Sunday, February 19, 2012

Endometriosis and Depression (Part 2)

The Science of Endometriosis and Depression



Today I will be going over some of the more researched and scientifically backed purposed relationships between Endometriosis and Depression. [NOTE: I've also time traveled to update some of the research here--so if you see studies newer than the post date, that's why!]

Now, let me put a warning in now. I majored in neuropsych and spend my work hours in labs. I am sort of a nerd. And one occupational hazard is that I've become a bit desensitized to some jargon. But that's not in line with the site goals, so I'm trying to keep that part of me in check. Today, although I will be citing resources and discussing papers, I will be trying my absolute best to remain as plain language as possible. If there is anything you do not understand, please email me or leave a comment! That way, I can fix it for everyone. My goal is to write this for other people--not myself!


Why Is It So Hard To Explain The Connection Between Endometriosis And Depression?


First off, there are many different factors that make it difficult to identify exactly why there are such high rates of depression in women with endometriosis. However, the link is definitely there--women with endometriosis DO report much higher rates of depression (1,2). That much is clear; it's the why that seems to lead to debate.


The main problem is that without advances in endometriosis (good animal models, more funds, etc.), the exact nature of the relationship between depression and endometriosis is a bit of a mystery. In fact, some have even proposed that it may even be possible that women that are not vulnerable to depression experience less pain than women who are. Meaning, that the pain you feel with endometriosis could have more to do with anxiety/depression and less to do with endometriosis. 

This does not mean that it is a 'fake' disease--that is not what I am saying. But the experience of pain ('how bad it feels') may differ depending on one's mental state. Anyone with endometriosis can tell you that the amount of physical pain felt does not really correlate with the stage/severity of the disease (3). For instance, a women with 'only' stage 1 endometriosis could be experiencing much more pain than a women with highly advanced endometriosis. Part of it has to do with where the endometriosis is. 

But another part may have to do with your personality type (4). Past research assumed that personality type could lead to endometriosis, but more recent research is suggesting that depression/anxiety is more likely a consequence of endometriosis. Meaning, some researchers believed that certain personalities were more likely to develop endometriosis. They believed this because of the high rate of anxiety and depression in women with endometriosis. However, more modern research has shown the opposite--women are more at risk for these disorders because of complications with endometriosis. 


The Vicious Cycle


From what I've read in the current research, it seems that endometriosis and depression form a dangerous cycle. They feed into one another, each aggravating the symptoms and severity of the other. 

Consider this: Persistent pain from illness increases the likelihood of developing secondary disorders (such as mood disorders like depression and anxiety). Why? Essentially, it's because hurting all the time takes a toll on your mental state. In turn, these mood disorders affect how your body processes pain. Even problems such as mild depression can increase the severity of pain sensation (i.e., it hurts more than it used to). Then this pain furthers the risks for mood and mental complications. Which then increase the subjective sensations of pain (5). 

You see where this is going? Without preparedness, a patient like this could suddenly be caught in a dangerous downward spiral of pain and depression. To me, this is the biggest reason for why it is important to address both physical and mental complications, when we are trying to deal with the complications/difficulties/tragedies of endometriosis.


Contributing Factors



Other aspects of endometriosis also increase the risks of depression. Such as the restrictions that the pain causes on one's life. For instance, a common problem for endometriosis sufferers is that it disrupts their social activity, circles, and support  (6). Basically, when someone is experiencing continuous, severe pain, it can prevent them from having a healthy social life (or, in some cases, any social life). The pain keeps them from making and keeping connections with friends and loved ones. 

Without that support net, you are more susceptible to depression (7). Not to mention to other immunological hiccups. Meaning, people who frequently socialize or maintain strong friendships are not only more protected against depression, but also infections (8). The link is still being studied, but for whatever reason, people who socialize more recover/heal/defend better than those who socialize less. And the context of socializing isn't what's important--meaning, it's better to try and find ways to socialize within your comfort, than to give up on socializing in its entirety. 


Even aside from the disruption in socialization, pain alone can lead to higher rates of depression. As I said earlier, depression can increase the severity of how pain 'feels'.  Studies have found, in comparing endometriosis women with and without pelvic pain, the rates of depression are over twice as high in women with pelvic pain (9). This relationship between chronic pain and depression has been repeatedly researched; however, there is no agreement on whether the disease/disorder causes the depression or depression causes the disease/disorder. For our purposes, it is simply beneficial to keep this relationship in mind and be cautious of the risks of depression (especially when dealing with a chronically painful illness). Like I said earlier, you want to fight against the vicious cycle. 

