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Now for Something Completely Deferent

Unusual presentations of endometriosis are like a fascinating puzzle to unpick within the vast puzzle that is endometriosis, like a jigsaw made of rubik’s cubes. But it’s not only the inherent fascination with such oddities that interests me, but the fact that the unusual ways in which endometriosis occurs could tell us a great deal about how endometriosis arises in the vast majority of other cases. Perhaps the most unusual presentation of endo is when it arises in men. I’m not talking about endometriosis is trans-men (mostly because there is little to no research in this area, which is a definite shame and something I would like to see more research into), but endometriosis in cis-gendered males who, by all logic, should not be able to develop a condition that is typically associated with people who menstruate (although even then there are rare exceptions). It is something that should be impossible, but it happened anyway.

One case report (link to the full text article here) describes a 40 year old man who came to his doctor with intermittent abdominal pain moving down his right side, described as “a constant dull ache with intermittent sharp pains” and “feelings of being bloated with progressive abdominal discomfort”, is it sounding familiar to anyone yet? Aside from asthma and being a bit obese the patient was medically unremarkable, no long-term serious illnesses or unusual medical conditions to hint at what might be the cause of his pain, he didn’t even present with any other symptoms that would give the doctors a clue as to what the cause of the pain might be (like painful urination, painful/bloody bowel movements or diarrhoea that may indicate an infection or gastrointestinal issue). So the doctors decided to perform a series of scans, which revealed a mass, measuring roughly 9cm x 5.6cm (about the size of a avocado) between the bladder and the rectum apparently arising from the vas deferens (the tube that takes sperm from the testicles to the prostate and the inspiration for the incredibly tortured pun the title of this post). If you look at figure (a) in the diagram from this link you’ll be able to see it as the roundish, grey, pear shaped object roughly halfway between the small white bit near the bottom and the long white spine.

The doctors concluded the mass was a fluid filled cyst of some kind so decided to perform a laparoscopy that then became a laparotomy to fully explore the pelvic area and remove the mass, which was then sent away to the lab for testing. When the results came back they had a “highly unexpected” diagnosis of endometriosis. The cyst was filled with a cloudy brown fluid while the lining was composed of endometrial epithelium and stroma (the cells you would normally find in the endometrium or an endometriotic cyst). In fact, the description of the cyst they found has some definite similarities to ovarian endometriotic cysts. The question posed then is, where on earth did it come from? Perhaps the few other case reports of endometriosis in males could help answer this.

The authors of this case report have gone through the literature and found all the other cases of endometriosis in males, which you can find in the link to the full text, but I’ll briefly summarise below

This is very much a simplified version of all the data in the published paper, but it contains an overview of all the important information that was given. Do you notice any common themes running through these case reports? In the risk factors column there is an awfully high incidence of hormone therapy for prostate cancer, usually using estrogen-like drugs. In addition to this, other cases had increased estrogen due to liver cirrhosis, or obesity. Yet, liver cirrhosis and certainly obesity are common enough, so why are those described in the table above all the cases of male endometriosis known in the world? (at the time of me writing this anyway).

A few theories on the origin of endometriosis could provide an explanation for what we are seeing here. Some authors suggest that endometriotic metaplasia/stromal metaplasia could be responsible. This basically implies that exposure to high estrogen levels can cause some tissue to transform from one to type another, in this case, transform into endometrial-like tissue. But this doesn’t necessarily explain why we see cases of male endometriosis reported exclusively around the pelvic area.

One of the other more popular theories suggests that, during the development of a human embryo, pieces of tissue get displaced that remain dormant until stimulated by estrogen to become endometriosis. As a human embryo is developing the primitive reproductive organs comprise the gonads and two sets of tubes that will go on to form the fully formed reproductive organs; one called the Mullerian duct, the other, the Wolffian ducts. Given a certain set of biological signals from the embryo one set of ducts will regress and the other will develop into reproductive organs and the gonads will develop into either testes or ovaries. In basic terms if the embryo has a Y chromosome (and the accompanying SRY gene) the Mullerian ducts will regress and the Wolffian ducts will develop into all the various tubes leading from the testes and through the prostate. If the embryo doesn’t have the SRY gene, the Wolffian ducts regress and the fallopian tubes, uterus, cervix and vagina develop instead. A nice diagram illustrating the process can be found here.

However, if the Mullerian ducts don’t regress completely they could, in theory, leave behind patches of tissue capable of developing into endometrial-like tissue when stimulated by estrogen. If this were the case we would expect male endometriosis to develop around the bodily locations where the Mullerian duct would have been, i.e. the bladder and ducts leading from the testes to the prostate, indeed this is what we see if we look at the data in the table above. While this is indeed an attractive theory, there has been very little scientific testing done to show that these patches of Mullerian remnant tissue exist or that they can transform into endometriosis when stimulated with estrogen.

One of the most important factors to take note of here is menstruation, or rather the lack of thereof. None of the males in these case reports have a uterus, or have periods, so this has wider implications for the theories of endometriosis origin in women. Certainly, it casts serious doubt over the prevailing theory of endometriosis origin, retrograde menstruation, which states that pieces of endometrium are refluxed back into the pelvic cavity, where they implant and grow into endometriotic lesions. Sometimes understanding how something doesn’t work can be as important as understanding how it does work.

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Dr Matthew Rosser

I have over 15 years experience researching endometriosis, endometrial cancer and fibroids. During this time I have       noticed that whilst research is regularly published on               endometriosis very little is reported accurately to the public in mainstream media. This blog aims to educate and inform anyone who wishes to learn more about the science and research into endometriosis.