Scientist have known for years that poor sleep can link to obesity and metabolic disorders such as diabetes. And conversely, hormones can play a role in causing poor sleep even in normal weight patients, particularly in pregnant and menopausal women. This blog will explore the complex relationships between sleep and various hormones, and their role in weight.
What are hormones? They are chemical messenger molecules which help the body maintain homeostasis (balanced functioning). They are secreted in one of several glands (thyroid, adrenal, pancreas, sexual organs, pineal, etc) and travel to act on another part of the body. A hormone binds a chemical receptor on certain cells and causes a change or an action. There are two types of hormones: endocrine hormones are secreted directly into the bloodstream and exocrine hormones are secreted into certain ducts. Hormones can have many effects including: metabolic, growth, reproductive, behavioral, and immunological.
Sleep is a key time for hormone secretion. The endocrine system is timed by the overall circadian rhythm which sets sleep/wake patterns. During sleep, secretion of some hormones is increased and some are suppressed. At the same time, certain hormones can actually drive sleep and wake states. When sleep is fragmented or reduced, it can have significant impacts to normal hormone secretion.
The key time for secretion of many hormones is during slow wave sleep. This is a phase of non-REM sleep in which the neurons of the brain fire very synchronously, and in large bursts called delta waves. When a patient gets insufficient slow wave sleep for any reason (deprivation, insomnia, apnea), it can alter normal secretion patterns for 3 key hormones: growth hormone, pituitary/adrenal, and cortisol. You may recall that cortisol is also known as the stress hormone. The more of this we have, the more belly fat and other inflammatory markers like c reactive protein we generally have.
Many people take melatonin to help improve sleep. This is also known as the “dark hormone” because it is secreted at night. Melatonin is synthesized in the pineal gland from tryptophan (which is itself converted from serotonin). You may have heard of tryptophan as the chemical in turkey which contributes to the uniquely special food coma of Thanksgiving. There is a strong circadian component to the timing of melatonin secretion. Its release is inhibited by light. We have the highest levels at night (between 3-4 AM) and the lowest levels during the day. Excess melatonin is linked to sleepiness and may inhibit the wake-promoting regions of the brain. Age, menstruation, sleep deprivation, and drugs can all impact the naturally occurring amounts of melatonin.
Melatonin is widely used as an over-the-counter sleep aid. It has a rather mixed literature on efficacy. Studies show it is best administered during the day to help advance sleep latency at night. It may also reduce REM (rapid eye movement sleep) latency, or the time it takes to get into the dreaming state of sleep. Do note that prolonged use may have some effects on the reproductive system, particularly lowering sperm counts. But otherwise, it’s generally considered safe. It is also thought to be more effective for shift work and jet lag than just general insomnia. Interestingly, it has also been shown to be useful with blind patients. When the light doesn’t get processed through their eyes, it can throw off their natural sleep-wake cycle, but melatonin can help restore a natural order. Another small study showed it may help reduce REM-behavioral disorder (in which patients act out their dreams).
Another hormone strongly related to sleep is growth hormone. This is most commonly secreted in childhood to help with physical growth, but it continues to be secreted in small amounts at any age. It is stimulated by a variant of ghrelin (an appetite hormone we’ll cover soon). Its peak release is during sleep, right as you fall asleep and go into your first slow wave cycle. There is in fact a quantitative link between delta power (the high of the EEG wave) and the volume of growth hormone which is secreted. Studies also show that growth hormone is increased in recovering nights following sleep deprivation, and that injecting growth hormone can increase slow wave sleep. Interestingly, men tend to have a single peak secretion at night and women have more intermittent secretion through the day and night.
