Monday, July 25, 2011

Causes of Endometriosis

Causes of Endometriosis
This article is for those who wish to know more about the physical causes of endometriosis. It was written both for those with the disease and those wishing to learn about it.While it was published in 2011, I have continued to add and expand upon the article to improve its usefulness.

Endometriosis is a disease that disrupts and distorts normal female reproductive functions. It causes the bodily spread of a material similar to that which is shed during menstruation ('endometrium'). This growth and spread of 'endometrium' can cause: pain, inflammation, scarring, infertility, sickness, and disability. While the effects of endometriosis are well known, the causes of the disease are less understood. 

Technical Summary:
Endometriosis is hypothesized to be caused by a combination of genetic vulnerability and environmental effects. This interaction of innate bodily defects and immune dysfunction, along with the negative influences of foreign bodies, is believed to lead to endometriosis. 
Simplified Summary:
Research supports that endometriosis is likely to be caused by two primary factors: characteristics/qualities of a person's body (e.g., genes and physical makeup), and environmental factors such as toxins. Put simply, a person's genes and their environment combine to influence endometriosis. 

Innate Vulnerability
The characteristics of our bodies can encourage or discourage the development of diseases like endometriosis. Innate vulnerability is composed of the aspects of our body that are 'built' for an illness. They are the biological issues that make a person more likely to develop a disease. These include factors such as genetics and changes in the womb.

The Cup Analogy
For non-biology folks, think of it this way: a person's risk for illness is a cup. When the cup fills 100% or more, they will develop that illness. However, if the cup only partially fills, that illness will not develop. What fills these 'cups'? 

Innate Vulnerabilities are Water
Our cups are partially filled by our innate vulnerabilities. The characteristics and qualities our body has from birth.
In this example, we'll say that water (blue) is the cup's filling we have from birth. The amount of water represents how vulnerable a person is to an illness. Those with high vulnerability may have a cup 80% full of water, while those with low vulnerability have a cup 20% full of water. A cup filled with 100% water would mean a person was born with an illness. The less full cups represent fewer innate vulnerabilities, and that means they are more difficult to fill. 

Environmental Toxins are Orange Soda
A cup starts with a water filling at birth, yet that alone is often not enough to develop an illness. Environmental factors, like toxins, also help to fill that cup. And a cup's starting water (innate vulnerabilities) affect how easily it can be overflowed by those environmental factors.

For our cup example, imagine environmental toxins are orange soda, which is added by exposure to outside influences. For example, a group of people might experience 40% of a cups volume in environmental toxins (orange soda). For some people, that 40% is not a big deal. For others, a 40% filling is catastrophic. In our example, a 40% will not overfill a cup with 20% water, but it will overfill the cup with 80% water. (40+20=60, but 40+80=120).
Folks with low vulnerability will not fill their cup with environmental toxins, and they are safe from the illness. However, those with high vulnerability (80%) will overflow (120%), and they will develop endometriosis. Make sense? 
So, for endometriosis, what makes up the differences between those people with a cup 20% full of water, and those with a cup 80% full of water? What the heck did they do to earn that lesser predisposition to this horrible disease? Well, as the original water-fill of a glass is determined by innate qualities, they did not do anything to earn it. They were born with it. Certain innate qualities can make one less vulnerable (less water), while other innate qualities can make one more vulnerable (more water). 

Innate Qualities that Influence Endometriosis
There are certain bodily qualities that 'add more liquid to your vulnerabilities glass' and make endometriosis more likely. These qualities are related to what you inherit from family (your genetics) and the way your body reacts to certain environments (1).  

Uterine Outflow (Retrograde Menstruation)
Bodily qualities, which make the outflow of menstrual lining more difficult, can increase the likelihood of retrograde menstruation, and are linked to endometriosis. Remember, menstruation is another term for a period, when the uterus sheds its accumulated lining of blood and cells (endometrium). Retrograde menstruation is when the contents of menstrual lining flow backwards/inwards, into the body (the pelvic cavity) and is cited at a critical factor for endometriosis (2). These endometrium-like cells can then grow/divide and create a similar lining outside the uterus. This backwards flow can be caused by defects in proper outflow (for example, a narrow or partially obstructed cervix and heavy menstrual flow). However, retrograde menstruation alone is not considered enough to cause endometriosis.
The lack of attachment between the ovaries and uterine 
tubes results in an opening for Retrograde Flow
Unusual Cell Growth
This topic is a little harder for me to simplify, so I apologize if I sacrifice specificity for ease of reading. An older theory of endometriosis is called the 'coleomic metaplasia theory'. This theory suggests that certain qualities can make 'normal' cells, those on the outside of the ovary, change into cells similar to endometrirum (the cells that are responsible for the menstrual lining (the blood that is shed during a period)) (3). So, according to this theory, retrograde flow is not the only way to spread those cells outside of the uterus. Normal cells can change into endometrium-like cells, without originating from the uterus.

