Sex steroids and sleep: sleep disturbances in menopause.
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Aged↗
Biomedical subjects
P Polo-Kantola
Publications and source records attributed to P Polo-Kantola.
Climacteric vasomotor symptoms do not predict nocturnal breathing abnormalities in postmenopausal women.
OBJECTIVE: To study the association of climacteric vasomotor symptoms and nocturnal breathing abnormalities in a sample of healthy postmenopausal women. METHODS: Out of 71 postmenopausal women who took part in a large sleep study, 65 women were included into the present study. Sleep was monitored with polysomnography and nocturnal breathing with a static-charge sensitive bed and a pulse oximeter. Climacteric vasomotor symptoms were scored daily for 14 days and levels of oestradiol and FSH were measured in the serum. RESULTS: Altogether 21 (32.3%) women had some degree of breathing abnormalities during the study night. The occurrence of clinically significant sleep apnoea was low (1.5%) and of moderate type (OP-2). In contrast, increased respiratory resistance pattern, typical for partial upper airway obstruction, was frequent (16.9%). Seventy-eight per cent of the women had arterial oxyhaemoglobin desaturation events, but only in 4.6% of the women these events occurred more than 5 times/h of time in bed. Older women had more simple periodic breathing (P-1) and lower mean arterial oxyhaemoglobin saturation (SaO(2)). Body mass index (BMI) correlated with the apnoea frequency (OP-2) and inversely with the mean SaO(2). The severity of climacteric vasomotor symptoms or serum oestradiol concentration did not correlate with nocturnal breathing abnormalities. CONCLUSIONS: Nocturnal breathing abnormalities, especially partial upper airway obstruction, are common in postmenopausal women, but climacteric vasomotor symptoms do not predict their occurrence or severity. Increasing age and high BMI are important determinants of nocturnal breathing abnormalities.
Age Factors↗
Estrogen replacement therapy and nocturnal periodic limb movements: a randomized controlled trial.
OBJECTIVE: To evaluate the effect of estrogen replacement therapy on nocturnal periodic limb movements in a randomized, double-masked, placebo-controlled, crossover trial. METHODS: Seventy-one healthy postmenopausal women volunteered in answer to a newspaper announcement; 62 women completed the follow-up. Frequency of nocturnal body movements was measured with the static-charge-sensitive bed and all-night polysomnographic recordings. Serum estradiol (E2) and FSH concentrations were also measured at baseline and after each treatment period. The power of the study setup was 94%. RESULTS: Nearly half the women presented with episodes of periodic limb movements (30 of 62 women, or 48%, during placebo and 27, or 44%, during estrogen therapy). In 17 (27%) during placebo and 19 (31%) during estrogen therapy, frequency of periodic limb movements exceeded index level 5 per hour while subjects were in bed. Incidence or intensity of movements, movement durations, and movement intervals did not change with estrogen therapy. The arousal index was similar during the two treatments (medians = 1.7 for placebo and 1.3 for estrogen, P =.758). Variations in serum E2 concentration, age, and body mass index did not explain variations in movement activity. CONCLUSION: Estrogen replacement therapy in doses used to control climacteric symptoms does not alter the incidence or intensity of nocturnal periodic limb movements.
Administration, Cutaneous↗
Alzheimer's disease and estrogen replacement therapy--where are we now?
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Alzheimer Disease↗
Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep.
The aim of the present study was to evaluate the degree and duration of respiratory stimulation caused by medroxyprogesterone acetate (MPA), and compare the effect of MPA to that of nasal continuous positive airway pressure (nCPAP) in sleep-disordered breathing. Ten postmenopausal females with predominantly partial upper airway obstruction during sleep had an overnight sleep study at baseline, on the fourteenth day of treatment with MPA and after a 3-week washout period. Six subjects on nCPAP were also studied 3 months later. At baseline, the overnight mean+/-SD end-tidal pressure of carbon dioxide (Pet,CO2) was 5.5+/-0.4 kPa the arterial oxygen saturation (Sa,O2) 93.0+/-1.2%, Sa,O2 nadir 80.0+/-6.7%, and frequency of oxygen desaturation > or = 4% (ODI4) per hour 2.2+/-1.3. MPA decreased Pet,CO2 by 0.8 kPa (14.5%, p<0.001). After washout, the mean Pet,CO2 remained at 0.5 kPa (9.1%, p<0.001) lower than at baseline. Sa,O2 did not change. Pet,CO2 was lower on MPA than on nCPAP (4.7+/-0.2 kPa versus 5.0+/-0.3 kPa; p=0.037) but Sa,O2 was similar. Apnoea/hypopnoea index tended to be lower on CPAP than on MPA. Medroxyprogesterone acetate at a daily dose of 60 mg improves ventilation in postmenopausal females with partial upper airway obstruction during sleep without compromising sleep. The ventilatory improvement is sustained for at least 3 weeks posttreatment. Medroxyprogesterone acetate was more efficient in decreasing the partial pressure of carbon dioxide but continuous positive airway pressure was superior in decreasing respiratory efforts.
