Round in Circles

That’s what it feels like sometimes when dealing with endometriosis, like you’re in a boat with an oar on only one side, just paddling away but ultimately going no-where. Then hurray! Someone throws you another oar, but it’s bigger than the other one so you end up moving forward slightly but still round in circles. What you really need is an outboard motor of some kind, or maybe some sails....sorry I seem to have lost where I was going with that metaphor. Anyway, the oars in this case represent the two big conflicting ideas about where endometriosis comes from, namely retrograde menstruation and coelomic metaplasia. I’ve spoken about these conflicting notions before along with the theory of mullerianosis back in May and how there is evidence for both cases.

In one corner we have the stalwart theory of retrograde menstruation, which is generally accepted as how endometriosis comes into being, and there is evidence to support this. The fact that endometriosis bares such resemblance to normal endometrium, that endometriosis is found most frequently on the pelvic organs and experimental evidence which reported that forced surgical induction of retrograde menstruation in monkeys led to the development of endometriosis in 50% of cases.

In the other corner is coelomic metaplasia, which suggests that there are cells that already exist all throughout the body that can transform into functional endometrium given the correct stimulus. This theory best explains how endometriosis can arise in organs such as the brain and lungs and even the rare cases of endometriosis in males.

A body blow has just been dealt to retrograde menstruation in the form of a study that has just been published in the Journal of Paediatric and Adolescent Gynaecology. This study reported a case of endometriosis in a 20 year old girl who complained of serious pelvic pains. That’s nothing exceptional in itself, until you know that the girl also had Mayer-Rokitansky-Küster-Hauser syndrome, mercifully also known as MRKH. MRKH is characterised by the incomplete development of the female reproductive organs, in this case the girl did not have a uterus. Therefore, retrograde menstruation would have been impossible and cannot account for the development of her endometriosis, but coelomic metaplasia could. This round goes to coelomic metaplasia.

You’ll be glad to hear that this story has a happy ending though. The girl in question underwent electrocautery to destroy her endometriosis and was placed on oral contraceptives to reduce her symptoms, which significantly reduced her pain.

So the retrograde menstruation/coelomic metaplasia debate looks like it will have no resolve just yet. Nevermind, just keep on paddling.

Bloodlust

Endometriosis, like most living things and vampires, needs blood to survive. Those patches of endometriosis that grow within people need a constant blood supply because they grow at an accelerated rate. If you look at this picture you can see a blackish endometriotic implant and lots of little blood vessels leading up to it like some sanguine road map. The tricky thing about endometriosis is that it can form its own blood supply, generating new blood vessels from existing ones, a process called angiogenesis. This is one of the reasons endometriosis is so persistent, it’s one of the same tricks tumours use to survive.

Of course knowing this means it may be possible to use drugs that inhibit angiogenesis to effectively ‘starve’ the endometriosis of its blood supply. This has been the focus of quite a bit of research over the last few years with some studies looking at drugs that inhibit the growth of new blood vessels as a possible new therapy for endometriosis. Actual data on human trails is hard to come by, but what has been done is quite positive. One study found that treating women with a combination of Goserelin (a GnRH analogue) and Thalidomide (yes, thalidomide) caused regression of ovarian endometriotic cysts in 8 out of 10 cases after a 6 month course of treatment. Now I will be the first to admit this is a very preliminary and quite small study and I do have some reservations about the design of the study, but the results are encouraging nevertheless.

Most other work testing angiogenesis inhibitors for endometriosis is done on animal models, usually mice or rats. The results of these studies has also been supportive of the use of angiogenesis inhibitors for the treatment of endometriosis, most recently there’s been a study published very recently that reported the use of a drug called Fenofibrate (drug that is normally used to treat liver disease and high cholesterol ) reduced the growth of endometriosis in rats.

This also illustrates a cause that I am very supportive of, using drugs that already exist for the treatment of other diseases as possible novel therapies for endometriosis. This has several advantages, for example if a drug is already being used to treat something else then we know it is safe to use on humans and we know the side effects (angiogenesis inhibitors are something you should definitely not take when pregnant for example). Drugs can often have effects that are unforeseen by their developers, sometimes these effects can be very negative (such as the case of Thalidomide) or sometime they can be positive (such as the case of Thalidomide).

