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Climacteric Symptoms and Sleep Quality

From the Departments of Obstetrics and Gynecology and Clinical Chemistry, Turku University Central Hospital; the Departments of Physiology and Biostatistics, University of Turku, Turku; and the Department of Pulmonary Medicine, University of Tampere, Tampere, Finland.

Address reprint requests to: Päivi Polo-Kantola, MD Department of Obstetrics and Gynecology Turku University Central Hospital FIN-20520 Turku Finland E-mail: paivi.polo-kantola{at}tyks.fi

	Abstract

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Objective: To evaluate the effect of climacteric vasomotor symptoms on sleep quality measured by self-report and polysomnography in postmenopausal women.

Methods: Seventy-one healthy postmenopausal women were recruited, of whom 63 completed the study. Each subject recorded climacteric symptoms and subjective sleep quality for 14 days. Sleep quality was evaluated objectively by all-night polysomnography using the static charge–sensitive bed.

Results: During polysomnography, a high frequency of climacteric vasomotor symptoms was not associated with changes in sleep latency, percentage of sleep stages, number of arousals, sleep efficiency, or total sleep time. However, a high frequency of climacteric vasomotor symptoms (range 0–8.9, r = .60, P < .001), somatic symptoms (range 0–5.0, r = .25–.44, P < .05), and mental symptoms (range 0–5.0, r = .41–.51, P < .001) was related to impaired subjective sleep quality. In stepwise regression analysis, 32% of the impairment in subjective sleep quality was explained by vasomotor symptoms (P < .001), 14% by palpitations (P < .001), and 4% by mood instability (P = .029). High body mass index predicted impaired objective sleep quality, such as prolonged latencies to stage-2 sleep (r = .27, P = .031) and slow-wave sleep (r = .51, P = .003) and decreased oxygen saturations (r = -.54, P < .001). Older women had decreased sleep efficiency (r = -.27, P = .030) and lower oxygen saturations (r = -.36, P = .004). Serum estradiol level had only a minor effect on objective sleep quality.

Conclusion: Impaired subjective sleep quality associated with climacteric vasomotor symptoms did not manifest as abnormalities in polysomnographic sleep recordings. Body mass index and age appeared to have the strongest effect on objective sleep quality.

Sleep complaints, especially frequent nocturnal awakenings, increase with age.¹ Elderly women suffer more often from sleep problems and use more hypnotics than elderly men.² Somatic disorders such as chronic bronchitis, asthma, and cardiovascular symptoms affect sleep quality.³ Specific sleep disorders, including sleep apnea, cause insomnia or daytime sleepiness.⁴ Psychological factors also disturb sleep.⁵ It has been suggested that the decline of endogenous estrogen has an effect on sleep because sleep complaints increase rapidly after menopause.⁶ In addition to vasomotor symptoms, poor sleep quality is one of the most common symptoms of menopause. Climacteric vasomotor symptoms typically occur at night and interfere with sleep.⁷

We hypothesized that severe vasomotor symptoms are related to significant changes in the cortical electroencephalographic activity during sleep. However, sleep disturbances due to climacteric symptoms are poorly described in polysomnographic terms. To determine the type and the degree of specific electroencephalogram changes associated with vasomotor symptoms, we conducted all-night polysomnographic sleep studies in postmenopausal women who had a wide range of climacteric symptoms.

	Materials and Methods

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Seventy-one healthy postmenopausal women were recruited over 15 months through a newspaper announcement, and 63 women completed the study. The age range was 47–65 years (mean ± standard deviation [SD] 56.3 ± 4.4) and the minimum education was 7 years of basic school. Sixty-seven percent were married, 6% were single, and 27% were divorced or widowed. Forty-six percent were employed, 10% were unemployed, and 44% were retired. Postmenopause was defined as a serum FSH level exceeding 30 IU/L. Two women with FSH levels of 28 and 29 IU/L were accepted because of their ages (56 and 62 years). At the beginning of the study, the serum estradiol (E2) level was less than 50 pmol/L in all women except two, whose levels were 90 and 105 pmol/L, but whose serum FSH levels were postmenopausal (70 and 55 IU/L, respectively). Exclusion criteria included history of neurologic, cardiovascular, endocrinologic, or mental disease; medicated hyperlipidemia; malignancies; abuse of alcohol or medications; and heavy smoking (more than ten cigarettes per day). Latent systemic disorders possibly affecting sleep such as anemia, hypothyroidism, diabetes, and uremia were also excluded by measuring blood hemoglobin, leukocytes, sedimentation rate, serum thyrotropin, free thyroxine, vitamin B₁₂, creatinine, glucose, and cholesterol levels. All subjects were strictly advised not to use any medications that affect the central nervous system, or any antioxidants. Incipient depression was screened using the Beck Depression Inventory.⁸ A complete gynecologic examination was done. Subjects were given oral and written information about the study, and they all provided written informed consent. The study was approved by the Ethics Committee of Turku University and Turku University Central Hospital.

