Endometriosis Awareness Month 2013 – Part V

So another Endometriosis Awareness Month draws to a close and we should all be very proud of the achievements we made, whether it’s telling a friend about endometriosis or delivering the keynote address at an international symposium, everything we do matters. Of course, raising endometriosis awareness is an ever continuing endeavour, but with ever growing numbers of women having their voices heard it’ll not be long before the harmony of the righteous drowns the words of the ignorant.

So for the last blog post of this month I’ll be doing a quick overview of all the research I haven’t had a chance to cover in more detail.

To start us off is a paper examining other medical conditions young women with endometriosis suffer from. This study took 138 adolescent women who were diagnosed with endometriosis before the age of 21 and recorded the prevalence of any co-morbid pain conditions (interstitial cystitis, irritable bowel syndrome, chronic headaches, chronic low back pain, vulvodynia, fibromyalgia, temporomandibular joint disease, and chronic fatigue syndrome), mood conditions (depression and anxiety), and asthma. This study found that 56% of the girls suffered from co-morbid pain syndromes (with IBS being the most common), 48% had mood disorders (with depression being, unsurprisingly, the most common), additionally 26% also suffered from asthma. Interestingly 27.5% of the girls had a first degree relative with endometriosis. What this study highlights is the importance of recognising the signs and symptoms of endometriosis in young women, both by family and medical practitioners, because endometriosis, like many other chronic conditions, often has a greater chance of being treated successfully if diagnosed early.

 I’ve reported previously about the economic cost of endometriosis; it’s a sad fact, but a fact none the less, that if you want politicians and world leaders to take notice of something, tell them how much money it’s costing them. Recently there has been much greater interest in quantifying the economic burden of endometriosis and every study that does so vastly increases the chance of people standing up and taking notice. A new study from Austria does just that by calculating the healthcare costs of endometriosis in the country. This study concluded that, in total, endometriosis costs Austria €328 million (£278 million or $422 million) per year*, which as the authors point out, is comparable to the cost of Parkinson’s disease. The authors also make a good point with their concluding remarks in the abstract “The question arises as to whether more timely diagnosis, followed by better-targeted treatment, might have the potential to reduce these costs”. No doubt it would, whilst at the same time benefiting the patients.

*This may be a rather conservative estimate. If we take the total population of females of reproductive age in Austria (women aged 15-55) we get a total of 2,339,000 (according to The World Bank HNP Stats 2010). If we then assume an endometriosis prevalence of 10%, which would expected for a developed country like Austria, we get an estimate of 233,900 endometriosis cases. If we then multiply this by the average cost per endo patient (€7,712 according to this latest study), we get a grand total of €1,803,836,800 which is an awful lot more than previously estimated.

The fact that endometriosis has to be confirmed via an invasive laparoscopy is always going to get researchers interested in looking at different ways to assess the disease without operating on a patient. Several different imaging techniques exist today that allow us to peer inside the body without having to open it up. One of the best imaging techniques is MRI (Magnetic Resonance Imaging), therefore researchers will naturally want to investigate the use of MRI for assessing endometriosis before laparoscopic surgery. A recent study from Germany took this line of thinking further and examined what locations of endometriosis MRI is best at detecting. This study took 152 women with suspected endometriosis and gave them an MRI scan before they went for laparoscopic investigation. After the laparoscopies had been performed they then compared these results to the ones from the MRI to see how accurate the MRI was.

What they found was MRI seems to be very good at identifying endometriosis of the bladder, reasonably good at identifying endometriosis in the Pouch of Douglas, colon and ovaries, but not that good at identifying endometriosis of the peritoneum, which is a shame because peritoneal endo is the most common form of the disease. Still, refinement of the technique in the future may allow for better imaging of endometriosis prior to laparoscopic surgery, giving surgeons a ‘heads up’ as to where to expect to find endometriosis and hence, be more efficient with excising the disease.

