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The hormonal connection between insomnia and sleep disturbances is undeniable. Hormonal imbalances play a vital role in the quality of our sleep as well as how well we fall asleep and if we stay asleep. In today’s article, I will review everything you want to know about the hormones and neurotransmitters responsible for sleep disturbances and insomnia. I will also review some of the genetic variations, often referred to as single nucleotide polymorphisms (SNPs), which can influence neurotransmitter levels in the brain and potentially affect sleep patterns and susceptibility to sleep disorders. Let’s first review some of the important hormones.

Hormones Involved In Insomnia and Sleep Disturbances

Various hormones can impact our ability to fall asleep as well as stay asleep. Some of the hormones that can cause insomnia and sleep disturbances include.

  • Cortisol
  • Testosterone
  • Estrogen and Progesterone
  • Insulin and Blood Sugar
  • Thyroid hormones
  • Melatonin

The Hormones Involved in Insomnia

Hormones and Insomnia

There are few things worse than feeling exhausted and unable to shut off your mind. Insomnia has been called the world’s worst torture. While taking sleeping pills may help some fall asleep, prescription sleeping pills come with all kinds of side effects including dizziness, lightheadedness, headaches, diarrhea, nausea, allergic reactions, depression, and hallucinations all while leaving you feeling groggy the next morning. There is a better way to get restful sleep. Let’s review some of the hormone imbalance worth exploring when you suffer from Insomnia.

Melatonin & Cortisol

Two important hormones when it comes to insomnia you should be familiar with are Melatonin and cortisol. The sleep-wake cycle is called the circadian rhythm and disruptions in this rhythm cause a condition that over 70 million Americans experience every night is something called insomnia. But what is insomnia and how does the Circadian rhythm affect it?

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. These natural processes respond primarily to cycles of light and dark.

Your pineal gland’s main job is to help control the circadian cycle of sleep and wakefulness by secreting melatonin. The pineal gland is shaped like a tiny pinecone, which is how it got its name (“pine”-al gland)

When properly aligned, a circadian rhythm can promote consistent and restorative sleep. But when this Pineal gland’s circadian rhythms are thrown off, it creates tossing, turning, and feeling exhausted the next day.

Research is also revealing that Pineal gland circadian rhythms play an integral role in a variety of mental health disorders as well. Research shows that this circadian rhythm also affects our Sex hormones, Blood sugar, Cholesterol levels, and Metabolism including weight loss, White blood cell production, and cardiovascular disease

When people talk about circadian rhythm, it’s most often in the context of sleep and Insomnia. Here’s what happens.

Hormones involved in sleep disturbances and Insomnia_Melatonin

Melatonin Makes Us Sleepy

As night falls, the Pineal gland initiates the production of melatonin, a hormone that promotes sleep, and then keeps transmitting signals that help us stay asleep through the night.

During the day, light exposure causes the Pineal gland to produce less melatonin. When melatonin levels drop, we get an increase in other hormones that generate alertness and keep us awake and active.

Think about it like this. If you have a hormone messenger telling the body and mind to “wake up, don’t be sleepy” then you’ll have difficulty falling asleep, or staying asleep!

The primary “sleep hormone” is melatonin, and our key “awake hormone” is cortisol.

Hormones involved in sleep disturbances and Insomnia_ Low Testosterone

Testosterone and Insomnia

Did you know that if you suffer from insomnia or other sleep issues like sleep apnea, or low testosterone, a hormone needed by both men and women could be to blame?

Peak testosterone hormone production occurs during your sleep hours, according to a review of testosterone and sleep research published in the February 2012 issue of the journal Sleep. So, if you’re losing sleep, you’re also depriving yourself of testosterone production time.

While sleep deprivation lowers your testosterone, it also appears that low testosterone — also called hypogonadism — can contribute to insomnia, according to researchers who looked at hypogonadism symptoms in a group of male cancer patients and published their conclusions in the September 2012 issue of the Journal of Cachexia, Sarcopenia, and Muscle. (*) Low testosterone also appears to be linked to lower-quality sleep and fewer deep sleep cycles.

Researchers have observed that as testosterone hormones go down, the hormone Cortisol increases. (*) Elevated Cortisol levels contribute to wakefulness, resulting in shallower and shorter sleep, noted the February 2012 review in the journal Sleep. Let’s Look at some additional ways low Testosterone can contribute to sleep disturbances and insomnia.

