Tuesday, 23 August 2011

You’re never too old, or too young

Quick, if I were to ask you to name any times in a woman’s life when she shouldn’t suffer from endometriosis, what would you say? Most likely, anyone with a basic knowledge of the disease will say premenarcheal (before her periods start) and postmenopausal (after menopause) because endometriosis is a disease dependant on hormones, right? So before and after the time a woman can menstruate there should be no chance of endometriosis developing, it’s just logical to think that way.

Well if life teaches us anything, it’s that some things are not logical, and endometriosis is one of those things. In terms of logicality, endometriosis is kind of like sticking your head in a washing machine filled with Salvador Dali and M.C Esher paintings.

Pictured: endometriosis

Because of this there are cases (albeit very rare cases) of endometriosis occurring in young girls and older women. Of note there have been reports of symptomatic endometriosis in girls as young as 8 and in women as old as 80. So how can we explain these odd, seemingly illogical occurrences, can we even explain them?

The answer is a resounding “well, sort of”. Endometriosis in postmenopausal women is perhaps the easier of the two entities to explain. Postmenopausal women may be taking hormone replacement therapy (HRT) which would provide any endometriotic implants with a steady supply of estrogen to keep them going. Some reports have even stated that postmenopausal women taking HRT have an increased, but poorly defined, risk of previous endometriosis recurring.

But (and there is always a ‘but’ to complicate matters), there have also been reports of postmenopausal women with no past history of the disease, suddenly developing endometriosis. There are a number of explanations for this though. Firstly, the woman may have had endometriosis lingering in her body all along, and any number of contributory factors may have suddenly caused it to grow. Secondly, if the woman has had any major surgery in her pelvic area (e.g. hysterectomy, oopherectomy etc) tiny bits of the endometrium may have been spread around her pelvic cavity during surgery, which may then implant to form endometriosis later on (this mechanism is thought to be one of the ways surgical scar endometriosis occurs).

An unanswered question remains though, if a woman is past menopause and not taking HRT how does the endometriosis get the estrogen it needs to survive? After menopause a woman’s ovaries begin to shut down and a drastic reduction in estrogen production occurs over a period of about 4 years. However, androgens are still produced, albeit at a diminishing rate, by the adrenal glands and ovaries after menopause. Androgens are another group of hormones that could loosely be described as being responsible for the development of masculine characteristics. Women also produce androgens, but at a lower level than men and androgens in women can be converted into estrogen. However, you need certain enzymes to convert androgens to estrogens, the most famous of which is aromatase.

Aromatase is an enzyme whose job it is to take hormones like testosterone and convert them into estrogen. Aromatase is expressed in a number of cell types including the ovaries, fat cells, endometrium and guess where else? That’s right, in some but not all, endometriotic cells too. This means that any endometriotic implant that expresses the aromatase enzyme can essentially make its own estrogen. Even with the low levels of androgens produced in postmenopausal women, endometriosis with active aromatase could produce its own estrogen and hence survive in a woman who has gone through the menopause.

Well, you may think, that all sounds very plausible but is there any evidence to substantiate this little theory of yours? Good question and yes there is. You see, there is a group of drugs called aromatase inhibitors that are sometimes given to women with endometriosis and there are no prizes for guessing that these drugs inhibit the aromatase enzyme. In some cases of women with postmenopausal endometriosis there is evidence to suggest treatment with aromatase inhibitors can significantly reduce their symptoms. Of course, the problem with aromatase inhibitors is that they decrease estrogen levels even further, which if you are past the menopause it probably going to lead to complications and adverse side effects.

But what of premenarcheal endometriosis? There is, some good evidence, which I have mentioned previously, concerning the discovery of displaced endometrium, a hallmark of endometriosis, being found in unborn human foetuses. Conveniently, the research group who made these previous discoveries have recently published another paper of their largest study yet confirming the cells that preclude endometriosis can be found in girls before they are even born. So, it would appear we have a possible answer for why such young girls can develop endometriosis; the bigger question though is how, and therein lies the rub.

At present the ‘how’ is the unanswerable question. Is there any reasonable explanation for how girls who haven’t even reached puberty can develop endometriosis? There are of course arguments that environmental pollutants can bring about the development of endometriosis, but the evidence for this is rather weak and highly debated so we can’t (or rather shouldn’t) draw any conclusions from that particular line of evidence, yet.

There are so many factors which are thought to influence the development of endometriosis such as; genetics, epigenetics, diet, lifestyle, environment, immune function, family history, that we may never have a singular cause for endometriosis. Some women may inherit it, some women may acquire it. Perhaps we need not think of endometriosis as one giant jigsaw to be pieced together; perhaps we need to see each case as its own, individual puzzle.

Wednesday, 10 August 2011

Do not adjust your set

Don’t worry! This is the same blog as before! The eagle eyed amongst regular readers will probably notice that there have been a few aesthetic changes to the blog. Basically just to give it a bit more colour and generally make it nicer to read. However, due to my artistic (i.e. awkward and indecisive) temperament there may be a few more changes going on. Normal service will be resumed shortly.