Next is an interesting piece of research from France; this study took data from the French E3N cohort, which is a massive collection of information from 98,995 women aged 40-65 who were given questionnaires  in 1990, then follow up questionnaires every 2-3 years detailing aspects of their lives, past and present. What this study did was to look for those women who were surgically diagnosed with endometriosis (2,684 in total) and compare their early life activities and exposure with other women.  

The results of this study suggested that women with endometriosis had an earlier menarche and shorter menstrual cycles before the age of 17. In terms of environment, women with endo were more likely to have lived on a farm for 3+ months (although there was no link to a specific farm animal), had more exposure to indoor passive smoking, experienced food deprivation during WWII and walked for more than 5 hours a week between the ages of 8-15.

It’s difficult to know what to make of this information though; the results about menarche and menstrual cycle confirm what has been reported before, but the significance of the link to environmental exposures listed is a little harder to explain. The only link I can think of between farm living and endometriosis would be exposure to pesticides, as there has been some evidence linking organochlorine pesticides to endo, but most women with endo don’t grow up on a farm so it’s hard to draw a definitive conclusion. The association with passive smoking and exercise is even more of a head scratcher. Both smoking and regular exercise are thought to lower or attenuate estrogen production, being as endo is an estrogen dependant disease, one would think lower estrogen meant less disease risk, so these results are a bit puzzling.

Of course there are some sources of error that can creep into studies such as this, the main one being recollection. The questionnaires gathered data about environmental exposures from the ages of 8-17, but the participants were already aged 40-65 when the questionnaires were given. I’m 30 and I don’t think I could confidentially quantify how many hours of exercise I had, per day, when I was 8. So although this study certainly gave some interesting results, we definitely need further investigation into some of the associated environmental exposures and endometriosis.

Continuing with the theme of environmental exposures by moving on to heavy metal now and no I don’t mean men with long black hair and multiple facial piercing thrashing a guitar. I’m talking about a study conducted with Sri Lankan women with endometriosis, the aim of which was to assess the levels of Nickel, Lead and Cadmium metal in their blood (you can read the full article for free here). You might wonder what the point of looking at these specific metals would be, especially in relation to endometriosis. Well, it turns out that these metals have been documented as being able to activate estrogen receptors, effectively mimicking the action of estrogen within the body, earning them the name ‘metalloestrogens’. What this study found was that levels of Cadmium and Lead were not significantly altered in women with endo compared to disease free women. However the level of Nickel in the blood of the women with endo was significantly higher. To date there have been very, very few other such studies examining the levels of these metalloestrogens in women with endo so, at the moment, this field of investigation is in its infancy. Nevertheless, it looks like a promising area to follow for those interested in environmental exposures in relation to endometriosis.

The field of drug treatment for endometriosis moves pretty slowly. Drugs designed specifically for the treatment of endo are basically non-existent. Most of the drugs used for endo treatment today have been co-opted/altered from drugs for the treatment of other conditions. For example:

Leuprolide acetate – Initially used to treat prostate cancer

Medroxyprogesterone acetate – Used as a contraceptive

Birth control pills – Contraceptives

Danazol – Used for menstrual disorders (although Danazol was the first drug specifically to treat endometriosis, it is now over 40 years old and has an unfavourable side effect profile).

Recently there has been the development of Dienogest, which although used primarily as a contraceptive, was also designed with endometriosis treatment in mind. But that still means we’re getting a new endo specific treatment every 40 years or so, which is poor progress even by the most optimistic of standards.

In light of the lack of new drugs, other drugs are still being found that should help treat endo; two classes of which are Aromatase inhibitors and Cyclooxygenase (COX-2) inhibitors, which were designed for the treatment of breast cancer and autoimmune conditions respectively. The reason these are used for the treatment of endo is that they inhibit key enzymes endometriotic cells use to synthesise their own estrogen supply. Wouldn’t it be a good idea then, to use these types of drugs in combination to suppress endometriosis? It turns out maybe not. A recent study on mice examining the effect of an aromatase inhibitor (Anastrozole) and a COX-2 inhibitor (Celecoxib) found that, although these drugs worked well on their own to reduce the reduce of the growth of endometriosis, in combination they actually reversed their effects. Studies such as this highlight the need for better testing of drugs ‘borrowed’ from other treatments and the urgent need for drugs designed specifically for endometriosis.

