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.

Endometriosis and Age at Menopause

Menstruation, there’s good and bad things about it. Any post-menarcheal woman reading this will be more than familiar with the ‘bad things’ which include: pain, irritability, bloating, pain, nausea, headaches, tiredness, pain, bleeding, generally feeling shit, I could go on. So I bet you’re wondering where I’m going to pull the ‘good things’ associated with menstruation from. Well one thing I’ve noticed over the years is that the mere mention of menstruation is enough to halt any conversation dead in its tracks; and that can come in handy sometimes.

Seriously, give it a try, next time you’re at wedding or other such family gathering and get stuck talking to some boring relative just drop in a quick description of your last period and everyone within earshot will try to climb inside their own shoes, leaving you to enjoy the buffet in peace. Done something wrong at work and got called into the boss’s office? Start off the conversation by recounting a memorable menstrual episode and I guarantee you’ll be out of there scot free within five seconds. Pulled over for speeding? Tell the office on duty about how many tampons you get through a month and he’ll tear up your ticket there and then*. But there comes a time in woman’s life where menstruation stops, and that time is menopause.

*ok that last one may not work

Menopause, for those that don’t know, signals the end of a woman’s menstrual cycles. In the western world menopause occurs, on average, around the age of 52 and is usually a gradual process that takes place over months or even years. If you’re a lady and you’d like to know approximately when you’ll go through the menopause, a good indication is your mother’s age when she went through menopause. The reason that a woman’s menstrual cycles stop is that, as a woman gets older, her body’s hormone levels change, this means that the levels of oestrogen in her body will gradually decrease and the production of mature eggs (ovulation) will eventually stop and so menstruation becomes unnecessary.

This change in body hormone levels doesn’t come without consequences though. You’ve probably heard of some of the common symptoms of menopause such as hot flushes and mood changes and this is all tied in to the body adjusting to the new hormonal balance.

There are a number of factors that affect the age at which a woman goes through menopause. I’ve mentioned above that one of the major influences is her mother’s age at menopause, However, factors that may increase the age at menopause include: Having more than three children, being of high socioeconomic status, and having a high BMI. Factors that can decrease the age at menopause include: smoking and low BMI.

Why am I talking about menopause though? Well there was a study published recently that showed women who have a history of endometriosis are likely to have an earlier menopause. The study itself was quite thorough in its methods, they looked at surveys of 49,927 female, Japanese nurses between 2001 and 2007. In this population the average age at menopause was 49.5, that decreased to 48.8 for endometriosis sufferers. Why might this be the case? The authors of the paper suggest that surgical and medical treatments associated with endometriosis may contribute. For example, surgery involving the ovary, such as excision of removal, was found to decrease the age at menopause. The role of medical treatments was harder to judge as there are conflicting reports as to the effect of certain drugs on menopause. Certain studies on oral contraceptives, for example, show they increase the age at menopause, whereas other studies show they have no effect at all, so the jury’s still out on that.

Too old for this

Just a quick post this time, I found a report of two unusual presentations of ovarian endometriosis. One case was a woman of 57 and the other a woman of 80, which is the oldest woman with endometriosis I’ve heard of (although I’m willing to be corrected). Both cases are in post menopausal women, which in itself it pretty unusual in itself. The reason for this is that during menopause the ovaries start shutting down and stop producing estrogen. This isn’t so good when you consider the side effects - like hot flashes, mood swings, bone density loss etc – however, if you have endometriosis then lack of estrogen is generally considered a positive as estrogen is thought to be the ‘fuel’ of endometriosis. In case of point, a 15 year follow up study of 130 women with endometriosis from Norway found that 96.9% of them were pain free after menopause.

Considering that, it’s pretty obvious why most of the medical therapy for endometriosis is focussed on reducing estrogen within the body. However, if a woman’s menopause symptoms are particularly severe she may be offered hormone replacement therapy (HRT). This isn’t such a good thing if she has also had endometriosis as HRT basically puts estrogen back into the body, which may lead to resurgence of endometriosis. Of course, as most women with endometriosis don’t continue to have symptoms after menopause, it’s not a massive risk, but it is a risk and doctors need to be aware of this. Postmenopausal endometriosis can also be associated with some serious complications; the 80 year old woman mentioned above also developed a malignant endometrioid carcinoma; other complications which have been reported include: kidney failure associated with postmenopausal deeply infiltrating endometriosis, bowel obstruction, liver damage and a general increase in risk of malignant transformation of ovarian endometriosis (although solid evidence of the latter is lacking).

Therefore, it is important for all women who have gone through the menopause (either naturally or through surgery) and have endometriosis to be aware of any recurrence of symptoms, especially if they are also undergoing HRT.