Aged↗
Analysis of inspiratory flow shapes in patients with partial upper-airway obstruction during sleep.
STUDY OBJECTIVE: To study the spectrum of inspiratory flow signal shapes in patients with partial upper airway obstruction during sleep. DESIGN: We identified seven different inspiratory flow shapes and determined their frequencies in two groups of patients (10 postmenopausal women and 19 men after surgical treatment for sleep apnea) and in 9 control subjects. SETTING: Sleep research unit, Department of Physiology, University of Turku, Finland. MEASUREMENTS AND RESULTS: Nasal flow was recorded with nasal prongs. The shape analyses were performed with an automated attribute grammar recognizer. The inspiratory flow-shape distributions differed significantly between patients and control subjects. The flow shapes were also different between postmenopausal women and men after uvulopalatopharyngoplasty. CONCLUSIONS: The differences in the inspiratory flow-shape distributions between the control subjects and the two patient groups suggest that the upper airways behave differently in the three study groups. Automated inspiratory flow-shape analysis seems to be a promising tool to distinguish patient groups with different upper airway function to be treated with different treatment alternatives. The physiologic correlates of each flow-shape class remain to be elucidated.
Adult↗
Aetiology and treatment of sleep disturbances during perimenopause and postmenopause.
The sudden and predictable cessation of ovarian endocrinological function at menopause results in a marked decrease of endogenous estrogen and progestogen secretion. In addition to cessation of menstruation, a wide range of biological functions, including sleep, are affected. Sleep disturbances are more common in women than in men and their incidence increases with age. There are 2 distinct mechanisms by which menopause is known to affect sleep quality. One is menopausal insomnia, which can be considered as part of the symptomatology of the climacterium. Another is sleep-disordered breathing, where impairment of sleep quality is secondary to sleep apnoea or partial upper airway obstruction during sleep. The former is effectively controlled with conventional estrogen replacement therapy, whereas the latter could potentially be improved with progestogens. Many age-related conditions without a direct link with the menopause should also be considered when treating postmenopausal sleep disorders.
Aged↗
The effect of estrogen replacement therapy on cardiac autonomic regulation.
OBJECTIVE: To study the effects of estrogen replacement therapy (ERT) and sleep stage on autonomic cardiac regulation. SRUDY DESIGN: Seventy-one healthy postmenopausal women received transdermal ERT and placebo separated by a washout in a randomized, placebo-controlled, double-blind, cross-over trial. Polysomnography was conducted at the end of each treatment. Heart rate variability (HRV) was assessed in epochs of the awake state, stage 2, slow wave and REM sleep. The effects of estradiol and sleep stages on HRV were analyzed. RESULTS: ERT decreased heart rate in the awake state and quiet sleep, but not in REM sleep. ERT did not change the heart rate variability. Heart rate decreased and HRV increased during stage 2 and slow wave sleep compared with the awake state with placebo. In REM sleep, similarly, heart rate increased above awake values and the values of HRV parameters fell back to awake levels. CONCLUSIONS: The results suggest that ERT increases vagal tone, but does not change cardiac vagal modulation. Changes in HRV suggest a strong vagal influence in non-REM and a sympathetic influence in REM sleep.
Administration, Cutaneous↗
Prolonged endocrine responses to medroxyprogesterone in postmenopausal women with respiratory insufficiency.