Next up a study assessing the prevalence of endometriosis in women with adenomyosis and leiomyoma (uterine fibroids). This study took 220 women aged 40-50 who were undergoing hysterectomy for adenomyosis and/or fibroids; during their surgery these women had a thorough examination of the pelvic region conducted to look for any endometriosis. This study discovered endometriosis in 28.6% of all the women. Endometriosis was found in 40.4% of the women with adenomyosis only, endometriosis was found in 22.7% of the women with fibroids only and endometriosis was found in 34.1% of the women who had both adenomyosis and fibroids. These results show that these three conditions are frequently found together. It would’ve been interesting to see if these results were similar for different age groups but that’s something for future study.

It’s interesting that endometriosis and adenomyosis are found together so often because they are both characterised by endometrial-like cell displacement (although in adenomyosis the endometrial cells are found inside the muscle wall of the uterus). All together this provides a bit more evidence that endometriosis and adenomyosis are related, possibly established before birth and may even share a similar origin.

 Penultimately, here are a few case reports from the rogue’s gallery of endometriosis appearing in unusual places. First is a report of endometriosis of the perineum and secondly is a case report of endometriosis of the mons pubis.

Finally on our whistle stop tour through endometriosis research is a reminder that endometriosis is not a uniquely human concern. There are 16 species of primate (including ourselves) that can develop endo and it’s no stretch of the imagination to assume that the disease is as horrible for our monkey cousins as it is for us. So we’ll end on a lighter note with a study from Germany looking at medically treating marmosets with endometriosis. The authors of this study noted that marmosets with endometriosis showed significant deviations in social behaviour and cognitive tasks, which is unsurprising if they’re in pain all the time. The researchers gave the marmosets an unspecified medical treatment and noted that it improved their social and cognitive function. So at least it was a happy ending for the monkeys.

Thus concludes this run of blog posts for endo awareness 2013, hopefully you’ve learned something new, I know I have. It’s heartening to know that research into endometriosis is more popular than ever and looks set to gain ever more interest in the future.  

Endometriosis Awareness Month 2013 – Part IV

Rapidly continuing our voyage into endometriosis research over recent times we find ourselves in familiar territory. I’ve always had an inkling that endometriosis is a condition women are born with, but without a body of evidence to support it, it would remain just an hunch. However, over the years I’ve been writing this blog there has been a noticeable growth in evidence supporting the notion that the decision as to whether a woman will, or will not development endometriosis, is made before she is born.

Recently another paper has been published from the research group that identified displaced endometrial tissue, characteristic of endometriosis, in human foetuses. Although this time the researchers were looking at genetic differences between normal endometrial tissue and endometriotic tissue. What they found was that two genes of particular interest were altered in the endometriotic tissue, namely BMP4 and GREM1. What makes these genes so interesting is that both appear to be involved in Müllerian duct differentiation. I’ve talked before about the Müllerian duct and how it is basically the precursor to the female reproductive system during foetal development. The process of differentiation is when cells become specialised to carry out a certain function within the body.  We all started off as a single cell, but in order to become the complex organisms we are, as our cells divided they had to acquire specialisations. So during the development of a female foetus, the Müllerian duct begins to differentiate into the specialised tissue types (such as endometrium, myometrium etc) it eventually becomes in an adult. What this piece of research highlights is that it appears as if, by some as yet unknown mechanism, endometriotic tissue arises because of an error in cellular differentiation during the formation of the female reproductive system long before you are even born.

