Wednesday 23 January 2019


Hello readers, my big news for the new year is that Endometriosis Update has now moved to a new, fancy looking site

All my new blogposts will be published there and I'll also gradually move updated versions of my old posts over their too

in the meantime, if Instagram is your thing, you can follow me @endoupdate as well for shorter research highlights and links

Wednesday 28 November 2018

The Kids Aren’t Alright – Part III

One of the biggest challenges in endometriosis today is the reduction in the time to diagnosis. Depending on where you are and what healthcare access you have, the time from initial onset of symptoms to diagnosis can be between 4-7 years (on average, but I’ve known individual cases which can be as short as a few months, or as long as 25 years). Obviously this is a continuing and serious issue affecting women with endo - delayed diagnosis means delayed treatment which means prolonged suffering. Of course it’s all very well and good me saying that diagnostic times need to improve, but how might that actually be achieved?

Awareness and education about endometriosis for both young girls and medical professionals is a great way to improve knowledge about the condition and therefore raise the bar in terms of quality of care received. It’s heartening to see that all the hard work of patient advocacy groups and charities has noticeably increased the presence of endometriosis in the collective consciousness. In the UK I’ve noticed far more awareness and promotion of endometriosis in just the last six or seven years. By some measures this appears to be working – in one study conducted in the US girls and women under 18 and over 18 with endometriosis were surveyed about their experience of the disease so far. The average time between symptom onset and surgical diagnosis for the under 18’s was 2 years, for the over 18’s this was 5 years. Hopefully this represents a trend of decreasing diagnostic delay for the future.

One of the key steps here is increasing endometriosis education for young girls (and it should be said, boys too). Why is educating young girls so important? A survey of over 4,000 adult women with endometriosis found that 67% experienced the onset of symptoms during adolescence. I’ve included some links at the bottom of this article that show endometriosis is not a disease of the ‘career woman’ as was the harmful stereotype for so long, it is a disease of the young girl, which becomes a battle for the adult woman.

Education of course would entail teaching girls about the signs and symptoms of endometriosis, along with how it is managed and treated. However, we’re making an assumption that endometriosis symptoms are the same in young women and adults. Several small studies in the past have been inconclusive as to whether adolescent endo is the same as adult endo in terms of symptoms and characteristics of the endometriosis lesions themselves. Some studies indicate that the physical appearance of endometriosis lesions in younger girls tends to represent ‘earlier’ stages of the disease, with atypical, subtle or red lesion types being more common in adolescents. This indicates that 1) endometriosis in young girls may be extra difficult to diagnose due to subtly of the disease, and 2) endometriosis may be progressive, becoming more advanced with age, highlighting a requirement of early intervention for effective pain relief and preservation of future fertility.

A larger systematic review of studies into adolescent endometriosis looked at results of multiple studies into the stages of endometriosis in adolescent and adult women, their findings are represented on the graph below

Adolescent data is that of those girls without failure of hormonal suppression. Adult data taken from this study,

So, while advanced stage endo does occur in adolescents, it is less common than adults. A larger study on the symptoms of endometriosis in women and girls under and over 18 found that, overall, there weren’t many significant differences in the symptom profiles, indicating symptoms of endo tended to be similar in young and adult women. Some of the key symptoms that were more common in adolescents were: non-cyclic pain that did not get better with hormone treatment, and nausea accompanying pelvic pain. These authors also found that, like adults, pain in adolescents interfered with school, work, socialising and sleep, but gastrointestinal symptoms also significantly interfered with these daily activities too. Young girls may find discussing symptoms related to periods, menstruation and gastrointestinal problems embarrassing, therefore are unlikely to openly talk about them. It is therefore important for educators, parents and doctors to have the information in these studies available to give to their children.

So far this post has focussed on the symptoms and type of disease found more frequently in young women and girls with endo. But what about the way in which endometriosis affects their lives? A recent study investigated this by giving quality of life surveys to 360 girls with surgically confirmed endometriosis (cases) and 207 girls with no history of endo (controls) between the ages of 10 and 24.

The quality of life surveys came in two parts, first a physical health component that covered: general health, bodily pain (limitation due to pain), role limitation (problems with work/daily activities) and physical functioning (the ability to perform any physical activity). Secondly, a mental health component that covered: mental health (feelings of anxiety and depression), role limitation – emotional (problems with daily activities due to emotional health), social functioning (interference with social activities due to physical and emotional problems) and vitality (levels of energy/fatigue).

The results of this study showed that the case girls scored significantly worse in every component on both physical and mental health aspects. This was particularly noticeable for general health, bodily pain, role limitation, social functioning and vitality.
A particularly interesting finding was the prevalence of anxiety and depression in young women in this study. The graphs below shows the percentage of participants reporting anxiety, depression and exercise avoidance during menstruation.

