Sleep Dysfunction in Women

Hormonal factors, pain syndromes, and psychological issues, most particularly depression, are common concerns when addressing sleep dysfunction in women. Poor sleep quality and inadequate sleep affect many of the measures of quality of life. Women are twice as likely as men to have difficulties falling asleep or maintaining sleep, although before puberty no significant differences are apparent. (See Etiology and Epidemiology.)

Terminology

Terminology relating to sleep dysfunction includes the following:

• Insomnia - Difficulty with falling asleep or staying asleep

• Sleep-onset insomnia - Difficulty with falling asleep

• Sleep-maintenance insomnia - Fragmented sleep, difficulty with maintaining sleep

• Circadian rhythm - Approximately 24-hour cycles that are generated endogenously by an organism

• Sleep-disordered breathing (SDB) - Some degree of sleep-related upper airway obstruction, ranging in severity from upper airway resistance syndrome (UARS) to obstructive sleep apnea (OSA)

• Restless legs syndrome (RLS) - Characterized by the urge to move legs or other limbs during periods of rest or inactivity

Complications

Persistent insomnia may lead to daytime fatigue, decreased daytime function, memory and concentration problems, higher incidents of automobile accidents, and depression. Patients with persistent insomnia tend to have more psychological and medical problems including those of the respiratory, gastrointestinal, and musculoskeletal systems.

Disturbed sleep and weight gain

Over the past decade, studies have focused on the association between reduced sleep and weight gain in healthy individuals. Evidence has grown to support a role for reduced sleep time as a risk factor for weight gain and obesity. A few mechanisms have been proposed to explain this risk. Sleep deprivation causes fatigue, which may lead to decreased physical activity. Shorter sleep time allows for additional time for food consumption. Sleep disturbance has been also associated with changes in the hormone leptin, an appetite-inhibiting hormone. Reduced sleep has been associated with a drop in the diurnal amplitude of leptin.

Data from the Helsinki Health Study, which surveyed more than 8000 men and women over 5 years showed that major weight gain was associated with reduced sleep time in middle-aged women. No such associations were found in men.[1]

As women are more likely to report insomnia, this may explain why women are more likely to be obese than men.

Fibromyalgia

A dose dependent association between sleep problems (reported as often and always) and risk for fibromyalgia has been reported in women.[2] The association was stronger in middle age and older women.

Psychological issues

Healthy women who reported poor sleep also reported greater psychological distress, including depression and anger. These feelings were not associated with the same degree of sleep disruption in men.[3]

Heart disease and diabetes

Women who report poor sleep have found to have increased levels of interleukin 6 and C-creative protein, both biomarkers of increased risk for metabolic syndrome.[3]

Untreated or undertreated sleep apnea may lead to cardiac arrhythmias, hypertension, and congestive cardiac failure. In addition, daytime fatigue has been associated with increased neuropsychological impairment. Patients with sleep apnea are at higher risk for traffic accidents and increased mortality rates related to cardiovascular complications. (See Prognosis, Presentation, Treatment, and Medication.)

Types of sleep disorders

Sleep-disordered breathing

SDB involves various degrees of pharyngeal obstruction ranging from UARS to OSA. Obstruction results from high negative pressure generated by the inspiratory effort and failure of the dilating upper airway muscles to maintain airway patency.

Contributing factors are degree of muscle atonia and various anatomic abnormalities that increase airway occlusion (eg, enlarged tonsils, macroglossia, even nasal congestion). Obesity is a known risk factor for OSA. Women with OSA are likely to be more obese than men, though fat distribution is different. The prevalence, nature, and severity of OSA in women changes with menopause.

Postmenopausal women have twice the rate of OSA that premenopausal women do. Women demonstrate more partial obstructive events (hypopneas) than complete OSAs. In addition, the duration of hypopneas, when present, tends to be shorter in women than in men. OSA is mostly evident during rapid eye movement (REM) sleep.

Regardless of age, OSA is less severe in women than in men. A possible explanation is the effect of a female hormone (probably progesterone) on the activity of the dilator muscle of the pharynx.[4] In a study performed in healthy women with regular menstrual cycles, upper airway resistance was found to be lower during the luteal phase of the menstrual cycle than the follicular phase.[5, 6] Progesterone levels are elevated during the luteal phase.[7]

Restless legs syndrome and periodic limb movement disorder

These are idiopathic disorders that can cause profound disruption. RLS, a waking disorder that usually occurs before sleep onset, is associated with discomfort in the calves causing restlessness in the legs, which is relieved by movement. RLS is more prevalent in women than men and occurs at higher rates during pregnancy.

Iron deficiency has been implicated in the pathophysiology of RLS. The possibility of a genetic basis has been suggested for primary RLS.

Periodic limb movement disorder (PLMD), occurring during sleep, involves isolated periodic movements of the lower limbs, usually followed by arousal from sleep. In severe cases, frequent leg movements can cause significant sleep interruption, resulting in complaints of insomnia or excessive sleepiness.[8, 9]

Narcolepsy

The 4 major features of narcolepsy are (1) daytime sleepiness, (2) hypnagogic hallucinations, (3) cataplexy, and (4) sleep paralysis. These features are related closely to features normally occurring exclusively during rapid eye movement (REM) sleep. The symptom of cataplexy, for example, which involves sudden loss of muscle tone during waking hours, is identical to muscle paralysis normally experienced during REM sleep. Thus, narcolepsy has been hypothesized to represent a dissociative process of REM sleep mechanisms and an intrusion of these mechanisms into waking hours.

