And Now for Something Completely Deferent

I’ve wrote before on the subject of unusual presentations of endometriosis, mostly because they’re 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 is male endometriosis. 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 rectified sooner rather than later), but endometriosis in cis-gendered males who, by all logic, should not be able to develop a condition that is typically associated with the uterus. It is something that should be impossible, but it happened anyway. I have covered this topic before, but there was another case report published in January of this year so I think its worth looking at this one and going over what this could mean for endometriosis in the wider context.

The 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 scan and found 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) at this link you’ll be able to see it as the roundish, 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

Patient Age	Location of Endometriosis	Symptoms	Risk Factors	Treatment
78	Prostatic urethral crest	Not reported	Estrogen therapy for prostate cancer	Not reported
52	Attached to bladder	Stabbing pelvic pain	Surgery for hernia, liver chirrhosis	Surgery
69	Paratestis	Swelling of the testis	Hormone therapy for prostate cancer	Surgical removal of testes
27	Epididymis	Scrotal pain	None reported	Surgery
82	Between vas deferens and testes	Mass felt on epididymis	Hormone therapy for prostate cancer	Surgical removal of testes
52	Attached to bladder	Lower abdomen pain	Surgery for hernia, liver chirrhosis	Surgery
83	Lower abdominal wall	Not reported	Hormone therapy for prostate cancer	Not reported
80	Bladder	Not reported	Hormone therapy for prostate cancer	Not reported
50	Bladder	Blood in urine	Hormone therapy for prostate cancer	Surgery
43	Paratestis	Abdominal pain	Cancer of the testes	Surgical removal of left testicle
73	Ureterovesical junction	Swelling of the kidney	Hormone therapy for prostate cancer	Not reported
49	Ductus deferens	Discovered during hernia repair	Surgery for hernia	Surgery
74	Ureteral orifice	Blood in urine	Hormone therapy for prostate cancer	Surgery
46	Found within a tumour of the testes	Cyst next to tumour	Obesity	Surgical removal of right testicle
Not reported	Scrotum	Not reported	Hormone therapy for prostate cancer	Not reported
40	Vas deferens	Abdominal pain	Obesity	Surgery

This is very much a simplified version of all the data in the published paper, it contains a brief 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. Estrogen cant be working on its own though; liver cirrhosis and certainly obesity are common enough, yet what you see in the table above are all the cases of this unusual presentation of endometriosis known in the world (at the time I’m writing this anyway).

A few theories on the origin of endometriosis could provide an explanation for what we are seeing here. One of the more popular ones suggests that, during the development of a human embryo, pieces of tissue get left behind that can go on to be stimulated by estrogen to become endometriosis. As the embryo is developing it has two sets of tubes that will go on to form the reproductive organs, one called the Mullerian duct, the other, the Wolffian ducts, and the gonads. 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 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.

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, which I’ve talked about before. If this were the case we would expect endometriosis to develop around the bladder and ducts leading from the testes to the prostate, indeed this is what we see if we look at 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.

Endometriosis Awareness Month – Part I

March is officially endometriosis awareness month and that means it’s time for me to get writing. Endometriosis awareness has come on in leaps and bounds since I started this blog way back in the dim and distant past of 2009 and even more so from the time before that. This has led to some noticeable real world differences. For me, I’ve noticed that when I talk about my research interests there are a lot more people who know about endo, or have at least heard of it; I certainly don’t get as many blank stares as I used to. However, endometriosis still doesn’t receive the attention that it deserves from governments and policy makers, so I salute those brave souls battling to raise awareness of this disease.

Endometriosis is far from rare, however there are rare ways in which endometriosis can present itself. This week’s post is dedicated to those rare forms of endo, found in unexpected places, to create an ‘endometriosis atlas’ of sorts.

Anyone who is familiar with endometriosis will know that it is usually found on or around the pelvic reproductive organs, such as the uterus, ovaries, fallopian tubes and the surrounding ligaments and structures. What is less well known is that endometriosis has been found in almost every part of the human body, although finding endo outside the ‘normal’ locations is rare to extremely rare depending on the location. I’ve scoured through the literature and come up with the diagram below showing all the places endo has been found in the body. 

(Click on image for larger version) Original image from clipartqueen.com

As I mentioned before, many of these incidences of endo are rare, some of the cases (like endo in the heart/brain/nose) have only ever been reported once or twice, so whilst they are not impossible, they are very unlikely. In a lot of these cases patients report cyclical symptoms, like pain or bleeding around the time of menses, which is really the only clue physicians have that endo may be the culprit.

