What Causes Endometriosis?

Every month the endometrial cells grow and the lining of the womb thickens in preparation for implantation of a fertilised egg. If this does not happen then most of the tissue is shed as the woman’s monthly period.

Endometriosis is a condition where this tissue grows and thickens in other parts of the body. Usually the endometrial tissue grows in the pelvic area, for example in the fallopian tubes and around the ovaries and ‘Pouch of Douglas’. However, endometriosis can also occur in more distant sites, such as the bowel, the abdomen and, in rare cases, the lungs. Unlike normal endometrial tissue which is shed on a monthly basis and removed via the vagina, the tissue that builds up elsewhere has nowhere to go, thus it remains where it is, potentially causing a chronic inflammatory reaction, pain and adhesions.

It is not known what causes endometriosis; however, there are a number of theories.

Coelomic metaplasia theory

The coelomic metaplasia theory states that other cells within the pelvis, which have a similar embryonic origin, somehow change into endometrial cells, presumably in response to a hormonal or environmental stimulus. This theory does not explain the more distant sites of endometriosis.

Embryonic rest theory

Another proposed explanation is the embryonic rest theory. This theory hypothesises that endometrial cells form outside the uterus, before birth. With puberty and, crucially, an increase in oestrogen levels, the wayward endometrial cells grow and form lesions. These lesions result in the pain and other symptoms frequently associated with endometriosis.

Transplantation theory

The most widely accepted of the current theories, however, is transplantation of endometrial cells. This theory hypothesises that endometrial cells are transported through the bloodstream or lymphatic system to alternative locations. Included in this theory is the process of retrograde menstruation, where menstrual blood flows into the fallopian tube. Whilst this theory is well-regarded and highly plausible, the problem is that up to 90% women experience retrograde menstruation, yet only 6-10% will have clinically diagnosed endometriosis. Therefore, other factors must be involved, most likely a hormonal imbalance, a problem with the immune system or a genetic predisposition.

Involvement of hormones and the immune system

Endometrial tissue grows in response to rising oestrogen levels. Women with endometriosis seem to have higher levels of one of the enzymes responsible for activating oestrogen (oestrogen synthase); this leads to a higher concentration of the hormone. In addition, endometrial cells seem to be resistant to immune attack. The identification of anti-endometrial antibodies in the blood of women with endometriosis suggests that the condition may be an autoimmune condition. There is however, to date, no clear consensus as to whether to classify it as this, or as an inflammatory condition.

Endometriosis and genetics

Endometriosis seems to run in families, a close family member with the condition increases your risk of developing it by up to six times. A variation in the DNA of women with moderate-severe endometriosis has been identified, and recent studies mapping the genome of women with endometriosis have revealed specific genetic abnormalities compared to healthy controls. Diagnosis of endometriosis is challenging; this sort of work on genetic variations opens up the possibility of using a biomarker-based panel of genes for diagnosis by blood test.

In conclusion, there is probably no simple answer to the question of what causes endometriosis. Most likely the cause is multifactorial, encompassing pathophysiological, hormonal and genetic components. To add to the complexity certain factors put women at greater risk of developing the condition; these include starting their periods at a young age, having shorter than average menstrual cycles (less than 27 days), never having given birth and having heavy periods.

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Sources:

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• Sapkota, et al. “Meta-Analysis Identifies Five Novel Loci Associated with Endometriosis Highlighting Key Genes Involved in Hormone Metabolism.” Nature Communications, vol. 8, no. 15539 , 24 May 2017, doi:10.1038/ncomms15539 .
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