The Rhythm is Gonna Get You

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 genes) and allows your body to anticipate events that happen repeatedly every day and produce the correct physiological 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. This HPG axis is important for driving the rhythms of several organs in your body, but most importantly for the subject of this week’s blog post, 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 all 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 pattern 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 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 as a direct result of shift work. Now before I go any further there is a question I would like you to consider. Does night shift work actually increase the risk of developing endometriosis, or does 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 severe and 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 and that was no mistake. 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.

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. 

This goes a 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 focussed on one particular aspect of the disease. A broader view of the disease and all of its strengths and weaknesses are needed before sufferers really see some benefit.