Can melatonin cause upset stomach. Is melatonin safe for long-term use. What are the common side effects of melatonin. How does melatonin affect blood pressure. Is melatonin suitable for children with sleep disorders. Who should avoid taking melatonin supplements.

The Basics of Melatonin: A Natural Sleep Regulator

Melatonin is a hormone naturally produced by the human body to regulate sleep patterns. As night approaches, melatonin levels rise, signaling the body to prepare for rest. However, some individuals may not produce sufficient melatonin, leading to sleep difficulties. In such cases, melatonin supplements can be a potential solution for improving sleep quality.

Dr. Carolyn Dean, a sleep expert and author, emphasizes that melatonin is not a sleep initiator but rather a sleep regulator. This distinction is crucial for understanding how melatonin supplements work and what to expect when taking them.

Common Melatonin Side Effects: What to Watch For

While melatonin is generally considered safe for short-term use, some individuals may experience side effects, particularly with long-term use or higher doses. Here are some common side effects to be aware of:

• Headaches
• Stomach discomfort (including cramps, nausea, and diarrhea)
• Dizziness or lightheadedness
• Irritability or mood changes
• Daytime drowsiness
• Low blood pressure

Is melatonin likely to cause severe side effects? In most cases, melatonin side effects are mild. However, it’s essential to monitor your body’s response and consult with a healthcare professional if you experience persistent or worsening symptoms.

Melatonin Dosage: Finding the Right Balance

Determining the appropriate melatonin dosage can be challenging, as individual needs vary. On average, most adults require less than 3 milligrams (mg) per night to improve sleep. However, some people may take higher doses.

How can you find the right melatonin dosage for your needs? Start with a low dose and gradually increase it if necessary. If you experience side effects, try reducing the dosage to see if symptoms improve. Always consult with your doctor to determine the most suitable dosage for your specific situation.

Melatonin Sensitivity: Why Some People Experience More Side Effects

Melatonin sensitivity varies from person to person. While one individual may tolerate 3 mg of melatonin without issues, another may experience side effects with just 1 mg. Factors such as age, overall health, and medication interactions can influence melatonin sensitivity.

Melatonin and Stomach Upset: A Common Concern

Can melatonin cause upset stomach? Yes, stomach discomfort is a relatively common side effect of melatonin supplements. Some people may experience cramps, nausea, or diarrhea after taking melatonin.

Why does melatonin cause stomach problems in some individuals? The exact mechanism is not fully understood, but it may be related to the supplement’s impact on the digestive system or individual sensitivity to the hormone.

If you experience stomach upset after taking melatonin, consider the following strategies:

1. Take the supplement with a small snack
2. Reduce the dosage
3. Try a different form of melatonin (e.g., sublingual tablets or liquid)
4. Consult with your healthcare provider for alternative sleep solutions

Melatonin and Blood Pressure: Potential Risks and Precautions

Does melatonin affect blood pressure? In some cases, melatonin supplementation can lead to abnormally low blood pressure. This side effect is usually mild, but it’s important to be aware of the potential risks.

What are the symptoms of low blood pressure caused by melatonin? Signs of low blood pressure may include dizziness, fainting, blurry vision, confusion, and fatigue. If you experience these symptoms, it’s crucial to consult with your healthcare provider.

Individuals with pre-existing blood pressure concerns or those taking blood pressure medications should exercise caution when using melatonin supplements. Always discuss potential interactions with your doctor before starting any new supplement regimen.

Melatonin for Children: Safety and Considerations

Is melatonin safe for children with sleep disorders? Melatonin can be beneficial for children experiencing sleep difficulties due to various conditions, including insomnia, circadian rhythm disorders, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and autism spectrum disorders.

However, melatonin use in children requires careful consideration and medical supervision. Dosages for children vary depending on their age, weight, and specific sleep issues. Some children may only need 1 to 3 mg per night, while others with conditions like ADHD or autism may require 3 to 6 mg.

What are the potential side effects of melatonin in children? According to Dr. Dean, reported side effects in children include:

• Nausea
• Diarrhea
• Headaches
• Mood changes
• Daytime sleepiness
• Bed-wetting

Parents should always consult with a pediatrician or sleep specialist before giving melatonin to children. A healthcare professional can help determine if melatonin is appropriate and guide dosage recommendations based on the child’s individual needs.

Who Should Avoid Melatonin Supplements?

While melatonin is generally considered safe for short-term use in most healthy adults, certain individuals should exercise caution or avoid melatonin supplements altogether. These include:

• People taking blood pressure medications
• Individuals on seizure medications
• Those with diabetes (melatonin may affect blood sugar levels)
• People taking blood-thinning medications
• Individuals on immunosuppressants
• Those using corticosteroids

Why should these groups be cautious with melatonin? Melatonin can interact with various medications, potentially reducing their effectiveness or causing unwanted side effects. For example, it may interfere with blood pressure control, affect seizure thresholds, or impact blood sugar regulation in diabetics.

If you fall into any of these categories or have concerns about taking melatonin, it’s crucial to consult with your healthcare provider before starting supplementation. They can assess your individual risk factors and recommend appropriate alternatives if necessary.