If you would like to read more on angiogenesis inhibitors and endometriosis there is a page on the World Endometriosis Society website about this very subject.

It Came From Outer Space

I’ve been going through some of the older papers on endometriosis recently and I’ve come across some rather peculiar reports, particularly this one, this one and this one. It would appear that years ago it was quite in vogue to get animals (monkeys in particular) and expose them to huge amounts of radiation and see what happened. Well the results weren’t that hard to predict, the animals died. However, what was interesting and slightly unexpected is that some of these animals developed endometriosis, apparently as a consequence of being exposed to radiation.

Various types of radiation were used, such as single energy protons, mixed energy protons, x-rays and electrons and the whole point of this seemed to be judging the affect of radiation exposure on women flying into space or in very high orbit around the earth. So the question to be asking really is unless you were one of these unfortunate monkeys how is a woman likely to be exposed to this radiation? Well unless you’re an astronaut or a high altitude pilot chances are you won’t get much exposure as this type of radiation can come from things called solar flares. Solar flares are massive releases of energy at the suns surface which shoot huge amounts of radiation into the solar system.

Now it’s generally thought that earth’s atmosphere protects us from the most harmful effects of this radiation, however some studies have indicated that solar activity can be related to the incidence of heart attacks and autoimmune disease. Therefore it may be that solar activity has some bearing on human health. So could it be that endometriosis is caused by exposure to radiation from outer space? Well I wouldn’t go adhering to any such theory yet. For a start I couldn’t get access to the full versions of the aforementioned papers that link endometriosis to radiation exposure, so it’s hard to judge the quality of their methods and analysis. Without being able to properly critique a study’s methods it’s impossibly to tell whether it’s worth taking it seriously or not. Nevertheless, it may be something that is worth looking into in more detail. Does anyone know where I can get a gamma ray emitter and some monkeys?

Associations

There have been a few studies published of late concerning what other conditions endometriosis is associated with.

First up is a study from Brazil which looked at the frequency of celiac disease in women with and without endometriosis. Just to give you a brief overview, celiac disease is a digestive disorder that leads to poor absorption of nutrients through the gut due to damage of the small intestine. Celiac disease can result in people not being able to tolerate things like gluten and presents with a variety of symptoms (For more information on celiac disease follow this link). The study found that 0.66% of women without endometriosis had celiac disease, whereas 2.5% of women with endometriosis had celiac disease. So although the numbers were relatively small women with endometriosis were more likely to have celiac disease. This is interesting because, from my experience, a lot of women with endometriosis also have food allergies or intolerances.

Next is a study from Australia that looked at the frequency of pre-eclampsia in women with endometriosis. Pre-eclampsia is a condition whereby during pregnancy a woman suffers from hypertension. This can be a very serious problem if left untreated for both the mother and child. However, the overall result of this study was that there is no increased chance of suffering from pre-eclampsia if you have endometriosis. In fact there is some evidence to suggest that if you have endometriosis you are less likely to suffer from pre-eclampsia, which is good news, for a change.

Juneau Biosciences are looking for Women with Endo

If you have diagnostically confirmed endometriosis then there is a study being conducted by Juneau Biosciences that you may be interested in. The main aim of their research is to look for genetic similarities between women with endometriosis to try and find out which women are more likely to develop endometriosis and why. This could, in turn, lead to better diagnostic and therapeutic strategies.
If you think you’d like to participate in this study get onto the website www.endtoendo.com and have a look at the study details. If you do qualify you can expect the following:

You will be contacted by a study coordinator and introduced to the organization conducting this research

They will send you a packet with a questionnaire, medical record release, and saliva sample kit

After completion, you will send these items back to their facilities in the postage-paid envelope provided

If you are interested, they will send you occasional information regarding the progress of their research

Now, they do require access to your medical records and personal information which I know may put a few people off. Therefore, I have personally been in touch with the company and screened them to make sure they’re genuine, however if you have any queries then don’t be afraid to contact them via the contact details on their website, they are very amicable.

How much endometriosis?