Equally, or perhaps more unusual than the odd locations of endometriosis in women, is the occurrence of endometriosis and endomyometriosis (a uterus like mass containing uterine muscle and endometrium) in men. There have only ever been around a dozen cases of male endometriosis reported, so it is an extremely rare phenomenon. Below is a diagram, similar to the one above showing, the locations of male endometriosis and endomyometriosis.

(Click on image for larger version)

Interestingly, the majority of these cases have been in men undergoing hormone therapy for prostate cancer, or men with a condition or medication that would alter their normal hormonal balance. One of the more plausible explanations for male endometriosis is that, during the very early stages of development, small pieces of embryonic female reproductive system precursors remain and can become ‘activated’ when exposed to external hormonal influences (I’ve given a better explanation of this previously). Maybe this could give us some insight into how endometriosis in women develops?

Here are the sources for each of the case reports where endo was found. It is probably isn’t a comprehensive list as there are multiple reports for each incidence, but I’ve only chosen one as a representative example.

Brain: http://www.ncbi.nlm.nih.gov/pubmed/3559727

Tear ducts: http://www.ncbi.nlm.nih.gov/pubmed/16974134

Nose: http://www.ncbi.nlm.nih.gov/pubmed/11917731

Heart, lungs and diaphragm http://www.ncbi.nlm.nih.gov/pubmed/23256014

Heart: http://journals1.scholarsportal.info/details?uri=/00029343/v29i0006/1072_seith

Lungs: http://www.ncbi.nlm.nih.gov/pubmed/20580323

Diaphragm: http://www.ncbi.nlm.nih.gov/pubmed/20601386

Navel: http://www.ncbi.nlm.nih.gov/pubmed/19944195

Liver: http://www.ncbi.nlm.nih.gov/pubmed/19587832

Stomach: http://www.ncbi.nlm.nih.gov/pubmed/25674531

Pancreas: http://www.ncbi.nlm.nih.gov/pubmed/15558937

Intestine: http://www.ncbi.nlm.nih.gov/pubmed/19886549

Kidney: http://www.ncbi.nlm.nih.gov/pubmed/16501686

Bladder: http://www.ncbi.nlm.nih.gov/pubmed/22813980

Skin: http://www.ncbi.nlm.nih.gov/pubmed/20422419

Buttock: http://www.jmig.org/article/S1553-4650(08)01028-5/abstract

Cervix http://www.ncbi.nlm.nih.gov/pubmed/24337728

Clitoral http://www.ncbi.nlm.nih.gov/pubmed/25680686

Perineum http://www.ncbi.nlm.nih.gov/pubmed/20862505

Vulva http://www.ncbi.nlm.nih.gov/pubmed/25707680

Mons Pubis http://www.ncbi.nlm.nih.gov/pubmed/23444127

Spine http://www.ncbi.nlm.nih.gov/pubmed/25192376

Leg Muscle: http://www.ncbi.nlm.nih.gov/pubmed/19152878

Male cases: http://ijs.sagepub.com/content/22/5/421.long

http://www.ncbi.nlm.nih.gov/pubmed/25298953

Endometriosis Awareness Month – Part 3

Endometriosis awareness month marches forward, quite literally. As you may have seen there have been awareness events taking place in many countries. Women with endometriosis and their supporters have been marching through major cities all over the world to help raise awareness for endometriosis and they have done an exemplary job.

Unfortunately I couldn’t make it to the UK event, but seeing the great turnout in all the cities and all the people who talked about it on Twitter/Facebook/blogs/forums etc, really showed just how much endometriosis awareness has changed for the better in the last decade. It certainly makes me hopeful for the future wellbeing of women with endo.

Speaking of the future, let’s have a look through some of the current research that will hopefully contribute to better prospects for women with endo everywhere.

We start then with a study from Denmark, which assessed the long-term reproductive status of women with and without endometriosis. To do this investigators examined medical records from tens of thousands of women across four national registries from 1977 to 2009.

 What they found was that, over the time course examined, women with endometriosis had around 7% fewer childbirths and 8% fewer naturally conceived children than women without endo. Not a massive surprise there; it’s well known that women with endo can find it difficult to get pregnant. Interestingly though the researchers found that as time went on (from 1980 to 1998), more women with endo had children, suggesting that it takes a long time for women with endo to conceive naturally (of course we must also remember that assisted reproduction wasn’t introduced until 1980). What is quite interesting is that they found that women with endometriosis were more likely to get pregnant with ART than women without by a small percentage.