Long-Term Use of Melatonin: Safety and Efficacy

Is melatonin safe for long-term use? While melatonin is generally considered safe for short-term use (one to two months) in most healthy adults, the long-term effects of melatonin supplementation are not well-established.

Some potential concerns associated with long-term melatonin use include:

• Disruption of natural melatonin production
• Tolerance development
• Increased risk of side effects
• Interactions with other medications or health conditions

If you find yourself relying on melatonin supplements for extended periods, it’s essential to discuss your sleep issues with a healthcare professional. They can help identify underlying causes of sleep disturbances and recommend appropriate long-term solutions.

Alternatives to Long-Term Melatonin Use

For individuals seeking alternatives to long-term melatonin supplementation, consider the following strategies to improve sleep quality:

1. Establish a consistent sleep schedule
2. Create a relaxing bedtime routine
3. Optimize your sleep environment (e.g., cool, dark, quiet)
4. Limit exposure to blue light from electronic devices before bedtime
5. Practice stress-reduction techniques like meditation or deep breathing exercises
6. Engage in regular physical activity (but not too close to bedtime)
7. Avoid caffeine, alcohol, and large meals close to bedtime

These natural approaches can help regulate your body’s internal clock and promote better sleep without relying on supplements.

Melatonin Interactions: Understanding Potential Risks

Can melatonin interact with other medications or supplements? Yes, melatonin can interact with various substances, potentially leading to adverse effects or reduced efficacy of certain medications.

Some common interactions to be aware of include:

• Anticoagulants (blood thinners): Melatonin may increase the risk of bleeding
• Antihypertensive medications: Melatonin can affect blood pressure control
• Diabetes medications: Melatonin may impact blood sugar levels
• Immunosuppressants: Melatonin could interfere with the effectiveness of these drugs
• Seizure medications: Melatonin may affect seizure thresholds
• Birth control pills: Hormonal contraceptives may increase melatonin levels

How can you minimize the risk of melatonin interactions? Always inform your healthcare provider about all medications, supplements, and herbal products you’re taking before starting melatonin supplementation. They can assess potential interactions and adjust your treatment plan if necessary.

Natural Sources of Melatonin: Boosting Your Body’s Production

While melatonin supplements can be helpful for some individuals, it’s also possible to support your body’s natural melatonin production through dietary and lifestyle changes. Some natural sources of melatonin include:

• Tart cherries and cherry juice
• Walnuts
• Almonds
• Goji berries
• Eggs
• Milk
• Fish (especially salmon, sardines, and trout)

Additionally, exposure to natural sunlight during the day and limiting artificial light exposure in the evening can help regulate your body’s melatonin production and improve sleep quality.

Melatonin and Pregnancy: Safety Considerations

Is melatonin safe during pregnancy? The safety of melatonin supplementation during pregnancy is not well-established, and pregnant women should exercise caution when considering its use.

While melatonin is naturally produced by the body and plays a role in fetal development, the effects of supplemental melatonin on pregnancy outcomes are not fully understood. Some potential concerns include:

• Impact on fetal growth and development
• Alterations in maternal hormonal balance
• Potential interactions with pregnancy-related conditions

Pregnant women experiencing sleep difficulties should consult with their healthcare provider for safe and appropriate sleep solutions. In many cases, lifestyle modifications and natural sleep-promoting techniques may be recommended over supplement use.

Melatonin and Breastfeeding: What You Need to Know

Can breastfeeding mothers safely take melatonin? As with pregnancy, the safety of melatonin supplementation during breastfeeding is not well-established. Melatonin can pass into breast milk, potentially affecting the infant’s sleep patterns or development.

Breastfeeding mothers should discuss the use of melatonin with their healthcare provider before starting supplementation. Alternative sleep-promoting strategies may be recommended to ensure the safety of both mother and baby.

Melatonin Overdose: Risks and Symptoms

While melatonin is generally considered safe when used as directed, taking too much can lead to unwanted side effects or, in rare cases, more serious complications.

What are the symptoms of melatonin overdose? Signs of excessive melatonin intake may include:

• Severe daytime drowsiness
• Confusion or disorientation
• Vivid or unusual dreams
• Nightmares
• Nausea and vomiting
• Headaches
• Changes in blood pressure
• Irritability or anxiety

If you suspect a melatonin overdose, seek medical attention immediately. While serious complications are rare, it’s essential to address any concerning symptoms promptly.

Preventing Melatonin Overdose: Tips for Safe Use

To minimize the risk of melatonin overdose, follow these guidelines:

1. Start with the lowest effective dose
2. Follow dosage instructions carefully
3. Avoid combining melatonin with other sleep aids or sedatives
4. Keep melatonin supplements out of reach of children
5. Use a reliable brand with third-party testing for quality and purity
6. Consult with a healthcare professional before increasing your dosage

Remember that more melatonin doesn’t necessarily mean better sleep. Finding the right balance is key to maximizing benefits while minimizing potential side effects.

Melatonin and Jet Lag: A Traveler’s Guide

Can melatonin help with jet lag? Melatonin supplements are often used to alleviate jet lag symptoms and help travelers adjust to new time zones more quickly.

