Managing sleep disturbance during the menopause transition.

The climacteric is the phase in the aging of women characterized by transition from the reproductive phase to the nonreproductive state. A woman is considered postmenopausal when she is over the age of 45 and has gone at least 12 months without a spontaneous menstrual period. The climacteric is sometimes, but not indispensable, associated with symptomatology. Symptoms associated with climacteric, such as hot flushes, night sweats, fatigue, headache, dizziness, numb, sore limbs, decreased attention, anxiousness and nervousness, insomnia, mood swings, and sorrow depression, are called “climacteric syndrome.” Women during menopausal transition are particularly vulnerable to mood disturbances and depression. This period is regarded as the important risk of these disorders. Depressive symptoms present increasing tendency during menopausal transition and decreasing tendency after menopause. Mood changes during menopausal transition have detrimental effects on these women’s quality of life. Decline of cognitive function during menopausal transition and menopause is referred to aging and to direct and indirect effects of hormonal changes on the brain. Direct effects concern direct influences of hormonal changes on the regions of neuronal system responsible for cognitive function control. Indirect effects are related to hormonal change influences on the brain which have impact on other symptoms like sleep, mood changes, and vasomotor symptoms. Vasomotor symptoms (VMS), which include hot flushes and night sweats, affect 70% of postmenopausal women <55 years of age. VMS often severely impact physical, sexual, and psychosocial life and overall well-being. Symptoms usually last from 6 to 10 years (median 7.4 years), and most women report that VMS are the most bothersome of all postmenopausal symptoms. Sleep disturbances are very meaningly affected by other menopausal symptoms such as hot flushes. Sleep disturbances may occur in the form of insomnia, sleep-disordered breathing, restless legs syndrome (RLS), mood and anxiety disorders, and other medical diseases associated with vasomotor symptoms and aging.KeywordsClimacteric syndromeVasomotor symptomsSTRAWMenopauseHot flushesNight sweats

The climacteric is the phase in the aging of women characterized by transition from the reproductive phase to the nonreproductive state. A woman is considered postmenopausal when she is over the age of 45 and has gone at least 12 months without a spontaneous menstrual period. The climacteric is sometimes, but not indispensable, associated with symptomatology. Symptoms associated with climacteric, such as hot flushes, night sweats, fatigue, headache, dizziness, numb, sore limbs, decreased attention, anxiousness and nervousness, insomnia, mood swings, and sorrow depression, are called “climacteric syndrome.” Women during menopausal transition are particularly vulnerable to mood disturbances and depression. This period is regarded as the important risk of these disorders. Depressive symptoms present increasing tendency during menopausal transition and decreasing tendency after menopause. Mood changes during menopausal transition have detrimental effects on these women’s quality of life. Decline of cognitive function during menopausal transition and menopause is referred to aging and to direct and indirect effects of hormonal changes on the brain. Direct effects concern direct influences of hormonal changes on the regions of neuronal system responsible for cognitive function control. Indirect effects are related to hormonal change influences on the brain which have impact on other symptoms like sleep, mood changes, and vasomotor symptoms. Vasomotor symptoms (VMS), which include hot flushes and night sweats, affect 70% of postmenopausal women <55 years of age. VMS often severely impact physical, sexual, and psychosocial life and overall well-being. Symptoms usually last from 6 to 10 years (median 7.4 years), and most women report that VMS are the most bothersome of all postmenopausal symptoms. Sleep disturbances are very meaningly affected by other menopausal symptoms such as hot flushes. Sleep disturbances may occur in the form of insomnia, sleep-disordered breathing, restless legs syndrome (RLS), mood and anxiety disorders, and other medical diseases associated with vasomotor symptoms and aging.KeywordsClimacteric syndromeVasomotor symptomsSTRAWMenopauseHot flushesNight sweats