This study also found that, for women with endo, the risk of ectopic pregnancy was twice that of women without. In addition, there were 21% more miscarriages in the group of women with endo. The reasons as to why this was the case remain unclear, it may be that the presence of active endometriosis in the pelvic area negatively affects pregnancy outcome somehow. Although, as the authors point out, there are other studies that have shown no increased risk of ectopic pregnancies in women with endo, so the jury is still out. In addition this study found that women with endo undergoing ART were at an increased risk of miscarriage, however another recent study found no increase in miscarriage risk. So whilst these studies are informative, they only represent the experiences of a certain population of women. 

One of problems with this study was that some of the women said to be diagnosed with endo, were only suspected to have it, not because they had laparoscopic diagnosis, meaning they may have had endo, or not, or another condition. Another issue is that this study wasn’t able to follow women throughout their entire reproductive life, so they didn’t have a complete picture of all the women’s reproductive history.

Nevertheless, what this study does tell us is that women with endo may require special prenatal care. If results such as these are the same in other countries it certainly suggests that additional provisions need to be made for women with endo (such as better monitoring of foetal and maternal health) and the medical community needs to be aware of this.

Moving on then, from the problems women with endo have to suffer with, to the ways in which the medical community is trying to solve those problems. Laparoscopic surgery is considered the best way of surgically removing endometriosis, but you need a good surgeon at the helm. Another problem is that not all endometriosis can be found and removed easily. One of the most troublesome forms of endo is deeply infiltrated endometriosis (DIE). This type of endo is very commonly associated with the most painful symptoms, such as chronic pelvic pain, painful sex, painful urination and painful bowel movements (depending on where the DIE is and how deep it has infiltrated).

Removing DIE is quite a challenge then, even for a skilled surgeon, which is why some surgeons are now trying robot assisted laparoscopy. Using ‘the robot’ does offer several advantages, such as better precision, better visualisation and more freedom to manoeuvre the instruments. Of course the downsides are that a surgeon will have to learn to use the robot and it is very, very expensive. Another point raised it that using the robot lacks a ‘tactile response’, that is, surgeons cannot feel the resistance or tension of some organs/tissues that might give them an idea of how to proceed with the surgery.

Therefore studies are needed to assess how well robot assisted surgeries fair in removing DIE. That is the subject of a recent paper from centres across the world.  This study looked at robot assisted operative results from 164 operations on women with DIE in different places to see how well the surgeons and patients faired.

Overall the average time for surgery was 180 minutes and the average hospital stay was 4 days, which, given the low rate of complications, seems like a long stay to me, but that may be due to different approaches to post-operative care in different centres/countries. 113 patients were followed up after an average of 10 months and 86.7% were found to be pain free, which is a god result by anyone’s standards.  

Other studies have shown that while robot assisted surgery takes slightly longer and is comparable in outcomes to conventional surgery with respect to stage I and II endometriosis, it may be beneficial for advanced stage endometriosis and has a lower risk of needing laparotomy.  

At the moment then the current evidence suggests that robot assisted and normal laparoscopy perform equally well in some respects, but that robot assisted surgery may be beneficial for women with advanced stage disease. However, more studies directly comparing the two surgical approaches are needed.

I will leave you then with an unusual case of endometriosis. A 52 year old man was sent for a CT scan after complaining about pelvic pain. What the doctors found was an inch long ‘cyst’ that, upon closer examination was found to be a tube like structure, with a muscular layer on the outside and an endometrial layer on the inside. Essentially this was a small uterus, but as it is displaced endometrium it still classifies as endometriosis (or endomyometriosis, to be technically correct). Unlike other male endometriosis cases, this patient hadn’t been undergoing any hormonal therapy and the man in question had no genetic or hormonal abnormalities that could account for this finding. In addition the patient had previously undergone surgery for a hernia near the area in which the ‘uterus’ had been found, so one would think this area of the body would have been examined thoroughly previously, indicating this problem may have arisen quite recently.

June Roundup

Its summer time! If you live in the UK that means you’re enjoying a hosepipe ban at the same time your caravan is floating down what used to be the high street.

Does using the hosepipe to lash yourself to a lamp-post violate the terms of the ban?