As you can see, young women with endo suffer more with mental health conditions and will withdraw from physical activity during menstruation far more than their endo-free counterparts. It is well known that anxiety and depression are more common in adult women with endo than adult women without endo, but seeing that this trend starts so early in life highlights how important early intervention for endometriosis are, not just for physical health, but mental health too.

Perhaps unsurprisingly, this study found that pain was the biggest impactor of quality of life in young women. Pain appeared to be the only factor in this study to be linked with a decrease in mental health quality of life score too. What is quite interesting is that lower quality of life scores, in particular for physical health, were also associated with starting periods before the age of 11. Another interesting finding was that underweight girls with endometriosis had lower physical quality of life scores than their normal weight counterparts. The reason this is interesting is that it fits with other research suggesting that lean or underweight body size during childhood is associated with an increased risk of endometriosis as an adult.

The question therefore arises, does low body weight cause an increased risk of endometriosis, or does endometriosis cause a low body weight in young women? Although there isn’t much research available to answer this question, one study (using a mouse model of endometriosis) suggests that endometriosis is associated with altered gene expression in the liver, leading to altered metabolic activity favouring leanness. Whether or not this is true in humans, remains to be seen.

Although this has not been a comprehensive examination of all the literature related to endometriosis in young women, we have seen that the signs of endometriosis can present at an early age, and that the symptoms of the disease can be just as bad in childhood as they are in adulthood. Given the negative impact that endometriosis can have on a young person’s life both physically and mentally, recognising the signs of the disease, treating girls’ concerns as valid and giving them effective treatment is the only way endometriosis can be tackled for future generations.


Want to know more? Here are some links to selected free articles on endometriosis in young women


Friday 23 November 2018

Bowel Surgery for Endometriosis

Hello again readers, 2018 is rapidly drawing to a close and I’m making an early new year’s resolution to update this blog more often, it is called ‘endometriosis update’ after all and I feel I haven’t been doing enough updating.

I recently had the pleasure of being invited to the Endometriosis Research Now! Conference in London organised by Endo UK, the World Endometriosis Research Foundation and supported by the Wellcome Trust. I gave a talk on the way in which scientific evidence about endometriosis is portrayed and how we can critique this evidence (pretty much everything I covered in this post from earlier in the year). It was a great day meeting other endo specialists and hearing the voices of women with endo to learn more about what I can do to further awareness. More on that to come in a later blogpost though when all the promotional material has been sorted by Endo UK.

For the subject of this post I’m going to talk about a recent study analysing the results of bowel surgery in women with endometriosis. You can read the full text of the source article here for more detailed information about the study.

Some forms of endometriosis can penetrate deep into the pelvic organs, one site in which this can occur is the tissue that divides the vagina and the rectum, called the rectovaginal septum (you can see some common sites of rectovaginal endo here, and learn more in the yellow fact box below). This form of endo can present a particular set of challenges when it comes to management and treatment of the disease. Evidence is mixed concerning the effectiveness of medical therapy for rectovaginal endometriosis, so surgery is often recommended as the preferred treatment choice. But what are the outcomes of this surgery, and how effective is it at managing symptoms of the disease?

A recent study published in the British Medical Journal examined data from 4,721 women undergoing planned surgery for deep rectovaginal endometriosis between 1st January 2009 and 30th June 2016 in centres belonging to the British Society for Gynaecological Endoscopy ‘Endocentres’ (specialist endometriosis treatment centres where patients are treated in multidisciplinary teams and surgeons audit their outcomes. For a list of such centres, see this link).

The authors of this study recorded a lot of information on these patients, in particular their pain levels, symptoms, bowel functioning, drug treatments, surgery complications, and quality of life surveys called the EQ-5D-3L (EQ5D) and the EuroQoL Visual Analogue Scale (EQVAS). All this data was recorded before surgery and at 6 months, 12 months and 24 months after surgery to see how/if any of those recorded factors had changed.

Let’s get right into the findings, starting with pain symptoms. For this study they asked the patients to rank their pain on a scale of 0-10, with 0 being no pain at all, and 10 being the worst possible pain.

Below are some graphs showing the average before and after surgery pain scores for different symptoms in the patients who participated in this study

It’s good to see that, on average, the pain scores decreased for all types of pain symptoms after 24 months post-surgery. In particular, cyclical and non-cyclical dyschezia (painful bowel movements) were lowered, although cyclical dyschezia did seem to increase slightly again after 2 years. Whether this represents a return of the disease or not requires further study.

So, pain symptoms are reduced after rectovaginal surgery, does this translate to improved quality of life? The graphs below show scores representing results of the two different quality of life surveys (the EQ5D and the EQVAS). The higher the number of each score, the better the average quality of life.

In both cases these scores increased and remained higher after surgery. This means factors like levels depression and anxiety got better, mobility increased and ability to do daily activities increased too. 

