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.  

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.

Endometriosis Awareness Month: Part 5

Hot on the heels of a previous report comes another study examining the burden of endometriosis on the individual and society as a whole. This one is a bit more in depth though, taking information from 909 women from 10 different countries including: Belgium, Denmark, Germany, Hungary, Italy, Netherlands, Switzerland, UK and USA. The women who took part in this study were given specially designed questionnaires that would assess the impact of endometriosis on their lives and included questions on a number of subjects from health care costs to work loss and quality of life. What makes this study different then from all the previous studies that have examined the costs of endometriosis? Well, this study is the only one I know of that has taken women from multiple countries, also other studies have usually only focussed on one aspect, such as health care or work productivity, never both.

But enough of the details, what did this study actually discover? The main finding from this study was a number, €9,579, equivalent to $12,635 or £7,990; this was the average cost of endometriosis per woman, per year. This breaks down to an average €6298 lost in work productivity and an average €3113 for health care costs (which is similar to health care costs of diabetes, Crohn’s disease and rheumatoid arthritis). So with those numbers in mind let’s do some maths. If the average total cost of endometriosis per woman is £7,990 (I’ll work in British pounds because that’s what I’ve got in my pocket) and the UK has approximately two million endo sufferers, this means endometriosis costs the UK economy around £15,980,000,000 per year (The authors of the study reported it as £8.3billion, but they estimated the prevalence at only 7%). That is what we technically call, in the scientific community, a shitload of money. Feel free to re-do the calculation for your own country and sit back and be shocked by how much money is being lost by governments who ignore endometriosis.

Endometriosis Awareness Month: Part 3

At what age did the symptoms of your endometriosis appear? A lot of women I’ve spoken to have told me that their symptoms appeared not long after they started their periods, and certainly, a great deal of women with endo find their symptoms were in full force by the end of adolescence. Of course, no matter when the symptoms began, the most universal challenge women with endometriosis face, is getting those symptoms taken seriously so a diagnosis can be made. Therefore, wouldn’t it be great if there were a set of guidelines regarding pelvic pain that doctors could use to flag up potential cases of endometriosis in young girls to speed up the whole diagnostic process.

Hopefully that is a reality not far off. Several studies published over the last few years have tried to formulate a procedure that will increase accurate diagnoses of pelvic pathology in young girls. It goes something like this; if girl complains of excessively painful menses, first off give her non-steroidal anti-inflammatory painkillers (NSAIDs) for three months. If these fail to work give the patient oral contraceptives and suggest referral to a gynaecological specialist for further assessment. That’s about it really, pretty simple. Of course it’s not that simple, because we must educate the patient (and doctors) about the different kinds of pain girls can present with.

For example, the most common pain symptom in women with endometriosis is dysmenorrhoea, or excessively painful periods. But what classes as excessively painful? Yes, pain is subjective, but if the pain is becoming debilitating (i.e. it is forcing you to take time off from school/work on a regular basis) then this is excessive and needs to be taken seriously and investigated further.

Then there is also chronic pelvic pain (CPP). This is pain that occurs in your pelvic area, either with or without your period, that lasts for over 6 months. If a girl is presenting with both CPP and dysmenorrhoea, this should raise a red flag with any doctor worth his salt.

Then we come to the ‘dys’s’, these are other pain symptoms frequently associated with endometriosis, such as dyspareunia (painful sex), dyschezia (painful bowel movements) and dysuria (painful urination). Any of these pain symptoms, especially if they occur more frequently during menses, are all indicators for doctors to be aware of it they are to get a rapid diagnosis and prevent undue suffering.

But why might some doctors be reluctant to refer girls to specialists? There is the age old “I know better, just get on with it” ignorant attitude that many women have to deal with, but doctors are also being put under pressure, especially these days, not to refer girls to specialists because of the cost implications, but let’s think about it logically for a second. If a girl is presenting with pain symptoms indicative of endometriosis at a young age, surely it would be better to send her to a specialist as soon as possible to get the problem treated whilst she is still young, rather than waiting until she is older and more likely to need multiple surgeries/treatments.

