Monday, 27 May 2013

The Size of the Problem

There has been some buzz lately about a new study into endometriosis - it’s been in news reports on a number of blogs and websites (such as this one and this one), you may have already heard about it. From the headlines in the news article you’ve probably gathered this new study is about the relationship between body size and endometriosis, specifically leaner women were found to be more at risk.

So, this study has found that thinner women are more likely to have endo; does this mean, in order to decrease your endo risk, you should all start reaching for the cakes and pies, forgo the use of even the most rudimental cutlery and just shovel food in your mouths with your hands like a mad combine harvester ploughing through a buffet?

Well no, definitely don’t do that. Most of the news outlets have done a pretty decent job of explaining the findings, but this month I’ll be looking over the original study and finding out exactly what was done, what was discovered and what we can learn from it.

Before we start though I know this study is controversial to some, so I will say I'm not going to comment on the worthiness of this study. I'm only going to give you an explanation of the findings and my interpretation thereof, then let you make up your own mind.

To start with it’s always a good idea to see if any other research like this has been done in the past and it turns out it has, and I’ve written about it before, way back in the dark murky past of 2010. So the finding that women with a low BMI are more likely to have endo isn’t a particularly new discovery. 

What’s different about this latest study? For a start it’s bigger, much bigger. The same US research group conducted a similar study in 2010 with 1,817 women with endo, this latest study includes 5,504 women with endo and the more people you have in your study, the more accurate your results. So where did they get all these women from? Well in the US since 1989, 116,430 female nurses from 14 different states have been filling in questionnaires about their health every 2 years. All this information together forms the Nurses’ Health Study II – a vast mine of information available to researchers looking into relationships between lifestyle and environment factors and the risk of all manner of illnesses.

This current study looked at all the questionnaires from 1989 to 2011, picked out the information from women who were diagnosed with endo and compared it to women who weren’t. The major factor being examined here was BMI, which is a ratio of height to weight. My BMI is around 20, which is classified as normal, but I’m a gangly leviathan, so someone who was a foot shorter than me but the same weight, would have a BMI of 28 and be classified as overweight (in my last post on this subject I air my grievances about BMI as a measure of body size).

BMI on its own isn’t a very reliable measure of body size, basically because a body builder and a fat guy could have the same BMI as it doesn’t take into account body shape. Fortunately BMI wasn’t the only factor these researchers were looking at; in order to get a better picture of body size they also took measurements of waist/hip ratio and waist circumference.

Anyway, enough of the methods, onto the results. The central finding of this study was that women with a higher BMI were less likely to be diagnosed with endometriosis – in fact morbidly obese women (i.e. with a BMI over 40) were 39% less likely to have a diagnosis of endometriosis than women with a BMI between 18.5 and 22.4.
What the researchers found was that there was an inverse correlation between endometriosis and BMI. What this means is that as BMI went up, endometriosis risk went down. Below is a graph from the paper which shows that relationship (the solid black line is the important one, don’t worry about the dashed lines).


Interestingly this study found that this association was stronger in women who were also infertile, but there is an important point to take into consideration first. The average age of women at the time this information was collected was around the mid-thirties, so it is very likely they’ve been living with endo for a long time. BMI tends to increase with age and, more importantly, many women who have suffered endo long term take medications that cause weight gain. Therefore, wouldn’t it be better to look at the BMI of these women when they were younger? Yes, and that is exactly what the researchers did - they looked at the BMI of these women aged 18. Below is the graph of the result.

(click to enlarge)

As you can see it looks pretty much the same and, despite the fact that the result was slightly attenuated, morbidly obese women were still 25% less likely to be diagnosed with endo.

Now, one thing we must be careful of here is not to assume this means women with a higher BMI can’t get endometriosis, it just suggests they are less likely to have it when they are younger. For example, if we look at the results of this study, women with a BMI of around 21 had the ‘average’ rate of endo, which is 1 in 10. However women with a BMI of over 40 had a 39% reduction in their endo rate, which is equivalent to about 0.6 in 10. So, in women with a normal BMI, around 10 in 100 would be expected to have endo, however in women who are morbidly obese, 6 in 100 of them would be expected to have endo.

So what of the other body size factors being investigated? The results of this study showed that a larger waist circumference was also associated with a lower risk of endo, but only for infertile women and there was no association with height and endo. Waist-to-hip ratio was a harder result to call as a lot of women didn’t have that information recorded. Although the researchers found that women with the smallest waist-to-hip ratio had a 3 fold increased risk of endo, this was only based on data from eight women, so it’s probably best not to pay much attention to that result until it can be verified.

Now we know the results, the next big question is, why might this be the case? At first appearance it doesn’t make sense, fat cells can produce estrogen, so the more fat cells you have the higher levels of estrogen you have. Being as endometriosis is an estrogen dependant disorder, shouldn’t women with more fat (and therefore a higher BMI) be more susceptible to the disease? Similarly, being underweight as a child is associated with later menarche and less menses, yet women with endo are known to have, on average, and earlier menarche so that doesn’t seem to add up either.

There are several ideas as to why we are seeing these results. It is known that obese women are more likely to have Polycystic Ovarian Syndrome (PCOS) and some researchers think that PCOS may be ‘protective’ against endo due to a reduced number of menstrual cycles and higher levels of androgen hormones which could suppress endo lesions. Although without knowing which women had PCOS in this study we can’t tell if this is the case. The androgen link may be important though. Studies have suggested that androgen hormones are elevated in obese young girls and women regardless of them having PCOS. Therefore, a higher level of androgens in obese girls and women may suppress endo and explain why we see a lower risk of endo in the high BMI group.

The authors of this study also suggest there may be a diagnostic bias for obese and morbidly obese women. Surgeons may be less likely to want to perform a laparoscopy on these women as it is just more difficult, therefore they would be less likely to be confirmed with endo. However, the authors point out that if this were the case there wouldn’t be such a strong association between endo and BMI in infertile women compared to women with pain symptoms alone.

There are several other factors that can modify BMI, such as medications, lifestyle factors and co-morbid conditions and these all need to be considered when examining a relationship between endo and BMI, which as far as I can see, this present study did not take into account. Another consideration about this study is the population of women from which it was drawn. All the women from whom the information was taken were nurses employed in that profession for at most 20 years. As endometriosis presenting with severe symptoms would hinder a woman’s ability to maintain long-term employment (especially a physically demanded job, like nursing), then it is likely that women with severe endo symptoms were not proportionally represented in this study, which may skew the results to favour women with less severe forms of the disease, who in turn would be more physically active and hence, have a lower BMI.

Of course it could be that whatever makes a woman susceptible to endo also makes her more likely to have a lower BMI at a younger age. A growing body of evidence suggests that endometriosis is condition you are born with and is hereditary - so it may, or may not, be that whatever genetic/epigenetic factors result in a woman developing endo, also affect her metabolism or fat deposition resulting in her having a lower BMI before she started taking hormonal medication. Unfortunately there are still a lot of questions that need to be answered before we can make any definite conclusions here, but when we eventually answer those questions, we will have a better understanding of this paradoxical disease.

This is my interpretation of the current study, as ever though I encourage everyone to do their own research and draw their own conclusions, so below is a link to the study I have been talking about this month, which you can read and download, in full, for free.