Circadian rhythm disorders

The most common circadian sleep disorder is delayed sleep phase syndrome (DSPS), with typical onset at puberty. DSPS is characterized by a significant delay (3-4h) in bedtime and wake time in the presence of a normal overall total sleep time. DSPS may also relate to an eveningness chronotype, an individual preference for increased activity at night. A Spanish study, investigating chronotypes in students aged 18-30 years, has shown a greater preference toward eveningness in men. Thus, gender differences are possibly the result of sex influences on the regulation of the biologic clock.

REM sleep behavior disorders (RBD)[10, 11, 12, 13]

Once thought to be a male predominant disorder, recent findings suggest that REM sleep behavior disorder may be underdiagnosed in women because the intensity of the behaviors is less prominent than in men. RBD is classified as a parasomnia andpresents as vivid dreams with complex, repetitive, and often violent motor behaviors during REM sleep, which classically is a time of muscle atonia. Both patients and their bed partners are at increased risk of injury from these movements. RBD has been reported in 60-100% of patients with synucleinopathies. Idiopathic RBD has been associated with the development of Parkinson disease. In the study by Koo et al, women with sleep apnea had a higher prevalence of REM-related sleep disordered breathing compared with men, particularly in those women younger than 55 years. The women younger than 55 years were found to be more obese than those in the older age group.

Hormonal factors, chronic pain conditions, and psychiatric conditions, particularly mood disorders, are closely associated with insomnia.

Hormonal changes

In general, sex steroids play a role in the etiology of sleep disorders in women, either by having a direct effect on sleep processes or through their effect on mood and emotional state. Sex steroids influence electroencephalographic sleep during the luteal phase by increasing the electroencephalographic frequency and core body temperature.[14, 15] Lack of estrogen later in life contributes to vasomotor symptoms, including hot flashes that cause sleep disturbances and insomnia.[16] Decreased estrogen also plays a role in the etiology of sleep apnea.[17]

Because estrogen and progesterone influence sleep, and possibly daytime sleepiness, sleep disturbances are more common during the premenstrual period and later in life, during postmenopausal years, when hormonal changes are pronounced. In addition, decreased level of estrogen during menopause has been associated with increased upper airway resistance, snoring, and OSA.[18]

Psychosocial issues

In today's society, many women cope with multiple roles in their families. With less time for themselves, they often cut back on sleep. In addition to sleep deprivation, increased stress has been associated with sleep-onset insomnia.

Psychiatric disorders

Mood disorders are more prevalent in women than in men, primarily those that are unique to the female reproductive system (eg, premenstrual dysphoric disorder [PMDD], pregnancy affective disorder, postpartum depression, perimenopausal mood disorder). While anxiety disorders often are associated with trouble falling asleep, depression typically is associated with early morning awakening.

Age

The frequency and severity of major sleep disorders, such as SDB, RLS, and PLMD, increase with age.

Weight

Obesity plays an important role in the pathophysiology of SDB. RLS has also been shown to have a correlation with body mass index (BMI).

Occurrence in the United States

The difficulty most frequently reported by women is insomnia. Insomnia rates during puberty have been described in girls, but not in boys. Women are at 41% greater risk for developing insomnia as compared with men, and this risk increases with age. By age 65 years, the insomnia risk is approximately 73% greater for women.

The prevalence of pathologic SDB has been estimated at 5.2% for women aged 40-64. Over 30% of elderly persons demonstrate at least mild sleep-related breathing abnormalities, as defined by an apnea/hypopnea index of 5 or greater. Postmenopausal women are 2.6 times more likely than premenopausal women to have an apnea-hypopnea index (AHI) of greater than 5.

The incidence and prevalence of SDB during pregnancy is unknown. Generally, sleep studies have found no evidence of significant SDB during pregnancy, possibly reflecting increased circulating levels of progesterone.[19, 20]

The prevalence of PLMD increases significantly with age. Studies have estimated that as many as 45% of the independently living population older than 65 years show the minimal criteria for a diagnosis of PLMD.

The prevalence of RLS has been reported at 10% for those aged 30-79 years. Higher rates of RLS have been reported in women as compared with men and Europeans as compared with Asians. Reported rates among Caucasians and African Americans are similar. Smoking, diabetes mellitus, pregnancy, increasing age, and greater BMI significantly increase the incidence of RLS. Iron deficiency anemia has also been associated with RLS.[21]

International occurrence

Across Europe, the prevalence of insomnia varies with France having the highest prevalence at 27% and the Netherlands having the lowest prevalence at 14%. However, across all the countries studied, women were significantly more affected by sleep disturbances than men.

In the Netherlands, the prevalence of general sleep disturbance was reported to be 32.1% of a population sample. Specifically, prevalence rates were: 43.2% for insufficient sleep, 8.2% for insomnia, 5.3% for circadian rhythm sleep disorder, 6.1% for parasomnia, 5.9% for hypersomnolence, 12.5% for restless legs disorder and limb movements during sleep, and 7.1% for sleep-related breathing disorder. Female adolescents reached the highest prevalence rates for most sleep disorders, insufficient sleep, and daytime malfunctioning.[22]

A Japanese nationwide survey of the general population reported the overall prevalence of insomnia to be 32.7%.

In a large study performed in China, the prevalence of reported sleep difficulties in the past month was 25%; slightly lower that the number reported by other countries. Like in other studies, Chinese females reported poorer sleep quality than men. However, the prevalence of general sleep disturbance did not differ between men and women in this very large sampled population.[23]

The estimated prevalence of SDB in a study from Iceland was reported at 2.5% for women aged 40–59 years.