Low testosterone levels have been linked to an increased risk of developing sleep apnea, a sleep disorder characterized by repeated interruptions in breathing during sleep. (*)These interruptions can significantly impact sleep quality and lead to insomnia symptoms. Conversely, sleep apnea itself can further reduce testosterone levels by disrupting sleep and reducing the amount of REM sleep, during which testosterone levels typically rise.(*)

Testosterone can impact the structure of sleep, known as sleep architecture. For example, men with lower testosterone levels might experience less REM sleep, which is important for memory consolidation and mood regulation.(*) REM sleep typically includes the majority of vivid dreaming, and a reduction in this phase can affect overall sleep quality. (*)

Testosterone imbalances can lead to mood disorders such as depression and anxiety, which are common culprits behind sleep disturbances and insomnia. Lower levels of testosterone have been associated with lower energy levels and fatigue during the day, which might seem counterintuitive, but daytime lethargy can lead to difficulties in initiating and maintaining sleep at night.(*)

Testosterone levels can influence or be influenced by other hormonal systems in the body, such as cortisol, the stress hormone.(*) An imbalance in these regulatory systems can lead to increased stress and anxiety, making it harder to fall asleep and stay asleep throughout the night.

Feeling tired and fatigued is also a symptom of low testosterone, according to the American Urological Association. Reduced testosterone can sometimes be linked to snoring and insomnia symptoms as well, which can create a vicious cycle of reduced testosterone levels and poor sleep. Hormone optimization may be one more thing to consider as part of the BIG picture when it comes to getting a good night’s sleep once again. If you suspect a hormone imbalance contact my office to see if my program is right for you.

Hormones that cause Sleep disturbances and insomnia- Cortisol

Cortisol and Sleep Disturbances

Another hormone worth knowing about when it comes to sleeping problems and insomnia is Cortisol. Known as the “stress hormone,” cortisol is produced by the adrenal glands. It normally follows a diurnal pattern, meaning it has a natural cycle that should align with the day-night pattern. Normally, cortisol levels are high in the morning and low at night. This makes sense. We don’t want to have elevated stress hormones when it’s time for our bodies to go to sleep.

When you’re stressed, your body produces more cortisol to prepare for the need to respond to a challenging situation. This heightened state of alertness can make it difficult to relax and fall asleep, which can lead to insomnia. There are several ways that high cortisol (stress hormones) can lead to insomnia and poor sleep.

If you suspect adrenal fatigue or you suspect high cortisol levels, I have a free Adrenal quiz you can take here. Within a few minutes, you will know if investigating the adrenal glands and cortisol levels makes sense.

As previously mentioned but worth repeating, elevated or dysregulated cortisol levels at night can disrupt your circadian rhythm, leading to difficulty falling asleep or maintaining sleep. If your body is not following its natural cortisol rhythm, the internal signals that tell your body it’s time to sleep can be out of sync.

Even if you do manage to fall asleep, high levels of cortisol can affect the quality of your sleep by increasing the frequency of awakenings or reducing the amount of time spent in the deeper, restorative stages of sleep, such as slow-wave sleep (SWS). This can result in non-restorative sleep, making you feel tired even after a full night’s sleep.

Long-term stress can lead to continually elevated levels of cortisol, which not only contributes to the development of chronic insomnia but also may cause a range of health issues, including immune dysfunction, endocrine problems, and metabolic disorders.

High cortisol levels can exacerbate other health problems that may also interfere with sleep, such as chronic pain, gastrointestinal issues, or cardiovascular disease.

Finally, Elevated cortisol levels can also negatively impact your sleep by suppressing your body’s melatonin production. What I often find with patients who have trouble falling asleep is an elevated evening cortisol levels and low evening melatonin levels. This is just the opposite of what we want to see. We want to see which is low cortisol in the evening and normal melatonin levels at night. Follow these 5 tips if you have high cortisol

Thyroid Hormones (T3 and T4) and Sleep Disturbances

Thyroid hormones are released by the thyroid gland and are important for metabolism and energy levels, but they are also important for sleep. Both hyperthyroidism (high levels of thyroid hormones) and hypothyroidism (low levels of thyroid hormones) can lead to sleep disturbances. Hyperthyroidism can cause anxiety, palpitations, and nighttime sweating that disturb sleep, while hypothyroidism can lead to fatigue, brain fog, anxiety, and difficulties achieving deep, restorative sleep. If you suspect a thyroid problem, you can take my thyroid quiz which will help guide you and assess your thyroid function. You can take my Thyroid quiz here.