Another way to assess whether or not the results of the surgery was successful, is to look at the use of medication before and after the surgery. The graphs below show the different types of medication the women in this study were using (i.e. paracetamol, NSAID – non-steroidal anti-inflammatory drugs like ibuprofen, or opiates like codeine) and the average percentage of people using that medication type before and after their surgery.

Overall the use of any type of pain medication, on average, fell sharply at the 6 months after surgery point, but crept back up slightly at the final 2 year point. This is consistent with some of the other graphs showing slight pain recurrence at the same 2 year point. While the use of pain medications is reduced after surgery, for paracetamol and NSAIDs their use still hovers in the 50-60% range, meaning more than half of women still needed to take pain medication. Whether the continuing need for pain medication is just due to rectovaginal endometriosis related symptoms, or to other types of endo, or other conditions all together, needs further clarification.

One of the tricky parts of rectovaginal surgery is that it can deal with operating on a particularly challenging organ – the bowel. Your bowels are in pretty heavy use all the time and work hard to move digested food where it needs to go. So operating on this sensitive part of the body can, rarely, result in complications arising during, and after surgery. Below is a diagram showing the percentage of perioperative complications, that is, complications arising during surgeries in this study.

 As you can see, the vast majority of surgeries went without complications. Of the few complications that did arise, the majority were unexpected injuries, or the need to covert the laparoscopic surgery to laparotomy. Both of these are manageable by a multidisciplinary team such as the ones used in this study and, although it means further monitoring of patients after the surgery is complete, it wouldn’t necessarily mean the patient didn’t get a good outcome.

Those are the complications that arose during surgery, what about complications that came about after surgery? The diagram below shows the percentage of post-operative complications.

 Again we can see that most women didn’t have any complications after surgery. Of those that did, the most reported type of complications were pelvic haematoma (when blood collects outside the blood vessels), pelvic abscess (as the result of infection), bowel leak (bowel incontinence), and bowel fistula (a hole that forms between one organ to another). All of these complications are manageable as long as patients stay aware of any unusual symptoms after surgery and report them to their doctor as soon as possible.

Of course, not all types of surgery are the same, depending on the type and extent of endometriosis, some will require more complex or extensive removal, and so, have the potential to lead to more complications. The graph below shows the percentage of complications arising depending on whether the surgery involved any bowel surgery at all, bowel shaving (where a thin slice of the bowel surface is removed and any endometriosis excised), disc resection (where a small section of the bowel is cut out), or segmental resection (where a larger portion of the bowel, plus a small part either side of the affected area, is removed and the remaining parts joined back together).  

From these results we can see that, although complications were overall infrequent, disc resection and segmental resection had the higher complication rate. This is perhaps unsurprising given that these techniques do involving cutting into and removing part of the bowel, but it is also a testament to how advanced surgery techniques and skills have become that so few complications do occur.

What are the overall conclusions of this study? You can draw your own from the results I’ve shown here, but I think the main take home message is that complex surgery for the removal of endometriosis, especially when it involves the bowel, requires a multidisciplinary team of experienced surgeons. When it is done right, rectovaginal surgery for the removal of deep endometriosis decreases pain scores and symptoms, and improves quality of life over at least a two year period, so women with endometriosis need to have access to these specialist treatment options to effectively manage their condition.


Thursday 12 July 2018

And Now for Something Completely Deferent

I’ve wrote before on the subject of unusual presentations of endometriosis, mostly because they’re like a fascinating puzzle to unpick within the vast puzzle that is endometriosis, like a jigsaw made of rubik’s cubes. But it’s not only the inherent fascination with such oddities that interests me, but the fact that the unusual ways in which endometriosis occurs could tell us a great deal about how endometriosis arises in the vast majority of other cases. Perhaps the most unusual presentation is male endometriosis. I’m not talking about endometriosis is trans-men (mostly because there is little to no research in this area, which is a definite shame and something I would like to see rectified sooner rather than later), but endometriosis in cis-gendered males who, by all logic, should not be able to develop a condition that is typically associated with the uterus. It is something that should be impossible, but it happened anyway. I have covered this topic before, but there was another case report published in January of this year so I think its worth looking at this one and going over what this could mean for endometriosis in the wider context.

The case report (link to the full text article here) describes a 40 year old man who came to his doctor with intermittent abdominal pain moving down his right side, described as “a constant dull ache with intermittent sharp pains” and “feelings of being bloated with progressive abdominal discomfort”, is it sounding familiar to anyone yet? Aside from asthma and being a bit obese the patient was medically unremarkable, no long-term serious illnesses or unusual medical conditions to hint at what might be the cause of his pain, he didn’t even present with any other symptoms that would give the doctors a clue as to what the cause of the pain might be (like painful urination, painful/bloody bowel movements or diarrhoea that may indicate an infection or gastrointestinal issue). So the doctors decided to perform a series of scan and found a mass, measuring roughly 9cm x 5.6cm (about the size of a avocado) between the bladder and the rectum apparently arising from the vas deferens (the tube that takes sperm from the testicles to the prostate and the inspiration for the incredibly tortured pun the title of this post). If you look at figure (a) at this link you’ll be able to see it as the roundish, pear shaped object roughly halfway between the small white bit near the bottom and the long white spine.

