Fig. 6.1
A hypnogram showing cycling of stages of sleep throughout sleep duration
Fig. 6.2
Sleep across the lifespan. The figure depicts typical sleep patterns with respect to sleep duration, structure, and timing across the lifespan [2]. The proportions of time spent in each type of sleep each night at each life stage are shown, and these cycles repeat throughout the night. During infancy, 50 % of the time sleeping is in the stage of rapid eye movement (REM). By primary school age, REM sleep has decreased to roughly 20 %, and slow-wave sleep (SWS, stages 3 and 4) also referred to as “deep sleep” increases. If adolescents are allowed to sleep the amount they prefer, they would go to sleep later and stay in bed longer. Sleep would increase to roughly 9.5 h/nightly with a decline in SWS and slow-wave activity (SWA) on polysomnography (PSG). This decline in SWS/SWA continues into adulthood, but is modulated by alterations in estradiol and testosterone [3]. Recent findings from the Study of Women’s Health Across the Nation (SWAN) suggest that rapid increases in FSH are associated with reports of poorer sleep quality [4]. Sleep duration decreases across adulthood until the seventh decade and levels off or increases after retirement [5]
The most common sleep disturbances are disorders related to initiating and maintaining sleep, the insomnias. Some people experience most difficulty falling asleep and can take up to several hours to accomplish this. Others complain of waking during the night, with interruptions in sleep that may or may not be explained by external factors, such as a snoring partner or a night sweat. They also may or may not have difficulty in returning to sleep. If waking occurs frequently, patients often describe their sleep as restless. Still others are bothered by early morning awakening, with the inability to fall back to sleep. Many times these sleep issues co-occur.
A more comprehensive definition of insomnia, according to the DSM-V, the diagnostic manual for psychiatric disorders, is the dissatisfaction with sleep quantity or quality, with one or more of the following symptoms: difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening. The sleep disturbance causes significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning. Sleep difficulty occurs at least three nights per week and is present for at least 3 months, despite adequate opportunity for sleep. The insomnia does not co-occur with another sleep disorder. The insomnia is not explained by coexisting mental disorders or medical conditions [6]. Using this definition, sleep disturbance that is isolated to the menopause transition and is not due to one of the sleep disorders described below would be considered insomnia due to a general medical condition, rather than a primary insomnia disorder.
Stages of reproductive aging including menopause transition and distinction between early and late stages of menopause have been discussed in Chap. 1 of this text and are summarized in Fig. 6.3 [7]. From the perspective of psychological well-being, the late premenopause stage is of clinical importance, as studies have shown that risk for depression [8] and cognitive decline [9, 10] during the transition to menopause begins to increase at these earliest stages of declining reproductive physiology. Sleep disturbances can be seen as early as the late reproductive years and continue into the postmenopause [11].
Fig. 6.3
Adaptation of STRAW – stages of menopause
Sleep-Related Burden and Risk Factors
Sleep disturbance can be one of the most troubling symptoms experienced by a woman during the menopause transition. Although changes in sleep are typical as one ages, the menopause transition represents a period of both an exaggerated magnitude and increased bother from sleep alterations. The prevalence for self-reported difficulty with sleeping during the early stage of the menopause transition is up to 40 % [11] and could increase to 46 % in women in the late menopause transition when frequency of menstrual cycles can be decreased to once or twice in a 12-month period [12]. Polysomnography (PSG)-based studies have demonstrated objective evidence of changes in sleep during the menopause transition, with decreased sleep efficiency in the perimenopausal, compared to premenopausal women [13]. Others however have found no significant differences in sleep patterns on PSG, nor has PSG data consistently coincided with subjective sleep disturbance in perimenopausal women [14].
