A free e-book on pelvic pain

This month seems to be the month for free online books. This time its an e-book on pelvic pain, which I know will be relevant to many of my readers, by Dr Susan Evans and Ms Deborah Bush.

Topics covered include:

• Period Pain
  


• Endometriosis
  


• Bowel and Bladder pain



• Painful Sex



• Fatigue and more
  

To download the book follow this lin

http://www.drsusanevans.com/e-booklet.html

and click on 'Click here to download'

Free online book on heavy menstrual bleeding

This may be of interest to some of my readers, but I noticed that the National Collaborating Centre for Women's and Children's Health and the National Institute for Health and National Institute for Health and Clinical Excellent have published their guidelines for the assessment and treatment of heavy menstrual bleeding (HMB), a problem that can affect women with endometriosis.

To read the guidelines in their entirety follow this link

http://www.ncbi.nlm.nih.gov/books/NBK56536/

and click on ‘PDF version of this title’ in the right hand margin

Although the guide is aimed more at clinicians, I think it contains a lot of relevant and interesting information for patients who suffer with heavy menstrual bleeding. The guide covers such topics as:

• How we define HMB

• The risk factors for HMB and its prevalence

• How doctors should assess and test for HMB

• Education for women about HMB

• Medical and surgical treatments for HMB

Although these guidelines have been drawn up for the use in the UK, the evidence upon which the guidelines have been based was taken from international studies and are applicable to women all over the world.

Highlights from the WCE 2011: Part 2

Another set of interesting bits from the World Congress on Endometriosis 2011, so let’s get started with...

S. Banerjee from St Peter’s Hospital, Chertsey, UK (S#2-5) presented their work entitled

Identification of non-invasive markers of peritoneal deep infiltrating endometriosis in women with chronic pelvic pain.

The aim of this study was to record the symptoms and clinical observations of a group of 401 women with chronic pelvic pain. These women would then go for diagnostic laparoscopy to find the cause of their pain, then the results from the pain surveys and observations would be analysed to show if there is any difference between women with different diagnoses.

After the laparoscopies 167 women (42%) were diagnosed with deeply infiltrating endometriosis (DIE), 150 (37%) were diagnosed with superficial endometriosis and 84 women (21%) were found to not have endometriosis as the source of their symptoms. So, the focus of this study was to look at the difference in demographics and symptom profiles of women with DIE and compare it to women with superficial endometriosis to see if there were any significant differences that may help identify DIE before diagnostic surgery. This is how those factors broke down: women with DIE were on average 31 years old compared to 33 years old for those without. Dyschezia (painful bowel movements) throughout the month, a clinically immobile uterus, a palpable nodule, and the presence of an endometrioma (ovarian endometriotic cyst) were all more common in women with DIE. Interestingly, the authors then quantified the risk; so if all the above factors were present in one woman from this group, this raised their chance of being diagnosed with DIE from 42% to 82%. Conversely if all the above factors were absent it decreased the chance of them being diagnosed with DIE to 10%.

In conclusion this study will hopefully allow gynaecologists to identify women who have the highest chance of being diagnosed with DIE from the features of their pain symptoms and clinical observations, which in turn should make it easier for surgeons to know what they are looking for.

M.Takamura from University of Tokyo, Japan (S#4-1) resented the results of their study entitled

Probiotics inhibit the growth of endometriotic lesions in a murine model

You’re probably aware of some of the various commercial probiotic yoghurts and drinks available on the market at the moment, I must confess I have a probiotic drink myself with breakfast (it’s an acquired taste, I’ll tell you that much). Basically these products contain live bacteria that are supposedly beneficial to ones digestive system, if the marketing is to be believed. According to the authors of this study, these probiotics are recently gaining attention due to their ability to modulate the immune system in a favourable manner. This got the authors thinking that, due to the many immune system abnormalities associated with endometriosis, perhaps these probiotics may illicit some beneficial effects against the disease.