This chapter presents the factors relevant to assessing sleep problems in the menopausal transition that have changed over time. Expectations regarding menopause have changed over time, particularly since the advent of hormone replacement therapy. Increasing interest in reproductive aging and the advent of women's health as a specialty has led to a great deal of research on the menopausal transition. It is possible that there has been an increase in sleep disturbances in women across all menopausal status categories, but that the rank order of increasing prevalence of sleep problems among pre-, peri-, and post-menopausal women prevails. Preliminary analyses from the "Sleep in Midlife Woman" sub study, with biannual in-home polysomnography, continue to support the hypothesis that the risk of sleep apnea increases with advancement through the menopausal transition. There are important clinical implications from current thinking on sleep in the menopausal transition.

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This narrative review examines the complex relationship between sleep changes during the menopausal transition and cardiometabolic risks. The most common complaint about sleep is increased awakenings during sleep. Other complaints include having trouble falling asleep, waking up too early, insufficient and non-restorative sleep, and overall poor quality. Sleep determined using objective methods also indicates that greater awakenings after sleep onset are associated with the period of menopausal transition. Polysomnography recordings suggest physiological hyperarousal during sleep. Changes in other sleep metrics, such as sleep latency and sleep duration, are less consistent, and some studies suggest they may not worsen during the menopausal transition. These sleep issues are influenced by multiple factors, such as hormonal fluctuations, vasomotor symptoms, and psychosocial factors, and evidence suggests that hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurons are key underlying mechanisms for these associations. The menopausal transition is also associated with increases in cardiometabolic risk factors, such as body fat, altered lipid profiles, blood pressure, and vascular health. Emerging evidence suggests that poor sleep health during this period is associated with increased cardiometabolic risks and adverse cardiovascular outcomes. Thus, addressing sleep disturbances is crucial for comprehensive healthcare during the menopausal transition to safeguard long-term cardiometabolic health. Future research is needed to investigate interventions that can improve sleep and their impact on cardiometabolic health in this population experiencing increases in cardiometabolic risk.

A long-standing, but unproven hypothesis is that menopause symptoms cause cognitive difficulties during the menopause transition. This 6-year longitudinal cohort study of 1,903 midlife US women (2000-2006) asked whether symptoms negatively affect cognitive performance during the menopause transition and whether they are responsible for the negative effect of perimenopause on cognitive processing speed. Major exposures were depressive, anxiety, sleep disturbance, and vasomotor symptoms and menopause transition stages. Outcomes were longitudinal performance in 3 domains: processing speed (Symbol Digit Modalities Test (SDMT)), verbal memory (East Boston Memory Test), and working memory (Digit Span Backward). Adjustment for demographics showed that women with concurrent depressive symptoms scored 1 point lower on the SDMT (P < 0.05). On the East Boston Memory Test, the rate of learning among women with anxiety symptoms tested previously was 0.09 smaller per occasion (P = 0.03), 53% of the mean learning rate. The SDMT learning rate was 1.00 point smaller during late perimenopause than during premenopause (P = 0.04); further adjustment for symptoms did not attenuate this negative effect. Depressive and anxiety symptoms had a small, negative effect on processing speed. The authors found that depressive, anxiety, sleep disturbance, and vasomotor symptoms did not account for the transient decrement in SDMT learning observed during late perimenopause.

Sleep disturbance is common during the menopausal transition, with numerous downstream consequences to health and functioning, including reduced quality of life, impaired mental health, and increased physical health morbidity. Insomnia affects approximately 50% of midlife women and is characterized by nocturnal symptoms of difficulties initiating or maintaining sleep (or both) and daytime symptoms that impair occupational, social, or other components of functioning. In addition, approximately 20% of midlife women develop sleep-disordered breathing during the menopausal transition. This commentary summarizes the prevalence, risk factors, and treatment options for each of these sleep disorders in midlife women, with specific focus on first-line treatments for insomnia (cognitive behavioral therapy for insomnia) and sleep-disordered breathing (continuous positive airway pressure) and unique considerations for treating sleep disorders in midlife women. Future directions are also discussed.