How does melatonin work for jet lag? By taking melatonin at the appropriate time, you can help reset your body’s internal clock to align with the new time zone. This can improve sleep quality and reduce daytime fatigue associated with jet lag.

Tips for using melatonin to manage jet lag:

• Start taking melatonin a few days before your trip to prepare your body for the time change
• Take melatonin close to your target bedtime in the new time zone
• Use a low dose (0.5 to 5 mg) to minimize side effects
• Combine melatonin use with other jet lag management strategies, such as exposure to natural light and adjusting meal times

As with any supplement use, consult with your healthcare provider before using melatonin for jet lag, especially if you have any underlying health conditions or take other medications.

Natural Alternatives to Melatonin for Jet Lag

If you prefer to avoid melatonin supplements, consider these natural strategies for managing jet lag:

1. Gradually adjust your sleep schedule before traveling
2. Stay hydrated during your flight
3. Avoid alcohol and caffeine close to bedtime
4. Expose yourself to natural light at appropriate times in the new time zone
5. Practice relaxation techniques to promote sleep in unfamiliar environments

These methods can help your body adjust to new time zones without relying on supplements.

Melatonin and Sleep Disorders: Beyond Insomnia

While melatonin is commonly associated with treating insomnia, it may also be beneficial for other sleep disorders. Some conditions where melatonin supplementation might be helpful include:

• Delayed Sleep Phase Syndrome (DSPS)
• Shift Work Sleep Disorder
• Non-24-Hour Sleep-Wake Disorder
• REM Sleep Behavior Disorder

Melatonin Side Effects and Safety 101

Can’t sleep and looking for a nonhabit-forming sleep aid?

It’s not unusual to deal with insomnia from time to time. You may have difficulty falling asleep. Or if you’re able to fall asleep quickly, you may wake up after two or three hours. This can cause daytime sleepiness, irritability, and decreased productivity.

One night of bad sleep might not wreak too much havoc on your body. But when the problem goes on for days, weeks, or months, supplementing with melatonin can get your sleep back on track.

Melatonin is a hormone that your body makes naturally. Your melatonin level increases a couple of hours before bedtime, which signals your body to prepare for rest. (1) It’s important to note, however, that melatonin isn’t a sleep initiator but rather a sleep regulator, explains Carolyn Dean, MD, a sleep expert and author of 365 Ways to Boost Your Brain Power: Tips, Exercise, Advice.

Some people, however, don’t produce enough melatonin. And as a result, sleep doesn’t come easily. But while melatonin is a natural hormone that can help reset your circadian clock, oral melatonin isn’t right for everyone. (2)

What Are Melatonin Side Effects?

Melatonin needs vary from person to person. On average, most people need less than 3 milligrams (mg) per night to sleep better. Yet some people take more. (3)

Melatonin is generally safe for short-term use of one to two months in most healthy adults. But some people are more sensitive to the oral hormone and experience side effects. Adverse effects tend to occur with long-term use or when a person takes too much. (2,4)

Possible side effects of oral melatonin include: (1,3,5)

• Headache A mild to moderate headache can indicate that you’ve taken too much or that your body is sensitive to oral melatonin.
• Stomach Problems Melatonin also causes stomach discomfort in some people. This may include cramps, nausea, and diarrhea.
• Dizziness Some people who take melatonin also report mild dizziness, lightheadedness, or vertigo.
• Irritability Too much melatonin can also affect mood. You may feel cranky, anxious, or have periods of depression.
• Drowsiness Even though melatonin doesn’t usually cause a “hangover effect,” some people do experience daytime drowsiness. This can reduce alertness and make it difficult to drive or operate machinery. If you take melatonin, wait at least five hours before operating machinery. Keep in mind that some medication may intensify drowsiness, such as depressants and selective serotonin reuptake inhibitors. (1)
• Low Blood Pressure Sometimes, melatonin causes abnormally low blood pressure. Melatonin side effects are usually mild. (6) However, untreated low blood pressure can lead to life-threatening complications. Low blood pressure means that your body can’t carry enough oxygen to your organs. This can affect heart and brain function. Symptoms of low blood pressure include dizziness, fainting, blurry vision, confusion, and fatigue. (7)

If you experience mild side effects of oral melatonin, reduce your dosage to see if symptoms improve. Talk with your doctor about your dosage if your symptoms persist or worsen. Everyone’s body is different. So while one person may be able to tolerate 3 mg of melatonin a night, another person may be able to tolerate only 1 mg.

Melatonin for Children

Adults aren’t the only ones with acute or chronic sleep problems. Melatonin is also safe for children who have difficulty sleeping due to insomnia, circadian rhythm disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), autism, and other neurological disorders.

Dosing for children varies. Some children may need only 1 to 3 mg a night, whereas a child with ADHD or autism may need 3 to 6 mg per night. But because oral melatonin is a supplement and is not regulated by the U. S. Food and Drug Administration, experts caution that parents should consult with a doctor before allowing children and adolescents to try melatonin. (10,11)

Your doctor can help you understand whether melatonin is right for your child and review the risk of side effects. “Side effects reported for children include nausea, diarrhea, headaches, changes in mood, sleepiness the next day, and bed-wetting,” notes Dr. Dean.