Polysomnographic sleep recording included continuous monitoring of electroencephalogram, electrooculogram, electromyogram, and electrocardiogram. A finger pulse oximeter (Biox Ohmeda 3700e; BOC Company, Louisville, CO) was used to monitor arterial oxyhemoglobin saturation. A static charge–sensitive bed (BioMatt; Biorec Oy, Helsinki, Finland)⁹ was used to record body movements, breathing patterns, and heart rates. Original analog signals were amplified and digitized at a frequency of 250 samples per second with 12-bit amplitude resolution and were recorded with custom software (UniPlot, Unesta Oy, Turku, Finland). Conventional criteria¹⁰ were used for sleep staging, which included stage-1, stage-2, slow-wave (including stage-3 and stage-4), and rapid eye movement sleep. Staging was carried out by the same scorer in all subjects. The scorer was masked to the presence of climacteric symptoms.

Episodes of alpha arousals and body movements during sleep also were analyzed. Their frequencies were expressed as the number of episodes per hour of sleep. For all arousals, electroencephalogram alpha activity of at least 2 seconds was required. Arousal movement events were further classified with the static charge–sensitive bed as movement arousals (arousals with body movement) and electroencephalogram arousals (arousals without body movement). High-amplitude signals in the static charge–sensitive bed without simultaneous electroencephalogram alpha activity were considered body movements.

This study was part of a larger survey evaluating the effect of estrogen replacement therapy (ERT) on sleep.¹¹ In the original study design, randomization into two treatment groups was made in six-person blocks using random permuted blocks. Thirty-two women first received the placebo for 3 months and then, after 1 month washout with the placebo, estrogen for 3 months (group A). The remaining 31 women were treated in the reverse order (group B). Sleep studies were done twice in each subject at 4-month intervals, after placebo and after estrogen treatment. Data for the present report were collected using the placebo nights only. A statistically significant carryover effect was observed for three variables: latency to slow-wave sleep, percentage of stage-1 sleep, and electroencephalogram arousals in non–rapid eye movement sleep. For these variables, data were included only from group A. All the data were also analyzed with the 32 women in group A.

The subjects self-reported daily climacteric symptoms for 14 days before the sleep study: vasomotor symptoms (hot flushes and sweating separately), sleep complaints (sleeping problems, insomnia), somatic symptoms (palpitations, numbness, muscular pain, dizziness, headache, fatigue), and mental symptoms (anxiety, depression, mood instability, memory problems, and lack of initiative). The intensity of the symptoms was evaluated on a six-step scale: 0 ("not at all"), 1 ("very little"), 2 ("to some extent"), 3 ("moderately"), 4 ("much"), 5 ("very much"), and 6 ("I cannot say"). To get an overall intensity score, the 14 daily scores were averaged. Some women express their vasomotor symptoms as hot flushes, whereas others feel incidental sweating. Therefore, the sum score of hot flushes and sweating on a scale from 0 to 10 was used to describe the severity of the vasomotor symptoms. For sleep complaints, somatic symptoms and mental symptoms scores ranged from 0 to 5. The few level-6 responses ("I cannot say") were excluded from the analyses.

Spearman correlation coefficient was used in the analysis of correlations. Because subjective symptoms were interdependent, stepwise regression analysis was used to study the connections among subjective sleep quality, climacteric vasomotor symptoms, and other climacteric symptoms. P < .05 was considered statistically significant. The power of our population to show the correlation r .40 was greater than 90%. Statistical calculations were done using the SAS program package (SAS Institute, Cary, NC).

	Results

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The mean (± SD) body mass index (BMI) was 26.9 ± 4.0 kg/m² (range 19.8–39.0), and the mean Beck Depression score was 4.0 ± 3.8 (range 0–15). In the morning after the sleep study, the mean serum E2 and serum FSH levels were 28.8 ± 20.5 pmol/L and 70.4 ± 22.7 IU/L, respectively. The subjects had not used ERT for at least 4 months before the sleep study. Before entering the study, 47 women (75%) had taken ERT previously, with a mean duration of 41 ± 55 months (range 1–252). The mean time off ERT was 37 ± 55 months (range 5–226). Each woman had had a hysterectomy for benign indications. Twenty-four (38%) had had oophorectomy, unilateral in nine (14%) and bilateral in 15 (24%).