The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression. Women with depressive disorders, hot flashes, and sleep disturbance were randomly assigned to transdermal 17β-estradiol 0.05 mg/d, zolpidem 10 mg/d, or placebo for 8 wk. Changes in serum estradiol, perceived sleep quality, objectively measured sleep, and hot flashes were examined as predictors of depression improvement [Montgomery-Åsberg Depression Rating Scale (MADRS)] using multivariate linear regression. Seventy-two peri/postmenopausal women with depression disorders were randomized to 17β-estradiol (n = 27), zolpidem (n = 31), or placebo (n = 14). There was no significant difference between groups in depression improvement (overall MADRS decrease 11.8 ± 8.6). Increasing estradiol (P = 0.009) and improved sleep quality (P < 0.001) predicted improved mood in adjusted models but reduced hot flashes (P = 0.99) did not. Post hoc subgroup analyses revealed that the therapeutic effect of increasing estradiol levels on mood was seen in perimenopausal (P = 0.009), but not postmenopausal, women. For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression.

In the prospective long-term Zurich study, we re-examined the hypothesized association between mental health problems in women and the transition through menopausal stages. One hundred sixty-eight women from a population-based Swiss community cohort were prospectively followed up from age 21 to 50. At age 50, the occurrence of hot flushes/night sweats and sleep disturbances was significantly more frequent in peri- and post-menopausal women. Irritability/nervousness was increased only in peri-menopausal women, but that association was accounted for by neuroticism trait scores at age 30. Transitions to peri- or post-menopause were not related to changes in either the prevalence rates of DSM major depressive episode or anxiety disorders, or the course of psychopathological syndromes as assessed by the Symptom Checklist 90 - Revised. The null associations held when adjusting for duration of reproductive period or age at menopause. Preceding mental health problems between ages 21 and 41, increased neuroticism trait scores at age 30, and concurrent psychosocial distress were significantly related to mental health problems occurring between ages 41 and 50. Depending upon the cut-off point that was chosen, the arbitrary dichotomization of a continuous depression outcome produced spurious associations with the menopausal transition. We conclude that mental health problems between ages 41 and 50 are probably not directly related to the menopausal transition, and that previously reported associations could be false positives due to inadequate dichotomizations, reporting bias, undisclosed multiple adjustments or overfitting.

Depressive disorders and the menopause transition

Objective: The study was designed to determine the prevalence of menopausal symptoms during menopausal transition in middle age (30-60 years) women in Vadodara (N=1000). Method: They were interviewed by means of standard Menopause Rating Scale questionnaire (MRS) to report on the menopausal symptoms which were divided into somatic, psychological and urog. A predesigned questionnaire was used to assess their knowledge associated with menopause along with self-reported health profile. Results: The mean age of the study population was 42 + 5.1; where mean age of premenopausal group was 40.07 + 3.79, peri menopausal group was 41.72 + 4.28 and post-menopausal group was 46.4 + 5.32. The women reported pain in hands or legs as the most prevalent symptom (73.6%), followed by anxiety (67.4%), physical and mental exhaustion (66.8%). Other symptoms like dryness of vagina (48.5%), heart discomfort (45%), mood swings (35.5%) and irritability (32.8%) were reported by nearly half of the population. Severity of symptoms were observed for anxiety (2.7%), heart discomfort (2.3%), sleep disturbances (2.3%), bladder problems (2.1%). The mean total MRS was found to be rising up during transition from premenopause (4.60 + 3.07) to perimenopause (6.53 + 3.93) and showed a decline during transition from perimenopause to postmenopause (5.78 + 3.03). Amongst the three subscales of MRS, the mean of the Psychological domain (2.59 + 1.91) was higher followed by somatic symptoms (2.03 + 1.54) and least by the urogenital symptoms (0.92 + 0.99). A similar trend was observed during all stages of reproductive life, i.e. premenopausal, perimenopausal or postmenopausal (p

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