Hormones involved in sleep disturbances and Insomnia_Insulin

Insulin and Sleep Disturbances

Insulin, a hormone produced by the pancreas, plays a crucial role in regulating blood sugar levels by enabling cells to take up glucose from the bloodstream. The relationship between insulin and sleep is bidirectional, with sleep disturbances impacting insulin sensitivity and insulin levels affecting sleep quality.

Frequent disturbances in sleep can lead to reduced insulin sensitivity (also known as insulin resistance).(*) When the body’s cells become less responsive to insulin, the pancreas needs to produce more insulin to help glucose enter the cells. Over time, this can lead to higher blood sugar levels and potentially type 2 diabetes. Elevated blood sugar at night may lead to increased urination, interrupting sleep and causing insomnia. (*)

The body’s internal clock, or circadian rhythm, influences insulin secretion. Disruptions to the circadian rhythm, such as those caused by shift work or jet lag, can affect how the pancreas releases insulin and how the body utilizes glucose, potentially leading to dysregulation and sleep issues.

Both low (hypoglycemia) and high (hyperglycemia) blood sugar levels can disturb sleep. Hypoglycemia during the night can trigger the release of stress hormones like adrenaline, which can cause awakening and make it difficult to return to sleep. On the other hand, hyperglycemia can increase the need to urinate during the night, leading to sleep disruptions.

Consuming foods high in sugar or carbohydrates, particularly close to bedtime, can lead to fluctuations in blood sugar levels during the night. These fluctuations can affect sleep quality by causing spikes and crashes in blood sugar, leading to potential awakenings and disturbed sleep patterns. (*)

Conditions associated with insulin resistance, such as obesity and metabolic syndrome, are often linked with poor sleep quality and duration. Excess weight, particularly around the abdomen, can increase the risk of sleep apnea and other sleep disorders.

Addressing sleep disturbances related to insulin involves managing blood sugar levels, maintaining a healthy weight, engaging in regular physical activity, and establishing consistent sleep patterns.

If you are experiencing sleep issues and suspect your sleep issues may be related to insulin or blood sugar levels, take my blood sugar quiz. This Quiz can assess your symptoms and risk factors for a blood sugar problem.

Hormones involved in sleep disturbances and Insomnia_Estrogen and Progesterone

Estrogen and Insomnia

Imbalances in the hormone estrogen can significantly impact sleep quality and contribute to sleep disturbances and insomnia. There are several ways hormones like estrogen disrupt sleep.

Estrogen plays a role in the body’s temperature control. An imbalance in estrogen can trigger hot flashes and night sweats, which are sudden feelings of heat and profuse sweating. These can occur during the night and contribute to sleep disturbances.

Fluctuating or low estrogen levels can also affect mood, leading to increased incidence of depression and anxiety, which in turn disrupt sleep. A calm and stable mood is conducive to good sleep, and disturbances in mood can lead to difficulties initiating or maintaining sleep.

Estrogen modulates the body’s response to stress by regulating cortisol levels. When estrogen levels are low, cortisol may not be as effectively regulated, leading to increased stress and potential disruptions to the sleep-wake cycle.

Progesterone and Insomnia

Just like estrogen imbalances can lead to insomnia, Low levels of the hormone progesterone can also hurt sleep quality and contribute to sleep disturbances including insomnia.(*) As women get older there will be a natural tendency for progesterone levels to decline. While this is natural, and a normal part of life, this is also a time when women are most vulnerable to a condition known as estrogen dominance. Progesterone is incredibly important when it comes to sleep for several reasons. For starters, Progesterone has natural sedative properties and can promote sleepiness. Low levels of progesterone can therefore make it more difficult to fall asleep.

Progesterone stimulates the respiratory center in the brain, helping to maintain normal breathing patterns during sleep. Lower levels of progesterone might contribute to sleep-disordered breathing, such as sleep apnea, which can fragment sleep.(*)

Progesterone metabolites like allopregnanolone interact with GABA receptors in the brain, which are part of the inhibitory system responsible for reducing neuronal excitability. When progesterone levels are low, this inhibitory effect is lessened, which could lead to sleep disturbances. (*)

It’s important to consult with a Functional Medicine Practitioner for proper diagnosis and treatment of hormone-related sleep issues, as hormone therapy is not appropriate for everyone and may carry certain risks.

Neurotransmitters that cause sleep disturbances and insomnia

Various Neurotransmitters and Genetic SNPS can impact our ability to fall asleep as well as stay asleep. Some of the Neurotransmitters that can cause insomnia and sleep disturbances include.