Continuing along a similar line is the next paper which examines what happened to mice whose mothers have been exposed to hormonal manipulation whilst they were pregnant. This study took pregnant mice and exposed them to a compound called ethinyl estradiol during days 11 to 17 of their pregnancy. Ethinyl estradiol (EE) is a synthetic version of the human form of estrogen; it’s most often used in hormone replacement therapy (HRT) or in combination with a progestin in contraceptive pills. After the mice were born they were kept up to the age of 28 weeks old then killed and their reproductive organs examined. What the investigators found was that mice exposed to EE prenatally developed a far greater number of endometriosis like lesions on their ovaries and adenomyosis was also found to be far more obvious in the uteri of exposed animals.

It’s interesting to note that the authors didn’t record any endometriotic lesions in any other locations apart from the ovaries in these exposed mice. In last week’s post I mentioned a piece of research that subtlety hinted ovarian and peritoneal endometriosis may have different origins and this study also hints at the same possibility (Although, if you want more than just hints, there have been whole reviews dedicated to the difference between the different types of endometriosis, by authors far more knowledgeable than myself).

Of course when considering this latest study we must take several things into consideration. Most importantly that this was a study using mice and although mice make good models for investigating human disease they can never be considered perfect, especially when looking at reproductive conditions. If we look at the difference between the female reproductive system in the mouse and human, not only do they look different, but they function differently as well. Mice, for example, have oestrus cycles (i.e. they can only get pregnant when they are ‘in season’) but humans have menstrual cycles which differ in many ways. Therefore, although this research does certainly gives us pause for thought, we can’t make a leap of suggesting the same hormones will have the same effect in different animals.

Pictured above - not a human (Image courtesy of morgueFile)

 Finally for this week is a study into digestive function after surgery for endometriosis involving the rectum. This study followed 75 women undergoing surgery for deep endometriosis infiltrating the rectum; 24 of whom underwent surgery when more radical methods were in favour, and 51 who underwent surgery when conservative methods were more in vogue. Afterwards each patient was given a number of different questionnaires to assess the health and function of their bowels as well as assessing their overall health, both physical and mental.

This study found that 67% of women undergoing surgery during the radical phase had a colorectal resection (where part of the bowel is removed), compared to only 20% of women who underwent surgery during the conservative phase. Women who underwent the more conservative surgery mostly had either localised excision of the disease or a procedure delightfully known as rectal shaving (Googling that term gives a number of very interesting, but unrelated results, so I’ll spare you the blushes and just link to a relevant video of rectal shaving of endometriosis actually being performed).

After the results of the various questionnaires had been analysed it was found that women who underwent the conservative surgeries fared much better in terms of digestive function and bowel movements than those who underwent radical surgery. Overall this study shows that the ‘sledgehammer to crack a walnut’ approach to removing colorectal endometriosis is not always in the best interests of the patient and more extensive training in conservative techniques is needed for surgeons treating women with endometriosis.

Endometriosis Awareness Month 2013 – Part III

 Endometriosis awareness month continues to power forward and I think this year has already been a major success – the buzz on Twitter, Facebook and all over the internet is incredible. I think 2013 may turn out to be the best year for endometriosis awareness yet and the only way is up!

So without further ado, let’s have a look at a few more selected pieces of endometriosis research that’s been published recently.

First up is a review paper examining all the current evidence concerning the link between chronic pelvic pain and bladder pain syndrome (BPS). The term bladder pain syndrome is often used interchangeably with interstitial cystitis (which is different from bacterial cystitis) and is characterised by painful inflammation of the bladder leading to frequent need to urinate and painful urination.  The cause of BPS is often difficult to ascertain unknown (or requires trial and error investigation to find out).  The above review found that, out of 1016 patients with chronic pelvic pain, 61% had BPS and 70% had endometriosis. Interestingly, in those women with endometriosis, BPS was recorded in 48% of cases. This means that almost half of women with endometriosis may suffer from bladder pain. This raises some interesting questions, perhaps most obviously –what is causing such frequent bladder pain in women with endo? Women with endometriosis are known to suffer from recurrent urinary infections, but this can be distinguished from interstitial cystitis as a urinary tract infection will clear up with antibiotic treatment. Another obvious conclusion could be endometriosis of the bladder is causing BPS. The problem is, endometriosis of the bladder is considered uncommon, occurring in around 1% of patients according to reports. It may be that, because the bladder and places endometriosis is more commonly found are close together, chronic inflammation related to pelvic endometriosis irritates the bladder as well. In order to see whether this were true, it would be useful to conduct a study  following women with BPS and endo, who have had their endometriosis surgically removed and see if their BPS abates after surgery.