The way in which they studied this was to use a murine (mouse) model of endometriosis. Basically this involves surgically inducing endometriosis in a mouse. Now, although I’ll not go into detail about the positives and negatives of animal models, I will say though that despite the fact mice make excellent animals in which to model diseases and have a large amount of similarities to humans in more ways than you’d expect, in terms of modelling reproductive diseases, mice don’t have a menstrual cycle and have a distinctly different reproductive systems to humans so the true value of using mouse models may be someone questionable. Nevertheless it is one of the best tools we have, so until better comes along, we’re stuck with mice.

The authors then administered various doses of probiotics (containing such inventively named bacteria as L.acidophilus, L.casei, Bifidobacterium bifidium and Streptococcus thermophilus) to different groups of mice and noted any effects they had on the size or number of endometriotic lesions. Overall, the results of the study showed that mice receiving oral doses of the aforementioned probiotics suppressed the development of endometriotic lesions, reducing the size/growth, but not the number, of lesions. The authors note that, if this treatment works in a similar manner in humans, that fact that it causes no alteration to hormone levels may be beneficial for women.

G.M. Buck Louis from National Institute of Health, Rockville, USA (S#4-5) presented work from their collaborative research group entitled

Persistent organic pollutants and endometriosis: importance of biologic media for defining exposure – the endo study.

Now, talking about the relationship between endometriosis and environmental pollutants is opening a rather large can of worms because there are arguments both for and against the involvement of environmental pollutants in endometriosis. The arguments ‘for’ work on the premise that the mode of action of a lot of pollutants should increase the likelihood of developing endometriosis due to their ability to mimic estrogen and negatively affect the immune system in the human body. The arguments against rightly point out that the evidence supporting the role of pollutants in endometriosis is sketchy at best and, at present, does not prove any links between pollutant exposure and increase endometriosis risk in humans.

This study has obviously aimed to address some of the issues surrounding previous studies and provided a study with, from what I can see, is an extremely comprehensive methodology (which I’ll not go into here as it will take up too much space and may induce sedative effects). The study took women from 14 clinical centres undergoing laparoscopy or MRI for the diagnosis of endometriosis, then gave them questionnaires and took samples of blood, urine and fat and analysed the levels of various pollutants in these samples. The important difference to this study was the inclusion of analysing fat samples from women. Previous studies frequently use blood for analysis, but the problem with that is pollutants are transferred from the blood and accumulate in fatty tissue around the body, so sampling fat would be a much better indicator of pollutant exposure.

The results showed that the levels of several polychlorinated biphenyls (PCBs) and hexachlorobenzene were significantly higher in the fatty tissue (but not blood or urine) of women with endometriosis. This further highlights the importance of selecting the correct biological sample when looking for relationships between environmental pollutants and endometriosis. It also adds weight to the argument supporting the role of environmental pollutants in the development of endometriosis, how exactly these pollutants elicit their effects remains to be conclusively proven.

Highlights from WCE 2011: Part 1

As I mentioned briefly in my last post I attended the 11^th world congress on endometriosis in Montpellier a few weeks ago. It’s a tough life having to travel to beautifully picturesque Mediterranean cities, but hey, somehow I managed to cope. The main body of the conference was run over three days where experts from all over the world presented their latest research and shared up to date knowledge about endometriosis. If you would like to see the whole program for the conference you can download it here. All in all it was a very enlightening few days, but don’t worry if you couldn’t make it yourself because over the next few weeks I’ll be posting highlights from the conference. Unfortunately, I can’t post about everything that was discussed because it would probably take more years to write than I will live, so I’ve gone through the different talks and posters and picked out the ones that I hope you’ll find the more interesting. I’ll start off with the oral presentations that were given then move onto the posters that were presented. I’ll also give a bit of my own interpretation of the science, but I won’t be doing much critical appraisal. So without further ado, let’s jump straight in.