Another major set of hormones is broadly referred to as the corticotropic (HPA) axis. This stands for hypothalamic-pituitary-adrenal, and all three of these work together in many complex ways. The HPA access mediates our response to stress and also has circadian oscillations. Even without any major sources of stress in our lives, cortisol levels are naturally the highest early in the morning and lowest in the late evening/at sleep onset. Unsurprisingly, low cortisol seems to drive the sleep impulse and high cortisol seems to drive the waking impulse. This is obvious to anyone who has ever had stress-based insomnia. A problem for patients with sleep apnea or night time leg movements is that arousals from sleep trigger cortisol secretion. Indeed, as we age, we all have more fragmentation in our sleep (e.g. more frequent arousals, and therefore we tend to see a rise in cortisol as we age. We do see cortisol drop dramatically in recovery sleep following acute deprivation.
Cortisol is often referred to as the “stress hormone.” It’s secretion in normal (non stressed/non sleep deprived) patients is based on circadian cues and starts to rise around 2 hours before awakening, with peak levels between 8-9 AM. It declines thereafter and reaches its low point around midnight. Indeed, slow wave sleep suppresses cortisol. This too makes natural sense, some cortisol is normal to get the body up and running for the day. The problem is when it becomes excessive, or secreted because of acute or chronic stress.
The thyroid stimulating hormone (TSH) is also worth touching on. It, too, has a circadian pattern of secretion with maximum levels around 2 AM and lowest levels at mid-day. The earlier phases of sleep (the first period of slow wave) seems to inhibit TSH and prolonged sleep deprivation dampens circulating TSH overall. Secretion of TSH is particularly sensitive to circadian disruptions from jet lag or shift work.
Metabolic Hormones: Insulin is perhaps the best known of these hormones. Insulin signals the cells to take up glucose and regulates energy storage and use. Generally, secretion of insulin falls during sleep (though it may have a slight increase right at sleep onset). It tends to be a bit higher in NREM sleep and lower in REM. Getting good sleep appears to keep insulin levels stable, but sleep deprivation (particularly a lack of the deepest stage of sleep) has been linked with insulin resistance.
This means not getting enough sleep could predispose patients to diabetes! Diabetes is particularly co-morbid with obstructive sleep apnea (a condition in which you partially or completely stop breathing during sleep). Both diseases are more prevalent in the obese and one study found 86% of obese patients with type 2 diabetes also had apnea. Conversely, up to 40% of patients who have apnea also have diabetes and snoring is independently associated with a doubled risk of developing diabetes after a 10 year period. Several studies have shown a link between apnea and insulin resistance/intolerance even when controlling for obesity. Other studies have found a correlation between the severity of hypoxia (reduced oxygen due to apneas) and the degree of insulin resistance, meaning when your oxygen levels drop, it is causing cellular damage and increasing risk for diabetes.
In the other direction, diabetes may also worsen apnea. Specifically, patients with associated neuropathy may have increased risk and severity of apnea due to diminished respiratory function and a less stable airway. On the plus side, there is some evidence that treating apnea with CPAP (continuous positive airway pressure) can improve insulin sensitivity, and that more hours of CPAP use correlated to better insulin levels. This was particularly true for those with the most severe apnea.
A lesser known hormone associated with sleep and metabolism was discovered relatively recently in the context of narcolepsy. Hypocretin (also known as orexin) regulates sleep and wake. It rises during waking times and falls during sleep. But patients with narcolepsy tend to have diminished levels of this in the brain, which plays a role in cataplexy (the tendency for narcoleptics to fall asleep and lose all muscle tone in periods of excited emotions). This hormone spikes during sleep deprivation as it tries to keep you awake, and it’s also involved in the control of appetite (perhaps this is why if you’ve ever pulled an all-nighter, you’ve had the urge to eat random junk food).
Two other related appetite hormones are leptin and ghrelin. Sleep deprivation causes a decrease in leptin and an increase in ghrelin. Both of these changes can increased hunger and caloric intake. Interestingly, ghrelin also promotes deep sleep.