Race-related demographics

The prevalence of obesity is higher in black women than in white women. Obesity places women at higher risk of developing OSA, particularly after menopause. Sleep apnea is pervasive in non-European–American women. Compared with European-American women, non-European–American women have more blood oxygen desaturations during sleep.

No significant differences were found between Caucasians and African Americans in the risk for RLS.

Sex-related demographics

In general, gender differences have been found in circadian rhythm regulation and the homeostatic sleep process. Specifically, chronotype studies have found that men have a stronger tendency toward eveningness compared with women.

Sex differences in the sleep-wake cycle appear to increase in response to sleep loss, suggesting different regulation of sleep homeostasis between men and women. Compared with men, women show more slow-wave sleep (SWS), more spindling activity during SWS, and slower age-related reduction of SWS.[24]

Poor sleep affects women more than men. Women who experience sleep disturbance are at higher risk for hypertension, diabetes type-2 weight gain, and psychological distress including anger hostility and depression.

Insomnia

Starting at puberty, the incidence of insomnia in females differs from that of males. At puberty, insomnia rates for girls are almost triple that of boys. As women, the difference is augmented to a 41% greater risk for the development of insomnia as compared with men, and by age 65 years, the risk is 73% greater as compared with men. Conditions such as bipolar disorder, stable coronary artery disease, and certain anxiety and depressive disorders that exhibit higher rates in women are associated with insomnia.[25]

Findings of increased prevalence of insomnia among women compared to men have been shown in Europe, Japan, and China. Findings in Europe show adolescent females as having the highest rate of reported insomnia.

Obstructive sleep apnea

Women are more likely to have UARS, less likely to have positional apnea, and more likely to have REM-related OSA. While women have less prevalence of OSA than men, pregnancy and menopause increase the risk for sleep apnea.

Narcolepsy

Men have a greater relative risk of narcolepsy with cataplexy (1.2:1).

Restless legs syndrome

Symptoms of RLS are more frequently reported by women.[26] During pregnancy, prevalence rates of 11-23% have been reported.

Age-related demographics

In general, sleep is sounder and less prone to disturbances in younger people. As women age, physical and hormonal changes take place that make sleep lighter and less sound. Women older than 40 years are 1.3 times more likely than age-matched men to report insomnia. Risk of insomnia, sleep apnea, periodic leg movements, and restless legs syndrome increase as women get older.

In the years surrounding menopause, sleep disturbances occur with increased frequency. Women take longer to fall asleep, wake up more often at night, and are more tired during the day. Hot flashes and night sweats, associated with decreased levels of estrogen, may contribute to midsleep awakenings. The prevalence of SDB increases significantly after menopause.

During postmenopausal years, sleep efficiency further decreases, and waking after sleep onset increases. Factors affecting sleep during this period include pain, certain medical and emotional conditions, and physical discomfort.[27] Polysomnographic changes in elderly women include decreased SWS stages 3 and 4, which results from decreased electroencephalographic amplitude, and shorter REM sleep latency.[28] In one study, older women who slept more than 9 hours per night had a higher risk of ischemic stroke.[29]

When treated, sleep apnea has an excellent prognosis. Shortly after treatment with nasal continuous positive airway pressure (CPAP), patients report increased alertness, decreased nocturnal awakenings, and an improved sense of well-being.

The prognosis of persistent insomnia is good when the treatment plan involves resolution of the underlying problem. Because of the large number of contributing factors, effective treatment relies on an understanding of the differential diagnosis and available treatment options.

Morbidity and mortality

Studies have shown that sleep problems are linked to more physical and emotional disturbances in women than in men. Among women, those with worse sleep showed more emotional distress and depression. They also had a higher BMI, more inflammation, and less sensitivity to insulin.

Insomnia is a significant comorbidity in many disorders. The most common disorders associated with insomnia are psychiatric illnesses. Major depression and dysthymia are most closely associated with insomnia. Numerous studies have also shown a close association of chronic pain syndromes with insomnia.

Most common comorbidities with sleep disorders

Snoring, often a sign of partial airway obstruction, has been shown to be associated with high blood pressure and increased risk for OSA. Snoring increases during pregnancy, particularly during the last trimester. It has been reported that about 14% of women who report habitual snoring during pregnancy have pregnancy-induced hypertension. In addition, snoring may be responsible for nighttime increases in blood pressure in preeclampsia.[30] Finally, it was found that infants born to mothers who were habitual snorers more frequently had low birth weights.

Snoring is also a risk factor in the development of OSA in postmenopausal women. Other contributing factors are weight and neck size. In addition to sleep disturbances and daytime sleepiness, OSA can lead to cardiovascular complications.[31]

Other common comorbidities include the following:

• OSA has been associated with hypertension, as well as with insulin resistance and metabolic disease[32]

• Older women who sleep more than 9 hours of sleep are at higher risk for ischemic stroke[33]

• As mentioned, psychiatric conditions, particularly depression and anxiety disorders, are the most common comorbidities with insomnia

• RLS may be secondary to medical conditions that have iron deficiency, including iron deficiency anemia, renal disease, and pregnancy

Women who present with excessive daytime sleepiness should be warned about the dangers of driving and operating heavy machinery. This warning should be documented in the patient's chart. This is particularly important because in most sleep labs, the time interval between initial evaluation, ordering of a sleep study, and initiation of treatment can be as long as weeks and even months.