R.S. Bevan from the Brighton and Sussex Medical School, UK (S#1-3) presented their work entitled ‘Alcohol consumption and endometriosis: A multi-centre, case-control study’

This study took 1,418 women from 10 countries that were undergoing laparoscopic surgery for either suspected endometriosis or tubal ligation. After surgery the main group were divided into three groups: Those who were found to have endometriosis (745 women), those who had symptoms but no disease was found (565) and those women undergoing sterilisation who had neither symptoms nor endometriosis (86). These women were asked to complete a questionnaire which gave included questions about alcohol consumption.

The results of this study showed that alcohol consumption between the three groups of women did not significantly vary. Although there is still more analysis of this data to be done it is still interest to see these preliminary findings. I think there may have been some expectation that alcohol consumption may be increased in women with endometriosis, perhaps due to the fact alcohol can give pain relief, so the results are interesting from that pint of view. There was also some discussion as to whether alcohol consumption increases the risk of endometriosis. I’m not sure whether or not this is folly. Mainly because the symptoms of endometriosis tend to begin around adolescence, but alcohol consumption doesn’t even seriously start for most people until their late teens, so I’m sure whether there could really be any connection between the two.

S.A. Missmer from Havard Medical School in Boston, US (S#1-4) presented their work entitled ‘Vitamin A and endometriosis risk: A prospective cohort study’

This study analysed consumption of different micronutrients in 1382 women with laparoscopically diagnosed endometriosis. What this study found was that increased consumption of vitamin A seems to reduce the risk of endometriosis. Or rather, I should say, reduced the risk of being diagnosed with endometriosis. These investigators reported a 21% reduction in risk of diagnosis of endometriosis when comparing the highest consumers of vitamin A with the lowest, with the association most prominent in women with no history of infertility, who had a BMI below 25 and who had smoked during their lifetime. The investigations are still undergoing to find out why this reduction in diagnosis risk was observed.

M.Kvaskoff from The Gustave Roussy Institute, France (S#1-5) presented their work entitled

‘Early life events and the risk of endometriosis: The French E3N cohort’

This study analysed questionnaire data from a large group of women with health insurance in France. The purpose of this study was to see if women with endometriosis had exposure to different factors during childhood that made them more susceptible to endometriosis in later life. This study found that both exposure to cats or dogs at home and living on a farm for more than 3 months during childhood increased the risk of endometriosis in later life.

Girls who started their periods before the age of 12 or who had short menstrual cycles before the age of 17 (a short cycle being anything less than 24 days, were also found to be at a higher risk of endometriosis.

Whilst the level of out if school exercise was unrelated to endometriosis risk, more time spent walking (i.e. greater than 5 hours per week) between the ages of 8 and 15 appeared to increase the risk of endometriosis. Higher exposure to UV radiation at place of birth was found to decrease endometriosis. There were a number of early life factors that were found to have no influence over the risk of endometriosis including: birth height/weight, being born premature, breast feeding and maternal smoking.

So what do we make of this study? Well firstly it is important to distinguish causal factors from incidental factors. What do I mean by causal and incidental? Firstly I’ll stop asking rhetoric questions, then I’ll tell you that a causal factor is a factor that is likely to actually increase the risk of endometriosis, whereas a incidental factor is one that is associated with a causal factor so appears to be associated with endometriosis even though it could have no baring directly on the development of the disease.

Let me give you an example; this study found that young girls who undertook more walking exercise were at higher risk of endometriosis. Does this mean that we should stop all young girls from walking so much? No, because if we look at the rest of the results we can see that girls who lived on a farm were at higher risk; girls who lived on a farm are likely to do more walking, so we can see that walking isn’t directly linked to endometriosis risk, rather it is incidentally linked to endo via other factors (such as childhood environment).

More highlights coming soon!