The median score for climacteric vasomotor symptoms (hot flushes plus sweating; scale 0–10) was 2.6 ± 2.5 (range 0–8.9), and the median score for sleep complaints (scale 0–5) was 1.5 ± 1.1 (range 0–5.0). Women with subjectively impaired sleep experienced more climacteric vasomotor symptoms (r = .60, P < .001). They also had more climacteric somatic symptoms, such as palpitations, numbness, headache, and fatigue. More climacteric mental symptoms, such as anxiety, depression, mood instability, memory problems, or lack of initiative, were also present (Table 1). Climacteric symptoms were interdependent, so a stepwise regression analysis was performed. Thirty-two percent of the impairment in subjective sleep quality was explained by vasomotor symptoms (P < .001), 14% by palpitations (P < .001), and 4% by mood instability (P = .029). Body mass index, age, serum E2 level, or FSH level did not correlate with subjective sleep quality.

Women with higher BMI had a longer latency to stage-2 sleep (r = .27, P = .031) and to slow-wave sleep (r = .51, P = .003). High BMI was related to low mean arterial oxyhemoglobin saturation (r = -.54, P < .001) and minimum arterial oxyhemoglobin saturation (r = -.37, P = .003). Older women spent more time awake during the study night (r = .30, P = .019), and their sleep efficiency was decreased (r = -.27, P = .030). They also had more body movements in stage-1 sleep (r = .34, P = .007), lower mean arterial oxyhemoglobin saturation (r =-.36, P = .004), and lower minimum arterial oxyhemoglobin saturation values (r = -.25, P = .047). Serum E2 correlated with only one objective sleep measurement: Low estrogen concentration predicted a high frequency of movement arousals in slow-wave sleep (r = -.39, P = .002). Serum FSH concentrations did not correlate with objective sleep measurements.

The number of arousals per hour of sleep through various sleep stages is shown in Table 4. Movement arousals (movements with alpha activity) and electroencephalogram arousals (alpha activity without movements) were most common in stage-1 sleep but were extremely rare in slow-wave sleep. The frequencies of body movements (movements without alpha activity) were similar in stage-1, stage-2, and rapid eye movement sleep, but in slow-wave sleep, the frequency of body movements was low. Women with frequent vasomotor symptoms had a sleep architecture (sleep-stage distribution) similar to those with a low frequency of symptoms. The data also were analyzed with the group of 32 women who received placebo first in the original study, with substantially the same results as for the entire 63-woman group.

	Discussion

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The questionnaires indicated impaired subjective sleep quality in women with a high frequency of climacteric vasomotor symptoms. Somatic and mental climacteric symptoms were also more common in women with frequent sleep complaints. In contrast to the self-reported findings, polysomnography did not show any specific impairment of sleep architecture, sleep efficiency, or frequency of arousals induced by or related to climacteric vasomotor symptoms. The discrepancy between subjective and objective sleep quality was even more evident for climacteric mental symptoms, which impaired subjectively but improved objectively measured sleep. Serum E2 levels did not have a major effect. Age and obesity, rather than climacteric symptoms, appeared to have the strongest impact on polygraphic sleep variables.

Sleep complaints and insomnia have been connected to menopause, especially to climacteric vasomotor symptoms. This connection is supported by a reversal of sleep complaints during ERT.¹¹ Our results agree with these findings. Few studies have objectively measured sleep after menopause,^7,12–15 and most of these studies focused on the effect of ERT on sleep quality, relating climacteric vasomotor symptoms to objective sleep quality. Erlik et al⁷ reported an association between hot flushes and waking episodes. Unfortunately, we did not monitor hot flushes or skin temperature during the sleep-recording nights. It is possible that the subjective scoring of climacteric symptoms reported during the 14 days before the sleep study could not predict objective vasomotor symptoms during the laboratory night. Hot flushes and sweating do arouse women, especially from light sleep (stages 1 and 2).⁷ Most of the arousals occurred from light sleep, but factors other than vasomotor symptoms, such as BMI, seemed to explain better the variation in arousal frequency.

