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?