A quick update about emailing blog posts

Just a quick update to let you know about a feature I've enabled. If you've read one of my blog posts and you know someone who you think it may be of interest to, you can now share that blog post by clicking on the little symbol at the bottom of each post that looks like this:

and then filling out all the relevant bits on the page that pops up, easy!

Wishing you all the best

Matt

My First Publication!

Well it’s been a busy week, I’ve just returned from the 11^th world congress on endometriosis in France, where I learnt a lot of new things about endometriosis, met a lot of experts in the field and also had a bit of time to enjoy the Mediterranean weather. I’ll be talking about the conference later, but before that I'm going to wallow in immodesty by talking about my very first proper scientific publication on endometriosis entitled “The emerging role of epigenetics and microRNAs in endometriosis” which was published in the Journal of Expert Reviews of Obstetrics and Gynaecology. You can find a link to the abstract here but unfortunately this isn’t the sort of journal you could go down to your local newsagent and pick up. You may also be slightly disheartened to see that in order to read the full article you have to pay $60 (£30) for the privilege (I hasten to add I don’t receive a penny of that money).

Should you be willing to pay the publisher’s charge then that is all very fine and dandy and I hope you enjoy the drive home to your palace in your gold plated Ferrari. If however, you would like to receive the general gist of the article there is a way to access the information it was based upon which would incur you no extra cost. You see, the article itself is taken from what I wrote in my master’s thesis, so if you could read my master’s thesis, you would have a good idea of what is in my article. Fortunately, my university have started keeping an online repository of all recently submitted theses in an electronic format, including mine, which you can find and download here in PDF format.

However, it would be pretty rude of me to just say “here’s my work, enjoy” then stroll off into the sunset, without putting it in context, particularly because the esoteric nature of scientific literature means it is often inaccessible to the public. It would also be pretty silly of me to dedicate this blog to explaining the scientific work of others without explaining my own, so here goes.

The subject of my work, in this instance, concerns the involvement of epigenetics and microRNAs in endometriosis and how the disease originates and progresses. If you’re reading this then chances are you don’t need me to explain endometriosis, but I’ve had several requests to clarify what are epigenetics and microRNAs. The term ‘epigenetic’ loosely means ‘on top of genetics’, so we should probably explain genetics before we tackle epigenetics.

In broad terms genetics is the study of DNA and the way in which it works. DNA is the universal code for life, some of you may have seem this picture before

Image source

That is the structure of the DNA molecule, made from just a handful of different elements joined together in a special arrangement; it is a long list of instructions for making you. Encoded in that double stranded helix is a great deal of information about you; from the colour of your eyes, to the shape of your nose, it dictates the fate of many a feature we use to describe ourselves. Almost every cell in your body contains DNA, and it is a large set of instructions by any account. In total, human DNA contains around 30,000 different individual instructions and each of these instructions we call a ‘gene’. The purpose of most genes is to produce a protein which carries out a specific function. Some of the proteins produced are enzymes that make hormones; others are receptors that allow cells to communicate with one another, the list of functions is quite literally staggering, but all work together to keep your body running. So how do we go from DNA to protein?

Firstly the instructions in the gene have to be read. In order to do this the double strands of the DNA split apart and are transcribed by an enzyme called polymerase. This transcription produces messenger RNA, essentially little pieces of single stranded DNA that contain the information to make a single protein. The messenger RNA then travels to a protein called a ribosome which translates the messenger RNA by bringing in transfer RNAs which have amino acids bound to them. As the transfer RNAs bind to the messenger RNA the chain of amino acids grow longer and as the chain grows it begins to fold into a specific shape that will dictate the function of the protein. Sometimes it is better to visualise these processes as a diagram so below is a picture of the whole transcription and translation process.

Image source

An easier way to think about the whole process is to imagine it as a construction site. The gene is like a blueprint to make a house (protein). The information in the blueprint (DNA) is relayed by the foreman (messenger RNA) to the construction workers (transfer RNAs) who, using their building materials (amino acids), build the house (protein).