Promoting good sleep hygiene

Physicians should educate women about habits and behaviors that help promote good sleep. These behaviors help most women sleep better, regardless of the type of sleep problem. The following sleep hygiene instructions should be emphasized:

• Get up about the same time every day

• Go to bed only when sleepy

• Establish a relaxing presleep routine, such as reading or listening to relaxing music

• Avoid heavy meals or consuming caffeinated beverages within 5-6 hours before bedtime

• Avoid smoking close to bedtime; avoid sleeping pills for periods longer than few weeks; be careful not to drink alcohol while taking sleeping pills

• Maintain a regular daily schedule that includes exercise, downtime, and regular mealtimes; avoid strenuous exercises within 6 hours before bedtime

• Older women should try to take a daily afternoon nap at a regular time to prevent early evening dozing

For patient education information, see the Mental Health Center, the Sleep Disorders Center, and the Women's Health Center, as well as Sleep Disorders in Women, Disorders That Disrupt Sleep (Parasomnias), Insomnia, Narcolepsy, REM Sleep Behavior Disorder, Periodic Limb Movement Disorder, andMenopause.

Taking a careful sleep history is an essential part of the evaluation of sleep disorders. This is particularly important for women who present with insomnia, as insomnia constitutes a symptom rather than a disorder and may be related to various problems, including psychiatric and medical conditions. Accurate differential diagnosis is essential before formulation of a treatment plan. The nature of the difficulty, the duration of symptoms, medical and psychiatric history, and careful assessment of current and previous sleep patterns are all essential pieces of information in the differential diagnosis.[34, 35]

Nature of sleep difficulty

Women typically present with 1 or a combination of the following symptoms.

Difficulty falling asleep

The inability to fall asleep suggests psychophysiologic or primary insomnia. Typically, this type of insomnia, often termed "learned" insomnia, is more frequent in younger individuals. It is characterized by an initial level of increased somatized and psychological tension, which may lead to occasional sleep disturbance and later may be reinforced by maladaptive behavior targeted at preventing the sleep disturbance. Often, a learned insomnia is associated with anxiety disorder, certain personality styles, and a stressful lifestyle.

Difficulties maintaining sleep

Multiple awakenings during sleep are more frequent in older individuals and suggest major sleep disorders, such as OSA or PLMD, as well as other medical and psychiatric conditions. Older women who suffer from arthritis and other painful conditions, women on certain medications, and women in their last trimester of pregnancy are some of the groups likely to present with difficulties in maintaining sleep.

Excessive daytime sleepiness

In older postmenopausal women, excessive daytime sleepiness suggests SDB and PLMD. Severe sleepiness in young women is more likely to be associated with sleep deprivation or narcolepsy.

Duration of symptoms

Short, acute sleep disorder is typically associated with an identifiable cause and almost always can be traced to an acute medical or psychological event. Chronic insomnia often begins as an acute insomnia, which later develops into a chronic condition.

Understanding the patient's coping style and identifying measures that helped in the past may help to identify the cause of the sleep problem.

Sleep-wake pattern

An irregular sleep pattern may point to impaired sleep hygiene or a circadian rhythm disorder. In delayed sleep phase syndrome, women consistently go to bed very late and are unable to get up in the morning.

Women who present with persistent early morning awakenings are more likely to suffer from depressive disorders.

Loud snoring and restless sleep suggest SDB. Multiple brief awakening and periodic leg kicks indicate the possibility of PLMD.

Medical and psychiatric history

This is an important part of sleep history and should include a thorough investigation of present and past medications that potentially can interfere with sleep, such as antihypertensive medication.

A number of medical conditions potentially can disturb sleep and need to be ruled out. These include chronic cardiac or lung disease, thyroid disease, gastroesophageal reflux, chronic pain, and other conditions.

Similarly, psychiatric history should include information regarding previous hospitalization, present and past use of psychoactive medication, and history of alcohol and drug abuse.

Insomnia, especially with early morning awakening, is one of the most common symptoms of depression. Women who suffer from anxiety disorder or chronic stress may also sleep poorly.

Women with sleep apnea often present with other, concomitant sleep disorders, such as RLS and insomnia. The relationship between sleep apnea and hypertension and between sleep apnea and insulin resistance render these conditions suspicious for OSA comorbidity.

Family sleep history

Assessment of family history provides additional information regarding the causes of the sleep disorder. For example, a family history of daytime sleepiness may point to a neurologic sleep condition, such as narcolepsy.

Hormonal status

Low estrogen levels may be responsible for affective symptoms, including depressed mood, anxiety, fatigue, forgetfulness, and decreased concentration.

Premenstrual insomnia

Sleep disturbances have been described as part of a constellation of physical and emotional symptoms—historically termed premenstrual syndrome (PMS)—occurring during the premenstrual (late luteal) phase of the menstrual cycle. Women who experience PMS report having sleep disturbances, including increased sleep latency and midsleep awakenings. They also report a significant increase in daytime sleepiness and increased difficulties in waking up.[36]

The hormonal fluctuations of the menstrual cycle have been recognized as possible contributors to the pathophysiology of mood disorders. In a small percentage of women, severe symptoms associated with PMS, including sleep disturbances, mood lability, irritability, and anxiety, may interfere with daily activities and cause a mood disorder.[37, 38]

In its current definition, as PMDD, the syndrome is included in the 1994 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Women with PMDD often show a pattern of advanced sleep phase with an earlier bedtime and early morning awakening.