 Next up is a study, which you can read in full here, looking at the involvement of macrophages in endometriosis. A good place to start would be asking, what is a macrophage? Macrophages (literally translated meaning ‘big eater’) are one of the many different types of cell that make up your immune system. Macrophages are found in every tissue of the body and their primary job is to ‘consume’ and destroy diseased/cancerous cells or pathogens like bacteria, then send out chemical signals recruiting other immune cells.  Normally macrophages should recognise endometriotic cells as abnormal and destroy them however, as this study points out, in women with endometriosis their macrophages are somehow defective and treat endometriosis as a wound rather than diseased tissue. What this means is that macrophages actually promote the survival of endometriotic cells. As the authors of this review point out though, this opens up quite a novel avenue for the treatment of endometriosis i.e. restore the correct function of these macrophages and let your own body destroy the disease without the need for drugs or surgery. Of course how one would go about doing that, I have no idea and I’m not even sure if the ability to do so exists yet. Nevertheless it’s a fascinating prospect to consider.

Finally for this post is a study looking at whether there are any differences in the clinical characteristics of adolescent girls with endometriotic ovarian cysts (endometrioma). This study took 376 women who were undergoing surgical treatment for endometrioma and divided them into four groups according to age: Group 1 – under 20 years old, Group 2 – 21-30 years old, Group 3 – 31-40 years old, Group 4 – 41-45 years old. The clinical characteristics of these groups (e.g. menstrual history, symptoms etc) were then compared to see if there were any differences or similarities.

Here are some points of interest from the results:

• Most of the Group 1 and Group 2 women sought treatment because of initial pain symptoms (77% and 72% respectively). Women in Group 3 and Group 4 also sought treatment for pain, but at a lower percentage (45% and 40%) with almost half their cases of endometrioma being discovered incidentally

• The authors speculate that adolescents who develop endometrioma may do so because they have more ‘adult like’ menstrual cycles (i.e. regular in terms of duration and timing). Although the authors point out a comparison with disease-free adolescents is necessary to confirm this.

• There was no significant difference seen in endometrioma size, position and stage between the four groups.

• Another interesting finding was that none of the women, in any of the groups, were found to have deep endometriosis. Although it is speculative to say, this does hint that endometrioma and deep endometriosis may have different origins.

It is important that studies such as these are being undertaken. Endometriosis in adolescents has, and still is, a grossly under recognised problem. More studies characterising the disease in young girls means greater awareness and earlier intervention.

 Bonus Content!

The 4^th annual scientific and surgical symposium on endometriosis has been held very recently by the wonderful Endometriosis Foundation of America. This conference brought together expert surgeons, scientists and women with endo from all over America and the world to talk about advances in our understanding of the disease.

If you couldn’t be there and missed the live broadcasts, don’t worry! You can watch all the talks and presentations as streaming videos via this link. They’re well worth a watch; I guarantee you’ll learn something you never knew about endo!

Endometriosis Awareness Month 2013 – Part II

Dietary advice is everywhere these days and the number of myriad ways in which people can shove or not shove foodstuffs down their gob seems to be steadily growing every year. For example Wikipedia lists some of the many, many diets you could go on for various reasons. Being bombarded with so much information regarding what we stuff in our mouths does create a lot of confusion though. Sometimes we will hear that a certain food is good for us, whilst simultaneously being told that same food is bad for us, usually by people with different agendas to push.