Sleep difficulty during perimenopause can contribute significantly to poor quality of life and is often associated with fatigue, depressive symptoms, and anxiety, just as is demonstrated in both case examples [15, 16]. Women who report more sleep difficulties tend to have higher perceived stress and a lower perceived overall health status. The hormone cortisol is involved in regulating the stress response and may also play a role in maintaining the circadian rhythm, as it typically rises throughout the night, peaking in the morning hours [17]. Lower morning cortisol levels are reported in the setting of poor nocturnal sleep, suggesting a possible dysregulation in this hormone’s circadian rhythm [3]. Many middle-aged women lead busy, demanding lifestyles, and poor quality of nocturnal sleep can lead to poorer functioning, just as noticed by Ms. A in Case 1. One study of perimenopausal women comparing women with insomnia to those without trouble falling asleep identified significantly more emergency department visits, greater activity impairment, and more occupational impairment (for those who were working) in the insomniac group [18]. Women with poor sleep report more fatigue and musculoskeletal discomfort seen with Ms. B in Case 2 [19]. There may even be a subset of women who experience insomnia, but actually exhibit normal sleep efficiencies on PSG; this subset is more likely to report greater psychological distress compared to those with objective PSG abnormalities [20].
Sleep disturbances are deemed as contributory to clinical depression and to depressed mood during and after the menopause transition [21]. Chronic sleep deprivation can alter the mood state; alternatively, sleep disturbance could be a symptom of depression instead (as discussed later). The relationship between depression, sleep, and vasomotor symptoms in actuality can be quite complex, as each may exacerbate the other. In one study, depressed women with vasomotor symptoms spent less time in bed and had shorter total sleep time, longer sleep-onset latency, and lower sleep efficiency compared with nondepressed women with vasomotor symptoms [22]. Reverse causality is also recognized as when depression is present, it can have an additive effect on sleep disturbance occurring with the menopause transition.
Although perimenopausal women may experience difficulty initiating sleep, frequent nighttime awakening, and early morning awakening, the nighttime awakening might be the most specific type of sleep issue common to the menopause transition [23]. Nighttime awakening, present in both cases described above, is most often associated with the late menopause transition or early postmenopause stage, presence of hot flashes, depressed mood, anxiety, and joint pain [3, 23]. Early morning awakening can also be common and tends to increase with age, even following the menopause transition [3]. PSG testing has also linked sleep symptoms with hot flashes, with lower sleep efficiencies and longer REM latency [19, 20, 24]. Nighttime vasomotor symptoms may also more directly lead to nighttime awakenings and poor sleep. Alternatively, women with more vasomotor symptoms are more likely to be depressed, which could lead to the sleep changes. Even if associated with vasomotor symptoms, it is not necessarily the case that the hot flash causes awakening, as one interesting study showed the arousal from sleep actually preceded a hot flash more often when the two were associated [25, 26]. Instead, a more generalized state of hyperarousal could lead to both. This may be the case for Ms. A, who is experiencing this complex symptom triad, as she has multiple sleep complaints. It is important to consider how the relationship between these symptoms could be different for each individual.
Reproductive Hormones and Sleep
Changes in reproductive hormones during the menopause transition such as the decreases in estrogen, progesterone, and testosterone could contribute to sleep disturbances [27]. Younger women experiencing an unnatural menopause, following oophorectomy or premature ovarian failure due to chemotherapy, can have abrupt, drastic decreases in ovarian hormones and tend to have high risk for insomnia [28]. The association seen between vasomotor symptoms and reported sleep disturbance in perimenopausal women has been demonstrated repeatedly [3, 26, 29], and this relationship could certainly be explained by a shared causal factor such as estrogen withdrawal. Rapidly rising serum follicle-stimulating hormone (FSH), possibly indicating a rapid shift in hormone levels and transition through menopause, has been associated with more slow-wave sleep and longer sleep duration, but poor overall sleep quality [27]. In studies of perimenopausal women, lower serum estradiol levels have been associated with poor subjective sleep quality [27], and lower testosterone levels have been associated with difficulties with initiating and maintaining sleep [3]. It has also been proposed that decreases in progesterone, which is considered a respiratory stimulant, may be an important factor for risk of sleep-disordered breathing in menopause [30].