Regardless of climacteric vasomotor symptoms, the total sleep time and the percentages of various sleep stages were within earlier reported reference values.¹⁶ Schiff et al¹⁴ observed an increase of rapid eye movement sleep and a shortening of sleep latency with ERT, as well as an alleviation of hot flushes. However, the authors did not correlate the alleviation of hot flushes with objective sleep quality. We could not establish this kind of connection: Neither the percentage of rapid eye movement sleep nor the sleep latencies correlated with climacteric vasomotor symptoms. Despite the many sleep variables studied, no correlation was observed between subjective and objective sleep quality, supporting the earlier report that subjective and objective sleep quality are not always parallel.¹⁷ Women with vasomotor symptoms and subjective sleep complaints remind one of patients with insomnia with Sleep State Misperception, who have a normal electroencephalogram. Only a few somatic climacteric symptoms were correlated with objective sleep indices, and the observed correlations seemed sporadic rather than logically connected.

Mental symptoms are central in the postmenopausal syndrome.¹⁸ According to the Beck Depression Inventory, none of our women were considered depressive.⁸ On the climacteric symptom questionnaire, some women did report climacteric mental symptoms, including depression, anxiety, mood instability, and memory problems. Sleep disturbances also occur in depression and anxiety, independent of menopause.⁵ Therefore, it could be argued that climacteric sleep disturbances are mediated through climacteric mental symptoms, which in the present study were more common in women with impaired subjective sleep quality. In stepwise regression analysis, however, variation in climacteric vasomotor symptoms explained the variation in subjective sleep complaints better than the variation in climacteric mental symptoms. Surprisingly, polysomnography showed that women with frequent mental symptoms had better sleep quality when assessed by less light sleep (stage 1) and by more rapid eye movement sleep.

Women with higher BMI fell asleep as soon as those with low BMI, but they had difficulty entering deeper stages of sleep (stage-2 and slow-wave sleep). The prevalence of sleep-disordered breathing increases after menopause.¹⁹ High BMI predisposes to upper-airway obstruction and sleep apnea.²⁰ Nocturnal breathing disturbances were not the focus of the present study. Some women, at least the most obese ones, could have suffered from partial upper-airway obstruction and increased respiratory resistance,⁹ which could have been responsible for lighter sleep. This interpretation is supported by the lower mean and minimum arterial oxyhemoglobin saturation observed in obese women. Periodic leg movements, which were not evaluated in the present study, also could have contributed to the reduced subjective sleep quality in women with vasomotor symptoms.

Our study population was a selected group of healthy women who responded to a newspaper announcement. Previous or latent diseases were effectively ruled out to exclude factors that could have influenced the relation between climacteric symptoms and sleep. Thus, the results of the present study cannot be directly extrapolated to clinical populations, in which menopausal symptoms often coincide with other physical and mental conditions. Moreover, the average climacteric symptoms scores in our study were quite low. By including more subjects with more severe vasomotor symptoms, we may have been able to show significant correlations with the objective markers of sleep quality.

We were well aware that sleeping for the first night in a new environment (the so-called "first-night effect") increases the arousal frequency²¹ and decreases sleep quality. However, it is also questionable to use data from the second night, during which the decreased sleep quality of the first night rebounds as "better than normal" sleep quality. Accordingly, only data from the third night should be accepted. However, a recent study showed no first-night effect in the distribution of sleep stages,⁴ so we compared the first nights in all subjects. Moreover, all women were studied in identical circumstances. Because we showed previously that placebo treatment had no effect on climacteric symptoms and sleep complaints,¹¹ we believed that we could also study climacteric symptoms and sleep complaints during placebo treatment. The bias of giving estrogen to 31 women 4 months before the sleep study was effectively ruled out by calculating the carryover effect before the initial data analyses. In addition, the results of the 32 women who received placebo first (group A) did not differ from those obtained in the 63 women (groups A and B combined). All of our subjects had low serum E2 levels and could be considered estrogen deficient. Because of the marginal variation of serum E2 levels, serum E2 had little correlation with other characteristics.

Why do climacteric vasomotor symptoms, which impair subjective sleep quality, not manifest as changes in objectively measured sleep? The two possibilities are that climacteric vasomotor symptoms do not induce marked specific changes in the polysomnogram or that polysomnography is insensitive to these changes. This study provides strong evidence that subjective and objective sleep are two distinct variables. It also calls into question whether sleep complaints can be regarded as an independent climacteric symptom or only as a consequence of the high frequency of vasomotor symptoms. Climacteric vasomotor symptoms seem to act as an alarm clock, causing arousals that women recall in the morning, but that do not have a sustained effect on sleep structure beyond the actual moments of arousal.

	Footnotes

We thank Anne Kaljonen, MSc, for statistical assistance.

PII S0029-7844(99)00284-7

Received October 23, 1998. Received in revised form January 26, 1999. Accepted February 10, 1999.

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