OBJECTIVE: To evaluate the endocrinologic changes associated with, and possibly responsible for, prolonged ventilatory improvement after short-term medroxyprogesterone acetate (MPA) in chronic respiratory failure. METHODS: Fourteen postmenopausal women with permanent or previous episodic hypercapnic or hypoxemic respiratory failure were enrolled in a placebo-controlled, 12-week, single-mask trial including 14-day treatment periods with placebo and MPA (60 mg daily) and a 6-week follow-up. We evaluated the duration of MPA-induced alterations on serum concentrations of progesterone, estradiol, testosterone, FSH, LH, sex hormone-binding globulin (SHBG), and prolactin. Hormones were measured four times: at baseline, after 14 days with MPA, and during the washout on days 21 and 42. RESULTS: With MPA, FSH decreased 42.7% (P <.001, 95% confidence interval [CI] -54.2, -31.6), LH 62.1% (P <.01; 95% CI -81. 0, -32.6), and SHBG 58.1% (P <.001; 95% CI -63.0, -43.9). Luteinizing hormone remained decreased (-28.7%; P <.01; 95% CI -42.0, -14.2) at the 3-week washout, whereas FSH and SHBG were back to pretreatment levels. Prolactin had a borderline initial increase of 23.5% (P =.097; 95% CI -3.5, 50.5) with MPA and a significant increase at the 3-week (31.9%; P <.05; 95% CI 1.0, 62.9) and 6-week (26.4%; P <.05; 95% CI 4.4, 48.3) washouts. CONCLUSION: Medroxyprogesterone acetate 60 mg daily for 2 weeks has both immediate (FSH, LH, and SHBG), prolonged (LH), and rebound endocrinologic (prolactin) effects up to 6 weeks after treatment. The MPA-induced widespread endocrine aftereffects could explain the earlier reported prolonged ventilatory improvement.
Chronic Disease↗
IGF-I and ventilation after short-term progestin in postmenopausal women with chronic respiratory insufficiency.
Progestins stimulate respiration. We have previously shown prolonged ventilatory improvement in chronic respiratory failure with short-term medroxyprogesterone acetate (MPA). The mechanism of the sustained respiratory effect is unknown. Insulin-like growth factor-I (IGF-I) and insulin have anabolic effects which could also improve ventilation in the long-term. To better understand the interactions between hormones and control of breathing, we evaluated the degree and duration of changes in IGF-I, insulin and cortisol after short-term MPA therapy in chronic respiratory insufficiency. Fourteen postmenopausal women with permanent or episodic hypercapnic or hypoxaemic respiratory failure were recruited for a placebo-controlled single-blind trial. After 14 days of placebo treatment and 7 days of washout, a daily dose of 60 mg MPA was administered for 14 days. Serum IGF-I, insulin and cortisol were measured five times at 3-week intervals: at baseline, after 14 days on placebo, after 14 days on MPA, and during the washout, on days 21 and 42. Serum IGF-I levels were 15.2 (SD 4.6), 20.8 (SD 6.8) and 17.2 (SD 6.4) at baseline, on MPA and after a 3-week washout. Serum insulin levels did not change [12.5 mU l(-1) (SD 4.1), 12.2 mU l(-1) (SD 4.8) and 14.5 mU l(-1) (SD 3.6), respectively]. Serum cortisol did not change. On MPA, IGF-I increased on average by 5.6 nmol l(-1) [95% confidence interval (95% CI) 1.4 to 9.9] or 42.0% (95% CI 6.3 to 77.8) from baseline. The IGF-I response coincided with the previously reported ventilatory improvement. MPA 60 mg daily for 2 weeks increases serum IGF-I in postmenopausal women with chronic respiratory insufficiency. During follow-up after MPA, there was a trend towards increased IGF-I and insulin levels. The role of these two hormones to induce prolonged ventilatory stimulation could not be excluded and further studies in larger populations are warranted.
Age Factors↗
Does P3 reflect attentional or memory performances, or cognition more generally?
The study evaluated the off-line relationship of attention, memory and other cognitive performances with the auditory event-related potentials P3 (P300) and N2. The sample comprised 200 middle-aged construction workers. Verbal, visuomotor and memory tests were administered. Attentional domains were examined using CogniSpeed software. Slowed reaction times in the test of sustained attention (vigilance) were associated with delayed P3 latency (p < 0.001) and decreased P3 amplitude (p = 0.005), as well as with delayed N2 latency (p < 0.001). Visuomotor slowing in Digit Symbol was also related to delayed P3 latency (p = 0.030) and decreased P3 amplitude (p = 0.014). In contrast, mild cognitive impairment, short- and long-term memory, and concentrating or sharing attention with high working memory demands were not related to P3. The results suggest that P3 is linked to attentional performance with low working memory demands rather than to effortful working memory updating, retrieval from memory stores, or mild cognitive impairment.
Adult↗
[Estrogen and sleep].
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Estrogen Replacement Therapy↗
Effect of short-term transdermal estrogen replacement therapy on sleep: a randomized, double-blind crossover trial in postmenopausal women.