Premenstrual hypersomnia

Premenstrual hypersomnia is a rare sleep disorder, occurring in association with the menstrual period, and is characterized by pronounced daytime sleepiness, which typically begins a few days prior to the onset of menstruation and ends a few days after the onset of menstruation.

Sleep in pregnancy

During the first trimester, an increase in total sleep time and daytime sleepiness is noted, whereas decreased sleep time and an increased number of nocturnal awakenings characterize the third trimester. The most common reasons for sleep disturbances given by pregnant women are frequent urination, heartburn, general discomfort, fetal movements, low back pain, leg cramps, and nightmares.[39, 40, 41]

Sleep disorders in menopause

These include the following:

• Insomnia

• SDB

• Postmenopausal sleep disorders

Difficulties with sleep onset and sleep maintenance are common in menopausal women. In cases of severe hot flashes, women can wake up several times during the night with a sensation of heat, increased heart rate, and, occasionally, a feeling of anxiety. In turn, sleep fragmentation associated with hot flashes can cause daytime fatigue, mood lability, irritability, and memory lapses. For some menopausal women who do not experience distressing vasomotor symptoms, insomnia may be associated with menopause-related mood syndrome.[42]

Increased body mass and decreased endogenous estrogen and progesterone levels, combined with loud snoring, may increase the likelihood of upper airway obstruction, leading to SDB. Women with SDB are more likely than men to have insomnia complaints and frequently have concomitant depression and other major sleep disorders, such as RLS.

As women age, sleep becomes lighter and more fragmented. While maintaining long hours of uninterrupted sleep becomes more difficult, maintaining long hours of wakefulness during the day also becomes more difficult. This can result in waking periods during the night and increased daytime fatigue. Compared with young people, older individuals go to sleep early in the evening and get up earlier in the morning.

Health issues and chronic conditions, together with the aging process, can further disturb sleep. Arthritis and other painful conditions, chronic lung disease, certain medications, heartburn, and frequent trips to the bathroom have been shown to be detrimental to sleep continuation. The use of hypnotics increases with age, with usage by women significantly higher than that by age-matched men.

Work and lifestyle

Women engaged in rotating and night shifts are likely to experience sleep problems. Women with inactive lifestyles may experience trouble falling asleep, while women who keep erratic schedules or those who go to sleep late on weekend nights and oversleep on weekend days are more likely to have trouble resetting their body clock to a normal schedule during the week.[43]

Drugs and alcohol

Use of caffeine, nicotine, or other stimulating drugs near bedtime may prevent women from falling asleep. Alcohol, often used by women to help them fall asleep, may cause sleep fragmentation and nightmares.

The examination of the woman presenting with sleep problems addresses 2 major issues: psychological and physiologic findings. General appearance and affect can be assessed early and during the examination. Chronic illness or chronic pain often is evinced in the general appearance and movement of a patient.

The examination focuses on addressing any major medical illness that may be associated with sleep symptomatology, as well as on risk factors that direct toward evaluation of sleep-related disorders, such as narcolepsy and OSA. Many patients with circadian rhythm disorders and insomnia may have normal physical examination findings.

General appearance

This includes an assessment of nutritional status as well as body habitus. General care, personal hygiene, and social exchange can also be surveyed. Elderly patients with osteoporosis may be identified for further evaluation by their posture. Chronic pain associated with fractures can disrupt sleep.

Vital signs

Hypertension has been associated with OSA.

Head and neck examination

Inspection of the head can direct the clinician to further evaluation for hyperthyroidism when exophthalmos is noted and evaluation for OSA when micrognathia or midfacial abnormalities are noted. Deviation of the nasal septum may also be associated with OSA.

Myopathic facies is another example that suggests further evaluation for sleep-related breathing disorder, as are findings consistent with atopic disease. Large neck size associated with obesity is predictive of increased risk of OSA; however, a thorough examination of the neck is also indicated to evaluate for tumors.

Chest

Chronic obstructive pulmonary disease and congestive heart failure are frequent causes of poor sleep in older patients. Inspection, auscultation, palpation, and percussion are all important elements of the examination. Digital clubbing is associated with chronic cardiac and pulmonary disease, but this may also be familial.

Abdomen

Excessive obesity and advanced pregnancy can affect breathing during sleep, especially in the supine position. Abdominal masses and tumors, depending on size and location, may also be problematic.

Neurologic examination

Patients with organic brain syndromes, dementia, or Alzheimer disease often have sleep abnormalities. Neuromuscular disease, such as spinal muscle atrophy, can be associated with hypoventilation during sleep and increased daytime sleepiness.

Polysomnography

Overnight sleep studies or polysomnograms may be done in sleep-disorder centers, at home, or as inpatient procedures. Indications include risk factors, symptoms or cardiovascular manifestations arising from sleep apnea, disorders of respiratory control, and chronic obstructive or restrictive lung disease.

Multiple Sleep Latency Test

The Multiple Sleep Latency Test (MSLT) is indicated in the assessment of excessive daytime sleepiness. It is performed following a supervised overnight polysomnogram. The presence of 2 or more sleep-onset REMs (SOREMs) in an MSLT following a normal polysomnographic study the night before supports a diagnosis of narcolepsy.

Sleep logs

While not technically a laboratory test, sleep logs are sleep-wake cycle diaries, generally kept for a 2-week period and correlated with the patient's subjective assessments of daytime alertness. These diaries can be particularly helpful in diagnosing circadian rhythm disorders.

