The Big Picture

As the Olympics have got well underway in my home country this month, I thought I would hold my own competition; but this isn’t one of sporting prowess, this is a competition to see who the best endometriosis researching country in the world is. Every time I look through the research on endometriosis I notice there is a lot of it coming from all sorts of different places. I report here about individual stories of interest but wouldn’t it be good to see all the research in a wider context, and who is the best at it?

Endometriosis is a global problem, it impacts negatively upon all the countries of the world both in terms of monetary value and in the surfeit of suffering the condition lays on all those affected. To that end then, it would be interesting to see which countries are at the forefront of tackling the problem of endometriosis, and which countries are falling behind. So over the last month I’ve been doing some research of my own to try and answer questions about the global scale of endometriosis research.

Let’s dive straight in and see how much research into endometriosis has been going on over the years. The graph below shows the number of articles published on the subject of endometriosis between 1925 and 2011. NB Click on any image for a bigger version

Research publications on endometriosis over time

As you can see it’s looking pretty good; the amount of research published on endometriosis has increased quite rapidly. In fact the research output over the last 11 years is double that of the preceding 60 years!

I suppose the next question to ask would be - where is all this research coming from? The map below shows which countries have produced the most research in endo over the years; the darker the country’s colour, the more research it has produced.

Map of endometriosis research published by country

Some surprises here. For example, did you know that Iran has published more research on endometriosis than Ireland? Or that Kenya has produced more endo research than Russia, despite the fact Russia is 30 times larger than Kenya. Unsurprisingly we can see that the vast majority of endometriosis research comes from North America, Western Europe and Japan. These countries (and continents) have always been the big hitters in the field of endo research, especially the United States, who lead the pack by quite some way. That’s an understatement really; according to the Scopus citation database the United Kingdom is the second most prolific endo research producing country in the world, with 1,659 articles published, which is pretty respectable. The UK however, looks like a dinghy compared the vast aircraft carrier of the United States contribution of 5,541 articles. With that in mind I thought it would be interesting to focus on the US and see which states are producing the most endo research. So I put together a map similar to the one above but just for the US.

Map of endometriosis research publications by US state

So it looks like New York, California and Texas are leading the pack with a pretty poor show from Idaho, Montana and Nevada.

Of course, what I’ve been showing thus far is all the research conducted to date, but how has the output of the world’s endometriosis research changed over time? To answer that the next few pictures show maps of the Top 10 endometriosis research producing countries, namely: United States, United Kingdom, Japan, Italy, Germany, France, Belgium, Spain, Canada and Australia, but I’ve also included four of the ‘up and coming’ countries of endo research, namely: China, Brazil, India and Turkey.

Each country is represented by its flag, and the size of the flag represents the proportion of its research output compared to the other countries. Let’s start with the groovy era of the 1960’s.

1960's

It’s plain to see where most of the endo research came from during these turbulent times. That said, between all the countries we are looking at, only 48 research articles were published on endometriosis during this entire decade. Let’s disco dance into the 1970’s and see how this changes.

1970's

Well the US still retains its dominance, but an important point is that out of the 14 countries we’re looking at, only 6 were doing any endo research in the 1960’s. By the end of the 1970’s, 13 out of our 14 countries were now doing some endo research. Also the amount of endo research published has increased by nearly 1500%, which is the highest increase in endo research in the entire history of the world! Let’s see how the mullet clad scientists of the 1980’s faired.

1980's

The 1980’s was known for many things, and most of these things involved unforgivable crimes against fashion. But in terms of endo research there were a few changes during the 80’s. Certainly research output from Western Europe and Japan increased. Japan in particular secured its place as the rising run of endo research by overtaking the European powerhouses of Germany, France, Italy and Britain.  Let’s see if this continues into the 1990’s

1990's

Whilst the fashion wasn’t much better in the 90’s, the global scale of endometriosis research was changing for the better. Japan and the UK grew in their output, as did Spain and Italy. France and Germany, whilst still generating a respectable amount of research, actually shrank a tiny amount. Belgium, despite being only a little country, showed it could hold its own against bigger countries like Canada and Australia. Also we see the sudden emergence of Turkey, a country that only produced two articles during between 1960 and 1989 suddenly, during the 90’s produces forty articles in one decade. Moving on to more recent times now, and the period between 2000 and 2011.

