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.