These theories are not really in conflict with one-another either. Rather than meaning that it is one cause or the other, research on this topic helps to explain how endometriosis happens in patients that have not had a period (children) or those than have never experienced retrograde flow. And, while the theory is older, there is current research that supports it (4). This 'abnormal growth' can be more likely to happen in certain women, increasing their likelihood of developing endometriosis.

Immune Dysfunction
A second innate quality that impacts endometriosis, is a failure of the immune system to clean up menstrual debris (those that do not properly exit the body).
Based on the information above, it can be fairly easy for endometriosis cells to grow in or escape into the rest of the body. Thankfully, in most women, the immune response is able to stop or clean this debris, preventing it from becoming a problem. However, an immune defect in this cleaning of 'loose' menstrual debris is linked to increases of endometriosis (5). This is also reinforced by studies that look at 'biomarkers' for endometriosis patients. These studies support that certain proteins, ones that help 'instruct' immune clean up, are reduced in endometriosis patients (6). Meaning, there is evidence that the immune system does not have enough of these proteins to do the job 'well'.

How critical is this immune dysfunction? It is hypothesized that, while 70-90% of women experience some amount of retrograde menstruation in their lives (7), but only about 7-10% of women develop endometriosis. Even in that percentage, there are ranges of severity. Again, retrograde menstruation can occur rather easily; uterine tubes (AKA fallopian tubes) are not directly attached to ovaries, and are open to the pelvic cavity. The immune function of 'clean up' is thus a fairly important factor in endometriosis development.

[Personal note, although there is disagreement between scientists about endometriosis occurring in higher rates in women with autoimmune diseases, my personal experience supports the correlation. I have both moderate chronic asthma and IBD, and both flare up when I have worse problems with my endometriosis. Hormones have a pretty powerful effect on the body, and I personally believe in a strong link between these three diseases.
Note UPDATE: Since I wrote this article, there has been an explosion in evidence linking endometriosis to immune problems and deficiencies. Most research supports the connection!]

External Influences on Endometriosis
[Note: the following section is somewhat out of date, and in need of more recent sources. Please proceed with caution until I can better update it with my current knowledge and understanding--04/2017]

A variety of environmental toxins have been linked to endometriosis. An environmental toxin can be defined as any contaminant that enters an organism and introduces harm to it. Some identified toxins that have been linked to endometriosis are stimulants (coffee, amphetamines, and nicotine), xenoestrogens, phthalates (plastics), PCBs, dioxins.

Stimulants
The exact relation of stimulants is complicated, and at the time of my writing this, the papers were a little beyond my experience. The key message I can summarize, is that stimulants can affect the growth rate and spread of endometriosis. Stimulants can disrupt a body's natural control of growth of the endometrial cells, the rate at which they spread out from the uterine cavity, and the behavior of immune cells responsible for their clean up (8). To summarize: they can amp up how fast and far the endometrial cells spread.

Stimulants disrupt the immune function by affecting the actions of monocytes. Monocytes are a type of immune cell, and their primary function is too dissolve and eat things that are not where they should be. They can help control the spread of migrating tissue, and their receptors are affected by stimulants. Monocytes can turn into macrophages (think of these as the giant garbage eating immune cells that clean up foreign/dangerous/dead tissues), which are also affected by stimulants. As research shows these already are reduced in concentration for women with endometriosis (9), consider how important it is to reduce interference from outside influences like stimulants. 

The take home message from this, without any mumbo-jumbo? Avoid stimulants. If you want to help limit the growth of endometrium and avoid interfering with its clean up, limit your stimulant intake. Try doing yoga in the morning instead of drinking coffee. Maybe try switching to decaf (slowly) or reducing your intake. If you smoke, quit smoking. It wreaks havoc on endometriosis. And if you have ADHD, consider incorporating behavioral therapy into your treatment, to possibly reduce the amount of dosage required (remember to always talk with your doctor when considering changes in your health regimen). I myself, use a combination of behavioral, physical, and medication therapies.
Xenoestrogens
Xenoestrogens are chemicals that mimic the hormone estrogen. Hormones are a way that our body sends messages to different organs (using a network called the 'endocrine system'). Our body uses hormones to regulate our organs and their functions, helping to establish a balance throughout our system. Estrogen is a key hormone for the regulation of reproductive functions. Our body can use estrogen, at different amounts and times, to send critical messages across our system. Puberty, menstruation, pregnancy, and menopause are all influenced by estrogen. 