So where does epigenetics fit into the picture? Well, genetics only tells us what proteins should be made; it doesn’t tell us when they should be made. It is an interesting fact that the DNA in all your cells contains all the genes to make any protein. For example, the cells in your fingers contain the genes to make teeth and the cells in your brain contain the genes to make kidneys. Why is it then, that we don’t have teeth-hands or brain-kidneys? Well this is where epigenetics comes into play. Epigenetic mechanisms are like switches that can turn genes on or off. There are several epigenetic mechanisms, but the ones I have studied most are DNA methylation and microRNAs.

DNA methylation involves sticking methyl groups to DNA which stops the process of transcription; microRNAs on the other hand act by binding to the messenger RNA, either stopping it being read by the ribosome or signalling that the messenger RNA be destroyed. If we go back to our construction site analogy; DNA methylation would be like someone taking a black pen and blanking out all the bits of information on the blueprint that aren’t needed. MicroRNAs would be like lawyers, who stop the foreman and tell him he can no longer build. Epigenetic mechanisms such as these are extremely important for making sure that your cells function properly, any errors in the way these mechanisms work can be disastrous for your body.

I’m hoping my cobbled together explanation of genetics and epigenetics has made at least some sense, but how does it all fit into endometriosis? Well, there have been several studies that suggest that epigenetic mechanisms malfunction in endometriosis. Despite the work of a few pioneering scientists, our understanding of the subject is not complete by any means as epigenetics is a relatively young field of science, having only really existed for the last 20 years or so. Nevertheless, epigenetics has told us a great deal about the way in which complex diseases like cancer work, so the aim of my article was to take what we do know so far and see what it can tell us about some of the mysteries of endometriosis.

I’ll summarise what I wrote about in my paper, and keep it brief for everyone’s sake.

• There are altered patterns of DNA methylation in endometriotic cells that may explain why they are so resistant to drugs and how they can produce their own estrogen supply

• The pattern of microRNAs is different in endometriotic cells compared to normal endometrium, this could explain a number of features of endometriosis, including some of the immune system abnormalities associated with endometriosis

• The altered pattern of microRNAs and DNA methylation could also potentially explain the rare instances when endometriosis of the ovary can turn into ovarian cancer

• Because microRNAs are also found in the blood, the pattern of microRNAs in women with endometriosis may be different from that of disease free women (I found out only last week that this has been experimentally proven). Therefore, this could lead to a simple blood test for endometriosis

• · Epigenetic errors can be brought on by exposure to certain environmental toxicants. These epigenetic errors can be passed down family lines. This means that some pollutant that your mother, or even your grandmother, was exposed to may have increased your risk of developing endometriosis.

I’m currently writing another paper where I hope to expand on the role of epigenetic mechanisms in the malignant transformation of endometriosis. But enough of this self-congratulatory ego-massaging, as I mentioned at the beginning of this post, I’ve just returned from the 11th world congress on endometriosis so for the next few weeks I’ll be putting up ‘mini-posts’ about some of the more interesting things discussed at the conference.

You’re never too old, or too young

Quick, if I were to ask you to name any times in a woman’s life when she shouldn’t suffer from endometriosis, what would you say? Most likely, anyone with a basic knowledge of the disease will say premenarcheal (before her periods start) and postmenopausal (after menopause) because endometriosis is a disease dependant on hormones, right? So before and after the time a woman can menstruate there should be no chance of endometriosis developing, it’s just logical to think that way.

Well if life teaches us anything, it’s that some things are not logical, and endometriosis is one of those things. In terms of logicality, endometriosis is kind of like sticking your head in a washing machine filled with Salvador Dali and M.C Esher paintings.

Pictured: endometriosis

Because of this there are cases (albeit very rare cases) of endometriosis occurring in young girls and older women. Of note there have been reports of symptomatic endometriosis in girls as young as 8 and in women as old as 80. So how can we explain these odd, seemingly illogical occurrences, can we even explain them?