2000-2011

Well there’s a change; every country grows apart from the US (don’t worry American readers, it only shrinks relative to the other countries, the US still produces well over half the total endo research). The UK and Italy overtakes Japan; Belgium, Australia and Canada also make some decent growth. But by far the biggest surprise is China, Brazil, India and Turkey who explode onto the research scene, no doubt due to the economic surge in these countries. These four countries put together only produced less than 3% of the total endo research in the 1980’s, but produced 13% of the total output during the last 11 years. China in particular has, in the 2011-2012 period, overtaken most European countries except for The UK and Italy. Brazil and Turkey are both in hot pursuit. If the current trends continue, in the next ten to twenty years, these up and comers will be the dominant forces in the field of endometriosis research; but can anyone challenge the top spot of the mighty US? That remains to be seen. 

So far we’ve looked at certain countries and their research output, but what about the centres of endometriosis research within these countries, who can boast begin the best? Below is a leader board of the top ten endometriosis research producing institutions and their associated countries.

No surprise the see the US well represented here again. It’s also a rather excellent achievement for the University of Sao Paulo, ranking 5^th in the world is no mean feat, especially as they have only relatively recently started putting serious effort into endo research. But the gold medal goes to the University of Milan, felicitazioni! to you my friends.

To finish though, I think we need to acknowledge the individuals who contribute most to taking the monster of endometriosis by the horns and trying to beat it into submission. Below is a list of the Individuals who have contributed most to the field of endometriosis research by way of peer reviewed publications.

The world owes a great debt of gratitude to these people who work so tirelessly to better understand endometriosis and, if one day, I could make it onto that list, I would go to my grave a happy man. Of course it doesn’t end here, there are many, many people out there deserving of our praise; from doctors to awareness raisers, advocates, scientists and women who refuse to be defeated by endometriosis. There are too many of you to name, but you know who you are and you are all an inspiration.

If our collective was a living being and each of us represented a different part of that being, the excellent doctors who understand a woman’s struggle would be the healing hands; the researchers and scientists would be the enquiring mind, always thinking ahead; and the women who suffer this disease? You who face it every day, yet in facing it do not allow it to overcome you? You would be the heart and soul, you are the driving force without which the world’s interest in endometriosis would wane and grind to a halt. When the cure for endometriosis arrives, it will be because of someone like you.

All information on published works were retrieved from the Scopus database, where the title/abstract/keyword contains the word ‘endometriosis’ published up to the end of 2011 unless otherwise stated. Additionally, countries that no longer exist (such as the Soviet Union or Czechoslovakia) were not included in the search.

Only articles using the Greek/Latin term endometriosis were included in the search, therefore some articles which use language specific variations of endometriosis would have been omitted.

For the US map, a search was conducted for articles where the state affiliated with the article was given; therefore some publications will have been missed.

For the top ten lists only articles which contained the word ‘endometriosis’ in the title were considered. For the institutional and individual lists, research output was quantified by total number of publications over all years.

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).

New Study for Couples Living with Endometriosis in the UK

Living with endometriosis generally isn’t much fun, there’s an understatement. The disease puts so many extra strains on your life and relationships, yet it’s this personal aspect of the disease that often goes under recognised in the research. So wouldn’t it be nice if someone tackled this issue to help raise awareness about how difficult it is to live with endo and at the end of it, maybe find a way to help people be more understanding? Well, are you someone currently in a relationship living with endometriosis that resides in the United Kingdom? Then you may be eligible to take part in some research aimed at getting a better understanding on how endometriosis impacts relationships.

Here is an outline from the research team of the work being carried out

                                                                                                                                                 

Endopart - Endometriosis: Improving the well-being of couples

Would you and your partner consider taking part in research about your experience of living with endometriosis?

Researchers at De Montfort University, Birmingham City University and the University of Nottingham are carrying out research into the impact of endometriosis on couples in the UK. The team will use the findings to make recommendations about how women with endometriosis and their partners can best be supported and how care can be improved. The research, led by Prof Lorraine Culley, has been funded by the UK Economic and Social Research Council and has received ethical approval.

The team would like to interview heterosexual couples living in the UK:

.       who have been living together for at least one year,

.       where the woman has experienced endometriosis-related symptoms for at least one year and

.       where the woman has a diagnosis of endometriosis following laparoscopy.

Each partner will be interviewed separately. Findings from the study will be anonymous. If English is not your first language the team can arrange for an interpreter to be present.

If you and your partner would be interested in taking part:

.       Visit www.endopart.co.uk to find out more and register your interest online or

.       Contact Caroline Law, Research Assistant, at claw@dmu.ac.uk or on 0116 2506124.

                                                                                                                                                

If that sounds like something you’d be interested in I heartily encourage you to check out the website and get in touch. I can recommend it especially as my wife and I have already taken part and I’m also an advisor to the research group, so it comes with my own personal seal of approval (if I had one).

From my own personal experience I can say the interviews are informal and relaxed, the people who do the research are lovely and you also get a £20 shopping voucher for taking part!