Also, as I hinted earlier, it's been suggested that the severity of pain can correlate with the the severity of depression. However, it's important to note that this relationship has not been explored fully. It's something to keep in mind, but it's not the sole defining factor of either issue. And, as an additional reminder: remember that the stage of endometriosis is not linked to the risks/severity of depression (10). This means that the stage of endometriosis is less of a factor for depression than the experienced pain. To oversimplify it: someone with Stage 4 Endometriosis and no pain will be less at risk for endometriosis-linked depression than someone with Stage 1 Endometriosis and high pain.  


What About The Hormones?

With the major role hormones play in the progression of endometriosis, one would expect to see a lot of research on the connection between hormone imbalances and depression. After all, as one endometriosis fighter once said: there is a horrible imbalance of hormones in an endo-sufferers body. That alone can trigger mood swings and social difficulties. And the research is there--studies show that irregular and excessive estrogen can increase a woman's risk for depression. 

However, it's difficult to show what role these changes play, and even more difficult to identify if they are the cause or the result of depressive factors. For one, every women's 'normal' balance of hormones is different ('normal' meaning pre-menopausal, non-ovulating, non-menstrual). What seems to matter most is when these hormones fluctuate in an abnormal way, for that specific woman. And it's even more difficult to establish a baseline for that in multiple women (a standard to compare against). And studies would need to be able to reliably control those hormones, to be able to say that the erratic hormones caused the depressive symptoms.

Furthermore, there are a lot of factors that get in the way of measuring and changing those levels. There are many different hormones and chemicals that affect reproductive hormones, and everything from diet to habits can change the levels of hormones within a single woman. Even a healthy woman goes through a barrage of hormonal changes every month. 

To understand the difficulties of controlling hormone levels, consider the process of a healthy woman trying to find the 'right' birth control pill. I was unable to find hard data on this (unfortunately), but I've probably spoken with at least 300 women about their birth control (both with and without hormonal abnormalities). It was incredibly rare to speak to a woman that had only tried one contraceptive pill. Generally speaking, the minimum was 2-3; most women will try a few different brands before finding one that doesn't make her nauseated, anxious, etc.. 

For hard data, consider how many different pills are currently manufactured. By brand names alone, there are 20 different types of just the combination type-pill, which uses different mixes of two hormones to prevent pregnancy. And while generic pills will have the same ratio of 'active' drug, that filler affects how those hormones are 'absorbed'. Some women may do equally fine on two different generics, but other women will respond differently to the generics. 

Now, in this scenario (healthy period), that's just to get the hormones in a general range to stop ovulation (which, though an impressive result, is not that difficult to achieve--it's a surprisingly wide range). There is so much 'fuzz' in the way of what that normal is, that we have a robust market for different birth control companies and products. Try to think how much more difficult that sort of control would be for women with dysfunctional periods.

So Hormones Are Difficult--Big Surprise--What Can We Do?


To study the direct link between endometriosis and hormones--to actually study it--we need to start with a simpler view. Generally speaking, that view would involve animal models. 

Thanks to the privilege of getting to work at of the National Primate Research Centers, I have seen the spectrum of attitudes on animal research. I know that some people believe it's never acceptable, and I know others that think it's over-regulated. I can say that I am a huge animal lover, and I am very fond of certain rat breeds as human companions.

However, opinions aside, anyone who has ever received medical treatment should thank the animals that made that treatment possible. The truth is, some research cannot be ethically done on human beings. Even for issues that are, for all intents and purposes, 'harmless', humans are often not sufficient. As I mentioned before, our bodies are complicated, which makes measurements complicated. But it also makes it hard to say what-caused-what. Animals live shorter lives and it is much more ethical to completely control an animal's environment. Meaning, it's generally frowned upon to put a new human in a box and say 'you live here now'.

But animals--especially lab rodents--mature fast, live short lives, and do well under strict environmental regulation. And, by regulating that environment, it takes away a lot of those 'fuzzing' factors. For a complex disease like endometriosis, that control would be a game changer. It would be the only way to control the environment and explore all the many factors of endometriosis. 

However, there is one major problem. Researchers cannot use just any rodent. When rats or mice are studied for disorders and disease, researchers use a specially bred 'model'. These models have issues that mimic specific diseases and disorders in humans. Such models have facilitated life-changing developments for serious diseases, such as diabetes and HIV (11,12). They have rat models for ADHD even! (I have ADHD--I'm not saying it's not important--but I wish that endometriosis got the same level research funding that ADHD does).

There are some lines of rodents that have been used for endometriosis research, but they are not the ideal model. Their imitation of endometriosis is lacking, and it limits the quality of research that can be done (13). And while I found some studies with an experimental endometriosis model, I have yet to find research announcing a ready-for-testing model (14). 


Thus, without an appropriate animal model, our understanding of the chemical aspects of endometriosis are sub-par at best. 