The answer is a resounding “well, sort of”. Endometriosis in postmenopausal women is perhaps the easier of the two entities to explain. Postmenopausal women may be taking hormone replacement therapy (HRT) which would provide any endometriotic implants with a steady supply of estrogen to keep them going. Some reports have even stated that postmenopausal women taking HRT have an increased, but poorly defined, risk of previous endometriosis recurring.

But (and there is always a ‘but’ to complicate matters), there have also been reports of postmenopausal women with no past history of the disease, suddenly developing endometriosis. There are a number of explanations for this though. Firstly, the woman may have had endometriosis lingering in her body all along, and any number of contributory factors may have suddenly caused it to grow. Secondly, if the woman has had any major surgery in her pelvic area (e.g. hysterectomy, oopherectomy etc) tiny bits of the endometrium may have been spread around her pelvic cavity during surgery, which may then implant to form endometriosis later on (this mechanism is thought to be one of the ways surgical scar endometriosis occurs).

An unanswered question remains though, if a woman is past menopause and not taking HRT how does the endometriosis get the estrogen it needs to survive? After menopause a woman’s ovaries begin to shut down and a drastic reduction in estrogen production occurs over a period of about 4 years. However, androgens are still produced, albeit at a diminishing rate, by the adrenal glands and ovaries after menopause. Androgens are another group of hormones that could loosely be described as being responsible for the development of masculine characteristics. Women also produce androgens, but at a lower level than men and androgens in women can be converted into estrogen. However, you need certain enzymes to convert androgens to estrogens, the most famous of which is aromatase.

Aromatase is an enzyme whose job it is to take hormones like testosterone and convert them into estrogen. Aromatase is expressed in a number of cell types including the ovaries, fat cells, endometrium and guess where else? That’s right, in some but not all, endometriotic cells too. This means that any endometriotic implant that expresses the aromatase enzyme can essentially make its own estrogen. Even with the low levels of androgens produced in postmenopausal women, endometriosis with active aromatase could produce its own estrogen and hence survive in a woman who has gone through the menopause.

Well, you may think, that all sounds very plausible but is there any evidence to substantiate this little theory of yours? Good question and yes there is. You see, there is a group of drugs called aromatase inhibitors that are sometimes given to women with endometriosis and there are no prizes for guessing that these drugs inhibit the aromatase enzyme. In some cases of women with postmenopausal endometriosis there is evidence to suggest treatment with aromatase inhibitors can significantly reduce their symptoms. Of course, the problem with aromatase inhibitors is that they decrease estrogen levels even further, which if you are past the menopause it probably going to lead to complications and adverse side effects.

But what of premenarcheal endometriosis? There is, some good evidence, which I have mentioned previously, concerning the discovery of displaced endometrium, a hallmark of endometriosis, being found in unborn human foetuses. Conveniently, the research group who made these previous discoveries have recently published another paper of their largest study yet confirming the cells that preclude endometriosis can be found in girls before they are even born. So, it would appear we have a possible answer for why such young girls can develop endometriosis; the bigger question though is how, and therein lies the rub.

At present the ‘how’ is the unanswerable question. Is there any reasonable explanation for how girls who haven’t even reached puberty can develop endometriosis? There are of course arguments that environmental pollutants can bring about the development of endometriosis, but the evidence for this is rather weak and highly debated so we can’t (or rather shouldn’t) draw any conclusions from that particular line of evidence, yet.

There are so many factors which are thought to influence the development of endometriosis such as; genetics, epigenetics, diet, lifestyle, environment, immune function, family history, that we may never have a singular cause for endometriosis. Some women may inherit it, some women may acquire it. Perhaps we need not think of endometriosis as one giant jigsaw to be pieced together; perhaps we need to see each case as its own, individual puzzle.