When we think of endometriosis, size does not usually factor into our concerns. If you look at and endometriotic implant such as these ones, which are between 1 and 5mm in size, they typically tend to be quite small. In fact some patches of endometriosis are so small they cannot be seen with the naked eye. The only exceptions are endometriomas (or chocolate cysts), which are ovarian cysts of varying size that are caused by endometriosis. Endometriomas can range from being small (like the size of a marble), to being quite large (like the size of a grapefruit). Generally any endometriomas in excess of 5cm requires surgical attention.

Spare a thought then for the woman who is the subject of the following case study published in the Journal Clinical and Experimental Obstetrics and Gynaecology. The report states that a 51 year old, morbidly obese woman was admitted to hospital with anaemia, respiratory problems and kidney failure, so her story doesn’t start well. Further investigation revealed a large mass in her abdomen that had to be surgically removed. Analysis of this mass found it to be an astounding 64Kg (that’s just over 10 stone) of endometrioma.

I’m not sure but I think that’s some sort of record.

If Red is your favourite colour are you more likely to have endometriosis?

Firstly I’d just like to point out that the answer to the above question is, quite obviously NO. There has never been any evidence suggesting that colour preference is related to endometriosis susceptibility because the two factors are unrelated. But what if there was a scientific study that said women who have red as their favourite colour are more likely to have endometriosis. Would you change your favourite colour to blue? Or green? I don’t think so, because you know colour preference makes no difference. In a similar sort of vein a study from New Zealand found that people who drive silver cars are 50% less likely to have an accident than those who drive white cars, and people who drive green cars are almost twice as likely to have a serious accident as those who drive white cars. In fact if you’re interested you can read the paper yourself by following the link here. So what should we do? If you own a green car should you rush out to the nearest shop and stock up on silver spray paint? Again the rational answer is, of course, no. The likelihood of having an accident in a car depends on the skills and factors affecting the driver not the colour of the car. The fact that silver car drivers are less likely to have a serious accident is purely coincidental, even if the study that found these associations was well designed and executed.

Okay by now you’re probably wondering where I’m going with this but bare with me. The reason I’ve put in all the preceding text is that a study has just been published in the Scandinavian Journal of Work, Environment and Health which found that women who work as a flight attendant, service station attendant or nurse may be more likely to have endometriosis. Again this is a fairly well designed an executed study, but couldn’t it all just be a coincidence like the car colours?

Well for starters, although this study seems well designed there are definite problems with it, mainly what is known as sample size. Basically if you are going to compare one group of people with another for whatever reason, the more people you have the better as it narrows the likelihood of errors occurring in the proceeding analysis. This study took 341 women with endometriosis and 742 women without endometriosis, which may seem like a lot and would be fine, but these large groups were then divided by job type. So for example, in the service station attendant category they were only comparing 4 women with endo to 2 women without, and in flight attendant category 5 women with endo were compared with only 1 without.

That’s the first problem, the second is the significance of the results. Say you had compared one group of people with another and found a difference between them. How do you know that difference is significant? Well scientists have long boring equations that you put your results into and it pops out with a number called the P value. If the P value is less than 0.05 then the result is significant, if the P value is less than 0.01 then it is really significant. Anything above 0.05 is considered pretty unconvincing. The authors of this study have put their results into these tedious but necessary equations and found that although there was a difference in the number of women with endo in these different job groups they were not significant. The nurse job group, for example, had a P value of 0.23, which is suggestive, but definitely not what is considered significant.

There is also the assumption that job has any bearing on endometriosis risk. Certain authors have said that exposure to certain environmental toxicants may have an effect on developing endometriosis and the level of these toxicants varies with job type. This has never been proven thought, so we must treat this assumption with some caution. For example there was a study that suggested women who work in wood and paper mills may be more likely to develop endometriosis due to exposure to certain chemicals involved in the wood processing industry. However, it must be remembered that no environmental chemical has ever been unequivocally proven to increase the incidence of endometriosis in humans.

In conclusion the study of relationship between job title and endometriosis is an area worthy of investigation but I personally doubt any job type confers an increased risk of developing endometriosis. Endometriosis is such a complicated disease it is far more likely that a whole host of factors play a role in risk of developing the disease. So don’t go changing your job (or your car) just yet.

If you would like to read the full article from the Scandinavian Journal of Work, Environment and Health, follow the download link on this page