Anyway, enough of my stereotypical British weather bashing; we’ve got endometriosis news to go through.

If you read last month’s post you may recall I reported on a case of male endometriosis; “It’s another report of endometriosis occurring in a man” I said, “I say ‘another’ as if it happens all the time, but this is only the fifth or so record of endo in a man, ever” I said, flippantly rebuked myself. Haha, yeh endometriosis in a man, it’s not like it happens every week is it? Well fate sure likes to make me feel like an idiot because, not more than a week after I joked about the infrequency of male endometriosis, there was another case report in the literature. 

A highly realistic portrait of my reaction

Unlike last month’s report though, where the man in question had mysteriously developed endometriosis after taking anti-estrogen therapy for infertility, this latest case is more what you would call a ‘typical’ case of male endometriosis and it just goes to show how strange the world is when the phrase ‘typical male endometriosis’ exists. This reason I call this case typical is because the man in this latest case was an elderly gentleman undergoing long-term estrogen therapy for prostate cancer. Out of the 6 cases of male endometriosis I know of, 4 have been in men undergoing estrogen therapy for prostate cancer. This could be further evidence of endometriosis arising from metaplasia, where some cells in the human body have the ability to transform in endometrial cells given the correct stimulus (which in this case, would be estrogen). Of course it could also be that endometriosis arose in this man due to embryonic rests, where tiny fragments of the primitive female reproductive system are found in men and can become active given the correct stimulus (estrogen, again). Either way, understanding the origin of endometriosis in males, may uncover some of the key mysteries of how endometriosis develops in women, so I’ll be keeping an eye on this.

Seeing as we’re on the subject of strange cases of endometriosis, I nearly fell off my chair when I found an article making reference to endometriosis in horses.  I’ve only ever seen reported cases of naturally occuring endometriosis in primates, so to suddenly see reports in horses threw me somewhat; especially as there were cases of this so-called horse endometriosis going back decades! Has this strange phenomena been under my nose all these years, an important piece of the endometriosis puzzle left ignored?

No, no it has’t. It turns out that when the term endometriosis is applied to horses, it doesn’t mean endometriosis. Allow me to clarify; horse ‘endometriosis’ refers to a progressive degeneration of the endometrium inside the uterus, leading to problems conceiving and retaining foetuses. That’s bad for the horses, but that’s not what endometriosis is. Endometriosis is correctly defined as the presence of endometrial glands and stroma in locations outside the uterus. So, veterinarians have dropped a massive ball on this one and need to come up with a different name for the endometrial degeneration seen in horses, sorry guys, ‘endometriosis’ is taken.

Moving on now to something we’d all like to see, and that’s better diagnostic methods for endometriosis. It seems that research into new diagnostics for endometriosis is really taking off at the moment as I’m seeing more and more papers on the subject being published, which can only be a good thing.

The first of the studies published this month is from Oxford, UK, which looked at whether it was possible to predict the outcome of a woman’s laparoscopy by asking her to fill in a questionnaire regarding her symptoms and other characteristics (such as overall health and previous diagnoses of other conditions). This was a fairly large study including 1,396 women that hadn’t yet been diagnosed with endometriosis from nineteen hospitals across 13 countries. What the researchers found was that by asking the right questions it was possible to identify women most likely to be diagnosed with stage III and IV endometriosis with a good degree of accuracy. This is important for several reasons; firstly it will allow women with a high risk of stage III and IV endometriosis to be identified earlier, thus decreasing diagnosis times. Secondly, if the surgeon knows what to expect before doing a laparoscopy it will make it easier for them to plan ahead with regard to what they are likely to encounter and how to treat it.

Next up is a study from Poland looking at markers to help diagnosis of endometriosis in girls aged between 13 and 19. Specifically these researchers were looking for markers in the blood or peritoneal fluid that may identify young girls as having endometriosis. This study took 50 girls who underwent laparoscopies for chronic pelvic pain and then, depending on the results of their surgery, divided them into two groups. Group 1 consisted of 33 girls who were diagnosed with endometriosis and Group 2 was the remaining 17 girls who had no evidence of endometriosis. The researchers then analysed the blood and peritoneal fluid of the girls from each of these groups for levels of proteins called interleukin-4 (IL-4) and interleukin-2 (IL-2). These proteins are involved in regulating the immune system and are also know to be involved in the process of inflammation. They found that, in the girls with endometriosis, levels of IL-4 were significantly higher in both the blood and peritoneal fluid and levels of IL-2 were lower. This is excellent news as it could be a way of developing a blood test for endometriosis in young girls with chronic pelvic pain, which would decrease diagnosis times and hopefully mean they get treatment sooner. That said, laparoscopy would still be a necessity to confirm the diagnosis because, although an accurate blood test would tell you if endo was present, it wouldn’t be able to tell you where the disease was, how severe it was or if any adhesions are present. It’s still a massive step in the right direction though.