The doctors concluded the mass was a fluid filled cyst of some kind so decided to perform a laparoscopy that then became a laparotomy to fully explore the pelvic area and remove the mass, which was then sent away to the lab for testing. When the results came back they had a “highly unexpected” diagnosis of endometriosis. The cyst was filled with a cloudy brown fluid while the lining was composed of endometrial epithelium and stroma (the cells you would normally find in the endometrium or an endometriotic cyst). In fact, the description of the cyst they found has some definite similarities to ovarian endometriotic cysts. The question posed then is, where on earth did it come from? Perhaps the few other case reports of endometriosis in males could help answer this.

The authors of this case report have gone through the literature and found all the other cases of endometriosis in males, which you can find in the link to the full text, but I’ll briefly summarise below

Patient Age
Location of Endometriosis
Risk Factors
Prostatic urethral crest
Not reported
Estrogen therapy for prostate cancer
Not reported
Attached to bladder
Stabbing pelvic pain
Surgery for hernia, liver chirrhosis
Swelling of the testis
Hormone therapy for prostate cancer
Surgical removal of testes
Scrotal pain
None reported
Between vas deferens and testes
Mass felt on epididymis
Hormone therapy for prostate cancer
Surgical removal of testes
Attached to bladder
Lower abdomen pain
Surgery for hernia, liver chirrhosis
Lower abdominal wall
Not reported
Hormone therapy for prostate cancer
Not reported
Not reported
Hormone therapy for prostate cancer
Not reported
Blood in urine
Hormone therapy for prostate cancer
Abdominal pain
Cancer of the testes
Surgical removal of left testicle
Ureterovesical junction
Swelling of the kidney
Hormone therapy for prostate cancer
Not reported
Ductus deferens
Discovered during hernia repair
Surgery for hernia
Ureteral orifice
Blood in urine
Hormone therapy for prostate cancer
Found within a tumour of the testes
Cyst next to tumour
Surgical removal of right testicle
Not reported
Not reported
Hormone therapy for prostate cancer
Not reported
Vas deferens
Abdominal pain

This is very much a simplified version of all the data in the published paper, it contains a brief overview of all the important information that was given. Do you notice any common themes running through these case reports? In the risk factors column there is an awfully high incidence of hormone therapy for prostate cancer, usually using estrogen-like drugs. In addition to this, other cases had increased estrogen due to liver cirrhosis, or obesity. Estrogen cant be working on its own though; liver cirrhosis and certainly obesity are common enough, yet what you see in the table above are all the cases of this unusual presentation of endometriosis known in the world (at the time I’m writing this anyway).

A few theories on the origin of endometriosis could provide an explanation for what we are seeing here. One of the more popular ones suggests that, during the development of a human embryo, pieces of tissue get left behind that can go on to be stimulated by estrogen to become endometriosis. As the embryo is developing it has two sets of tubes that will go on to form the reproductive organs, one called the Mullerian duct, the other, the Wolffian ducts, and the gonads. Given a certain set of biological signals from the embryo one set of ducts will regress and the other will develop into reproductive organs and the gonads will develop into either testes or ovaries. In basic terms if the embryo has a Y chromosome (and the SRY gene) the Mullerian ducts will regress and the Wolffian ducts will develop into all the various tubes leading from the testes and through the prostate. If the embryo doesn’t have the SRY gene, the Wolffian ducts regress and the fallopian tubes, uterus, cervix and vagina develop.

However, if the Mullerian ducts don’t regress completely they could, in theory, leave behind patches of tissue capable of developing into endometrial-like tissue when stimulated by estrogen, which I’ve talked about before. If this were the case we would expect endometriosis to develop around the bladder and ducts leading from the testes to the prostate, indeed this is what we see if we look at the table above. While this is indeed an attractive theory, there has been very little scientific testing done to show that these patches of Mullerian remnant tissue exist or that they can transform into endometriosis when stimulated with estrogen.

One of the most important factors to take note of here is menstruation, or rather the lack of thereof. None of the males in these case reports have a uterus, or have periods, so this has wider implications for the theories of endometriosis origin in women. Certainly, it casts serious doubt over the prevailing theory of endometriosis origin, retrograde menstruation, which states that pieces of endometrium are refluxed back into the pelvic cavity, where they implant and grow into endometriotic lesions. Sometimes understanding how something doesn’t work can be as important as understanding how it does work.

