Menopause Exacerbates Sleep Disorders Among Women

With changes in biological life cycles and extreme hormonal change and with advancing age, women are at increased risk of sleep disorders such as insomnia, poor sleep quality and sleep deprivation, as well as sleep disorders such as obstructive sleep apnea (OSA), restless legs syndrome (RLS), depression, and various mood and anxiety disorders.

There is emerging evidence that hormonal loss associated with menopause contributes to this elevated risk of sleep disorders, but age is also an important factor. The current review will discuss various aspects of menopause and sleep disorder in light of the available scientific evidence.

The incidence increases from 16%-42% to 39-47% in perimenopause and 35%-60% in postmenopause. Difficulty sleeping has been reported in 38% of older women and age-adjusted rates have been reported higher in late perimenopausal (45.4%) and surgically postmenopausal (47.6%) women.

Studies have reported that between 33 and 51% of women show a dramatic increase in sleep disturbance in their middle-aged years, a time when they enter menopause, that is, during the transition from perimenopause to the menopause.

The menopausal transition is associated with increased insomnia-related symptoms, particularly difficulty staying asleep, which has a negative impact on quality of life.

Vasomotor symptoms ( VMS) are a key component of sleep disruption during such a transition. Furthermore, studies have shown that a high association between fibromyalgia and early and late perimenopause and surgical menopause are one of the other factors for a high incidence of sleep disorders during the menopause transition.

The most commonly encountered comorbid conditions with sleep disorders in menopausal women include restless legs syndrome, periodic leg movement syndrome, depression, and anxiety.

Epidemiological studies state that women experience sleep-related difficulties and depressive symptoms around times when there is generally alteration in sex hormone levels, such as at the time of puberty and menopause. Furthermore, sleep disorders during menopause may be an independent risk associated with arterial stiffness in menopause and may lead to a higher incidence of cardiovascular-related morbidity and mortality.

Obstructive sleep apnea ( OSA) is another very common comorbid condition associated with sleep disorder. It is a chronic disorder of adults characterized by episodes of recurrent upper airway obstruction, accompanied by frequent reopening of the airways during sleep. OSA is associated with oxidative stress, intermittent hypoxia, sympathetic overactivity, leading to high mortality and cardiovascular morbidity. It is more common in men than women, and this is attributed to differences in anatomy and functional respiratory components.

Furthermore, in postmenopausal women, high BMI and abdominal obesity are sources of sleep disorders, decreasing deep sleep and sleep efficiency, while increasing the risk of OSA. It is also well known that the prevalence of sleep-disordered breathing (SDB) among postmenopausal women increases in patients with obesity or metabolic comorbidities.

Additionally, conditions such as gastroesophageal reflux disease, diabetic neuropathy, vitamin D deficiency, and muscle cramps related to sleep disorder have also been found among postmenopausal women. It is also known that many medications such as beta blockers, bronchodilators, corticosteroids, diuretics, stimulant antidepressants, central nervous system stimulants also negatively affect sleep quality.

Women generally have better sleep quality compared to men, evident by longer sleep times, shorter sleep onset latency, and greater sleep efficiency. Despite all this, women generally tend to have more sleep-related complaints than men. The amount of slow wave sleep slowly decreases with age in both men and women.

Normal physiological periods, which are associated with altered hormonal levels such as puberty, menstruation, pregnancy and menopause, are associated with alterations in sleep patterns. Insomnia studies support a female preponderance, with a greater divergence of prevalence between men and women in the older age group.

There are many ways that women experience sleep differently than men. New research is unraveling aspects of sleep pathology in women and the importance of sex hormones in determining sleep regulation as well as arousals and possibly the etiology of sleep-related disorders.

Additionally, studies indicate that during periods of hormonal disruption, women are predisposed to various sleep-related disorders, such as decreased sleep quality and sleep deprivation, as well as other sleep disorders such as OSA, RLS and insomnia.

Women are more likely than men to complain of insomnia, headaches, irritability and fatigue than the typical symptoms of loud snoring and cessation of breathing during sleep.

Compared with premenopausal or perimenopausal women, postmenopausal women were more frequently reported to have difficulty falling asleep and possible sleep onset insomnia disorder. Postmenopausal women were also more likely to test positive for OSA compared to premenopausal women. The two groups did not vary in sleep dissatisfaction, daytime sleepiness, sleep maintenance insomnia disorder, and leg rest syndrome.