Who Shouldn’t Take Melatonin?

Some herbal and dietary supplements can interact negatively with prescription medication, and melatonin is no exception.

Before you take this supplement to improve the quality of your sleep, speak with your doctor.

Melatonin doesn’t interact with every prescription drug, but it can make some medicines less effective, like blood pressure and seizure medication. It can also boost blood sugar and is therefore not recommended for people with diabetes, warns Dean.

The supplement can also interact with blood-thinning medication, immunosuppressants, and corticosteroids. There’s also the risk of increased drowsiness when taken with birth control pills, depressants, or selective serotonin reuptake inhibitors. (1)

If you have chronic pain due to an inflammatory disease, melatonin might seem like a safe solution for better sleep. But this supplement isn’t recommended for people who have an autoimmune disease like lupus or arthritis. (12)

Melatonin can stimulate the immune system, triggering an inflammatory response and worsening these diseases.

There is no definitive research on the safety of using melatonin during pregnancy or while breastfeeding, so experts recommend talking to your doctor if that’s something you want to consider. (13)

Melatonin is preferred by some because it’s nonhabit-forming and a natural sleep aid. But the supplement isn’t right for everyone, and side effects can occur if not taken properly.

If you experience side effects, reduce the amount you take. If symptoms continue, stop taking oral melatonin. Also, don’t forget to consult your doctor before combining melatonin with a prescription medication.

For the most part, melatonin should be used only as a short-term remedy. See your doctor or a sleep specialist if sleep problems worsen or don’t improve after a few months.

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Side effects of melatonin – NHS

Like all medicines, melatonin can cause side effects, but most people will not have any side effects.

Common side effects

Melatonin does not have many common side effects but there are things you can do to help cope with them:

Feeling sleepy or tired in the daytime

Do not drive, cycle or use tools or machinery if you’re feeling this way. Do not drink any alcohol as this will make you feel more tired.

If you’re taking more than one 2mg tablet talk to your doctor to see if you can reduce your dose. If this does not help, talk to your doctor as melatonin may not be the right medicine for you.

Headache

Make sure you rest and drink plenty of fluids. Do not drink too much alcohol as it can make your headache worse, and it affects the way that melatonin works. Ask a pharmacist to recommend a painkiller.

Talk to a doctor if headaches last longer than a week or are severe.

Stomach ache

Try putting a heat pad or covered hot water bottle on your tummy. Talk to your doctor if the pain continues or is severe.

Feeling sick (nausea)

Take melatonin tablets or liquid after food. Stick to simple meals and do not eat rich or spicy food. It can help to eat and drink slowly and have smaller and more frequent meals.

Feeling dizzy

If taking melatonin makes you feel dizzy, stop what you’re doing and sit or lie down until you feel better. Do not drive, cycle or use tools or machinery if you’re feeling dizzy. Do not drink alcohol as it will make you feel worse.

Feeling irritable or restless

If this does not get better after a few days, stop taking the medicine and talk to your doctor.

Dry mouth

Chew sugar-free gum or suck sugar-free sweets.

Dry or itchy skin

Apply a moisturiser often. Try using an oil-free face moisturiser for sensitive skin.

If this does not get better after 1 week, stop taking the medicine and talk to your doctor.

Pains in your arms or legs

If this does not get better after a few days, stop taking the medicine and talk to your doctor.

Strange dreams or night sweats

If this does not get better after a few days, stop taking the medicine and talk to your doctor.

Speak to a doctor or pharmacist if the advice on how to cope does not help and a side effect is still bothering you or does not go away.

Serious side effects

Serious side effects are rare and happen to less than 1 in 1,000 people.

Speak to your doctor if you start feeling low or sad as this could be a sign of depression.

Call your doctor or call 111 now if you:

• get changes to your eyesight, such as blurred vision
• feel faint or pass out
• start feeling confused or dizzy, or things seem to be spinning around you (vertigo)
• have any bleeding that does not stop, unexplained bruising or blood in your urine

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction (anaphylaxis) to melatonin.

Immediate action required: Call 999 now if:

• your lips, mouth, throat or tongue suddenly become swollen
• you’re breathing very fast or struggling to breathe (you may become very wheezy or feel like you’re choking or gasping for air)
• your throat feels tight or you’re struggling to swallow
• your skin, tongue or lips turn blue, grey or pale (if you have black or brown skin, this may be easier to see on the palms of your hands or soles of your feet)
• you suddenly become very confused, drowsy or dizzy
• someone faints and cannot be woken up
• a child is limp, floppy or not responding like they normally do (their head may fall to the side, backwards or forwards, or they may find it difficult to lift their head or focus on your face)

You or the person who’s unwell may also have a rash that’s swollen, raised, itchy, blistered or peeling.

These can be signs of a serious allergic reaction and may need immediate treatment in hospital.

Other side effects

These are not all the side effects of melatonin. For a full list, see the leaflet inside your medicine packet.

Information:

You can report any suspected side effect using the Yellow Card safety scheme.

Visit Yellow Card for further information.

