Endometriosis theories initiative

M Canis August 2024

As the mechanisms explaining the presence of endometrial cells are present in every woman and the potential risks factors are numerous so that at least one of them may be present in most woman, I propose that something else has to be involved in the pathophysiology of endometriosis, an additional cause has to explain why the disease happens in some women and why it does not in others. I propose that a trauma may be the mechanism which initiates the disease.

Surgical trauma is known to induce endometriosis, abdominal wall endometriosis is known as a consequence of cesarean section. Similarly perineal endometriosis may be a consequence of episiotomy. From the following proposal, adenomyosis and endometriosis should probably considered as a syndrome whose diseases are induced by different trauma.

The proposed hypothesis is the following. 

First, the extent and the surgical phenotype of the disease may be related to the initial anatomic localization, type, severity and duration of the causal trauma. This implies that severe phenotypes are likely not always the results of a long process of aggravation and may appear within few months or weeks, as the initial trauma was severe.

Second, in most patients, if the trauma is stopped and the injured tissue repaired properly, the severity (i.e., the number and the extent (or size) of endometriotic lesions) will not increase significantly. As the delay between the onset of clinical symptoms and diagnosis of the disease is often long, the initial event or trauma may (probably often) halted before the diagnosis and the initiation of the treatment, so that the number of lesions will rarely if ever increase after the diagnosis. However, ongoing (probably often unidentified) trauma may explain the worsening observed in some patients (repeated mechanical trauma and or ongoing infections could be proposed as the more commons).

Third, from this idea, we propose that true recurrences of the disease may be rare, unless a new trauma induces further endometriotic lesions. The most common probably being recurrent trauma to the ovary !

Besides surgery, many potential trauma could be proposed as possible etiologies of endometriosis. Ovulation and corpus luteum hemorrhage are common ovarian trauma. Adenomyosis could be related to surgical trauma and or to pregnancies. Infection is a possible cause of peritoneal disease. Peritoneal palpation with a probe during diagnostic laparoscopy could damage the peritoneal surface and facilitates the appearance of peritoneal lesions. Trauma to the posterior cul de sac may occur during sexual activity, as it has been showed in cows that trans rectal examination of the ovaries may induce peritoneal trauma without entering the peritoneal cavity. 

Once the disease is initiated the phenotype of the lesion depends on the organ on which the cells are implanted. Smooth muscle hypertrophy appears in muscle, cyst in the ovary, small cyst and fibrosis in the peritoneum.

In many cases the trauma stopped and healed properly so that the disease will not get worse after the diagnosis. However potential mechanisms may be proposed to explain a worsening of the disease:

– ovarian endometrioma may increase in diameter because of endo-cystic menstruation

– Adnexal adhesions and new peritoneal lesions may appear because of an undiagnosed and untreated infection or bacteriological contamination. 

– Hyperperistaltism in smooth or striated muscle may be traumatic enough to explain an increase in size of the muscular lesions, particularly the worsening observed in adenomyotic lesions. This hyperperistaltism could even be propose as a possible cause of damages to the peritoneal surface of the bowel when its function is abnormal (partially obstructed) because of a large deep infiltrating lesion.  

– Inflammation could produce growth factors and damages to the peritoneum and induces new implants. However, an associated cause seems likely as peritoneal disease often appears as a self limiting disease. 

– Repeated and probably painful sex may traumatize a nodule developed in the posterior cul de sac and explain its increase in diameter. 

From this proposal, endometriosis rather appears as a syndrome, whose potential evolution will depend on the interruption or the persistence of the trauma and or of the initial phenotype of the disease. Based on these ideas, the management of each patient should be adapted to the clinical situation and it appears impossible and unfair to propose only one attitude, a one size fits all approach, which may obviously not be adequate for most patients. 

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