Saturday, 30 March 2013

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.  

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