Page last reviewed: 13 February 2023

Next review due: 13 February 2026

Melatonin and premenstrual syndrome

The life of the human body, like other living beings, is subject to biological rhythms, which in turn are formed by internal drivers and are more or less influenced by the external environment, adapting the body to its changing conditions. The reproductive system lives according to the laws of low-frequency biorhythms, a classic example of which is the lunar (circal-lunar, or circa-monthly) menstrual cycle, which is necessary for conception. Monthly cyclic changes in the uterus and ovaries result from the action of hormones, including estrogens, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), the secretion of each of which bears features not only of a circa-monthly, but also of a high-frequency ultradian rhythm.

Biological rhythms do not exist in isolation, they interact with each other, organizing a complex system for maintaining homeostasis. One of the most important regulatory roles is played by mid-frequency circadian (daily) rhythms, among which the sleep-wake cycle is best studied. The interaction of the menstrual cycle and circadian processes changes the diurnal variability of REM sleep and basal body temperature during the luteal phase compared to the follicular phase [1], which can be explained by the influence of sex hormones. In particular, estrogens prolong the REM phase, reduce the time to fall asleep and the total number of spontaneous awakenings during the night, and increase the total duration of sleep. Progesterone stimulates benzodiazepine receptors and thus increases the activity of γ-aminobutyric acid (GABA), the most important inhibitory mediator responsible for the onset of sleep.

On the other hand, it should be taken into account that circadian rhythms are formed mainly by the pineal gland, and the hormone melatonin produced by it has a significant effect on the neuronal regulation of the menstrual cycle, mediating it mainly through the neuronal network of gonadotropin-inhibiting hormone [2]. Melatonin, apparently, is able to directly influence the production of hormones. In particular, reduced progesterone production by luteal cells as a result of oxidative stress is restored under the action of melatonin [3]. It can be assumed that melatonin has a similar effect in the brain, restoring the balance of neurosteroids.

Melatonin itself, which plays the role of an adaptogen in the central nervous system (CNS), is affected by numerous exogenous and endogenous factors that can change its secretion [4]. These changes, designed to synchronize internal and external biorhythms, with significant and / or long-term alterations, can become the basis for the development of a number of diseases, accompanied by sleep disorders.

The chronobiological basis of affective disorders is known. Mental illnesses such as major depressive disorder, seasonal affective disorder, bipolar disorder, and schizophrenia are associated with circadian rhythm dysregulation [5], and genetic abnormalities of the biological clock have been identified in patients with bipolar disorder and schizophrenia [6, 7]. Among gynecological diseases, pronounced desynchronosis includes premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) [8], for which sleep disorders are very characteristic [9].

The term “premenstrual syndrome” refers to a clinical condition representing a variety of cyclically recurring physical, emotional, behavioral and cognitive symptoms that develop during the luteal phase of the menstrual cycle and disappear with the onset of menstruation [10]. About 200 premenstrual signs have been described, and more than 80% of women have experienced them at some point in their lives. But in 30-48% of women in the middle and younger fertile groups and approximately 20% of women in the older fertile group, these symptoms disrupt the quality of life and persist throughout most menstrual cycles, thus falling under the criteria for the diagnosis of PMS [11, 12].

The classification of the disease has been refined by the consensus of the International Society for Premenstrual Disorders (ISPMD). In accordance with the recommendations of the ISPMD, for the diagnosis of PMS, its symptoms must be severe enough to negatively affect daily activities and/or interfere with work, study, and/or disrupt interpersonal relationships [13]. Signs of PMS are non-specific and recur during ovulatory cycles. The variety and number of symptoms vary greatly from individual to individual, but some individuals may have predominantly mental, or predominantly somatic, or mixed symptoms. A single symptom can become the basis for diagnosing a disease if its “behavior” corresponds to the diagnostic definitions.

In accordance with the ISPMD consensus [14], the diagnosis of PMS should not be based solely on a retrospective evaluation of symptoms. No matter how classic the symptom complex looks, the clinician must convince the patient to keep a diary for 2-3 menstrual cycles, in which she must write down the symptoms and assess their severity on a 10-point scale (1 – absent, 10 – unbearable severity). In principle, any symptom can be attributed to the manifestation of PMS if it meets the following characteristics for at least 2 cycles:

– the patient rates it at 4-10 points;

– the symptom is present for 2-14 days of the cycle preceding menstruation (luteal phase), but absent (severity 0-3 points) for at least 6 days of the follicular phase (it is the first 7 days from the onset of menstruation that are important).

The severity of premenstrual symptoms can be different and range from moderate to very severe when it comes to diagnosing not PMS, but premenstrual dysphoric disorder (PMDD). “Late luteal phase dysphoric disorder” has been isolated and listed in the DSM-III-R section entitled “Suggested Diagnostic Categories for Further Study” at 1987 d. After 7 years, a working group on “late luteal dysphoric disorder” recommended that the condition be included in the DSM-IV section “Mood disorders without further specification” under the name “premenstrual dysphoric disorder.” Currently, PMDD is included in the DSM-V and is defined as a severe form of PMS, including physical, mental and behavioral symptoms that recur regularly during the luteal phase of the menstrual cycle and decrease within a few days after the onset of menstruation [15]. The criteria for this condition, which occurs in 3-8% of women in the population, are the following positions [4].

