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.