  • Serotonin
  • Glutamate
  • GABA
  • Histamine
  • COMT (Catechol-O-Methyltransferase):
  • MAOA (Monoamine Oxidase A):
  • TPH2 (Tryptophan Hydroxylase 2)
  • SLC6A4 (Serotonin Transporter)
  • 5HTTLPR (serotonin-transporter-linked polymorphic region)
  • GABRA2 (Gamma-Aminobutyric Acid Type A Receptor Alpha2 Subunit)
  • DRD2 (Dopamine Receptor D2

Neurotransmitters Involved In Insomnia and Sleep Disturbances

It turns out that hormones are not the only thing that causes insomnia and sleep problems. It turns out that various neurotransmitters also play an important role in the sleep-wake cycle.(*)

Neurotransmitters are chemicals in the body that enable neurons to communicate with each other. When they operate in balance, the body works as it should. Some researchers believe that over 80 percent of Americans have neurotransmitters that are out of balance in some way. Stress, eating the wrong foods, medications, Fluctuating blood sugar levels, toxins in the environment, and genetic mutations or SNPS are all possible reasons for this imbalance.

Two kinds of neurotransmitters function in the body and imbalances in either of these can cause insomnia. Excitatory neurotransmitters function by stimulating neurons in the body to fire. Inhibitory neurotransmitters function to help the body to relax and calm the brain’s activities. Inhibitory neurotransmitters help in creating balance but can be easily depleted if excitatory neurotransmitter function becomes overactive. Another neurotransmitter worth mentioning in relationship to sleep disorder and Insomnia is Serotonin.

Neurotransmitters that cause sleep disturbances and Insomnia

Serotonin and Insomnia

While most people may be familiar with serotonin concerning depression, what you might not know is that serotonin plays an important role in sleep as well. Serotonin, a key neurotransmitter in the brain, significantly influences sleep, mood, pain, and overall how we feel.

One way Serotonin affects sleep has to do with the sleep-wake cycle. Serotonin is needed for the production of melatonin, the hormone that signals the body it’s time to sleep. Serotonin is synthesized from an amino acid called tryptophan, and this conversion is influenced by light exposure. At night, serotonin is converted into melatonin in the pineal gland and even small disruptions in serotonin levels can throw off the body’s sleep-wake cycle.

Since serotonin also plays a critical role in moderating mood and anxiety levels, low serotonin can lead to conditions like depression and anxiety disorders, which commonly co-occur with sleep problems. Difficulty falling asleep, waking up during the night, or waking up earlier than desired are frequent sleep-related complaints among individuals with mood disturbances stemming from serotonin imbalances.

Healthy serotonin function is associated with restorative sleep and the ability to cycle through these stages appropriately. Low serotonin levels can result in disrupted sleep architecture, reducing sleep quality and recuperation. Serotonin also has a role in pain regulation. As chronic pain can interfere with sleep, disruptions in serotonin levels can exacerbate this issue, leading to a cycle of pain and sleeplessness.

Studies have shown that both an excess and a deficiency of serotonin can lead to sleep disturbances and the relationship between serotonin and sleep is highly individual and influenced by various factors, including genetic predisposition, lifestyle, and overall health.

neurotransmitters that cause sleep disturbances and insomnia

The Role of Glutamate and GABA, When It Comes To Sleep Disturbances

Glutamate and GABA (gamma-aminobutyric acid) are neurotransmitters with opposing functions that have significant roles in the regulation of sleep and can be central factors in the development of sleep disturbances and insomnia. Glutamate is the main excitatory neurotransmitter in the brain. It is crucial for various brain functions, including learning, memory, and the regulation of brain activation. Glutamate is associated with increased neuron activity and wakefulness. High levels or overactivity of glutamate can lead to overstimulation of the nervous system, which can make it challenging to settle down and fall asleep. A person with elevated glutamate levels may struggle with insomnia because their brain remains in a state of heightened alertness and cannot easily transition into the restful, quiet state necessary for sleep.

GABA is the main inhibitory neurotransmitter that counters the effects of excitatory neurotransmitters like glutamate. It promotes relaxation of the brain and plays a significant role in reducing neuronal excitability. GABA’s role in the brain is akin to putting the brakes on a car—it slows down neuron firing. This “cooling off” of brain activity is crucial for the initiation and maintenance of sleep. An increase in GABA activity promotes relaxation and is conducive to falling and staying asleep.

Insufficient GABA activity can lead to insomnia, characterized by difficulty falling asleep and staying asleep. Low GABA levels can mean that the inhibitory effects are not strong enough to counteract excitatory signals, resulting in a brain that is too “active” at bedtime.