Other Sequelae to Disturbed Sleep
Insomnia can have many serious health consequences, including an increased risk for obesity [31], cardiovascular disease [32, 33], and all-cause mortality [34, 35]. Studies of individuals undergoing sleep deprivation have demonstrated an increase in levels of inflammatory markers that could play a role in the risk for various types of disease [36]. In a longitudinal cohort of younger adults, each additional hour of sleep at baseline was negatively associated with change in body mass index over the follow-up period of 10 years [31]. Possibly changes in insulin sensitivity or levels of hormones important for appetite and weight, such as leptin or ghrelin, occur with fewer hours of sleep. Interestingly, in a large population of older adults followed for 14 years, higher mortality was associated with both too few and too many hours of sleep, with least risk at 7 h per night of sleep [32]. Risk for death due to cardiovascular disease significantly associated with fewer hours of sleep only in the women in this study. Clearly adequate sleep is tremendously important for maintenance of vital functions, and sleep disturbances in menopause leading to consistently fewer hours of sleep per night would be expected to pose similar risks.
Differential Diagnoses
Before assuming that a sleep disorder is due to menopause, other medical conditions that contribute to disturbed sleep should be considered. See Table 6.1.
Table 6.1
Common disorders in menopausal women causing sleep disturbance
Disorders | Sleep symptoms |
|---|---|
Medical disorders | |
Obstructive sleep apnea | Nighttime awakening due to interrupted breathing, snoring |
Restless legs syndrome | Sensation of needing to move legs at bedtime, during sleep |
Periodic limb movement disorder Urinary disturbances | Involuntary movement of limbs during sleep causing awakening Urinary frequency interfering with falling asleep, staying asleep; episodes of incontinence causing awakening |
Psychiatric disorders | |
Major depressive disorder Bipolar disorder | Difficulty falling asleep, nighttime awakenings, and often early morning awakening Decrease in need for sleep when manic; sleep symptoms seen in depressive episodes similar to above |
Generalized anxiety disorder | Difficulty with falling asleep initially or after nighttime awakening due to anxiety |
Panic disorder | Panic attacks occur during night, causing awakening |
Post-traumatic stress disorder | Hyperarousal may cause difficulty falling asleep, nightmares |
Obstructive sleep apnea (OSA)
defined as an apnea hypopnea index of 5, indicating at least five complete or partial obstructions of the airway per hour, usually resulting in an awakening is quite common among menopause-aged women. OSA often involves symptoms of loud snoring, daytime sleepiness, shortness of breath, witnessed apnea episodes, dry mouth, and morning headaches. Of early postmenopausal women showing 68 % experienced decreased sleep efficiency, 50 % had apnea, 7.8 % had periodic leg movements, and 2.6 % had bruxism (involuntary gnashing and grinding of the teeth during sleep) on PSG [37]. These postmenopausal women had 3.5 times the risk of OSA compared to premenopausal women. Even among patients with similar sleep-related complaints, postmenopausal women have been found using PSG to have significantly more sleep-disordered breathing than premenopausal women [38]. Other risk factors for OSA include obesity, wider neck circumference, narrow airway, and cigarette smoking. Therefore, a clinician assessing Ms. B in Case 2 should strongly consider a diagnosis of OSA and order a sleep study given her obesity, nighttime awakenings, and daytime fatigue.
Restless legs syndrome (RLS)
can also lead to sleep disruption in older women [39]. The disorder is thought to be caused by dysregulation in iron metabolism and dopaminergic function [40]. However, diabetes mellitus, obesity, thyroid disease, certain medications, and sleep deprivation can contribute to symptoms of RLS [40]. RLS involves uncomfortable sensations in the legs, especially when sitting or lying down, accompanied by an irresistible urge to move the affected limb. These symptoms, which occur more often at night, can interfere with sleep. Being twice as common in women than men, prevalence of RLS increases with age and parity, during pregnancy, and in the presence of vasomotor symptoms during menopause [39, 41]. Hormone therapy does not seem to change risk for the development of RLS, however [41].
Periodic limb movement disorder (PLMD)
is another movement disorder, with jerking movements and cramping of limbs throughout the night leading to disruptive sleep. Movements of arms and legs are involuntary in contrast to RLS which involves the sensation of needing to move legs, with voluntary movement. The prevalence of PLMD is more common in women than men and more common during pregnancy. Risk also increases with age, but its prevalence during the menopause transition, and hormone therapy’s effect on its symptoms, is not clear [42]. PLMD is often secondary to multiple other disorders and factors common in this population, including OSA, diabetes, anemia, and antidepressant use. If PLMD is suspected, a thorough medical investigation is needed. The presence of both RLS and PLMD should both be considered in the case of Ms. B even though she does not identify these issues, as her diagnosis of diabetes mellitus and her obesity and possible OSA increases her risk.
