Sleep Dysfunction in Women 

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

Restless legs syndrome (RLS) is more prevalent in women and occurs at higher rates during pregnancy.

Definitions and terminology

• 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 - Characterized by the urge to move legs or other limbs during periods of rest or inactivity

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 EEG sleep during the luteal phase by increasing the EEG frequency and core body temperature.^{[1, 2]} Lack of estrogen later in life contributes to vasomotor symptoms, including hot flashes that cause sleep disturbances and insomnia.^[3] Decreased estrogen also plays a role in the etiology of sleep apnea.^[4]

In addition to hormonal factors, psychiatric conditions, particularly mood disorders, as well as chronic pain conditions are closely associated with insomnia.

Pathophysiologic factors in some of the major sleep disorders seen in women are as follows:

Sleep-disordered breathing: This 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 anatomical abnormalities that increase airway occlusion (eg, enlarged tonsils, macroglossia). 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 as compared to premenopause. 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 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.^[5] 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.^{[6, 7]} Progesterone levels are elevated during the luteal phase.^[8]

Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): 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. Iron deficiency has been implicated in the pathophysiology of RLS. The possibility of a genetic basis has been suggested for primary RLS. 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.^{[9, 10]}

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 (3-4 h) in both 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 biological clock.

Frequency

United States

The difficulty most frequently reported by women is insomnia. Insomnia rates during puberty have been described in girls but not 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. In addition, 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.

The prevalence of pathological 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) 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.^{[11, 12]}

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 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 body mass index significantly increase the incidence of RLS. Iron deficiency anemia has also been associated with RLS.^[13]

International

Estimated prevalence of SDB in a study from Iceland has been reported at 2.5% for women aged 40-59.

Mortality/Morbidity

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 higher body mass index (BMI), more inflammation, and less sensitivity to insulin. Specifically, the most common comorbidities with sleep disorders are as follows:

• 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. About 14% of women who report habitual snoring during pregnancy had pregnancy-induced hypertension. In addition, snoring may be responsible for nighttime increases in blood pressure in preeclampsia.^[14] Finally, 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.^[15]
• OSA has been associated with hypertension and more recently with insulin resistance and metabolic disease.^[16]
• Older women who sleep more than 9 hours of sleep are at higher risk for ischemic stroke.^[17]
• 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.

Race

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

In general, gender differences have been found in both 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.^[18]

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.^[19]

Obstructive sleep apnea: Women are more likely to have upper airway resistance syndrome (UARS), less likely to have positional apnea, and more likely to have REM-related OSA.

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.^[20] During pregnancy, prevalence rates have been reported between 11-23%

Age

• 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.
• 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.^[21] Polysomnographic changes of elderly women include decreased slow-wave sleep stages 3 and 4, which results from decreased EEG amplitude, and shorter REM sleep latency. In one study, older women who slept more than 9 hours per night had higher risk of ischemic stroke.^[22]