Getting endometriosis treated quickly not only makes more sense from a patient centred approach, it also makes sense from an economic approach, especially when you consider the impact endometriosis in adult women has. Let’s put it in political (i.e. monetary) terms. A study from Canada estimated the cost of endometriosis to be $5,200 per patient, per year for surgically confirmed cases of endometriosis. This adds up to a hefty $1.8 billion annually in Canada just for surgically confirmed cases of endometriosis. Where are these costs being incurred though? Obviously there are the medical costs, but endometriosis is incapacitating, so it affects all aspects of a woman’s life. A study from Puerto Rico amply demonstrates this by assessing the quality of life and work productivity of women with endometriosis. What they found was that women with endometriosis presenting with quality of life scores “denoting statistically significant disability in the physical and mental health components”. I should probably point out that when they say significant disability in the mental health component, they are referring to mental aspects of the disease such as stress and depression, they’re not suggesting you’re all mentally handicapped!

The study goes on to say women with endometriosis lose, on average, one day a week in work time due to the disease symptoms. Lose 13% of work time, lose 64% of work productivity, have a 65% impairment of work and a 60% impairment of daily activities.

All those billions of dollars lost, all those hours of life spend needlessly suffering, all that time lost, all those lives ruined; where does all this lead back to? To the diagnostic and treatment delays in endometriosis. If the disease is diagnosed and treated early and effectively we can begin to eradicate the negative impact it has. So, to all those people, doctors, nurses, family, partners, anyone, who dismisses and marginalises the suffering women with endometriosis must endure, you are not only catastrophically harming the life of an individual, you are damaging society as a whole.

Tick, Tock, Tick, Tock

Those of you with a better memory than mine may remember a post from July last year about the cost of endometriosis in terms of lost work hours. Well since then some more information has come to light and I’ve been doing some calculations. Specifically, how much loss of earnings can be attributed to endometriosis? I therefore apologise for the mathematics that follow, but rather than just shout numbers, I’d rather go through the sums with you (mostly because if I’ve made a mistake or my logic is flawed you can chastise me in the comments).

So let’s get started, first off I’ll be concentrating on the United States as there is more data available from there. How many women have endometriosis in the U.S? The short answer is simply ‘we don’t know for sure’ but we can take an educated guess. It is universally stated that endometriosis affects around 10% of women of reproductive age (i.e. between the ages of 15-65 years old), so how many women of reproductive age are there in the U.S? According to the U.S Census Bureau there were 102,161,823 women of reproductive age in 2008. To estimate the number of women with endo we need 10% of 102,161,823 which is 10,216,182.

Now we need to know how much endo is costing each woman, according to the WERF study last year each endo sufferer loses an average of 11 hours per week, so that’s 572 hours per year. According to the U.S Bureau of Labor Statistics, the average female wage was $20.90 an hour in 2009. So, in order to approximate how much loss of earnings can be attributed to endometriosis we calculate:

(Number of women with endo) X (Number of hours lost per year X Average wage per hour)
Or
(10,216,182) x (572 x 20.90) = $122,132,416,160 per YEAR

Or to put it in slightly more sensationalist terms $3,971 per SECOND

Now, seeing as most of the money people earn goes back into the economy in the form of tax and spending, can the U.S government afford to ignore endometriosis in such times of economic uncertainty? It may be worth asking your local representative. Investing more money into treatments and diagnosis for endometriosis is a directive that can be ill ignored by any government.

Now I must point out that these numbers are just estimates based on the information available so don’t go quoting them as fact, the real cost could be lower or higher. Although, as these calculations don’t take into consideration the additional cost of people caring for those with endo, or welfare paid out or the cost to the healthcare system, it is likely to be much higher. Nevertheless it gives us a good idea of what to expect, nearly four thousand dollars a second, tick, tock, tick............