The Rhythm is Gonna Get You
It’s been a busy month, both for myself and the endo community. If you live in the UK you will probably notice that endometriosis has been in the news a lot recently. A BBC news article highlighted the massive impact that endo can have on people, which even prompted an investigation by the UK government into how health systems are failing to meet the treatment needs of endo sufferers.
I’ve been busy settling in to my new research job; it’s good to be back researching endo again and hopefully it won’t be long before we have some interesting results I can share with you. In the meantime, for this blog post I’m going to re-do one of my old blog post from Feb 2016 on the role of our body clocks and endometriosis, so let's begin...
Are you a morning person, no? Me neither. We all tend to have a rhythm to our days that we prefer; some of us prefer to go to bed at 9pm, some us at 2am. Your preference for patterns of waking and sleeping actually has a biological basis called the circadian clock. This is, essentially, your body’s internal clock (which is essentially the timed switching on and off of certain biological processes and functions in your body) and allows your body to anticipate events that happen repeatedly every day and produce the correct response (like feeling sleepy or awake at certain times). Our circadian clocks are controlled by a small part of the brain called the suprachiasmatic nucleus (SCN) located within the hypothalamus. The SCN is responsible for coordinating rhythms in the hypothalamus and the pituitary gland which in turn form part of the hypothalamatic-pituitary-gonadal (HPG) axis. Ok, lots of acronyms and unnecessarily long words, that's fairly typical in science, but what has it got to do with endometriosis? This HPG axis is important for driving the rhythms of several organs in your body, but most importantly, for our concern, it orchestrates the rhythms in the reproductive organs.
In women the regulation and rhythm of the menstrual cycle is a tightly controlled systems involving the HPG axis. Below is a diagram that summarises how the components work together.
Interestingly several organs in the human body have their own distinct clock (called a peripheral clock) that are linked to the clock in the brain (the central clock). One such peripheral clock is in the ovaries. The ovaries, in concert with the brain, control the monthly variation in hormonal levels and the menstrual cycle. However, not only do levels of hormones change over the month, but also over the course of a day. A good example of this is that the monthly LH surge, mentioned above, requires a certain signal at the end of a resting period, which is why 80% of women have their LH surge around 8 a.m. However, it is not fully understood (in humans at least) how the monthly and daily variations in hormone levels are regulated.
Altering the patterns of exposure to light, food and sleep can disrupt the body’s clock which can have negative effects ranging from feeling sluggish to serious illnesses (in the case of long term disruption). Disturbances in the normal cycle of waking/sleeping/eating etc have been suggested to cause alterations in hormone levels. Indeed some studies have shown that even partial sleep deprivation can lead to temporary increases in estrogen and luteinizing hormone, as well as altering the production of several other hormones. Another study showed that women with certain mutations in a gene that is turned on in an area of the brain that controls circadian rhythms, leads to those women experiencing more miscarriages and less pregnancies than those women without the mutation. So clearly there is an important link between cycles in the brain and the reproductive system and shows disrupting one can adversely affect the other.
As modern society creates the necessity for longer and more varied working hours it is inevitable that some people will work at times that are out of synch with the ‘normal’ waking/sleeping rhythms we are used to. Disruption of the normal patterns of sleep because of shift working has been suggested to increase the risk of conditions such as cardiovascular disorders, gastrointestinal disorders, cancer and mental health conditions. So clearly there are negative health effects associated with shift work.
Of particular interest then are studies that have suggested that night shift work can increase the risk of having endometriosis, in some cases by as much as 50%. This same study found that there were no associations between endometriosis and mutations involving genes that regulate circadian rhythms, which leads me to believe the increase in risk was due to changes in hormones, possibly as a result of shift work. Now before I go any further there is a question I would like you to consider. Could night shift work actually increase the risk of developing endometriosis, or could night shift work increase the severity of endometriosis related symptoms making it more likely to be diagnosed? I very much doubt that night shift work can actually cause endometriosis, but it is certainly feasible that disruption of hormonal cycles by shift working could worsen the symptoms.
Indeed some studies have shown that, while levels of FSH and LH are not affected by night shift work, levels of estrogen are significantly increased, possibly due to a lengthening of the follicular phase of the menstrual cycle. Additionally melatonin (a hormone whose production is greatly affected by light/dark cycles but also has anti-estrogenic effects) has been shown to be reduced in shift workers. Perhaps as a result of this, further studies demonstrated that shift work can cause alterations to menstrual cycle length and regularity.
Is there any way we can tie these effects to the symptoms of endometriosis? We know that when it comes to endometriosis, heightened levels of estrogen are bad. Pretty much all medical therapies for endo are based on reducing estrogen levels. Estrogen leads to increased growth and inflammatory action of endometriotic lesions. Estrogen also increases the production of enzymes that produce chemical messengers called prostaglandins. Prostaglandins have several different functions, but in the uterus, they control the contractions of the uterine muscle, which are more commonly known as menstrual cramps. Excessive prostaglandin production can lead to chronic inflammation and severe, debilitating menstrual cramps (dysmenorrhoea), which is the most common symptom experienced by women with endometriosis. Therefore it could be that increased estrogen levels as a result of shift work could increase the severity of endometriosis associated dysmenorrhea.
I mentioned melatonin before as well. There has been a lot of interest recently in melatonin as a treatment for endometriosis associated pain. Whilst most of the studies have only been lab based so far, some clinical trial data suggests that melatonin therapy could reduce the chronic pain associated with endometriosis as well as improve sleep quality, although there is much more work required for this therapy before we draw any firm conclusions.
In some ways the symptoms of endometriosis may be forming a vicious cycle. Some studies have shown that a substantial proportion of women with endo (of the cul-de-sac in the case of this study) experience sleep disturbances, insomnia and daytime fatigue. Other studies show that pain symptoms interfere with sleep, in both adults and adolescents to a 'moderate-extreme degree'.
This goes some way to show how treating endometriosis should be viewed from many different angles to achieve maximum effectiveness. At present most medical therapies for endo are focused on one particular aspect of the disease. A broader view of the disease and all of its symptoms is needed before we really see some benefit.
Cover image is by Moose Photos from Pexels.com