 1927 Sampson suggested that cells from retrograde menstruation could implant and develop. For a recent update read GORDTS S et al . Since this could not explain all forms of endometriosis, the metaplasia theory was proposed, and later the hematogenic and lymphangenic spread.

The initiation of endometriosis lesions

Pathophysiology of endometriosis: The genetic epigenetic theory
All women are born with some genetic-epigenetic defects

Additional incidents occur during life because of

  • pollution
  • oxidative stress mainly retrograde menstruation
  • infection

beyond a treshold of incidents endometriosis lesions initiate

  • Thus each type of lesion has a different set of incidents
  • Thus even similarly looking lesions can have very different sets of incidents eg progesterone resistance

Growth of endometriosis lesions

  • The set of genetic-epigenetic incidents will determine the evolution towards typical, cystic or deep lesions
  • Growth is moreover influenced by the immunology and the peritoneal fluid environment inherited at birth, and the oxidative stress of retrograde menstruation
  • also bleeding in the lesions will cause a repetitive tissue trauma and repair (RETIAR)
  • Most lesions grow for a certain time but growth is self limiting. When we make the diagnosis most lesions are no longer growing. Some however either are still growing, or will keep growing.

Clinical consequences of the genetic-epigenetic theory

  • subtle endometriosis is normal endometrium implanted on the peritoneum and thus not a disease.
  • the original cell is no longer important for understanding endometriosis
  • each endometriosis lesion is G-E different
    • this is the heterogeneity in respons to therapy
    • a benign tumor.
  • the role of oxidative stress and of the peritoneal mirobiome explains
    • the importance of food intake
    • the problem of repetitive retrograde menstruation
    •  how to organise prevention of endometriosis
    • the importance of adolescent endometriosis
  • Endometriosis is
    • not a recurrent disease : if removed completely there are no recurrences. New lesions however can develop.
    • not a progressive disease in most women.

 

 

Historical considerations

Pathophysiology of endometriosisCullen described already in 1880 rectovaginal endometriosis. Sampson described Cystic ovarian endometriosis in 1921. Because of endometriosis in women without a uterus the metaplasia theory was proposed. Only ofter 1975 we realised that typical lesions were so frequent. In 1986 Janssens described the non-pigmented subtle endometriosis. The history of deep endometriosis starts with the paper of Cornillie and Koninckx in 1989

In 1921 Sampson proposed that menstrual cells that arrive in the peritoneal cavity by retrograde menstruation can implant and can develop further to endometriotic lesions. However, retrograde menstruation occurs in most women, and not all women develop endometriosis. This theory fails to explain why progression occurs in some women only or why endometriosis is heriditary.

Metaplasia theory is based upon the fact that mesothelial cells in the peritoneum can be transformed by menstrual blood into endometrial cells.  Progression and further development is identical to the implantation theory.

Haematogenic spread explains the occurrence of endometriosis in the lungs and on the pleura.
In deep endometriosis endometrial cells are found in 50% of women in the lymph nodes. The significance of this is unclear.

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