A . In most menstrual cycles in the last year, 5 or more of the following symptoms (mandatory presence of at least one of symptoms 1, 2, 3, 4) were observed for the longest time during the last week of the luteal phase, began to subside within a few days after the onset of the follicular phase and were absent within a week after the cessation of menstruation:

1) visibly depressed mood, feelings of hopelessness or ideas of self-abasement;

2) noticeable anxiety, tension, feeling of agitation;

3) pronounced emotional lability;

4) anger or irritability, or aggravation of interpersonal conflicts;

5) subjective feeling of difficulty concentrating;

6) drowsiness, fatigue or marked lack of energy;

7) marked change in appetite, overeating or craving for particular foods;

8) pathological drowsiness or insomnia;

9) subjective feeling of shock or loss of control;

10) somatic symptoms, eg painful breast engorgement, headache, joint or muscle pain, bloating, weight gain.

B. The disorder noticeably interferes with work or study or regular social activities and relationships with others.

B. Possible exacerbation of symptoms of another medical condition, such as depression, panic disorder, dysthymic disorder, or personality disorder.

D. Criteria A, B and C must be confirmed by prospective daily assessments for at least two consecutive symptomatic cycles (a provisional diagnosis may be made before this confirmation).

Four subtypes of so-called “variant” disorders have also been described that do not meet generally accepted criteria.

The first subtype is premenstrual exacerbation of the underlying disorder, which means worsening of the course of the underlying disorder during the luteal phase of the menstrual cycle. Similar cyclicity occurs in patients with diabetes, depression, epilepsy, bronchial asthma, migraine, etc.

The second subtype, non-ovulatory premenstrual disorders, occurs in cycles without ovulation. The origin of these disorders is unknown, the current hypothesis is that the symptoms may be caused by ovarian follicular activity.

The third subtype, progestogen-induced premenstrual disorders, is provoked by exogenous progestogens present in combined preparations for contraception and menopausal hormone therapy. Against the background of purely progestogenic contraception, similar symptoms may occur, but, due to non-cyclicity, they are not included in the classification and are considered side effects (probably with similar mechanisms) of the continuous use of this group of drugs.

The fourth subtype includes premenstrual disorders in amenorrhea in women who, in the presence of ovulatory cycles, do not have periods due to hysterectomy, endometrial ablation, or use of long-term progestogen contraception.

In any type of PMS and its classical clinical picture, an important place among the symptoms is occupied by transient or persistent sleep disturbances, which are observed in 66-70% of patients and are considered as one of the diagnostic clusters of PMDD [8, 16]. Sleep disorders in patients with PMS/PMDD are usually expressed in a deterioration in the quality of sleep, frequent nocturnal awakenings, a long falling asleep, and a feeling of dissatisfaction with sleep. At the same time, only minor changes can be detected during polysomnography, for example, an increase in the representation of non-REM sleep in the luteal phase of the cycle. However, most objective studies of sleep in women with PMDD have been conducted with small sample sizes or with women who have not actively sought medical attention [17], which may have confounded the results.

According to subjective assessment, sleep disturbances are also observed in relatively healthy women [18]. It is likely that the anxiety inherent in women with PMDD exacerbates the course of natural sleep changes after ovulation and makes them clinically significant. From these positions, PMS and PMDD are similar to paradoxical insomnia.

The origin of sleep disorders, like the pathogenesis of PMS itself, is not well understood. Modern ideas about PMS interpret it as a maladaptive condition, reflecting an inadequate response of the brain to normal fluctuations in steroid hormone levels within the ovulatory menstrual cycle. The pathogenesis of the disease includes disorders of various neuronal systems and the exchange of neurotransmitters such as norepinephrine, epinephrine, serotonin, dopamine, and opioid peptides. Despite the fact that the “central” nature of the disease is not in doubt, the specific area of ​​\u200b\u200bthe brain responsible for the onset of symptoms has not been named. Obviously, the cause of premenstrual disorders has no topical binding and lies in the violation of the metabolism of neurotransmitters and neurosteroids in various parts of the central nervous system in response to normal fluctuations in the levels of sex hormones, most of all, to an increase in the level of progesterone in the luteal phase of the cycle.

One of the candidates for the role of the pathogenetic factor of PMS is the neurosteroid allopregnenolone, a neuroactive progesterone metabolite that stimulates GABA receptors in the brain and, therefore, determines behavioral responses, response to stress, mood changes, and the onset of sleep. The content of allopregnenolone in the peripheral blood of patients with PMS is reduced compared to that in healthy women, especially in the luteal phase of the cycle [19].

Another participant in the pathogenesis of PMS/PMDD is serotonin – a decrease in the level of this neurotransmitter leads to an increase in the sensitivity of the brain to progesterone. The hypothesis about the role of serotonin deficiency in the development of symptoms of PMS and, especially, PMDD is supported by the well-known fact about the effectiveness of the use of selective serotonin reuptake inhibitors (SSRIs) in this category of patients [20]. At the same time, the close relationship between the symptoms of the disease and sleep disorders suggests the existence of pathogenetic mechanisms mediated by melatonin secretion.