Sex Hormones: These can play more of a role in sleep than you would expect. Before puberty, there is similar sex hormone secretion (in low amounts) for both boys and girls. These include the lutenizing hormone and follicle stimulating hormone. Secretion of both of these is higher at sleep onset. When puberty hits, males see a rise in testosterone at night and females see a rise in estrogen/progesterone during the day.
For grown men, testosterone secretion remains linked to sleep, with the lowest levels late in the evening and maximum levels early in the morning. The peak time for secretion is around 90 minutes prior to the first REM period. The impact of poor or interrupted sleep is that it can lower testosterone levels (as can untreated sleep apnea). Higher total sleep time mirrors higher testosterone in healthy men, and treating apnea can return testosterone levels to baseline. Being of the male gender increases your risk for sleep apnea, but by menopause, the risk equalizes. It is thought that androgens pose a risk for apnea and/or estrogens may help prevent it. Androgen therapy in both genders, or those undergoing gender re-assignment therapy, seems to worsen apnea risk and overall sleep quality.
For women, there are many changes through their menstrual cycle and beyond which impact sleep. There are 2 phases to the menstrual cycle. In the follicular phase, poor sleep is reported during secretion of the follicular stimulating hormone (which occurs at the beginning and end of each cycle). Indeed, severe PMS has been linked to insomnia, interrupted sleep, and even negative dreams! The other phase is luteal, and this is associated with dampened body temperature rhythms and increased sleep spindle frequency (and thus more of the stage of sleep we call N2). We also see earlier and less REM sleep in this phase. In general, women who do shift work can see a disruption in their menstrual cycle and sex hormones. Untreated apnea in women can be linked to impaired ovarian function and potentially poorer fertility. A higher degree of apnea is also linked to lower estrogen/progesterone secretion, and unlike in men, there’s less indication that CPAP therapy can reverse this.
Pregnancy and Sleep: In general, pregnant women tend to sleep a bit longer, but they have increased interruptions to sleep. Often, excessive daytime sleepiness and even insomnia can develop (especially later in the pregnancy). Snoring can increase by 15-20% due to increased weight, and higher estrogen levels can narrow the upper airway, causing an increased risk for sleep apnea. After birth, sleep in the mother is lower for around 3 months after (likely because her child is waking up frequently at night).
PCOS: Polycystic Ovarian Syndrome is the most common endocrine disorder in premenopausal women, with a prevalence of ~ 5-8%. Symtpoms of this include ovarian failure, irregular menses, obesity, excess angrogens, and lower estrogen/progesterone. PCOS is also associated with a higher risk of glucose intolerance and diabetes. Over 90% of PCOS patients have sleep complaints, and they show 9 times the risk of being excessively sleepy during the day. Low estrogen is thought to cause the worsened sleep quality. Women with PCOS also show 30 times higher risk for apnea! This works out to about 70% of PCOS patients having apnea. It is unclear if it is caused by higher testosterone, lower progesterone, or insulin resistance, perhaps it is a combination of factors.
Menopause: Perhaps unsurprisingly to anyone in this time of life, there is strong evidence that sleep quality worsens after menopause. 50-80% of menopausal women report sleep issues, and they tend to have more than 3 times the odds of having a sleep disorder. Hot flashes correspond to pulses in the lutenizing hormone and tend to occur earlier in the night. We also see a reduction in growth hormone and increase in cortisol – bummer all around! Combination hormone replacement therapy has been shown to improve sleep quality and be somewhat helpful for obstructive sleep apnea (it lowers the severity but doesn’t cure). By the end of menopause, the circadian pacing of sex hormones essentially ceases.
Nothing happens in a vacuum: Hormones often play on one another and in feedback loops with many organs of the body. In all of the cases explored above, a bidirectional relationship exists between sleep quality and the endocrine system. It is certainly clear that sleep and metabolism, as well as sleep and normal sex hormone function are closely related. Taking care of your sleep health can promote healthy weight and sexual health, and conversely, healthy weight and sexual functioning can promote good sleep!
If you need help reaching your sleep goals, we offer sleep coaching virtually to help!
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