OBJECTIVE: To evaluate the effect of estrogen replacement therapy on sleep architecture, arousals, and body movements. DESIGN: A 7-month, prospective, randomized, double-blind, placebo-controlled crossover trial. SETTING: Departments of obstetrics and gynecology and a university sleep center in Turku, Finland. PATIENT(S): Seventy-one postmenopausal women, 4 of whom were excluded and 5 of whom withdrew from the study; the final study group consisted of 62 women. INTERVENTION(S): Two periods of treatment with either estrogen or placebo. MAIN OUTCOME MEASURE(S): Polysomnography for measurement of sleep and arousals and a static charge-sensitive bed for monitoring of movements and breathing. Self-reports of climacteric symptoms for 14 days. RESULT(S): Estrogen effectively alleviated hot flashes, sweating, sleep complaints, and headaches. Estrogen decreased the total frequency of movement arousals but increased alpha-arousals, especially during light non-rapid eye movement sleep (stage 1). Sleep latency, distribution of sleep stages, sleep efficiency, and total sleep time were similar during treatment with estrogen and placebo. Changes in serum E2 concentrations correlated with neither subjective nor objective sleep quality. CONCLUSION(S): Estrogen replacement therapy improves objective sleep quality by alleviating the frequency of nocturnal movement arousals. It also reduces climacteric symptoms, especially vasomotor symptoms. Estrogen replacement therapy does not seem to have any effect on sleep architecture.
Aged↗
Climacteric symptoms and sleep quality.
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.
Aged↗
Climacteric vasomotor symptoms do not imply autonomic dysfunction.
OBJECTIVE: To study whether oestrogen replacement therapy has an effect on autonomic haemodynamic control in postmenopausal women. DESIGN: A placebo-controlled, prospective, randomised, double-blind cross-over trial. POPULATION: Fourteen healthy postmenopausal women who had had a hysterectomy, of whom 12 were double-blind. METHODS: At the end of each treatment period we conducted autonomic nervous system tests: the Valsalva manoeuvre, the deep breathing test, study at rest and the active orthostatic test. Baroreflex sensitivity was evaluated non-invasively from the Valsalva manoeuvre. Heart rate variability was assessed in time and frequency domains during supine rest and standing. Serum oestradiol was also measured and the previous two weeks' symptoms were assessed. RESULTS: Autonomic nervous function was mostly normal for age and unchanged by oestrogen. Vasomotor symptoms were not associated with autonomic dysfunction. Baroreflex sensitivity was 13.3 ms/mmHg (SD 7.4 ms/mmHg) with placebo and 10.5 ms/mmHg (SD 5.4 ms/mmHg) with oestrogen (P = 0.052). This was mostly due to a fall in three of the highest indices. In the orthostatic test the 30 s blood pressure overshoot in two women exceeded the normal 90% confidence interval upper limit, making the mean response strong, especially in the symptomatic group (n = 7). Oestrogen attenuated this overshoot. CONCLUSIONS: Oestrogen did not have a consistent effect on the autonomic nervous system. Oestrogen attenuated a highly sensitive baroreflex and a strong 30 s blood pressure rise in the orthostatic test. This minor effect of oestrogen could be due to the fact that, in general, women with menopausal symptoms do not have impaired autonomic haemodynamic control. The effect of oestrogen in women with autonomic nervous system dysfunction remains to be studied.
Autonomic Nervous System↗
Respiratory insufficiency in postmenopausal women: sustained improvement of gas exchange with short-term medroxyprogesterone acetate.
STUDY OBJECTIVES: The degree and duration of respiratory stimulation of medroxyprogesterone acetate (MPA) in postmenopausal women. DESIGN: A placebo-controlled single-blind trial. SETTING: University hospital in Turku, Finland. PATIENTS: Fourteen postmenopausal women with permanent or previous episodic hypercapnic or hypoxemic respiratory failure. INTERVENTIONS: A 12-week trial including 14-day treatment periods with placebo and MPA (60 mg daily) and a 6-week follow-up. RESULTS: Thirteen of 14 patients completed the trial. The mean (+/- SD) PaCO2 at baseline was 42.8+/-4.5 mm Hg and the mean PaO2 was 71.2+/-9.0 mm Hg. The average reduction of PaCO2 was 6.3 mm Hg (14.7%, p < 0.001) on MPA and 3.0 mm Hg (6.1%, p = 0.001) after a 3-week washout. At 6 weeks after MPA, the PaCO2 had returned to baseline. The mean changes in PaO2 (+6.0+/-18.0 mm Hg on MPA and +3.8+/-22.5 mm Hg after a 3-week washout) were not significant. The PaO2/PaCO2 ratio increased, and bicarbonate and base excess decreased (p < 0.001) on MPA but not during washout. The systolic BP did not change on MPA but decreased on average 14.8+/-15.0 mm Hg (p = 0.016) after a 3-week washout. The diastolic BP remained unchanged. CONCLUSIONS: Our results suggest that postmenopausal women with chronic respiratory insufficiency consistently improve on MPA at a dose of 60 mg daily for 14 days. Lower PaCO2 is sustained for at least 3 weeks after cessation of MPA. The sustained effects in gas exchange and favorable after-effects in BP warrant further studies into the therapeutic efficacy and possible benefits of MPA pulse therapy.