However, xenoestrogens imitate estrogen; they mimic the 'shape' and 'signal' of estrogen in our bodies (10). This can disrupt, block, and wreak havoc in estrogen messaging. By introducing additional 'fake estrogens', these mimics upset a careful balance of estrogen amounts/timing, changing the messages our body receives. This means, xenoestrogens can send messages our body would not otherwise send, and cause changes that can harm our body. They cause growth and changes, in women and men, outside of a body's blueprint, without intention.
For example, in the reproductive system, xenoestrogens accelerate the irregular spread and growth of endometrial cells (11). When any balance is upset in the body, trouble tends to follow. In the case of endometriosis, excess estrogen influences excessive growth of endometrial tissue outside of the uterus. Xenoestrogens can augment this problem.
What does that mean for us? The take home message is to avoid as much xenoestrogens as possible. And to avoid them, we have to be aware of where they are. According to Wikipedia
"Xenoestrogens are "foreign" estrogens often widely used industrial compounds such as PCB, BPA and Phthalates, that have estrogenic effects on a living organism even though they differ chemically from the naturally occurring estrogenic substances internally produced by the endocrine system of the organism." 
Xenoestrogens are found in commercial, non-organic meats, pesticides, cleaners, some lotions/creams--essentially can be found in most commercial products made from (or containing) added artificial chemicals. I will post a couple links to handy lists for either what contains them or how to avoid them. For myself, I cut out red meats (mammal meat, or 'furry friends'), non-organic meats, limited myself to organic produce and groceries as best I could, and am careful with my use of cleaners/lotions. I use BPA free plastics, and when using a microwave, I only heat food in ceramic containers. I also only eat/drink from BPA free materials (such as glass, ceramic, metals, or safe plastics). Xenoestrogens can be difficult to avoid, but it's best to try as much as possible. They are perhaps some of the most dangerous agonists (essentially chemical increasers) of endometriosis around.

To be Continued
Thank you very much for reading, I hope you found it educational! 
Here are the links I mentioned: 

References:

  1. Simpson, J. L., Elias, S., Malinak, L. R., & Buttram, V. C. (1980). Heritable aspects of endometriosis: I. Genetic studies. American journal of obstetrics and gynecology, 137(3), 327-331.
  2. Sakura, Y., Masaki, T., Sudo, K, Nomura, M., and Shino, A. (1990). Histological studies on the therapeutic effect of sustained-release microspheres of a potent LHRH agonist (leuprorelin acetate) in an experimental endometriosis model in rats. Endocrinol. Jpn. 37, 719–729.
  3. Matsuura, K., Ohtake, H., Katabuchi, H., & Okamura, H. (1999). Coelomic metaplasia theory of endometriosis: evidence from in vivo studies and an in vitro experimental model. Gynecologic and obstetric investigation, 47(Suppl. 1), 18-22.
  4. Laufer, M. R., Sanfilippo, J., & Rose, G. (2003). Adolescent endometriosis: diagnosis and treatment approaches. Journal of pediatric and adolescent gynecology, 16(3), S3-S11.
  5. Olive, D. L., and Henderson, D. Y. (1987). Endometriosis and mullerian anomalies. Obstet. Gynecol. 69, 412–415.
  6. Borrelli, G. M., Abrao, M. S., & Mechsner, S. (2013). Can chemokines be used as biomarkers for endometriosis? A systematic review. Human Reproduction. 29(2), 253-266.
  7. Halme, J., Hammond, M. G., Hulka, J. F., Raj, S. G., and Talbert, L. M. (1984). Retrograde menstruation in healthy women and in patients with endometriosis. Obstet. Gynecol. 64, 151–154.
  8. Wu MH, Sun HS, Lin CC, Hsiao KY, Chuang PC, Pan HA, Tsai SJ 2002 Distinct mechanisms regulate cyclooxygenase-1 and -2 in peritoneal macrophages of women with and without endometriosis. Mol Hum Reprod 8:1103–1110
  9. Berbic, M., Schulke, L., Markham, R., Tokushige, N., Russell, P., & Fraser, I. S. (2009). Macrophage expression in endometrium of women with and without endometriosis. Human reproduction, 24(2), 325-332.
  10. Sonnenschein C, Soto AM. An updated review of environmental estrogen and androgen mimics and antagonists. J Steroid Biochem Mol Biol. 1998;65:143–150.
  11. Steinmetz R, Mitchner NA, Grant A, Allen DL, Bigsby RM, Ben-Jonathan N. The xenoestrogen bisphenol A induces growth, differentiation, and c-fos gene expression in the female reproductive tract. Endocrinology. 1998;139:2741–2747.
Last Edit: 4/20/17

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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.