The circadian rhythm is an internal biological clock of several physiological processes. This circadian pacemaker is located in the suprachiasmatic nucleus present in the hypothalamus. The circadian clock undergoes many changes throughout life, both at a physiological and molecular level.

The existence of sex differences exists, so the consequences of sleep disorders associated with menopause are a good example. Endogenous melatonin secretion decreases with increasing age and varies with gender, and in menopausal women it is associated with a significant reduction in melatonin levels, which affects sleep patterns.

The level of melatonin decreases (especially at night) with age, even more so during the perimenopausal period. Postmenopausal women tend to have a longer sleep latency, as well as more awakenings during the night and early in the morning.

Although these sleep-related complaints in menopause may be multifactorial (such as poor sleep hygiene, depression, primary sleep disorders, fibromyalgia), the decrease in melatonin secretion and the alteration of the circadian oscillator system also have substantial relevance, both with respect to disruptive sleep symptoms and direct impairment of sleep regulation. Since endogenous melatonin secretion decreases with aging among women, menopause is associated with a significant reduction in melatonin levels.

Reproductive hormones have a general protective effect on sleep apnea in women of the premenopausal age group. Progesterone stimulates benzodiazepine receptors, gamma-aminobutyric acid receptors, and therefore induces sleep and functions as an anxiolytic. Premenstrual drops in progesterone levels are associated with sleep disorders. Something similar has been postulated to be responsible for the increased incidence of sleep disorders during the perimenopausal and postmenopausal period.

Similarly, estrogen is involved in the metabolism of norepinephrine, serotonin, and acetylcholine. Increases rapid eye movement (REM) sleep, total sleep time, and decreases sleep latency and spontaneous awakenings. It is also known to have a thermoregulatory effect at night and indirectly improves sleep. Furthermore, by regulating 5HT, it can also exert an antidepressant effect and indirectly also contribute to improving sleep quality.

Sleep disorders in menopause are common. Although these disorders may be directly due to menopause, the etiology is multifactorial, including a wide range of associated conditions. They may simply arise as part of the physiological process of aging and not be particularly related to declining estrogen levels or, alternatively, due to other conditions, such as respiratory or limb movement syndromes, depression, anxiety, comorbid medical illnesses, medication, pain and/or psychosocial factors.

Chronic insomnia ( difficulty sleeping for more than 3 weeks) is usually common among postmenopausal women and is often associated with anxiety, depression or psychosis, or mood disorders.

If not treated properly along with the associated problem for at least 3 to 6 months, it can be very commonly associated with withdrawal or rebound insomnia. The incidence of short-term insomnia (difficulty sleeping for 3 to 21 days) is more common overall, but a higher incidence is seen during the menopause transition period. It may require treatment for more than 3 weeks in most cases.

Transient insomnia ( difficulty sleeping for 1 to 3 days) can be found with equal propensity in young, perimenopausal, or menopausal women. It may require treatment for a few days or it may not require any treatment.

Relatively less common sleep disorders in perimenopausal or menopausal women include: bruxism: involuntary grinding or clenching of teeth while sleeping; hypopnea syndrome: abnormally shallow breathing or slow respiratory rate while sleeping; narcolepsy excessive daytime sleepiness; cataplexy a sudden weakness in the motor muscles that can result in collapse and falling to the ground; night terror disorder/sleep terror: abrupt awakening from sleep with terror; parasomnias: disruptive sleep-related events involving inappropriate actions during sleep stages - sleepwalking; periodic limb movement disorder: sudden involuntary movement of arms and/or legs during sleep, for example, leg kicking also known as nocturnal myoclonus; rapid eye movement behavior disorder: depicting violent or dramatic dreams during REM sleep; sleep paralysis: characterized by temporary paralysis of the body shortly before or after sleep, it may be accompanied by visual, auditory or tactile hallucinations; sleepwalking or somnambulism; nocturia: a frequent need to go to the bathroom to urinate a few times at night that is differentiated from enuresis, or bedwetting, in which the person is not awake and continues to sleep, but the bladder, however, becomes empty and somniphobia : a state of extreme anxiety and fear even at the thought of going to sleep.

Since sleep disorders in postmenopausal women cannot be attributed solely to hormonal changes, there are other disorders that can cause sleep problems in these women. Therefore, it is very important to have comprehensive information for all other possible associated comorbid conditions that may independently affect sleep.