The balance between Glutamate and GABA is critical for healthy sleep. If the excitatory actions of Glutamate outweigh the inhibitory actions of GABA, the result can be trouble falling asleep or disrupted sleep during the night. Conversely, a properly functioning GABAergic system can neutralize excess brain activity and facilitate the transition into sleep.(*)

According to a study published in the journal Sleep, people who suffer from insomnia and sleep apnea have been shown to have up to 30% reduction in GABA levels when compared to people who sleep normally. Low levels of GABA also tend to make the sufferer feel anxious and unable to relax.(*)

Neurotransmitters that cause sleep disturbances Histamine

Histamine and Insomnia

Histamine is a neurotransmitter that plays several roles in the body, including immune response, gastric acid secretion, and functioning as a central nervous system neuromodulator. In the context of the brain’s sleep-wake regulation, histamine is known for promoting wakefulness and arousal. This means that elevated histamine levels in the brain can be associated with insomnia.

Histamine-producing neurons in the hypothalamus, specifically in the tuberomammillary nucleus (TMN), are active during periods of wakefulness and drop in activity during sleep. When histaminergic neurons are active, they release histamine, which promotes wakefulness and helps maintain alertness. Acute increases in histamine can therefore hinder the ability to fall asleep or maintain sleep.

Allergic reactions can cause a release of histamine throughout the body, leading to symptoms like itching and congestion. These symptoms, plus the generalized increase in histamine, can disrupt sleep. This is one reason why people with allergies often have sleep disturbances, including difficulty falling and staying asleep.

In summary, when it comes to hormonal imbalances and sleep, remember that hormones can impact the ability to fall asleep, stay asleep, or obtain quality sleep, leading to insomnia. For individuals experiencing insomnia, it’s important to consider potential hormonal causes. Treatments for hormonally-driven insomnia may include hormone replacement therapy, medications to correct imbalances, or lifestyle changes that help regulate hormone levels naturally. However, due to the complex interplay between hormones and sleep, a multifaceted treatment approach tailored to the individual’s needs will often be most effective.

Genetic SNPS Associated with Neurotransmitter Imbalances and Sleeping Disturbances

Neurotransmitters Involved In Insomnia and Sleep Disturbances

Genetic variations, often referred to as single nucleotide polymorphisms (SNPs), can influence neurotransmitter levels in the brain and potentially affect sleep patterns and susceptibility to sleep disorders. Here are some SNPs that have been associated with neurotransmitter imbalances and sleep

1. COMT (Catechol-O-Methyltransferase):
COMT Val158Met (rs4680): This SNP affects the COMT enzyme’s ability to break down catecholamines (like dopamine, epinephrine, and norepinephrine). The Met/Met genotype is associated with reduced COMT activity and higher dopamine levels, which could affect sleep, stress response, and mood regulation.

2. MAOA (Monoamine Oxidase A):
Variations in the MAOA gene can affect the degradation of monoamines, including serotonin and norepinephrine. Different MAOA SNPs can result in different enzymatic activities, potentially impacting mood and sleep.

3. TPH2 (Tryptophan Hydroxylase 2):
This enzyme is involved in the synthesis of serotonin from tryptophan. Variants in the TPH2 gene could affect serotonin levels and, consequently, sleep and mood.

4. SLC6A4 (Serotonin Transporter):

5-HTTLPR (serotonin-transporter-linked polymorphic region): This polymorphism in the promoter region of the serotonin transporter gene can affect the reuptake of serotonin. Short (S) alleles have been associated with reduced transporter efficiency and could impact emotional regulation and the risk of insomnia.

6.GABRA2 (Gamma-Aminobutyric Acid Type A Receptor Alpha2 Subunit):
Variations in this gene, which codes for a subunit of the GABA(A) receptor, may influence GABAergic neurotransmission and have been linked to different sleep phenotypes and risk for insomnia.

7.DRD2 (Dopamine Receptor D2:)

Genetic differences in dopamine receptor genes, like DRD2, which affect dopamine signaling, could be related to sleep disorders, particularly those involving circadian rhythm disruption.

For those curious about their genetic predisposition to neurotransmitter imbalances and sleep issues, contact our office. We can provide the proper testing and potential strategies to manage sleep health.

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Balancing neurotransmitters is a complex and delicate process and is not something an individual should take on by him/herself. Understanding how neurotransmitters function requires supervision by a healthcare professional who knows what to look for and how to use substances that can help restore balance to your neurotransmitters.

Need help in finding out why you are having trouble sleeping? When you consider working with our clinic, we leave no stone left unturned. We would love to help you find the reason why you are experiencing insomnia and provide you with answers. Contact us today for more information.