Urinary disturbances
can often lead to sleep disruption. This issue has been thought to be a more common problem in the postmenopause due to the effects of the loss of estrogen on the urethral tissue, with increasing episodes of urinary incontinence. A recent study demonstrated, however, that women in the late reproductive stage and early perimenopause had problematic urinary symptoms, with 72 % reporting nocturia at least once per night and 50 % experiencing urinary incontinence at least once per week [43]. There are various types of incontinence, including stress incontinence, urge incontinence, overactive bladder, and overflow incontinence, so as each type could involve nighttime symptoms, causing awakening; the presence of urinary symptoms and effects on sleep should be considered. Either Ms. A or Ms. B could be struggling with these symptoms, but may not link them with their sleep disturbance. As many women also find bladder issues embarrassing to discuss [44], the clinician may have to ask specific questions about toileting behavior to determine whether the presence of lower urinary tract symptoms is contributing to disrupted sleep.
Psychiatric Well-Being and Sleep
Although it is possible that insomnia can contribute to depression as previously discussed, disrupted sleep is a very common symptom of depression and other psychiatric disorders. Major depressive disorder (MDD), generalized anxiety disorder (GAD), post–traumatic stress disorder (PTSD), and panic disorder are 2–3 times more common among women than men and should be considered in the differential when women present with difficulty sleeping and daytime fatigue [45]. MDD involves symptoms of low mood, loss of interest in activities, lower energy, changing appetite, possibly suicidal ideation, and changes in sleep, often with insomnia [6]. After puberty and prior to the onset of menopause, women are twice as likely to be affected by depression as men, but this sex difference decreases once women reach the postmenopausal years [46]. In contrast, the perimenopause represents a time of increased vulnerability for depression for women during the process of aging. Perimenopausal women are 3–5 times at greater risk for the development of a major depressive episode during perimenopause compared to premenopause [8, 47].
Bipolar disorder involves the cycling between episodes of depression and episodes of mania, when patients experience a decreased in sleep, heightened energy, irritability, expansive mood, and delusions or engage in risk-taking behaviors [6]. Less is known regarding the risk for bipolar disorder in older female populations, but in younger populations, women with bipolar disorder have more risk for depressive and mixed episodes than men [47–49]. Retrospective studies of women with bipolar disorder during the menopause transition show that half of women with bipolar disorder report intense mood symptoms during the menopause transition, and depression occurs more often than mania [50, 51]. It is unclear whether hormone therapy is protective for these women.
The anxiety disorders that are most likely to affect sleep in older women are GAD, with excessive worry, muscle tension, fatigue, irritability, and insomnia, and panic disorder, with panic attacks, accompanied by fear of having panic attacks [6]. PTSD occurs less frequently, with anxiety symptoms following a traumatic event [6]. The incidence of anxiety disorders peaks in the fourth decade, but, as seen with depression, may increase in frequency during the midlife for women [45]. The majority of studies demonstrate an increase in anxiety symptoms during the menopause transition, especially in women with pre-existing anxiety [52, 53]. Risk for anxiety was elevated during perimenopause even for women with low levels of anxiety at baseline as well.
Sleep symptoms may vary with each psychiatric disorder. Early morning awakening is often experienced by depressed patients, although middle of night awakenings and difficulty initiating sleep can also occur [6]. Bipolar disorder is associated with a decreased need for sleep for periods of time, but the individual usually presents with other symptoms of mania, as described above [6], making it less likely that a clinician would misdiagnose bipolar disorder for a primary sleep disturbance. Patients with GAD often complain of their anxiety interfering with their ability to relax when attempting to fall asleep initially or during the night if they do wake [6]. Panic attacks involve intense fear, often with shortness of breath and rapid heartbeat, and can occur during the night waking a woman out of her sleep and are a common symptom among menopausal women [54]. Vasomotor symptoms have also been consistently associated with increased risk of anxiety during the menopause transition, and some women will even note a surge of panic-like anxiety immediately prior to onset of a hot flash [55, 56]. A core symptom of PTSD is hyperarousal, which frequently presents with difficulty sleeping with or without nightmares [6]. Determining whether the individual has experienced an event that was associated with intense fear, helplessness, or horror can help the clinician rule out the presence of PTSD.