If all the general advice we get isn’t confusing enough, we also get regular updates about what foods are supposedly good for certain medical conditions (regardless of whether it is true or not). Endometriosis is no exception to this and there are a number of ‘endo diets’ out there you can follow. Some women find adhering to these diets helps their symptoms, which is fantastic news, however some women find it makes no difference. So it seems to be the case that there isn’t a ‘quick fix’ diet solution that will suit the needs of all endo sufferers and it may be a case of trying lots of things before you find something that works for you. But if you do find something that works, it will definitely be worth it.

One of the problems that compounds the issue of diet and endometriosis is that there has been very little proper, scientific research done examining the effect of different foodstuffs on endometriosis. That said, there have been a few articles published recently examining the role diet plays in endometriosis.

Firstly, there was a study from Italy looking at the effect of a gluten-free diet on the pain symptoms of women with endometriosis. I know some women with endo find that reducing or eliminating gluten from their diet helps relieve their pain symptoms. This study seems to very much confirm this as 75% of patients reported a significant change for the better in their pain symptoms - very encouraging results. However I can’t get full access to the paper so I can’t see whether this study was properly controlled. What do I mean by controlled? Well, in order to eliminate false conclusions from being drawn, studies like this have to take into account any factors that could swing the results away from the true values. Let’s consider the study above, what are the factors that could possibly interfere with the results? Were the women also taking any kind of medical therapy that may also change their pain levels? Did any of the women have surgery during the time of the study? Did any of the women have a gluten intolerance that they either did or didn’t know of or other conditions like IBS or Crohns?  How was the patient’s diet monitored to ensure it was definitely gluten free over the 12 months?

Like I said, I don’t have access to the full version of this article so the authors may well have taken all the above factors into consideration and if you want to try a gluten free diet for yourself, by all means give it a try. However, next time you read a magazine or newspaper article giving details about a supposed ‘miracle diet’, think about how well the study was conducted and whether the people conducting the study did it right.

Next up is a study from the US looking at dietary and health records of 70,556 US women over a 14 year period, so it was quite a large study. What they found was that women who developed endometriosis consumed less dairy products than other women. This finding was in agreement with another, smaller US study published in 2011 which had a similar result. However, these two studies are in conflict with an Italian study in 2004 that found dairy product consumption didn’t significantly vary between women with and without endometriosis. Remember when I said it can get very confusing. And again we have issue with what conclusions can be drawn from these results. Some might claim this information shows dairy products are protective against endo, because women who don’t have endo consume more dairy products. Of course another way of looking at it could be that women with endo may be more likely to have a dairy (or lactose) intolerance, which there is some circumstantial evidence to support, hence why they consume less dairy products. 

"well do you want the milk or not, I've got stuff to do y'know" Image courtesy of FreeDigitalPhotos.net

What we really could do with is a review of all the information published on the relationship between diet and endometriosis, which then gives the results from a pool of data. Conveniently that is the final study I’ll be looking at in this blog post. So this review examined the results of eleven different studies into the connection between dietary factors and endometriosis. What they concluded, from all the information that is worth examining, was that women with endometriosis may benefit from eating more vegetables and less red meat and trans fats. Oh, not exactly a radical breakthrough in our dietary intake paradigm, its good advice for, well, anyone really but not exactly giving us anything concrete and specific about endometriosis.

But that, in effect was the other conclusion of the review. There simply isn’t enough robust evidence at the moment to support a link between any specific dietary component and the risk of endometriosis. This isn’t surprising either when you think about it; every woman’s disease is different and every woman’s dietary needs are different, some may have tolerances and intolerances that others don’t, so trying to say one thing with make a difference across the board just isn’t going to be true.

Fortunately a lot of women with endometriosis do find modifying their diet can help reduce their symptoms, unfortunately though it may involve a bit of a trial and error.  Just don’t try anything extreme, for example the Breatharian diet (in fact a good rule is, if a diet has a silly sounding name, just avoid it) and if in doubt consult a doctor or dietician.