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.