Monday 18 June 2018

Prove It

Well, it’s been far too long since I’ve posted anything here, but after a bit of an absence I’m back again and ready to get spreading the word of endometriosis research. Firstly a quick note on where I’ve been. I finally finished my PhD (more on that in the future), which required a year or so of pretty hard concentration in the final race to the finish, this meant I didn’t have as much time write all the other things I like, such as this blog! But I didn’t forget about it and have been constantly reading all the latest endo research and occasionally updating the @EndoUpdate Twitter account ready for my return here.

For this blog post I’d like to talk about something that is not directly related to endometriosis, but is still very important, which I think everyone needs to know a bit about, and that is the criticism of evidence. We use our judgement of evidence in our everyday lives all the time, it’s what helps us survive, and stops us getting all our money stolen by an email claiming to be from a Nigerian prince looking to offer us millions in exchange for all our bank details. For some things the definitive proof of whether something is true or not can be fairly straightforward, or it can be hard to ascertain, but by employing well tested methods of evidence analysis, we can arrive at a more accurate conclusion.

Let’s suppose you meet someone who claims to be able to turn iron into gold, and when you challenge them to do it, they can’t, then that’s pretty good evidence they weren’t telling the truth. But what if they did do it, what if the person waved their hands and instead of a lump of grey metal there was now a shimmering piece of gold? Would you automatically assume they possessed genuine transmutative abilities? Probably not, because the way to the truth and the way in which we analyse evidence is a complex deductive process that can require a great deal of testing to arrive at an acceptable level of certainty that what we have found is correct.

Let’s go back to the previous example, how would you test that the man who appeared to turn iron into gold was actually doing so? More than likely you would suspect he was performing a magic trick, so you might suggest replacing the initial piece of iron with your own piece, or one supplied by an independent person. You might suggest moving the activity to a controlled environment, where multiple people can observe at different positions, you might think of ways to test the supposed ‘gold’ afterwards to check that the outcome was genuine, or filming the trick with a slow motion camera. Either way you would come up with a list of ways to test the idea that this person can turn iron into gold and each way would give you a piece of evidence that would lead to an overall conclusion. The trick is judging what quality of evidence each of those tests would provide. In the biological and medical sciences the assessment of evidence quality is extremely important, because in many cases there are people’s lives resting on the outcome of certain experiments or trials. One of the staples of evidence quality judgement in this field is the hierarchy of evidence, which often takes the form of a pyramid like the one below (although there are minor variations on this, the basic premise remains the same), with the highest quality of evidence at the top and the weakest at the bottom.

This is a simplified example of what constitutes good and bad evidence and is being somewhat superseded by other evidence classification systems such as the GRADE system, which I won’t go into here, but I recommend following the link and reading a bit about.

Let’s talk a little bit about each stage of the hierarchy of evidence and what they mean. At the bottom of the pyramid you have case reports, opinion papers and letters. The last two form expert opinion that, although may be well informed, is still only the view of an individual or small group who may be biased towards ideas they favour themselves or represent one specific view point out of many, equally or more valid ones. Case reports are individual reports of something occurring, we see these fairly frequently in endometriosis, for example here and here are examples published within the last few months. These are still important as they document unusual presentations or novel ways to treat a disease, but they are still only the experience of a small number of people.

Next is animal trials and in vitro studies. This is basic lab based research involving animals or models of disease using cells or tissue grown under lab conditions. This is very useful basic research as it informs the direction for all the above steps in the pyramid, but it has its limitations. For example, animal research has the obvious drawback of not being done in humans, but there are some experiments that need to be performed in the context of the complexity of a living organism, but are simply too dangerous to test on humans. Often animal and in vitro (cell and tissue) experiments may only test a specific component of a disease under certain conditions and not the disease as a whole, so while it gives us an indication as to how pieces of the overall puzzle fit together, or help us to answer a specific question, it doesn’t necessarily tell us how it will translate to the human body. This type of research is very often misinterpreted in media outlets, for example I wrote before about how evidence of this kind can be misrepresented or overblown in media reports, leading to false impressions being given to the reader for the sake of sensationalism. This type of problem is called ‘extrapolation’, in that a piece of work focussing on something narrow, like the behaviour of cells in a lab experiment, is widened to the belief that this same effect will be observed in human body. It would be like seeing a horse running really fast, and observing the horse has legs, and you see you also have legs, and believing that therefore you must be able to run as fast as a horse because you both have legs.

Next up is cross-sectional studies, where information is collected from a group, or groups, of people at a certain point in their life to examine the relationship between a disease and whatever else the researchers are interested in. So let’s say for example we want to know what the diet of women with and without endometriosis is like in Eastern Canada. We could have 1000 questionnaires and send 500 to women with endo (these would be the cases) and 500 women without endometriosis (these would be the controls) in Newfoundland asking them about their diet and compare the responses. Sounds simple enough right? Well yes, on the surface, but there are lots of ways in which a study (and hence the evidence it provides) can be made better or worse. For example, in this hypothetical questionnaire, is it being sent out to cases and controls of roughly the same age? Do the cases have the same type of endo? Do they have the same symptoms? Are they from similar cultures that would have similar diets or very different cultures that would eat different foods? Do they have other conditions that may be affected by diet, or that diet might affect? How are you measuring food intake? Are you sure you have selected enough cases and controls to make the conclusions valid? What do you do if lots of people in one group don’t respond? These are just a few of the considerations that should be made when designing the study and taken into account when assessing the quality of the evidence that the results provide. If any of those considerations aren’t accounted for then this introduces error into your results, the more error there is, the weaker the evidence it provides.