Psychiatric disorders are also often comorbid with medical conditions such as the metabolic syndrome or obesity [6], which are known risk factors for OSA. Psychiatric treatments, such as antidepressants, can also contribute to symptoms of RLS and PLMD. Little is known regarding substance use disorders in menopausal women. However, the use of substances, even when a primary substance use disorder is not present, can also affect sleep, with caffeine intake impairing the ability to fall asleep, particularly if used later in the day, and alcohol use often leads to interrupted sleep or early morning awakening [57]. Misuse of sleep aids and alcohol should be considered in an individual with long-standing sleep disturbance as they may have been trying to self-medicate.
With respect to the cases presented, a psychiatric disorder should be carefully considered as a primary factor leading to sleep disruption for Ms. A in Case 1 with her complaints of depressed mood and anxiety.
Assessment
A full evaluation for sleep disturbances among reproductively aging (transitioning and menopausal) women should include a detailed history regarding sleep changes and physical examination. Specifically, the interview should involve assessing comorbid medical and psychiatric symptoms and conditions, social history, as well as spectrum of menopausal symptoms. A psychiatric disorder is not likely to present with sleep disturbance alone, although substance misuse is still quite possible. A history of caffeine and alcohol intake and use of over-the-counter sleep aids is critical. See Table 6.2 for suggestions for assessment tools.
Table 6.2
Assessment for sleep disturbance
Type of study | ||
|---|---|---|
Self-assessment tools | ||
Center for Epidemiologic Studies Depression (CESD) | Assesses risk for major depressive disorder | 10-item scale; does not assess suicidality |
Spielberger State-Trait Anxiety Scale | Assesses risk for anxiety disorders | 20-item; distinguishes anxiety from depression, but not specific anxiety disorders |
The Insomnia Severity Index (ISI) | Assesses severity of sleep impairment, effects on functioning, quality of life | 7-item; does not assess type of sleep disturbance |
Pittsburgh Sleep Quality Index | Assesses type of sleep disturbance as well as effects on quality of life | 19-item; more comprehensive |
Epworth Sleepiness Scale | Assesses level of sleepiness and risk for OSA | 8-item; excessive sleepiness may be due to other sleep disorders as well |
Objective sleep measures | ||
Sleep study | Assesses for sleep disorders such as OSA, RLS, PLMD | Utilizes electroencephalography (EEG), electromyography, and electrooculography |
Wrist actigraphy | Assesses for sleep interruptions, movements during sleep | Measures sleep duration and movement during sleep |
Self-report questionnaires can be used in the clinical setting to assess for depression and anxiety as well as nature and severity of sleep disruption. For depression, the Center for Epidemiologic Studies Depression [58] is a straightforward scale to complete; notably, this does not include a question regarding suicidal ideation, which may be a concern in a nonpsychiatric clinical setting. Anxiety rating scale such as the Spielberger State-Trait Anxiety Scale [59] is also self-administered and has clear cutoffs for mild, moderate, and severe anxiety. The Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, or Epworth Sleepiness Scale can be useful for diagnosis and determination of severity of disturbed sleep [60].
When a sleep-related disorder such as OSA, RLS, and PLMD is suspected, a sleep study will be meaningful to establish diagnosis to inform definitive treatment. A sleep study, comprised of PSG, with nighttime electroencephalography (EEG), electromyography, and electrooculography to detect brain wave, movement, and eye rhythm changes during sleep cycles, can detect breathing disturbances and periodic limb movements as seen in Fig. 6.4. Wrist actigraphy, using a portable watch-like device, can also provide objective measurements of nighttime sleep patterns and movements [61]. While we may only require a basic history from Ms. A prior to initiating treatment as we suspect a primary psychiatric disorder, a sleep study will be important for Ms. B to rule out diagnoses such as OSA, RLS, and PLMD, in order to choose the most appropriate treatment options.