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.

April Roundup

2012 seems to be flying by - April is already drawing to a close and soon summer will be upon us. Of course here in England that just means the weather switching sporadically from raining so hard it feels like the ocean is trying to climb onto the land, to irradiating levels of sunshine so intense a hydrogen bomb would seem like an air conditioner. 

But I digress, on a more relevant note you’ll be glad to hear that, even though endometriosis awareness month has come and gone, research into the disease is still carrying on apace. There hasn’t really been any one big piece of news that has caught my attention this month, so instead I’ll do a rundown of all the little bits of endometriosis research, from diagnosis to treatment, that have been published recently.

To start with; getting diagnosis. In order to get diagnosed, you first have to go see your local doctor, an activity many women with endometriosis will know does not always go well. So firstly, a report from France about how much knowledge general practitioners have about endometriosis diagnosis and care. To test this, the study gave a 36 item questionnaire to 100 doctors from a region of upper Normandy. The survey found that 63% of respondents were “ill at ease in the diagnosis and follow up of women presenting with endometriosis”. I’m not entirely sure what they mean by “ill at ease” but it doesn’t sound like a good thing and certainly doesn’t seem representative of a professional attitude.

According to this survey half of the doctors surveyed couldn’t name three main symptoms of endometriossis and only 24% would refer the patient without delay. Unsurprisingly the authors found that general practitioners were much more likely to give better answers if they had attended advanced gynaecology courses or followed up more patients who had been diagnosed with endometriosis. It seems then that if these advanced gynaecology courses are available to general practitioners, they should be made mandatory.

So let’s say you do get referred to a specialist, the next step is getting your condition confirmed. Traditionally this is done laparoscopically, but an interesting report from the Netherlands on the development of a new type of diagnostic method for endometriosis may change that in the future. Whilst the good old fashioned laparoscopy can’t be beat for accuracy and precision (in the right hands), it would be nice to have a different method for detecting endometriosis that didn’t involve having to be knocked out and cut open. Step up then ‘gadofosveset-trisodium enhanced magnetic resonance imaging’, I’ll not go into the technical details because frankly I don’t know what they are.  Basically it is a modification of the MRI detection system which is a scanning method that allows us to see inside your body, much like x-rays but without the radiation. The gadofosveset-trisodium is a chemical that is injected into the body to help the MRI pick up blood vessels more easily. Importantly though this method makes it easier to distinguish between older blood vessels and newer blood vessels which the endometriotic implants would grow to survive. The authors of this study testing the technique on mice that had been induced to have endometriosis and found that the newer blood vessels from the endometriotic implants did show up clearly on the MRI scan, meaning this technique could one day be used for the non-invasive detection of endometriosis in humans.

Onto medical treatment now, which is usually the first line approach to endo treatment. The drugs we have for the treatment of endometriosis are many and varied, some are quite good, others not so much. But if you’re trying to develop a new drug, where do you start? In the past scientists would turn to Mother Nature for inspiration and, although synthetic drugs are fairly dominant today, we still haven’t lost sight of the old ways.  This is highlighted by two studies which have looked at the potential of compounds extracted from plants as possible treatments for endometriosis. The first of these studies found that compounds called Kaempferol and Apigenin, which were extracted from red clover, showed some positive effects on endometrial cells grown in the lab. The trouble with this is that endometrial cells grown in the lab are very different from the cells found in endometriosis, so whether or not these compounds will have any real benefit remains to be seen.

The second study looked at a compound you can extract from hops called Xanthohumol. This study was a bit more in-depth than the first because they induced mice to have endometriosis, gave some of them the Xanthohumol and then observed what happened. What they found was that the mice given Xanthohumol had smaller endometriotic implants and the blood supply feeding the implants was also reduced.  These studies are encouraging because it means people are actively seeking new and better therapies for endometriosis and another advantage of these compounds is that they are non-steroidal, so should have much fewer side-effects. 

Hops - Source: Wikipedia

Red Clover - Source: Wikipedia

Speaking of medical treatments, a study was published recently concerning the effectiveness of a relatively new endometriosis drug called dienogest (also marketed as Visanne™). Unlike other drugs which are more commonly used for other reasons (such as the birth control pill), dienogest was designed specifically as a treatment for endometriosis. To put dienogest to the test this study took 252 women with endometriosis and gave 124 of them dienogest and 128 of them leuprolide acetate (also known as Lupron™) over a course of 24 weeks. To assess the effectiveness of each treatment the authors questioned the women about their endometriosis symptoms and their health overall.