The next rung on the pyramid is case-control studies. We discussed a bit about what cases and controls are in the cross-sectional study, but case-control studies are a bit different. For this type of study we would still be compared with endometriosis to women without like the cross-sectional study, but the information collected on them would be ‘retrospective’ i.e. asking them questions, or looking back through medical records, for information on things that happened in the past. The things we’re looking at could be any number of different categories, from exposure to environmental pollutants, to previous medications, to lifestyle and living conditions over time and so on. Let’s imagine a fictional study where we wanted to know if living in the countryside or the city during childhood years was associated with endometriosis in adult life. We could use a case-control study to ask women about where they lived and how rural/urban that place was. From this information we could compare the case and control groups to make a judgement on whether women with endo were more or less likely to live in an urban environment when they we children. The results of this would be presented as ‘odds’, and would be reported as something like ‘women with endometriosis are X times more likely to live in a city during childhood’. Now, can you see how this could be deliberately or unintentionally misinterpreted by a website, blog or news outlet? A finding such as this could easily become a sensationalist article with a title like ‘city living causes endometriosis!’, but that isn’t what the research was saying at all, it was just saying that women diagnosed with endometriosis as adults were more likely to live in a city as a child. It may be that there is some causal link between city living and endometriosis, but you would need a whole other study to confirm that idea. An important phrase here is ‘correlation does not equal causation’. This means that just because two factors change with one another, does not mean one is caused by the other.
A great example of this is at this link, which shows that, in the US up until 2007, the age of Miss America followed the exact same trend as the number of people killed by steam. Not very likely that those two are actually related. Another issue with case-control studies is that they rely on recalled information, in our example people had to recall the details of the environment they grew up in as children, which relies on the accuracy of human memory, which has inherent flaws. Another problem is that the association with urban living could be due to something else entirely (like the differences in diet between urban and rural communities), a factor that would be overlooked because it wasn’t included in the study design. Case-control studies are therefore good jumping off points for future research but don’t necessarily give the whole picture and the accuracy of their conclusions depends a great deal on how well they were designed. 

Moving up again, we get to the cohort study. Previously we have seen that a cross-sectional study looks at the present, case-control studies look at the past, but prospective cohort studies look at the future. Let’s say we want to investigate how the diet of women with endometriosis affects their day to day pain levels. With a cohort study you would recruit groups of women with endometriosis who have different dietary habits, like vegans, vegetarians, omnivores etc. then give them questionnaires to fill out (or get them to attend regular meetings with you) to gather information about their diet and day to day pain. This would continue for however long you planned the study for, it could be any amount of time really, a year, 3 years or even 20 years (studies conducted over a long period of time are called ‘longitudinal’). However long it was, once you reached the end of the study you would then be able to compare all the data from the different groups and see whether one type of diet was better or worse than the other for day to day endometriosis related pain. One thing you have to be careful of here are ‘cofounding variables’. Because people’s lives are complex and varied, diet is unlikely to be the only thing influencing pain, confounding variables in this study could be all manner of other factors like: exercise level, type of endometriosis, medication, stress, other medical conditions besides endo, healthcare access, financial stability, support network, etc etc. Fortunately, although these confounding variables can lower the significance of a discovery and weaken the strength of evidence it provides, if they are taken into consideration while planning the study and recorded as the study progresses, they can accounted for with fancy mathematical statistics. A solution to the confounding variable problem is ‘matching’ patients, this basically means making sure the women in your chosen groups have similar characteristics, for example making sure they are all of similar ages, BMI, activity levels and on the same medications. This does drastically reduced the confounding problem, but narrows the scope your result to a very particular population.
So let’s imagine you did this study and it turned out that, over 5 years, in Caucasian women with endometriosis aged 20-30, with moderate levels of exercise, not taking any hormonal medication or pain killers, those with a vegetarian diet experienced less pain than vegans or omnivores. It’s a very specific answer to a very specific question, and it would be very wrong for someone else to take that finding and report it as ‘women with endometriosis reduce pain with veggie diet’ because what our imaginary study found was not applicable to all women with endo, just the cohort we selected.

