Anorexia and Estrogen

I'm sure that most people know that anorexia occurs more often in women than in men, though overall in about 0.3-0.6% of the population. What a lot of people DON'T know is that anorexia nervosa is a highly heritable disease. In fact, cases of anorexia nervosa have been reported as early as the 16th century or even earlier, long before being incredibly thin became a fashionable norm, which has led to the idea of anorexia as being a disorder that is more far-reaching than a desire to be thin.

Anorexia is characterized by severe weight loss or failure to gain weight when you're supposed to, and is accompanied by intense fear of gaining weight, as well as body image distortion, usually believing that your body is far fatter than it actually is. Severe weight loss like this can lead to heart problems, and of course anorexia is also associated with other psychiatric disorders such as depression and anxiety, so people with anorexia have a high suicide rate as well.

Anorexia itself is actually divided into the traditional anorexia that we think of, which is the food restricting type, and the binge purge type of anorexia, which we usually call bulimia. Scientists now believe that they are two different symptoms of a similar disorder, and some scientists also consider aspects of anorexia to be highly similar to obsessive/compulsive disorder.

The question is, though, what makes anorexia heritable? What kind of genetic changes result in someone wanting to drastically restrict or control their food intake?

What if it had to do with estrogen? Versini et al. "Estrogen Receptor 1 Gene (ESR1) is Associated with Restrictive Anorexia Nervosa" Neuropsychopharmacology, 2010.

*I did consider titling this "does this estrogen make me look fat", but this is a rather serious subject and I threw that one out.

There are several good reasons to want to look at sex hormones, like estrogen, in anorexia. First off, there are far more anorexic women than men. There are 9 anorexic women to every 1-3 anorexic men, and that can't all be due to the ideal body image for women right now being slim.

Secondly, there are no children with anorexia. Anorexia usually comes on around puberty, which is about the time you start getting cycles of hormones such as estrogen (though obviously lots of other changes too).

Not only that, estrogens themselves may be different in people with anorexia. High levels of estrogen induce anorexia in rats, and receptors for estrogen are located in areas which help to control food intake.

So what the authors here wanted to do was to look a families with anorexia and without, and look for a specific set of genes, in this case the genes which code for the two estrogen receptors. They thought that they would be more likely to see changes in the Estrogen receptor 1 (ESR1) over ESR2, because changes in female rats who have been ovarectomized (no ovaries, thus very little estrogen) show changes in feeding behavior which correlated with changes in ESR1.

Sure enough.


What you can see here is an association between various haplotypes for ESR1 and anorexia (a haplotype is a combination of alleles, which are various optional forms of a DNA sequence for a gene, on a chromosome that they transmitted or inherited together). You can see (above the p=0.05 line, which shows significance) that there are a bunch of haplotypes that are associated with anorexia.

Not only that, the scientists also tracked whether the haplotypes were coming from the mother or the father. They did see significant transmission from the mother, but they ALSO saw some REALLY significant transmission from the father, which could help explain the really high heritability of the disorder.

This is a rather cool study, in my opinion. First off, it helps explain the high heritability of anorexia. Secondly, it helps to explain why far more women suffer from anorexia than men. After all, though men do need estrogen for things like sperm maturation, they don't utilize high levels of estrogen like women do, and certainly don't go through the same cyclical patterns with peaks and troughs. If some women have significant differences in the way they respond to estrogen (say with a super sensitive ESR1, though the function of this wasn't really discussed), this could lead to some of the food restriction seen in anorexia.

Obviously this isn't all she wrote about anorexia. There are lot of other factors, like what kind of estrogen levels women with anorexia have (as opposed to the estrogen receptor levels that were studied here), as well as things like their responses to stress (women with anorexia have very messed up HPA axes, which is how the body responds to stress), and of course there are societal factors which can precipitate the appearance of anorexia in the population. But this is a start, and knowing what causes the heritability of anorexia can go a long way to finding way to treat it.

Versini, A., Ramoz, N., Le Strat, Y., Scherag, S., Ehrlich, S., Boni, C., Hinney, A., Hebebrand, J., Romo, L., Guelfi, J., & Gorwood, P. (2010). Estrogen Receptor 1 Gene (ESR1) is Associated with Restrictive Anorexia Nervosa Neuropsychopharmacology DOI: 10.1038/npp.2010.49

5 responses so far

  • jerry anning says:

    Have their been reports of m-f sex reassignment patients developing anorexia when they started taking the hormones and/or after castration?

  • Scicurious says:

    Jerry, good question. I sure don't know. But I can look. I think it would also have to be a family including the genetic factors, though.

  • [...] nervosa has a hereditary element: some cases tend to run in families. Read scicurious’ excellent blog article covering the recent research paper exploring [...]

  • gad says:

    fantastic post! thanks so much

  • Mary says:

    Recently there have been reports of eating disordered behaviors presenting in very young children (I think I read that they've seen them in kindergarten aged children.)I I don't have any sources to cite, asI can't quite remember here I read it, and I know it certainly isn't as common in early childhood than in early adolescence, but I think it's an important thing to note.

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