Imaging studies

Imaging studies may be required in the case of patients with OSA and craniofacial dysmorphologies to evaluate potential surgical strategies (eg, jaw advancement). They also may be utilized in the workup of neurodegenerative disorders.

Treatment of sleep disorders is directed at the particular problem and includes behavioral and pharmacologic components, as well as implementation of a sleep hygiene program.

Continuous positive airway pressure (CPAP) therapy

The treatment of choice for SDB is CPAP therapy. This treatment uses forced air pressure to keep the upper airways open.

Oral appliance

Oral appliance therapy uses a dental device to effect advancement of the mandible and tongue in order to increase airway opening. Oral appliance therapy is indicated for mild-to-moderate sleep apnea and when individuals are unable to tolerate CPAP therapy. There are many types of oral appliances. Although not as effective as CPAP for the treatment for OSA, oral appliance treatment is less obtrusive and easier to tolerate than the CPAP device.

Cognitive behavioral therapy for insomnia (CBT-I)

Behavioral approaches to the treatment of insomnia are effective and should be used as first-line treatment for chronic insomnia. Specifically, in a study from the National Institutes of Health (NIH), CBT-I produced longer-lasting effects than medication. According to the 2005 NIH consensus statement, CBT-I is as effective a treatment for insomnia as sleeping pills for the short term and is more effective than hypnotics in the long term. CBT-I involves the modification of certain sleep-related maladaptive behaviors and the identification of dysfunctional perceptions and attitudes related to sleep patterns. CBT-I has also been found to be effective in special populations, including geriatric groups and patients with chronic pain conditions.

Medications

See Medication.

Surgical care

Uvulopalatopharyngoplasty (UPPP) is a surgical procedure performed to eliminate loud snoring. It involves surgical removal of excess tissues of the soft palate (including uvula) in order to enlarge the area of the upper airways for the purpose of improvement of air exchange.

Diet

In general, women should avoid eating heavy meals within 4 hours before bedtime, as this can have a stimulating effect on sleep. Pregnant women are prone to heartburn, particularly during the last trimester of pregnancy. Therefore, they should maintain a balanced diet and avoid eating spicy food at least 2-3 hours before bedtime.

Activity

For older women, maintaining long hours of sound sleep during the night and long hours of complete alertness during the day becomes increasingly difficult. This can result in waking periods during the night and increased daytime fatigue. In addition, decreased physical activity, an irregular sleep-wake schedule, and a lack of outdoor light exposure may be involved in changes of the circadian rhythm. Older women should be encouraged to maintain a structured daily schedule that includes physical activity and light exposure and that allows a daily afternoon nap at a regular time.

Generally, premenstrual insomnia disappears a few days after menstruation begins. For some women, however, the associated tension and irritability can result in lingering sleep problems and even in chronic insomnia. These women should pay attention to their sleep needs, maintain a regular sleep-wake schedule, avoid stress when possible, and eat a healthy diet.

Because of underlying circadian disturbances in women with premenstrual symptoms, evening bright-light therapy has been reported to be effective in preventing early morning awakening in women with this complaint.

Women diagnosed with PMDD are more susceptible to major depressive disorder when their condition goes untreated. Studies have shown that, like patients with major depression, women with PMDD respond to treatment that incorporates sleep deprivation. Total and partial sleep deprivations have been shown to effectively reduce depressive symptoms, although these methods still are considered experimental.

Relatively little is known about the health significance of sleep disturbance in pregnancy. Pregnancy can pose a risk for developing SDB,[44] back pain, and leg cramps. It can also trigger episodes of sleepwalking and PLMD.[45]

In addition, sleep disturbance during pregnancy also can be associated with frightening dreams, postpartum blues, and sometimes even major depression and postnatal psychosis.[46]

Throughout their pregnancy, women need to pay extra attention to their sleep pattern by making sure that they get enough sleep, maintain a regular sleep-wake schedule, and avoid excessively stressful conditions.

Because sleeping pills and alcohol can harm the baby, other measures to improve sleep need to be considered. The practice of muscle relaxation technique prior to bedtime may be effective in promoting better sleep and reducing the discomfort of pregnancy.

To avoid exacerbating heartburn, women should maintain a balanced diet and avoid eating heavy meals and spicy food for at least 2-3 hours before bedtime.

After delivery, getting enough rest continues to be very important, as severely disturbed sleep may place women at risk for postpartum depression and child abuse.[47]

Narcolepsy

Most patients with narcolepsy rely on stimulant and antidepressant medication to maintain daytime alertness and to control cataplexy; therefore, cessation of medication during pregnancy can cause excessive sleepiness or cataplexy, which may result in injury. In addition, withdrawal from medications also may affect sleep patterns.

No adverse fetal outcome was described in 2 case reports on women with narcolepsy who continued to take amphetamine throughout pregnancy and during nursing. Despite these findings, caution must be used in the administration of these medications during pregnancy, because the long-term sequelae have not been fully assessed.

Women can alleviate their menopause-related sleep disturbances by paying attention to their sleep habits, controlling their bedroom temperature, adjusting the light, and using comfortable (preferably cotton) bed linen. In addition, they should eliminate caffeine, sugar, and alcohol from their diet.

Estrogen therapy has been found to be quite effective for women with severe sleep and mood disturbances who have no history of affective illness. Hormone replacement therapy (HRT) has also been the treatment of choice for sleep interruptions related to hot flashes. However, study results have caused the safety of this treatment to be questioned.[48]

A combination of antidepressant medications and supportive psychotherapy should be considered for women who have had long-standing difficulties with sleep, depression, and anxiety.