Blood Gas Analysis↗
Serum estrogen level, attention, memory and other cognitive functions in middle-aged women.
OBJECTIVE: To evaluate the relationship between serum estradiol level and cognitive processing efficiency and memory. METHODS: Sixty-three healthy women aged 45-65 years were recruited through a newspaper announcement. The subjects were divided into two subgroups (low-estrogen group, n = 37 and high-estrogen group, n = 26) according to their serum follicle stimulating hormone (FSH) and estradiol levels. In the high-estrogen group, estrogen was either endogenous or supplied by estrogen replacement therapy. Automatic and controlled cognitive processing and attentional resources were measured using CogniSpeed software, together with conventional tests of cognitive performance: similarities, digit span, digit symbol, block design, object naming and recall, paired word associates (PWA) recall, Benton visual retention and paced auditory serial addition test (PASAT). The Beck depression inventory was also assessed. RESULTS: Cognitive reaction speeds were similar in both groups. Women with low estrogen levels made more errors in the vigilance test (sustained attention, p = 0.040). There were no differences in short-term or long-term memory, or verbal, visual or working memory between the study groups. Older women were slower in the ten-choice reaction time (10-CRT) test (r = 0.25, p = 0.047) and made more errors in the test of suppressing attention (Stroop incongruence test; r = 0.34, p = 0.007) and in the sustaining attention test (vigilance test; r = 0.47, p < 0.001). Depression scores did not correlate with cognitive variables. CONCLUSIONS: Cognitive performance was well preserved in healthy middle-aged women. Cognitive speed, accuracy, attentional resources and memory did not show impairment with decline of serum estrogen level in this age group.
Attention↗
When does estrogen replacement therapy improve sleep quality?
OBJECTIVE: Our purpose was to evaluate the effect of estrogen replacement therapy on sleep complaints by postmenopausal women and to assess the predictive factors involved. STUDY DESIGN: Sixty-three postmenopausal women entered a 7-month prospective, randomized, double-blind, crossover study consisting of two 3-month treatments with estrogen and placebo with a 1-month washout period between. Eight Visual Analogic Scale statements about different sleep complaints, the Basic Nordic Sleep Questionnaire, scoring of climacteric symptoms, The Beck Depression Inventory, and serum estradiol and follicle-stimulating hormone level controls were the main outcome measures. RESULTS: Estrogen replacement therapy improved sleep quality, facilitated falling asleep, and decreased nocturnal restlessness and awakenings (p < 0.001). The subjects were less tired in the mornings and in the daytime (p < 0.001) when taking estrogen replacement therapy. Estrogen-induced sleep improvement was associated with alleviation of vasomotor symptoms (r range 0.27 to 0.55), alleviation of somatic symptoms (palpitations and muscular pain, r range 0.26 to 0.36), and alleviation of mood symptoms (r range 0.28 to 0.37) on estrogen replacement therapy. The severity of initial insomnia predicted only one estrogen-induced sleep improvement effect: the more the subjects experienced insomnia, the better the estrogen replacement therapy facilitated falling asleep (r = 0.26, p = 0.040). Estrogen-induced sleep improvement was also reported by the 15 climacterically asymptomatic subjects. In these subjects initial insomnia scores strongly predicted estrogen-induced sleep improvement (r range 0.50 to 0.75). CONCLUSIONS: Estrogen replacement therapy significantly diminished sleep complaints among postmenopausal women. Alleviation of climacteric symptoms was the most important predictive factor for the beneficial effect of estrogen replacement therapy on sleep complaints. The use of estrogen replacement therapy in women without self-reported climacteric symptoms could also be considered because women do not always recognize their climacteric symptoms or they ignore them.
Climacteric↗