Sticking with novel diagnostics and a study from Atlanta examining the differences in the endometrium between women with and without endometriosis. There have been several studies over the years that have shown that the normal endometrium in women with endometriosis is different in certain ways to the endometrium in women without endometriosis. Most notably the recent finding that women with endometriosis are much more likely to have nerve fibres in their endometrium. This latest study is a logical extension of this as they were looking at the levels of proteins that cause nerves to grow (called neurotrophins) in the endometrium. What they found was that there was a far higher level of proteins called BDNF and NT-4/5 in the endometrium of women with endometriosis. What this means is that there are now ways to identify women with endometriosis purely from an endometrial biopsy. Although this still wouldn’t be able to replace a laparoscopy, it all goes towards reducing diagnosis times and may even be able to predict a woman’s fertility status, giving her the best options for treatment.

Speaking of fertility, you may recall last month I talked about the outcome of IVF in women with endometriosis and how women with endometriosis were more at risk of preterm birth (though the child’s overall health wasn’t affected). Well this month a study may go some way to explain why this might be the case. This latest investigation suggests that it is inflammation that plays a role in preterm birth in women with endo. It has been known for a long time that endometriosis is a disease of chronic inflammation and it’s not surprising when you look a little deeper at how the disease works. We’ve probably all seem pictures of what an endometriotic implant looks like, usually a red or bluey-black spot that grows and bleeds. Your body reacts to this in much the same way it would to any other injury, i.e. it initiates an inflammatory reaction. If you cut your hand this inflammatory reaction speeds up the healing process and helps prevent infection; but inside your body this inflammatory reaction to the endometriosis is persistent and is thought by some to contribute to the pain generated by endometriotic implants. Your body controls the inflammatory reaction by secreting proteins which tell the immune system when and where to initiate it and we find a very high level of these inflammatory proteins in the peritoneal fluid and blood of women with endometriosis. All these inflammatory proteins floating around in your body may have an effect on your ability to conceive and subsequently may also put you at an increased risk of preterm birth. It will probably come as little surprise then that another study, published very recently, found that pregnancy rates were significantly improved after endometriotic implants had been surgically removed.  

A quick rundown of a couple more stories before we end for this month. Starting with a review from authors in Oxford, UK looking at the evidence concerning the age at which a girl starts her periods (menarche) and how this relates to her subsequent risk of developing endometriosis. The authors examined 45 papers published between 1980 and 2011 and found that, once they had narrowed the studies down to those with the best methodology, that a woman with endometriosis is 55% more likely to have started her periods earlier than a woman without endo.  Of course that’s not a massive majority because it means if you picked two women at random, one with endo and one without, only around half the time the woman with endo would have started her periods earlier. It’s still significant though and it raises the question of whether an early menarche is cause or effect, i.e. do you have endometriosis because you started your periods early, or did you start your periods early because you have endo? These questions still remain unanswered.

Finally is a piece of research about vitamin supplementation for the treatment of endo pain symptoms. In the past I’ve read plenty of supposed ‘research’ about vitamin supplements as a panacea for everything from cancer to AIDS and invariably they turn out to be a complete load of bullcrap by some quack doctor trying to exploitatively sell their worthless snake oil to desperate and  vulnerable people.

