Lack of Sleep Disrupts Body Clock, Hormones

In addition to sunlight, sleep and eating patterns can reset the body's circadian rhythm. Otherwise known as the biological clock, circadian rhythm controls the body's internal clock that regulates many functions.

Therefore, people who live on reverse schedules — working and eating at night and sleeping during the day — can experience difficulties because of a misalignment in their circadian rhythm with the external environment.

For example, sleep deprivation in male night-shift workers makes them prone to increased tiredness, low energy and low libido. In addition, insufficient sleep decreases testosterone, the main anabolic hormone, and increases cortisol, the main catabolic hormone, resulting in catabolic-anabolic imbalance.

These are also symptoms consistent with hypogonadism. Hypogonadism occurs when the body doesn't make enough testosterone. This condition can originate in the testicles, in the hypothalamus, or in the pituitary gland. Essentially, the brain does not send the proper message to the testicles to produce enough testosterone.

Peter Liu, MD, PhD, investigator at the Lundquist Institute and professor of medicine at the David Geffen School of Medicine at UCLA, Los Angeles, in conjunction with researchers at Washington State University, examines this issue in his new co-authored study, "Endogenous diurnal patterns of adrenal and gonadal hormones during a 24-hour constant routine after stimulated shiftwork." Furthermore, he explains how to decide if an individual has hypogonadism and if so, how to treat it.

According to Liu, endocrinologists can assess for hypogonadism by measuring blood testosterone soon after a patient wakes up — not necessarily in the biological morning as is normally done in day-shift workers.

He points out that correcting circadian misalignment (ie, through changing shiftwork schedules) will not fix hypogonadism. "If testosterone is low and there are symptoms and physical signs consistent with hypogonadism, then testosterone therapy can be considered," says Liu. "In an individual where testosterone levels are consistently in the normal range, then the symptoms are unlikely due to hypogonadism and other causes for those symptoms should be explored."

Medscape Medical News asked Liu to elaborate on some key elements of his new study findings and discuss how circadian rhythm affects hormones and our bodies as a whole.

What's the overall importance and impact of circadian rhythm?

Circadian rhythms developed as a way for us to anticipate and coordinate with the environment. The "body clock" is 24 hours in duration, controlling the sleep-wake cycle to align with the earth's cycle. The metabolism is also under circadian control in anticipation of times of eating and activity.

How does circadian rhythm affect hormones in a general sense?

Hormones are bloodborne signals that coordinate important bodily processes, eg, puberty, growth, reproduction, metabolism. Cortisol, the stress hormone, is under the control of the "central circadian pacemaker" in the suprachiasmatic nucleus in the brain that is believed to control and coordinate metabolic processes throughout the body. Cortisol regulates the metabolic processes by causing the release of glucose from the liver, which provides energy. In addition, cortisol regulates how effectively the body processes fats, carbohydrates, and protein.

What might be the specific connection between hypogonadism and male night-shift workers, in terms of mechanism?

Night-shift workers have a behavioral cycle which is mistimed to the internal clock (the central circadian pacemaker). Every cell in every body contains a molecular clock that receives signals from the central circadian pacemaker as well as from the environment. When these signs are in desynchrony, this is believed to impair cellular function, which can lead to insulin resistance (even in the absence of sleep loss). One plausible mechanism, therefore, would be that circadian misalignment leads to hypogonadism. Sleep loss could also lead to hypogonadism because sleep loss reduces testosterone.

Because your findings show that correcting circadian rhythm misalignment through schedule changes isn't feasible and will not fix hypogonadism, what treatment potentially could work for male night-shift workers?

One of the key findings is that circadian misalignment does not affect testosterone, despite the fact that circadian misalignment is a very plausible mechanism as to why male night-shift workers could be hypogonadal. Therefore, schedule changes won't fix hypogonadism if it's present.

Whenever a shift worker wakes up, if their testosterone is tested at the "right" time of day and if testosterone is low and there are symptoms and physical signs consistent with hypogonadism, then testosterone therapy can be considered. In an individual where testosterone levels are consistently in the normal range, then the symptoms are unlikely to be because of hypogonadism and other causes for those symptoms should be explored.

Circadian misalignment in and of itself does not reduce testosterone levels and therefore is unlikely to be a direct cause of hypogonadism. Sleep loss doesn't decrease testosterone. Instead, it may be caused by hypogonadism, and be responsive to testosterone replacement therapy. The point is that shift workers often have both circadian misalignment as well as sleep loss, and so if a shift worker has a significant degree of sleep loss rather than circadian misalignment, testosterone may decrease.

The other important issue here relates to how endocrinologists diagnose hypogonadism. We do that with a morning testosterone level because that is how the reference ranges were developed — but these reference ranges were developed in day-shift workers. Blood has to be collected at a specific time of day because we know that testosterone has a 24-hour rhythm; it is maximal in the morning. However, we showed in our paper that this 24-hour rhythm is not driven by the central circadian pacemaker. Instead, it's driven by behavior.

And from other studies that we and others have done we know that the biological clock is driven by cycles of sleep and wake. In other words, the pattern we see in blood testosterone is because of the rhythm of our sleep-wake cycle.

This means that for a night-shift worker, the correct time to check blood testosterone to confirm a diagnosis of hypogonadism is shortly after waking, irrespective of time of day and not necessarily in the biological morning.

What impact does a man's age have when it comes to adverse effects related to circadian misalignment?

This is a good question, but the answer is unknown because interventional studies where circadian misalignment is induced have generally been conducted in younger men not older ones. A related question is whether accumulated sleep debt across one's life — or accumulated episodes of circadian misalignment — could lead to increased prevalence of age-related diseases. Many scientists believe this to be the case, in part because "catch up" sleep isn't fully restorative.

What direction do you believe studies might take from here to mitigate metabolic harm related to testosterone-cortisol issues?

We need to identify the molecular target or targets of testosterone and/or cortisol that are responsible for metabolic harm. Perhaps some of these will be treated by medication. More importantly, in this research that I published in 2021, testosterone-cortisol balance is a mechanism of action by which insufficient sleep leads to insulin resistance, a critical pathogenic factor in the development of metabolic syndrome, prediabetes, and type 2 diabetes.

This finding is remarkable because no other putative mechanism by which sleep restriction could lead to insulin resistance has ever been verified through experimental manipulation in this fashion.

Knowing a mechanism bolsters the scientific rationale for scientists and physicians to promote sufficient sleep. Of course, at times insufficient sleep in unavoidable, but as a society, we should recognize sleep is important for health and encourage everyone to plan to get enough sleep.

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Credits:
Lead image: Yuri Arcurs/Dreamstime
Image 1: The Lundquist Institute

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Cite this: Lack of Sleep Disrupts Body Clock, Hormones - Medscape - Nov 11, 2022.