This hypothesis is supported by the fact that agomelatine, an effective antidepressant agent, an agonist of MT ₁ and MT ₂ melatonin receptors, has antagonistic activity against 5-HT _2C receptors. The presence of 5-HT _2C and MT1/MT2 receptors has been demonstrated in various brain regions, including the suprachiasmatic nucleus, hippocampus, nucleus accumbens, and amygdala [21]. Thus, the relationship between the two systems that regulate circadian rhythms and behavior becomes apparent [22].

In fairness, it should be noted that a decrease in the level of melatonin in patients with PMS/PMDD was not detected in all studies on this topic [23]. But more recent work has revealed the relationship between melatonin secretion and premenstrual disorders. In one of the clinical trials, women with PMDD underwent a complete examination 2 times within the same menstrual cycle in the follicular and luteal phases. The results of the study showed that in women with PMDD, the normal organization of the melatonin secretion rhythm was disturbed and the melatonin level was significantly reduced at night. During the onset of symptoms of the disease, the content of melatonin decreased even more [24]. This observation is consistent with data on an increased incidence of subsyndromal depression in patients with low endogenous melatonin secretion [25].

The management of patients with PMS involves a multidisciplinary and individualized approach [26]. The concepts of suppression of ovulation and thereby a decrease in progesterone levels, as well as an increase in serotonin levels and a decrease in the sensitivity of the central nervous system to progesterone, seem logical. The most popular method of inhibiting ovulation in patients with PMS is the appointment of combined oral contraceptives containing drospirenone, and an increase in the level of serotonin in the brain is achieved with the help of SSRIs. Several complementary therapies have proven successful in the treatment of PMS. Lifestyle correction, cognitive-behavioral therapy, the appointment of vitamin complexes are included in the complex of therapeutic measures.

For sleep disorders associated with PMS and PMDD, the treatment of choice is cognitive behavioral therapy [27]. This effective and safe method gives lasting results, helps to better cope with stress in everyday life and increases a woman’s resilience to the emotional “swings” that are characteristic of PMS/PMDD. The organization of cognitive-behavioral therapy is hampered by the rather high cost of a therapeutic session and an acute shortage of specialists.

But sleep disorders are a particular problem in the treatment of patients with premenstrual disorders, not only due to the limited availability of the cognitive-behavioral method. Insomnia and other variants of disorders are not always perceived as a pathology, and women often consider their disturbed sleep to be a variant of the norm, being skeptical about the need for medical advice. However, untreated sleep disorders, especially insomnia, prevent patients from adequately evaluating the result of treatment, so the standard methods of treating PMS and PMDD may not be effective enough. In these cases, it is advisable to correct sleep disorders with medication.

Most drugs for the short-term (benzodiazepines and their agonists) and long-term (antidepressants, antipsychotics, anticonvulsants) treatment of insomnia are also used to treat the symptoms of PMDD, but they are available only by prescription and require careful adherence to the patient regimen, and from the doctor – an understanding of possible drug interactions and adverse reactions. Only neurologists or psychiatrists have the right to prescribe such drugs in our country.

Patients with PMDD should definitely consult a psychiatrist. This type of premenstrual disorder often occurs against the background of borderline and subclinical mental disorders and may be their mask. Therefore, consultation with a psychiatrist is necessary not so much to establish a diagnosis as to conduct a differential diagnosis. It should also be remembered that sleep disturbances associated with the menstrual cycle can mask objectively existing sleep disorders in women [27]. Therefore, if there are doubts about the purely premenstrual nature of the existing disorders, it is advisable to refer the patient for a consultation with a somnologist.

A gynecologist may recommend over-the-counter medications such as melatonin for managing menstrual-related sleep disorders. Interacting with membrane and nuclear receptors, exogenous melatonin, like its endogenous counterpart, promotes sleep and organizes the daily rhythm of sleep and wakefulness. In addition, melatonin and its metabolites have antioxidant, anti-inflammatory, analgesic effects. Melatonin preparations are annotated for the treatment of sleep disorders, including those associated with PMS or PMDD.

One of the quick release melatonin preparations on the Russian pharmaceutical market is Melaxen. The drug Melaxen is prescribed at a dose of 3-6 mg 30 minutes before going to bed. Due to its short half-life, melatonin is more effective for difficulty falling asleep and maintaining sleep in the first half of the night. Taking into account the available data on the high efficacy and safety of the drug, Melaxen can be recommended to a wide range of patients with sleep disorders. Treatment of sleep disorders with the drug Melaxen is not accompanied by any adverse events, as well as an aftereffect.

Melatonin preparations prescribed for sleep disorders in women with PMS or PMDD appear to be effective in correcting other premenstrual symptoms. The use of melatonin for 3 months significantly improved the quality of life and contributed to a decrease in anxiety and the severity of neurovegetative disorders [28]. Certain pilot studies do not, of course, allow us to conclude that melatonin preparations are effective in the treatment of premenstrual symptoms. But the presence of sleep disorders in the structure of PMS/PMDD makes it possible to reasonably prescribe these drugs within the annotated indications. In the absence of a positive result from the prescribed therapy, a chronic sleep disorder should be assumed and the woman should be referred for a consultation with a somnologist.

