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The genetic-epigenetic (G-E) etiology of endometiosis

 

Pathophysiology of endometriosis

Endometriosis is a benign tumor which requires G-E incidents of a cell

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

Pathophysiology of endometriosisThe driving motors  are   pollution and  oxidative stress by blood of retrograde menstruation or by infection.
Observations on endometriosis
The G-E theory for the first time permits to explain ALL observations made on endometriosis including the clonality and heterogeneity of lesions.

the endometriotic disease theory

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

The Sampson theory

Sampson Theory
The Sampson theory is no longer valid to explain the etiology of endometriosis since it is not compatible with all observations of endometriosis such as endometriosis in man, and the clonal aspect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 beginning of endometriosis lesions

Pathophysiology of endometriosis: The genetic epigenetic theory
All women are born with some genetic-epigenetic defects,  which explains   predisposing ,  the infertility,  problems during pregnancy, and  immunologic and other changes

Additional incidents occur during life because of pollution; oxidative stress of mainly retrograde menstruation and  pelvic 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 

  • The set of G-E incidents determines the growth to typical, cystic or deep lesions
  • Growth is moreover influenced by the immunology and the peritoneal fluid environmen
  • 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; however, some  are still growing and keep growing.

Clinical consequences of the G-E etiology

  • subtle endometriosis is normal endometrium implanted on the peritoneum and thus not a disease.
  • each endometriosis lesion is G-E different like a benign tumor, and thus heterogeneous with a variable respons to therapy
  • the driving 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 therefore is
    • not a recurrent disease : if removed completely there are no recurrences. New lesions however can develop.
    • not a progressive disease in most women.

 

 

!!  spurious associations

Endometriosis  is NOT associated with cardiovascular diseasePathophysiology of endometriosis
 

 

 

Historical considerations of etiology of endometriosis

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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