What's Most Important


This might just be a small snippit of the big picture, but I hope this article has been informative. This is an uphill battle that women with endometriosis are fighting--every single one is at a greater risk for depression. Know that risk. And know how to fight it. And if you are in the place of a supporter, know these risks too. It helps to have a support team that knows little things to help.


For Part 3, I cover ways to deal with pain related depression. Keep on fighting!




References (Sorry, I haven't converted these all into APA yet--ran out of time!)
  1. Chen, L. C., Hsu, J. W., Huang, K. L., Bai, Y. M., Su, T. P., Li, C. T., ... & Chen, M. H. (2016). Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study. Journal of affective disorders, 190, 282-285.
  2. Sepulcri, R. D. P., & do Amaral, V. F. (2009). Depressive symptoms, anxiety, and quality of life in women with pelvic endometriosis. European Journal of Obstetrics & Gynecology and Reproductive Biology, 142(1), 53-56.
  3. Vercellini, P., Fedele, L., Aimi, G., Pietropaolo, G., Consonni, D., & Crosignani, P. G. (2006). Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Human Reproduction, 22(1), 266-271.
  4. BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE Volume 152, Number 1, 93-97, DOI: 10.1007/s10517-011-1463-0 
  5.  Psychoimmune Interactions in Women of Reproductive Age with EndometriosisGomibuchi H, Taketani Y, Doi M, Yoshida K, Mizukawa H, Kaneko M, et al. Is personality involved in the expression of dysmenorrhea in patients with endometriosis? Am J Obstet Gynecol. 1993;169: / 723 / /
  6. Peveler R, Edwards J, Daddow J, Thomas E. Psychosocial
    factors and chronic pelvic pain: a comparison of women with
    endometriosis and with unexplained pain. J Psychosom Res.
    1995;40: / 305 / /15
  7. Glass, T. A., De Leon, C. F. M., Bassuk, S. S., & Berkman, L. F. (2006). Social engagement and depressive symptoms in late life: longitudinal findings. Journal of aging and health, 18(4), 604-628.
  8. Baron, R. S., Cutrona, C. E., Hicklin, D., Russell, D. W., & Lubaroff, D. M. (1990). Social support and immune function among spouses of cancer patients. Journal of Personality and Social Psychology, 59(2), 344.
  9. Lorençatto, C., Petta, C., Navarro, M., Bahamondes, L., & Matos, A. (2006). Depression in women with endometriosis with and without chronic pelvic pain. Acta Obstetricia Et Gynecologica Scandinavica, 85(1), 88-92. 
  10. Depressive symptoms, anxiety, and quality of life in women with pelvic endometriosis Rodrigo de P. Sepulcri, Vivian F. do Amaral European journal of obstetrics, gynecology, and reproductive biology 1 January 2009 (volume 142 issue 1 Pages 53-56 DOI: 10.1016/j.ejogrb.2008.09.003
  11. Srinivasan, K., & Ramarao, P. (2007). Animal model in type 2 diabetes research: An overview. Indian Journal of Medical Research, 125(3), 451.
  12. McCune, J., Kaneshima, H., Krowka, J., Namikawa, R., Outzen, H., Peault, B., ... & Yee, E. (1991). The SCID-hu mouse: a small animal model for HIV infection and pathogenesis. Annual review of immunology, 9(1), 399-429.
  13. Tirado-González, I., Barrientos, G., Tariverdian, N., Arck, P. C., García, M. G., Klapp, B. F., & Blois, S. M. (2010). Endometriosis research: animal models for the study of a complex disease. Journal of reproductive immunology, 86(2), 141-147.
    • Francisco Delgado-Rosas
    • Raúl Gómez
    • Hortensia Ferrero
    • Francisco Gaytan,
    • Juan Garcia-Velasco
    • Carlos Simón
    • and Antonio Pellicer 
    • The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis Reproduction 2011 142 745-755





2 comments:

  1. What you say makes a lot of sense ashley! I never realized the extent of your pain and think that your blog is a wonderful means of communication and education for those of us who love and care about you! Keep it up! Aunt Carol

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    Replies
    1. Thank you, it's a really fun website for me to work on :)

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About The BedRiddenHead

I want to be happy. And this site is about that chance. How to strive to thrive in the body I've got and maybe turn my experiences into something worthwhile.

This site aims to help educate and reach out to people all over that struggle with pain or illness. To try and make something helpful. I work as a medical research writer, my background is in neuropsychology and biology, and I want to share what I learn in a way that is easy to understand. I am not a doctor. I'm definitely not your doctor. I am just some lady who wants to make someone's (anyone's) life a little bit better. Whether you have endometriosis, a chronic injury, a struggling friend, or just want to learn something new, I hope to make a place that has what you are looking for.

Thank you for stopping by, I wish you strength in your health and happiness.