Your typical cure-all vitamin supplement doctor

However, I am glad to say this latest research is nothing like that and is infact a serious scientific investigation into the effect of taking supplements of vitamins E and C on the painful symptoms of endometriosis. In order to test this the researchers took 59 women with endo and randomly assigned them to one of two groups; one group got the vitamin supplements (1200 IU of vitamin E and 1000mg of vitamin C) and the other group got a placebo (a fake pill that has no active ingredient).  What they found was that the women who received the vitamins had a 43% improvement in everyday pain; dysmenorrhoea (excessive period pain) was decreased 37% and dyspareunia (painful sex) was decreased 24%. Inflammatory markers, like the one I was taking about above, were also decreased in the group who took the vitamins. The one criticism I have of this study though is that it wasn’t double blind, and by that I don’t mean everyone having tape put over their eyes. Double-blinding means that neither the patient getting the treatment nor the doctor administering it knows whether they are having the real treatment or the fake placebo. The reason this is done is because in some people, if they don’t know they’re taking the fake pill, their body will react to the fake pill in the same way it would to the genuine treatment (this is called the placebo effect and we still don’t understand why it happens). But if a patient knows they are getting the fake pill this placebo effect disappears so we can’t accurately compare patient’s reaction to the genuine and fake pills.

It is confusing and no-one truly understands the placebo effect, but it has a real effect on drug trials so it must be taken into account. Nevertheless it is nice to see some proper science going into vitamin research, however I hope this doesn’t become a green light for charlatans to charge £50 for a bottle of vitamin tablets. If you want to try vitamin supplements for yourself I recommend your local pharmacy (I get a month’s worth of vitamin pills from mine for 99p which is roughly $1.50). If it works for you, that’d be fantastic, if not then you never know, next month they might find a cure (hey it has to happen sometime).

May Roundup

It’s an increasingly busy time for endometriosis research at the moment. In the last 31 days there have been 111 articles published on endometriosis, which means an average of just over 3 articles every day. That’s also pretty impressive when you consider that, in the same period of time ten years ago, there were only 33 articles published! So the march of progress rolls ever onward and it’s nice to know endometriosis isn’t being left behind; however this means it’s becoming harder for me to keep up with the research!  I shouldn’t complain really, so instead I’ll get on with a roundup of this month’s top endo research highlights.

I’ll start off with what, at first glance, would appear to be a report from the Twilight Zone. It’s another report of endometriosis occurring in a man. I say ‘another’ as if it happens all the time, but this is only the fifth or so record of endo in a man, ever. I’ve reported on endometriosis in males before and it is a very unusual thing to find for several, probably quite obvious reasons. However, previously reported cases have been in elderly men undergoing estrogen therapy for prostate cancer. The thought behind this was that the estrogen somehow caused certain cells in the male body to transform into endometrial cells. This new report throws a bit of a spanner into the works. If you click on the above link you should be able to read the full article, but basically a man was admitted to hospital with an inguinal hernia (a hernia located just above the testicles, in line with the bladder). Upon surgical inspection a cyst was discovered that was found to have endometriosis within in it. The really puzzling part here is that the man was undergoing anti-estrogen therapy for infertility, so how could the endometriosis possibly have developed? It makes no sense. 

Seriously, this picture makes more sense

 The authors of the paper point out that there are three main theories about how endometriosis develops; transplantation (aka retrograde menstruation), metaplasia and embryonic rest. Transplantation can be discounted straight away; metaplasia could make some sense as it relies on the transformation of tissue under the influence of inflammation or hormones, but the man was taking anti-estrogen medication so that doesn’t quite hold. That leaves embryonic rest theory. This basically states that, during development, microscopic pieces of the tubes which go on to form the reproductive organs end up getting misplaced around the body. These tiny pieces can then go on to develop into what we see as endometriosis. If this was to happen in a man, we would expect to see endometriosis developing along the ejaculatory and diferent ducts, which is exactly what the authors found, so it looks like we have a winner for embryonic rest theory.

Next up is study on the effects of different causes of infertility on the outcome of IVF/ICSI. Many women with endometriosis also present with subfertility or infertility, therefore a higher number of women with endo are likely to employ assisted reproduction technologies (ART) if they cannot conceive naturally. This may lead some women to wonder if all the problems endo causes will have any impact on the health of their baby. This study aims to answer those questions by taking patient records from 255 Finnish women (29 of whom were diagnosed with endometriosis) that had undergone successful assisted reproduction of some variety and comparing them to women who conceived naturally.

What they found was that women with endometriosis who underwent ART were at the highest risk of pre-term birth and thus, were more likely to have babies of low birth weight. However, though this may sound scary, the authors also found that these babies required an amount of neonatal care similar to that of all the other subgroups of women, indicating that though the babies were small, they were also healthy. Interestingly, although this was a relatively small study, it found that women with endo who conceived with ART were less likely to have a previous miscarriage, a chronically ill baby or foetal demise than healthy women who conceived naturally. So if you do have endometriosis and are considering IVF or another type of ART, hopefully this study will put your mind at rest a bit. If you would like to read the full article, you can by following this link.