Getting into very strong evidence territory now we arrive at the Randomised Control Trial (RCT).   In the world of medicine, testing whether or not a new treatment, be it a drug or therapy of any kind, is the most crucial part to healing. Therefore having the tools and skill necessary to get good evidence on a new treatment is a shining example of how proper evidence testing can make a huge difference to people’s lives. Imagine that you have invented a drug, you’ve gone through all the lab testing and now you’ve got approval to test it in humans as a new treatment for endometriosis. How do you ensure the test is fair, and provides the best evidence that the drug does or doesn’t work? Fortunately you don’t have to worry about that because hundreds of years of painful scientific work, often costing the lives of many people, have refined the process to a randomised controlled trial. So let’s break down each step to see why it is useful.

Firstly you have a group of volunteers who should be matched like we discussed before i.e. relatively similar in terms of age, disease type, BMI etc, who are willing to test the new drug. The people will be allocated into different groups, but to do this they should be ‘randomised’. That is, the way in which people are put into groups is random, so you could identify people by numbers then use a random number generator to put them in one group or another. This is done to prevent people with certain characteristics (either known or unknown) all being put into one group, essentially it is done to make sure each group has a good mix of people.

The next step is assign a treatment type to each group. In the case of the new drug you have developed, this would be Group 1 and Group 2 for example. Group 1 will be the treatment group who will receive the real drug, while Group 2 will be the ‘control’ group who will receive a placebo or no drug at all. A control group is essential to make sure the outcome you are measuring (in this case let’s say it is pain relief), is due to the intervention you are testing (i.e. your drug). The reason for this is that some people may get better or worse without any treatment, or their symptoms might change as a matter of course. In essence without a control group how would you know that the drug you’re testing was responsible for pain relief and not just people getting better by themselves?
                Placebos play an important part in drug testing, these are things with no medical value whatsoever (like sugar pills) given to patients in the control group, but they look and are administered in the exact same way as the real drug. This is to take into account ‘the placebo effect’, a bizarre but very real effect noted in medical trials, where some people will notice improvements even if they are just taking sugar pills i.e. their body reacts in the same way it would as if it was taking the real drug. This effect doesn’t happen for everyone of course, it only occurs in a very small number of people, but it is enough to alter the results of clinical trial. The placebo effect is a particular problem when testing pain relieving drugs or anxiety and depression modulating drugs, where the psychology of a patient can alter the presentation of their symptoms. There is also the flipside of the placebo effect which is the ‘nocebo’ effect. This is where someone’s symptoms will get worse if they believe what they are taking will harm them, even if it has no active ingredients at all.  A neat little animation about placebos can be found here. You may very well ask, why bother with a placebo at all? Just give the control group an older version of the treatment. Well you’d be pretty sharp in this observation because the use of placebos has raised some ethical concerns, especially when dealing with drug trials for potentially life-saving therapies. Modern clinical trials usually will compare old and new treatments and may just include a placebo group to get a baseline of patient reactions to taking what they believe is a drug treatment.

A further step in an RCT is ‘double blinding’. You remember that the placebo and nocebo effect are problems because they occur when people have an expectation of the outcome, well the same goes for those who are recording the results. If you are a doctor monitoring patients taking a drug being trialled, and you know whether they are taking the real drug or placebo, you are more likely to notice positive effects in the treatment group than the placebo group, because the doctor too is biased by their expectation of a particular outcome. Double-blinding removes this by making sure that neither the patient, nor the doctors administering the treatment, know which the real drug is and which the placebo/old drug is. Usually this is achieved by giving the medications and/or patient groups code numbers instead of names. So patient 1 might be randomised into group 1 and given drug code named ‘DRG01’ by a doctor. Neither the patient nor the doctor knows whether group 1 is the treatment or control group and whether drug ‘DRG01’ is the real drug or fake drug, therefore their expectations cannot influence the results. Once the trial is complete and the results have been collected, the researchers will be given access to what the codes mean and they can decrypt which patient had what drug and do their analysis.

Once enough randomised controlled trails and other scientific investigations have been done on a particular subject, these can be put together into a Meta-analysis or Systematic Review. This is where experts in a particular area gather all the available evidence about a particular subject (like ‘does drug A perform better than drug B at relieving pain?’), review it and write it up as an analysis of the strengths and weaknesses of all the evidence they have found. This is considered to be the highest and most reliable form of evidence, because the weak evidence is sorted from the strong and by comparing the results of many strong studies we can finally arrive at a definitive answer to the original question.