Furthermore, sleep disorders and insomnia remain largely a clinical diagnosis based on patients’ subjective complaints. The most commonly used tools for the assessment of depression and associated anxiety are the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale.

Careful evaluation should be performed by taking appropriate history not to establish a clinical diagnosis of insomnia or sleep disorder, but also to have an evaluation regarding common comorbidity . An accurate and detailed history from the patient, the patient’s partner, or a family member combined with a sleep questionnaire can help obtain critical information.

Most sleep-related complaints fall into three categories: insomnia, excessive sleepiness, or abnormal sleep behaviors.

First, the chief complaint should be carefully evaluated, such as when the symptoms began, any particular pattern of symptoms since onset, and other contributing factors (medical, environmental, occupational, psychological/stress, lifestyle choices) that may have predisposed or precipitated the illness.

Evaluate the impact of the sleep complaint on the patient’s life, and inquire about their eating and sleeping schedules, sleep hygiene, sensation of restless legs, snoring, presence of apnea episodes, sweating, cough, gasping/choking/snoring. , dry mouth, bruxism, excessive movements during sleep, periodic limb movements, any abnormal behavior during sleep, daytime sleepiness, presence of cataplexy, sleep paralysis and hypnagogic or hypnopompic hallucinations.

Next, assess for caffeine consumption, alcohol and nicotine use, as well as illicit drug use. Review relevant medical/surgical/psychiatric history and previous treatments, and their effectiveness or lack thereof. Carefully evaluate whether there is a family history of sleep disorders (snoring, OSA, narcolepsy, RLS).

 Laboratory tests that are rarely performed to evaluate and therefore treat sleep disorders include the polysomnogram (PSG) which is a comprehensive, overnight, laboratory monitoring that simultaneously records numerous variables during sleep. It includes several modalities, such as electrocardiogram, sleep staging (EEG), electrooculogram, submental electromyogram (EMG), nasal or oral airflow, respiratory efforts, oximetry, anterior tibial EMG, and position monitoring.

Depending on the clinical diagnosis, additional parameters may be added: transcutaneous CO2 monitoring or end-tidal gas analysis; muscle activity of the extremities; movement of motor activity; extended video-EEG; tumescence of the penis; esophageal pressure; gastroesophageal reflux; snoring; and continuous blood pressure recording.

Benzodiazepine hypnotics and the newer agents, zolpidem, zopiclone, and zaleplon, are preferable to barbiturates. Benzodiazepine compounds with a shorter half-life are preferred in patients with sleep onset insomnia. These compounds are considered appropriate for the elderly population due to the decreased risk of accidental falls and respiratory depression.

Benzodiazepines that have longer half-lives are preferred for patients who have significant daytime anxiety and who could tolerate next-day sedation but would otherwise be further affected by rebound daytime anxiety. These benzodiazepines are also appropriate for patients receiving treatment for major depressive episodes because short-acting agents may worsen early morning awakening.

However, longer-acting benzodiazepines may be associated with next-day cognitive impairment or late daytime cognitive impairment (after 2 to 4 weeks of treatment) as a result of drug accumulation with repeated administration.

Still, benzodiazepines remain the mainstay of treatment for most sleep disorders, including chronic insomnia.

Treatment of associated anxiety, depression or psychosis is important and the main line of treatment is the use of sedatives as an adjunct and gradual discontinuation after 3 to 6 months. However, the risk of tolerance and abuse is greatest among chronic insomniacs. A slowly eliminated drug is preferable due to rebound insomnia and withdrawal symptoms associated with such drugs.

For the short-term treatment of insomnia , the lowest effective dose of benzodiazepines, 30 minutes before bed after three nights of acceptable sleep, skip a few doses, and then use 2 to 4 times a week, no more than 3 weeks, is the recommended treatment strategy these days.

Similarly, for transient insomnia, the use of low-dose benzodiazepines, with short duration of action for 2 to 3 nights, preferably newer non-BZD hypnotics, has increased due to their rapid onset of action, minimal next-day deterioration and no buildup or minimal possibility of rebound insomnia upon stopping.

However, it is also to be understood that sedatives and hypnotics are absolutely safe in the elderly. The doctor should always try to look for other associated factors, such as anxiety, depression, dementia, loneliness, and loss of family support, while treating sleep disorders. Smaller doses than usual of short-acting BDZ, for example, Oxazepam, are preferred. If BDZ is not tolerated, the use of non-benzodiazepines such as Zolpidem and Zoleplon is recommended.