Moving on now to a couple of studies from our Teutonic cousins; the first of which looks at the age distribution of women with endometriosis. This study took information from 42,079 women who were diagnosed with endometriosis in Germany between 2005 and 2006 and divided them into three age groups; premenopausal (0-45 years), perimenopausal (45-55 years) and postmenopausal (55-95 years). What they found was that the majority of women with endo were in the premenopausal group (33,814 or 80.36%). That doesn’t come as much of a surprise as it’s the largest age group and the one we most commonly find women with endo in. What was quite surprising was the finding that 7,191 (17.09%) women with endo were in the perimenopausal group and 1,074 (2.55%) were in the postmenopausal group; which means nearly 1 in 20 women diagnosed with endo were over 45. This shows that endometriosis does not discriminate by age and that it is important for medical professionals to know that just because your periods have stopped, it doesn’t necessarily mean your endo has.

The second study from Germany examined the cost of endometriosis in terms of in-patient treatment in 2006. Coincidentally this follows on nicely from the previously study which was looking at number of women diagnosed and this one looks at the cost of treating those women. These authors found that a total of 20,835 women were admitted to hospital for endo treatment in 2006 at an average cost of 3,056.21€ each. In total this brings the cost of treating all those endo patients to 40,708,716.26€. That’s just in-patients treatment as well, it doesn’t take into consideration the addition cost of lost work productivity, out-patient costs, or other economic factors that endo impacts on. It wasn’t long ago that I posted about a study that examined the total cost of endo, and if 40 million Euros sounds like a large amount of money, the true cost is likely to be 10 fold.

The final study for this month seems a little controversial to me. Not because there is anything particularly offensive or contentious said, but the conclusions that are drawn are tenuous to my eye. You can read the summary here and make up your own mind, but I’ll tell you what I think. To summarise, the authors of this study conclude that endometriosis is rare in rural, isolated communities such as those in Northern Uganda, because the women there have a high number of children, have more teen pregnancies and a longer duration of breast feeding. An interesting conclusion but I can see several flaws in it. Firstly, I’m not sure I agree wholeheartedly with the opening statement “Women in Western nations are exposed to an "unnatural" high number of menstrual cycles”. Maybe it’s just the way it’s worded, but I don’t like that sentence. I can see where they are coming from; women in Western countries start their periods earlier and have fewer children than those in developing countries. But how is this ‘unnatural’? What is a 'natural' amount of menstrual cycles? Is there such a thing?

Also it doesn’t seem to take into account that women in developed countries have a far greater use of the contraceptive pill, which means fewer, lighter periods. For example, in the UK in 2008, 84% of women of reproductive age were taking the contraceptive pill; compare this to only 15% of women of the same age group in Nigeria (Source: Worldbank, I couldn’t find the stats for Uganda). So surely this indicates that saying women in the Western world have an ‘unnaturally’ high number of menstrual cycles, isn’t necessarily correct.

Another thing that’s bugging me is that, out of the 528 gynaecological consultancies performed over a year at the Ugandan Aber district hospital, only 1 woman was diagnosed with endometriosis thus, the authors conclude, it is rare in this part of the world. However, even in wealthy western countries, there is a very high rate of misdiagnosis and endometriosis specialists who can accurately and thoroughly diagnose the disease are in short supply; so how can you expect the same level of diagnostic accuracy in small rural hospital in a developing nation with no specialist training? It is very likely endometriosis is far more common than reported here, but inadequate facilities and ‘masking’ of the disease by high pregnancy rates leads to under-reporting of endometriosis in this part of the world.

Pictured: The developing and developed world; sadly the one on the right is only marginally better at diagnosing endo than the one on the left

 One last thing is that it’s assumed that number of menstrual cycles (and hence menstruation itself) is important for the development of endometriosis. Whilst there is still some debate about this, consider the fact I have reported (in this post and previously) on cases of male endometriosis, endometriosis in unborn foetuses, endometriosis in women who can’t menstruate and even endometriosis in animals that can’t menstruate. So I’ll leave you to think about how relevant menstruation may be in the development of endometriosis.

The problem is, I’m quite familiar with the work of the authors who wrote this paper and it’s usually enlightening and insightful. This is why I am somewhat dismayed to see this study where conclusions seem to have been drawn hastily and without much thought to alternative explanations.