The results of this study showed that dienogest and leuprolide acetate performed equally as well at reducing the symptoms of endometriosis; most of the women noticed a dramatic decrease in pelvic pain, dyspareunia and dysmenorrhoea.  However, it was when comparing overall health that the differences really start to show. The patients who took dienogest had much, much greater levels of improvement in overall physical and mental health, indicating that dienogest is much better tolerated and has far fewer negative side effects.  The authors of the study put this down to the fact that, unlike leuprolide acetate, dienogest doesn’t cause a huge decrease in estrogen levels which leads to some of the nasty side effects you can get with leuprolide acetate.

From medical treatment to surgical treatment. Some of you may have heard about the Da Vinci Robot system that can be used by surgeons to aid them in performing delicate operations. For those that haven’t heard about ‘the robot’, it’s basically a remote operated series of robotic arms (see picture below) that, according to the marketing on their website, makes minimally invasive surgery quicker, simpler and increases recovery rates. The trouble is there haven’t been many studies concerning how safe the robot is in real world use; although that is most likely because the robot hasn’t been in use for very long so large, long term studies concerning its safety probably won’t be coming out anytime soon. Nevertheless, a study was published recently from Taiwan where 60 patients underwent robot-assisted surgery for a number of different gynaecological conditions (including two resections of deep pelvic endometriosis). What the surgeons found was that robotic surgery “is feasible and safe for patients with complicated gynecologic diseases” and “surgeries were performed smoothly without ureteral, bladder or bowel injury” which is encouraging. The only problem is these surgeries were performed by specialists surgeons with a great deal of experience, it would be good to know how less experienced doctors fair with the robot before coming to any conclusions about its overall safety. 

The Da Vinci Robot System - Source: davincisurgery.com

Lastly, it turns out endometriosis is not a uniquely human condition. I’ve wrote here before about endo occurring in non-human primates, but a report from Japan was the first to find endometriosis developing spontaneously in a female Mandrill.

This is the happiest picture of a Mandrill I could find - Source: Los Angeles Zoo

Now on Twitter!

Well I've finally decided to get with the times and join twitter, if you want to follow this blog to get regular updates on endometriosis research you can @EndoUpdateBlog

Endometriosis Awareness Month: Part 6

This will be the final part of my endometriosis awareness month posting marathon; over the last few weeks I’ve noticed I’ve gained a lot more followers, which is great, so a ‘welcome’ and ‘thank you’ is deserved to new and old followers alike. I hope that I’ve managed to impart some useful knowledge over the last month because I’ve learned so much from women with endo over the years.

For the last post of this month I’m going to do a quick rundown of some of the top endo-related research highlights I haven’t had a chance to cover in full.

A study from Italy examined the incidence of endometriosis in the area of Piedmont and found that women from the South and Central provinces were at, in some cases, a 30% increase in risk of endometriosis than those women in the South-West. The authors of this study suggested that heavier pollution in these regions could be a contributing factor; however it is also possible that different populations in the different provinces may carry certain genetic mutations that make them more susceptible to endometriosis.

Another study from Italy found that women with endometriosis were more likely to be right handed and less likely to be left or mixed handed. Apparently handedness is determined whilst you are still in the womb and due to exposure to certain hormones, so there may be something to that. This study also found that there was no association with birth order, their mother’s age, smoking habits, weight gain or morning sickness. There was also no association between endo and having a low birth weight, being premature or whether or not you were breast fed.

Some good news for a change in the findings from a study in Denmark. This study looked at medical records for women diagnosed with endometriosis and registered to the Danish Hospital Discharge Register from 1977-2007, encompassing a grand total of 37,661 women, and checked to see what other medical conditions they presented with. This, rather large, analysis concluded that women with endometriosis were not at an increased risk of multiple sclerosis, systemic lupus, erythematosus, or Sjogren syndrome, yay!

Urinary tract endometriosis (UTE) was the subject for this article from France, which found that of the 221 women selected to undergo laparoscopic surgery for severe endometriosis, almost a fifth had some involvement of endometriosis on the urinary tract. Unsurprisingly the most common symptoms of women with UTE were dysuria (painful urination), blood in the urine and frequent need for urination. Fortunately, the authors noted that surgical treatment was very effective and diagnosing UTE can even be done with a non-invasive MRI scan.

To California now and a report of endometriosis found in the para-aortic lymph node (which is in the centre of your body, on roughly the same level as the kidneys) in a pregnant woman with a previous history of ovarian endometriosis. The authors state that this could be evidence that endometriosis can spread via the lymphatic system, however as this was the first ever reported case of endometriosis in this location, drawing such conclusions may be premature.

And finally, the award for the most self-explanatory article title goes to this paper.

Wishing you all well and see you again in April!