In the presence of SDB, nasal CPAP and/or an oral device should be offered, along with recommendations regarding weight management. Weight management also appears to be an important factor in the management of SDB in menopausal women.

HRT may be useful in the treatment of OSA in menopausal women. However, results from the Women's Health Initiative study have raised concerns about the safety of HRT.

Older women should be aware of sleep disturbances and not dismiss them as part of the aging process. In addition, the presence of significant daytime sleepiness should be investigated. A sleep study may be required to rule out major sleep disorders.

The physician should be aware of the patient's medical and psychiatric conditions and target the treatment at the cause of the disturbance rather than at the symptoms. General guidelines for better sleep habits should be provided.

Compliance with nasal CPAP treatment has been estimated to be 50-73% in the first 6 months of treatment. It decreases sharply to less than 60% by 18 months of treatment; therefore, long-term follow-up is essential to maintain the efficacy of this treatment.

Treatment of primary insomnia typically consists of a short-term cognitive-behavioral treatment, with follow-up visits at 3 and 12 months. In the presence of comorbid psychiatric conditions, psychological treatment typically is combined with medication, and long-term follow-up treatment is needed.

Strategies for preventing sleep dysfunction include the following:

• Good sleep hygiene - Maintaining good sleep hygiene improves the sleep of most women

• Stress management - Stress associated with daily life often contributes to sleep problems; learning stress management skills can help women to sleep better and prevent more serious sleep problems

• Body weight maintenance - Regular exercise and healthy diet promote good sleep; in addition, maintaining normal weight may prevent the development of obesity-associated SDB

Because of the multidisciplinary nature of sleep disorders, consultation with various specialists often is needed, including the following:

• Psychiatrist - A psychiatric consultation often is needed when severe insomnia does not respond to behavioral treatment

• Behavioral sleep specialist (board-certified in behavioral sleep medicine) - This is typically a psychologist trained in behavioral therapy for insomnia

• Neurologist - In the differential diagnosis of parasomnias (eg, sleep terror, sleepwalking, REM sleep behavior disorder), consultation with a neurologist often is needed to rule out sleep-related seizure disorders

• Pulmonologist - SDB is suspected in the presence of loud snoring and daytime sleepiness; occasionally, a pulmonologist is consulted to rule out related respiratory disease such as alveolar hypoventilation syndrome

• Dentist - For patients who are unable to tolerate nasal CPAP, oral appliances may prove effective in the treatment of SDB

Underlying disease can be treated with HRT, hypnotics, antidepressants, and behavioral therapy. Estrogen replacement can improve sleep in menopausal women, primarily through the reduction of vasomotor symptoms that disturb sleep. It may also improve sleep-related breathing disorders. Moreover, studies indicate that estrogen, either alone or combined with progestin (but not progestin alone), markedly reduces OSA in menopausal women.

Antidepressants are indicated for PMDD, postpartum depression, and clinical depression in patients of any age. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressive agents.

Class Summary

These agents have been the hypnotics of choice for many years because of their relative safety compared with barbiturates. By binding to specific receptor sites, benzodiazepines appear to potentiate the effects of GABA and to facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Benzodiazepines are used when additional anxiolytic effects are desired in addition to hypnotic effects. Intermediate and long-acting benzodiazepines are used for sleep-maintenance insomnia.

Triazolam (Halcion)

Triazolam, a short-acting agent, is good for use in sleep-onset insomnia. It has no significant residual effects in the morning.

Estazolam

Estazolam is an intermediate-acting agent with a slow onset of action and a long duration. It is a good agent for sleep-maintenance insomnia.

Temazepam (Restoril)

Temazepam is indicated for sleep-onset and maintenance insomnia. It should be taken at bedtime to prevent daytime aftereffects.

Quazepam (Doral)

Quazepam is used for sleep-maintenance insomnia. It enhances the inhibitory effects of the GABA neurotransmitter on neuronal excitability that results by increased neuronal permeability to chloride ions. The shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

Flurazepam

Flurazepam is frequently chosen as a short-term treatment of insomnia. It enhances the inhibitory effects of the GABA neurotransmitter on neuronal excitability that results by increased neuronal permeability to chloride ions. The shift in chloride ions results in hyperpolarization and stabilization of the neuronal membrane.

Class Summary

These agents are used for the treatment of acute and short-term insomnia.

Zolpidem (Ambien, Ambien CR, Edluar, Intermezzo)

Zolpidem is the drug of choice (DOC) for the treatment of primary insomnia (ie, sleep-onset insomnia). It is indicated for acute, short-term insomnia for a duration that does not exceed a few weeks. The extended-release product (Ambien CR) consists of a coated, 2-layer tablet and is useful for insomnia characterized by difficulties with sleep onset and/or sleep maintenance. The first layer releases the drug content immediately to induce sleep; the second layer gradually releases additional drug to provide continuous sleep..

Zaleplon (Sonata)

Zaleplon is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class. It has a chemical structure unrelated to benzodiazepines, barbiturates, or other hypnotic drugs but interacts with the GABA-benzodiazepine receptor complex. It binds selectively to the omega-1 receptor situated on the alpha subunit of the GABAA receptor complex in the brain. Zaleplon potentiates t-butyl-bicyclophosphorothionate (TBPS) binding and has preferential binding to the omega-1 receptor of the GABA receptor family. It is indicated for short term treatment of insomnia. It should be used for 7-10 days. Zaleplon has been shown to cause minimal daytime grogginess

Eszopiclone (Lunesta)

Eszopiclone is a nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown, but the drug is believed to interact with the GABA receptor at binding domains close to or allosterically coupled with benzodiazepine receptors.