Fig. 6.4
A sample sleep study
Disordered Sleep: Treatment
Non-pharmacological Treatments
Behavioral conditioning and maladaptive thinking patterns can exacerbate symptoms of insomnia. Increasing distress about poor sleep can lead to dysfunctional efforts to induce sleep and can cause conditioned arousal during bedtime [62]. Cognitive behavioral therapy for insomnia (CBT-I) is a form of psychotherapy which involves changing maladaptive thinking and behaviors that are contributing to insomnia, has been shown to be highly effective in various populations, and would be an appropriate choice for menopausal women experiencing sleep problems [62].
One component of CBT-I that may be effective on its own is the education piece about appropriate habits that can improve sleep, referred to as sleep hygiene. Sleep hygiene targets modifiable factors affecting sleep, such as factors regarding the chosen sleep environment, sleep schedule chosen, and avoidance of activating behaviors and substances near to bedtime. Recommendations for sleep hygiene, particularly for the perimenopausal woman, include: wearing lighter pajamas to bed and keeping a second pair of nightwear at hand, using lighter bedding and layering, keeping the ambient room temperature cool and keeping a fan nearby and a cool beverage near the bed, avoiding television and computer work in bed, attempting to have similar times for bedtime and morning wake-ups, limiting caffeine products throughout the day, avoiding alcohol and smoking, and avoiding exercise within 4 h of bedtime [63]. A regular bedtime that is not disrupted by environmental distractors, such as outdoor noises or a snoring partner, is critical to good sleep. In the case of disruption due to intermittent environmental noises, a constant sound machine or earplugs may offer some benefit [63].
A protocol of CBT for the treatment of climacteric symptoms (CBT-C) has also been developed [64, 65] and can be tailored more specifically to address sleep disturbances for the woman with moderate to severe vasomotor symptoms. CBT-C involves more focus on physical changes occurring with menopause and cognitive and behavioral strategies to challenge maladaptive thinking patterns regarding these changes – relaxation, exercise, and monitoring of vasomotor symptoms are key components of CBT-C. So far, research has demonstrated positive results of as few as ten sessions of weekly group CBT-C on reported sleep quality in peri- and postmenopausal women, in addition to benefits for mood, anxiety, and quality of life [64, 65]. Individual or group formats of CBT can be utilized.
Mindfulness-based stress reduction (MBSR), also often used in treatment of depression and anxiety, has been identified as an applicable treatment for vasomotor symptoms and insomnia in the peri- and postmenopause as well [66].
Options such as yoga, therapeutic massage, acupuncture, and acupressure have also shown benefits for treating insomnia during the menopause transition in small studies and can be considered given the low side-effect profile of these treatments [67–70]. Regular exercise has been shown to improve insomnia [71], but evidence in menopausal women is limited, showing small, but nonsignificant improvements in sleep with exercise [72]. More information regarding alternative treatments for menopausal symptoms in another chapter of this textbook is dedicated to this topic.
The option of CBT or MBSR would be helpful adjuncts to either in Cases 1 and 2, for both Ms. A and Ms. B, but is limited by availability of trained providers and the motivation of the patient, as both require individual or group sessions as well as daily homework practice. As long as there is no contraindication to regular exercise, massage, or acupressure/acupuncture, these alternatives are reasonable adjunctive interventions for most women including Ms. A and Ms. B.
Pharmacological Options
Menopausal Hormone Therapy (MHT) and Sleep
MHT remains the gold standard for vasomotor symptoms among the symptomatic peri- and early postmenopausal women. The North American Menopause Society (NAMS) supports the initiation of MHT around the time of menopause to treat menopause-related symptoms when the balance of potential benefits and risks is favorable for the individual woman [73]. While hysterectomized women can use unopposed estrogen therapy (ET), MHT regimen in non-hysterectomized women must in addition include a progestin or progesterone (EPT) to thwart endometrial hyperplasia and diminish the risk of uterine cancer [74]. MHT-prescribing practices vary from practitioner to practitioner and must be individualized, and a full review of these regimens is beyond the scope of this discussion, but is covered elsewhere in this textbook. If insomnia is a dominating complaint in a woman deemed to be in perimenopause, or in early menopause and poor sleep is due, at least in part, to night sweats, MHT is likely to improve consistency of sleep.
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