The problem of treating women suffering from PMS and PMDD is far from being resolved. Standard therapy (combined oral contraceptives and SSRIs) is not always acceptable due to a number of restrictions and contraindications. Cognitive behavioral therapy is not always available. Sleep disorders in PMS/PMDD occupy a significant niche and require the attention of a doctor, not only because they impair the quality of life of patients, but also due to the weakening of the effect of traditional therapeutic interventions. Therefore, the use of safe and well-tolerated melatonin preparations, pathogenetically justified for use in PMS and PMDD, can make a significant contribution to improving the treatment outcomes of women suffering from these disorders in the presence of sleep disorders in their symptoms.

The author declares no conflict of interest.

e-mail: [email protected];
https://orcid.org/0000-0001-5541-3767

5 Functions of Melatonin You Might Not Know About

Likbez

Health

November 27, 2020

Understanding why working at night can lead to heart disease and fertility problems.

What is melatonin

Melatonin is a hormone that is produced mainly at night in the pineal gland of the brain – the pineal gland, when a person is fast asleep. The secretion lasts 8–10 hours, but the peak release occurs at 3–4 am.

A small amount of melatonin is also synthesized by the organs of the digestive tract, blood cells, bone marrow, retina. Scientists have discovered the hormone in plants and animals, so part of it gets to a person with food.

Almost all tissues have receptors for melatonin; it can easily penetrate into cells. Therefore, due to the lack of a hormone, the whole body suffers.

Why melatonin is needed

Melatonin is called the sleep hormone, but its effects affect the functions of many organs and systems.

Improved sleep

Melatonin is not only produced at nightfall, it regulates human circadian rhythms – this is a change in wakefulness and sleep and related changes in organ functions, a decrease in body temperature. Therefore, if someone is forced to work at night or likes to stay up late, he may have insomnia and other problems.

Fighting tumors

Scientists have proven that melatonin is able to inhibit the appearance and growth of a cancerous tumor and stop the spread of metastases. This effect is associated with the fact that the hormone absorbs and removes substances that turn a normal cell into a cancer one.

Research shows that artificial melatonin can reduce the toxic effect of drugs on the cells of patients undergoing chemotherapy.

Reproductive maintenance

The female reproductive system functions in cycles. This process is regulated by hormones of the hypothalamus and pituitary gland, and melatonin performs the following tasks:

• helps to synchronize the rhythms of the endocrine cells of the brain;
• supports egg maturation and ovulation;
• reduces pain during menstruation;
• supposedly relieves premenstrual syndrome.

Therefore, women who work at night often have irregular periods or cannot conceive.

Cardiovascular protection

Melatonin affects the release of other hormones and substances that alter the activity of the nervous system. Due to this, it can reduce sharp fluctuations in blood flow to the brain, and by reducing the synthesis of the stress hormone norepinephrine, prevent blood pressure surges.

Researchers have proven that additional administration of melatonin to people with hypertension can stabilize their condition. Therefore, it is now considered as a promising agent for the treatment of arterial hypertension.

Activation and protection of the nervous system

The action of melatonin on the nervous system depends on the time of day. It has been found that at night during sleep, it helps to form new neural connections between brain cells, which improves the process of learning and memorization.

During the day, melatonin balances the nervous system. Therefore, a well-rested person is less quick-tempered and more calm.

But the effect of the hormone is not limited to this. The body generates free radicals that damage cell membranes. Melatonin is able to capture these compounds and protect the nervous system from the development of pathologies such as Alzheimer’s and Parkinson’s.

How to increase melatonin

The body itself can maintain the desired concentration of the hormone in the blood and brain, if it is not disturbed. But due to working at night or sitting at the computer for a long time, many people experience a feeling of fatigue and sleep disturbances. This is how melatonin is deficient. The following simple methods can be used to help the body, either alone or in combination.

Maintain a daily routine

An adult needs 7-8 hours of healthy sleep at night. Try to go to bed and wake up at the same time, even on weekends. This will allow the body to develop a clear rhythm.

If you can’t fall asleep, change your bedtime routine. Do not smoke or drink alcohol, try not to eat a lot in the evening, but do not lie down on an empty stomach.

You can take a nap during the day when you need it. If you have to work at night, make up for the lack of sleep by resting for a few hours during the day.

Change your diet

Melatonin is found in many foods of plant and animal origin. You can increase the concentration of the hormone in the blood if you include in the menu daily:

• eggs;
• fish;
• milk;
• strawberries;
• cherry;
• nuts;
• mushrooms;
• cereals;
• legumes.

Take pills

If you constantly complain about feeling tired and tired, you can’t get enough sleep, you need to see a therapist. He may recommend melatonin tablets. They are relatively safe and not addictive like other sleeping pills, but they are contraindicated for the following conditions:

• malignant tumors;
• alcoholism;
• mental disorders;
• diabetes mellitus;
• reduced immunity;
• liver diseases;
• organ transplant;
• epilepsy;
• pregnancy and lactation.