As important as what understanding is evidence, is understanding what is not evidence.  There is an exhaustive list of things that are not evidence, but here are some of the most common ones: YouTube videos, personal anecdotes (something like “oh a friend of friend tried this and it really helped”), gut feelings, websites that don’t reference their sources (or that use weak evidence and over interpretation), random one offs and blind luck (we’ve all heard anecdotes like “my grandad smoked 20 cigarettes a day and lived until he was 90!” while ignoring the thousands upon thousands of people who die early due to smoking related illness) and most news reports about medicine. These are not sources of evidence in any way, shape or form and that is which is proposed without evidence, can be dismissed without evidence. Unfortunately our brain can trick us, or be tricked, into thinking in certain ways that mean we shun evidence in favour of unreliable information. A great book on the subject is ‘Thinking Fast and Slow’ by Daniel Kahneman, which to not do it justice, explains how our brains like to save mental energy where they can. When presented with an argument our brains will default to the easiest conclusion based on our previously held beliefs rather than go for the mentally taxing complex and logical process of information evaluation. Like I said, I haven’t done the book justice, but if you’re interested in why your brain thinks the way it does, it’s worth a read.

A factor that plays into how we respond to evidence is something that is very human and difficult to get rid of, and that is bias. We are all biased in some way, we think our sports team is the best, our kids are the best, our country is the best and even sometimes that our thoughts and ideas are the best and we will often defend those biases against even the most compelling evidence. Scientists are just as prone to bias as anyone else and, although we have systems of evidence assessment I have talked about today, it still creeps in. One of the best examples is ‘conformation bias’, which is looking for evidence that supports our beliefs while ignoring evidence that disproves it. It also encompasses being more critical of evidence that disproves what we believe while ignoring the flaws in evidence that supports them (a good example of this is ‘cherry picking’, where someone will go through hundreds of pieces of evidence until they find one or two that support what they believe). I have seen this many times in my professional life, and I’ll admit I’ve found myself doing it sometimes as well, so it’s a difficult trait to rid yourself of.  

Bias is also prominently evident in scientific publishing, where there is a huge bias towards only positive results being accepted for publication. It is based on the (false) assumption that negative results are inherently not worth as much as positive findings. However knowing that something doesn’t work (like a drug for endometriosis) is just as important as knowing it does work. When we are dealing with people’s health, we must try to put these biases aside for the good of those being treated, if this is not the case and a person, or organisation, are ignoring evidence in favour of their own biases, then they do not have the patients wellbeing at heart, and are instead concerned with someone else (like reputation, fame, or most commonly, money).

Ok so let’s suppose you are a research scientist, you’ve got your snazzy lab coat and have been working hard on a drug that you think would be a great treatment for severe period pain women with endometriosis suffer with. The imaginary drug you have developed is the very creatively named ‘Drug X’. This drug is based on a compound that is naturally found in bananas, but you have modified the chemistry of the compound to make it easier to absorb by the body, so it’s a different compound from the naturally occurring one. Over the years and years you’ve done all your scientific experiments and have managed to perform a well-designed clinical trial which has shown that Drug X is actually effective at reducing severe period pain in women with endometriosis after they have had surgery, you even manage to get the results published in a prestigious journal. Can you take a guess, based on what we’ve learned so far, about what could happen to your results? There is a chain of interpretation of your research, which is very close to the interpretation of research I have seen actually seen happen in real life, that can lead to your findings being misinterpreted and used to spread false information. Below is an example of what could happen after the initial research paper was published.

Although this particular example is based on entirely fictional research, you may see similarities between this and real world reporting of scientific research. I’ve used this as an example of something you may come across in day to day life and with what we have learned throughout this post, hopefully you’ll cast a more suspicious and critical eye over any such claims in the future. In addition, it is often very difficult for someone outside of academic/research institutions to get hold of an original article due to restricted access and most articles being behind expensive paywalls. Similarly, academic writing is often quite specialised and difficult to understand unless you happen to be an expert in that field, so the majority of people rely on interpretation of this research elsewhere and put their trust in other to interpret the research correctly. What I’ve been discussing today hopefully gives you a better idea of how to interpret the interpretations and exercise caution when reading news about endometriosis.

People often think of scientists as being very rigid and closed minded, and in some cases that may be true, but a good scientist is one who is willing to accept any conclusion based on the proper evidence, and the more remarkable the claim, the more remarkable the evidence required to prove it. Similarly a real scientist is willing to change their mind based on new evidence, even if it means rejecting a deeply cherished belief. Of course there are some things we simply don’t know yet, and our natural instinct is to try and fill those gaps in our knowledge with some sort of explanation, but sometimes it ok to say “I don’t know” and wait until the answer is proven. Those gaps in our knowledge though are ripe fruit for those who push fraudulent information and quack remedies. Scientists certainly don’t have all the answers, but the ones we do have are the best ones (for now).

If you read that someone is claiming they have a cure for endometriosis, hopefully what I’ve written here will give you the basis to understand the evidence they present to support that claim (if any) and how strong or weak that evidence is. There are also other further reading resources to really sharpen your evidence assessing skills, such as these few to get started:

Ben Goldacre’s Books – Bad Science and Bad Pharma and accompanying blog

The Systems to Rate the Strength of Scientific Evidence – by the Agency for Healthcare Research and Quality

A favourite quote of mine, which has been attributed to many people over the years is “keep your mind open – but not so much that your brain falls out