Eszopiclone is indicated for insomnia to decrease sleep latency and improve sleep maintenance. It has a short half-life of 6 hours. Higher doses (ie, 2 mg for elderly adults and 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses (ie, 1 mg for elderly adults and 2 mg for nonelderly adults) are suitable for difficulty in falling asleep.

Ramelteon (Rozerem)

Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and to be involved in the maintenance of circadian rhythm and the normal sleep-wake cycle.

Class Summary

Estrogen replacement has been shown to improve sleep in menopausal women, primarily by reducing vasomotor symptoms that disturb sleep. In addition, it may improve sleep-related breathing disorders. Studies found that estrogen, either alone or combined with progestin (but not progestin alone), markedly reduced OSA in menopausal women. Oral Premarin is an example of an oral estrogen replacement. The choice of HRT should be made on an individual basis in consultation with a gynecologist.[49]

Conjugated estrogens (Premarin)

Multiple aspects of menopause respond to estrogen replacement therapy, including vasomotor symptoms and atrophic vaginitis. However, such therapy has not been shown to be effective in treating depression associated with menopause. Decisions for HRT should be made on an individual basis in consultation with a gynecologist. Dosing may need to be titrated individually, with each patient monitored for risks and adverse effects. Premarin is available in tablet form for oral administration in strengths of 0.3 mg, 0.625 mg, 0.9 mg, 1.25 mg, and 2.5 mg.

Class Summary

SSRIs are generally well tolerated and are currently the most frequently prescribed drugs for the treatment of depression. Pharmacologic treatment with antidepressants is indicated for PMDD, postpartum depression, and clinical depression in patients of any age.

Serotonin noradrenaline reuptake inhibitors (SNRIs) are also used. These agents exhibit noradrenergic and serotonergic effects in patients with depression.

Sertraline (Zoloft)

Sertraline is effective for the treatment of clinical depression in women. It is also indicated for panic disorders and obsessive-compulsive disorders.

Escitalopram oxalate (Lexapro)

Escitalopram oxalate is prescribed for insomnia associated with depression. A selective serotonin reuptake inhibitor (SSRI) and an S-enantiomer of citalopram, it is used for the treatment of depression. Its mechanism of action is thought to be the potentiation of serotonergic activity in the central nervous system (CNS) resulting from the inhibition of the CNS neuronal reuptake of serotonin. The onset of depression relief may be obtained after 1-2 weeks, which is sooner than for other antidepressants.

Fluoxetine hydrochloride (Sarafem)

Fluoxetine hydrochloride has been approved for the treatment of PMDD. It is indicated for the treatment of premenstrual insomnia associated with PMDD.

Class Summary

Alpha2-adrenergic antagonists increase the release of norepinephrine and serotonin but do not inhibit the reuptake of norepinephrine or serotonin. These agents exhibit noradrenergic and serotonergic effects in patients with depression.

Mirtazapine (Remeron)

Mirtazapine is a relatively new antidepressant and is not as widely used as sertraline. It exhibits noradrenergic and serotonergic activity. It has been shown to be superior to other SSRI drugs in cases of depression associated with severe insomnia and anxiety.

Class Summary

These agents may be effective in narcolepsy.

Modafinil (Provigil)

Modafinil's mechanism or mechanisms of action in wakefulness are unknown. It has wake-promoting actions like sympathomimetic agents.

Armodafinil (Nuvigil)

Armodafinil is an R-enantiomer of modafinil (mixture of R- and S-enantiomers). It elicits wake-promoting actions similar to those of sympathomimetic agents, although its pharmacologic profile is not identical to sympathomimetic amines. In vitro, armodafinil binds to the dopamine transporter and inhibits dopamine reuptake. It is not a direct- or indirect-acting dopamine receptor agonist. Armodafinil is indicated for the improvement of wakefulness in individuals with excessive sleepiness associated with narcolepsy, obstructive sleep apnea-hypopnea syndrome (OSAHS), or shift-work sleep disorder.

Class Summary

Dopamine agonists may be effective for the treatment of RLS.

Pramipexole (Mirapex)

Pramipexole is a nonergot dopamine agonist with specificity for the D2 dopamine receptor, but it also has been shown to bind to D3 and D4 receptors and may stimulate dopamine activity on nerves of the striatum and substantia nigra.

Class Summary

These agents may be effective for moderate to severe primary RLS. Neuropharmacologic evidence suggests that they have primary dopaminergic system involvement in RLS.

Ropinirole hydrochloride (Requip)

Ropinirole hydrochloride is a second-generation, nonergoline dopamine agonist that directly stimulates dopamine receptors in the brain. It has high specificity for the D3 receptor subtype. Ropinirole hydrochloride is taken at bedtime and is indicated for moderate to severe RLS.

Class Summary

Agents in this class block the binding of wake-promoting neuropeptides orexin A and orexin B to their respective receptors OX1R and OX2R, which may suppress wake drive.

Suvorexant (Belsomra)

Suvorexant is the first orexin receptor antagonist used for the treatment of insomnia. It is found to be generally safe and well tolerated by patients. Therefore, it can be used for chronic insomnia therapy.