Additionally, the doctor must remember that among this population there is a great possibility of drug interactions, if they are already taking other medications. The risk of falls and fractures increases in elderly people with long-term hypnotic therapy. Therefore, fall and fracture prevention techniques should be encouraged in these patients and the initiation of benzodiazepines should be planned preferably in the short term.

Treatment of associated anxiety, depression or psychosis is important and for this, use of sedatives as an adjunct and gradual discontinuation after 3 to 6 months should always be the approach in such cases. The risk of tolerance and the potential for abuse are greatest among chronic insomniacs. A slowly eliminated drug is preferable because rebound insomnia and withdrawal symptoms are less marked with such drugs.

For the treatment of other sleep disorders, monotherapy or a combination of the following drugs can be used very effectively, that is, tricyclic antidepressants, SSRIs, melatonin, duloxetine, fluoxetine, imipramine, nortriptyline or amitriptyline.

Other medications that may be helpful are eszopiclone, escitalopram, gabapentin, isoflavones, valerian, quiteiapine XL, citalopram, mirtazapine followed by long acting melatonin, ramelteon, Pycnogenol, can also be considered depending on additional requirement.

Menopausal hormone therapy improves sleep quality in women along with a concomitant improvement in VMS.

Ensrud et al.[ 33 ] suggested that among perimenopausal and postmenopausal women with hot flashes, both low-dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality.

However, Lindberg et al. Mirer et al. also reported some contrary results that failed to establish any superiority of hormone therapy over placebo in sleep disorders in both premenopausal and postmenopausal women.

Because there is a lack of consistency in the studies, partly due to the difference in hormone preparations, age, symptomatology, type of menopause and in light of few recent studies concluding that HT does not offer a significant advantage in the sleep disorders and, furthermore, due to the recent debate around the use of HT in menopause due to the established risk of breast cancer, cardiovascular risk, ovarian cancer, etc., HT is currently not recommended as a line of treatment for sleep disorders among postmenopausal women as per current Indian Menopause Society guidelines.

Self -hypnosis is a non-drug treatment for poor sleep and hot flashes in menopausal women. The goal of hypnosis is to help educate and train subjects to perform self-hypnosis to relieve underlying symptoms.

The use of hypnosis as a treatment for sleep deprivation has shown benefits for both acute and chronic insomnia. There were clinically significant improvements in reducing perceptions of poor sleep quality in 50 to 77% of women over time.

Cognitive therapy aims to change patients’ beliefs and attitudes about insomnia. The combined cognitive and behavioral technique, in addition to changing patients’ beliefs, has a behavioral component that may include stimulus control or sleep restriction therapy with or without the use of relaxation therapy that helps most postmenopausal women. who suffer from chronic insomnia.

Progressive muscle relaxation training also helps some of the patients dramatically. Furthermore, stimulus control therapy, sleep restriction therapy are also some important techniques that help many patients successfully.

In addition to this, preventive sleep hygiene practices should be recommended for overall benefit to postmenopausal patients with sleep disorders. Sleep only when you are sleepy, if you can’t fall asleep within 20 minutes, get up and do something boring until you are sleepy, don’t take naps.

Stay away from caffeine, nicotine, and alcohol at least 4 to 6 hours before bed; eat a light meal before going to bed; avoid sleeping during the day; stimulus control; set a regular bedtime; make sure your bed and bedroom are quiet and comfortable; avoid excess water before sleeping; wear comfortable clothing; turn off mobile phones; do not try to remember events of the day; Don’t worry about the next day; develop a regular bedtime; moderate exercise helps you sleep well; Warm milk is useful as it contains d-tryptophan which decreases sleep onset time.

Women are more likely to suffer from sleep disorders compared to men during menopause and with advancing age. Insomnia with or without associated anxiety or low-level depression is the most common manifestation.

Sleep disorders and insomnia largely remain a clinical diagnosis based on patients’ subjective complaints. Benzodiazepines remain the mainstay of treatment in most sleep disorders, including chronic insomnia.

Most important is the treatment of associated anxiety, depression or psychosis. HRT currently lacks concrete evidence to be used in menopausal women for sleep disorder. Preventative sleep hygiene practices, self-hypnosis, medication and exercise play a very important role.