Tuesday, 9 August 2011

Surgical treatment for Deeply Infiltrating Endometriosis (DIE)

If you suffer from endometriosis then you may be offered surgical treatment to remove the disease. I say you may be offered surgical intervention because there are several factors that determine how likely this option will be given to you, such as; the severity of your symptoms, your fertility, your age, your response to drug treatment, what country you live in and how wealthy you are (sad, but true). If you are offered a surgical treatment, one of your main concerns is going to be, how successful will the surgery be? After all, you are placing a great deal of faith in the hands of the surgeon and you don’t want that faith to be misplaced. No surgery is to be taken lightly, so you want to know the investment you’re making with your health is going to be worth the payoff.

There are several different types of surgery for women with endometriosis, with varying degrees of success, which broadly fall into the two categories of conservative (e.g. excision or ablation) and radical (e.g. partial or complete remove of affected organs). I’ve spoken about the success rates of different surgeries before, but I’ve yet to discuss the success of surgery in the context of what type of endometriosis is being operated on. So, first off, a basic reminder of the different types of endometriosis. There are superficial endometriotic implants, which appear on the surface of organs like the ones in the picture below. These implants come in a variety of colours such a red, blue or black and generally the colour denotes how active the implant is.

In this picture you can see some blue implants as well as reddish-brown ones.

Picture courtesy of

Then there are endometriotic cysts (endometrioma) which usually occur on the ovary and can range from as small as a pea to as large as a melon.

The endometrioma is the dark reddish-purple patch in the middle of the picture.

Picture courtesy of

And there is also deeply infiltrating endometriosis (DIE) which can be one of the most difficult types to visualise and hence, operate on. The reason this type of endometriosis is so difficult to see is that the implants can be very small, up the point of being microscopic and so, invisible to the naked eye. The reason it is known as deeply infiltrating is that, unlike superficial endometriosis, DIE can ‘burrow into’ organs at depths ranging from 2mm to over 15mm and this is thought to be a significant cause of the very painful symptoms associated with endometriosis.

I’m going to focus on DIE for the rest of this post because the article I’ve come across recently is about the success of surgery for this type of endometriosis. The article in question followed 193 women with and without DIE, undergoing excisional surgery in the Päijät-Häme Central Hospital, Lahti, Finland. Women undergoing surgery for DIE were found to have significantly higher rASRM scores than those with other forms of the disease.

rASRM, to clarify, stands for the revised scoring system of the American Society of Reproductive Medicine, who devised this scheme to classify the severity of different kinds of endometriosis. It is based on several features found inside the pelvis during surgery such as type, size and location of endometriosis, as well as the presence and severity of adhesions. The scoring system then classifies the endometriosis into one of four stages; minimal, mild, moderate or severe (although it is worth noting that severity of endometriosis appears to have little bearing on severity of symptoms). In this Finnish study, women with DIE had average rASRM scores that were very close to classing them with severe endometriosis. Women without DIE had average rASRM scores that would classify them as having moderate disease.

This study also found that women with DIE had significantly more previous surgeries for endometriosis and more were indicated for surgery because of pain. With respect to the surgical procedures performed; 60% of women with DIE had surgical excision of peritoneal lesions compared to 82% of those without DIE. This could be reflecting the difficulty of removing lesions in women with DIE, or it may be that women with DIE do not have as many peritoneal lesions.

92% of women with DIE had to have adhesions cut away compared to 69% of women without DIE. This might be reflective of the fact that women with DIE have had more previous surgeries, which would increase the chances of adhesions forming. Interestingly, 32% of women with DIE had a hysterectomy of some variety, compared to only 8% of women without DIE. The reason for this could be that, because deeply infiltrating lesions can be very challenging and time consuming to remove individually (hence, increasing the likelihood of serious complications arising), surgeons may opt for complete removal of the uterus as a quicker and safer procedure.

This study also looked at the completeness of excision of endometriosis during a single operation. Women with DIE compared favourably to those without in this aspect as complete excision was reported in 95% and 97% of cases respectively. However, excision during a laparoscopic surgery for DIE was only complete in 79% in of cases compared to 95% complete removal of endometriosis in women without DIE.

The final important finding of this study was that deep lesions are frequently found outside of the ‘typical’ locations i.e. the uterus, ovaries etc. This is significant because gynaecological surgeons may be unfamiliar with operating in atypical locations, therefore a multidisciplinary approach may be required involving additional specialist surgeons.

Then there is the issue of should patients have preoperative medical therapy? On the one hand some studies suggest that medical therapy before surgery may reduce the risk of complications arising during surgery. However some eminent specialists in endometriosis surgery forgo the use of drugs that may suppress endometriosis due to the fact that they may make the endometriotic implants harder to see whilst operating. If you are due to have surgical treatment for endometriosis anytime soon, these are issues you should raise with your surgeon. It is also important to remember that, if you do have deeply infiltrating endometriosis and are due for surgical excision, it is in your best interest to have a surgeon who is well experienced in this type of procedure and familiar with the problems this type of endometriosis can present.

Whilst we must always remember that one, relatively small, study such as this does not set the standard for all surgeries for DIE, it does give us a good example of what can be expected, the problems faced by patients and surgeons, and perhaps ways in which we can improve the surgical treatment of endometriosis.