Replication of restless legs syndrome loci in three European populations.

BACKGROUND: Restless legs syndrome (RLS) is associated with common variants in three intronic and intergenic regions in MEIS1, BTBD9, and MAP2K5/LBXCOR1 on chromosomes 2p, 6p and 15q. METHODS: Our study investigated these variants in 649 RLS patients and 1230 controls from the Czech Republic (290 cases and 450 controls), Austria (269 cases and 611 controls) and Finland (90 cases and 169 controls). Ten single nucleotide polymorphisms (SNPs) within the three genomic regions were selected according to the results of previous genome-wide scans. Samples were genotyped using Sequenom platforms. RESULTS: We replicated associations for all loci in the combined samples set (rs2300478 in MEIS1, p = 1.26 x 10(-5), odds ratio (OR) = 1.47, rs3923809 in BTBD9, p = 4.11 x 10(-5), OR = 1.58 and rs6494696 in MAP2K5/LBXCOR1, p = 0.04764, OR = 1.27). Analysing only familial cases against all controls, all three loci were significantly associated. Using sporadic cases only, we could confirm the association only with BTBD9. CONCLUSION: Our study shows that variants in these three loci confer consistent disease risks in patients of European descent. Among the known loci, BTBD9 seems to be the most consistent in its effect on RLS across populations and is also most independent of familial clustering.

Uvulopalatopharyngoplasty with an ultrasound scalpel or laser: is there a difference?

Uvulopalatopharyngoplasty (UPPP) is used for treatment of the obstructive sleep apnoea syndrome, mainly in the lower range of the apnoea-hypopnea index or partial upper airway obstruction. Significant severe pain after UPPP is associated in the area having surgery and therefore less pain causing methods should be investigated. In this study, we compared laser-assisted and ultrasound scalpel-performed UPPP. Sleep apnoea patients (n = 40) recruited to the study were divided into two groups. UPPP was performed with either laser-assisted or an ultrasound scalpel. Perioperative bleeding, operating room time and duration of operation together with histological injury of soft palate were analysed. A postoperative follow-up questionnaire included a self analysis of pain, dietary intake and pain drug consumption. In the same follow-up form, filled in by patients themselves, possible side effects and adequacy of pain medication together with any postoperative haemorrhage events were recorded during 10-day study period after UPPP. The ultrasound scalpel group had significantly fewer haemorrhagic events (P = 0.037) during postoperative follow-up time after UPPP when compared to laser-assisted group. The pain values of all 40 patients were significantly higher in the morning than in the afternoon (P < 0.001) or evening (P < 0.001). Pain increased up to the fifth postoperative day (visual analogue scale, VAS = 46). The significant relief of pain to the mild level (VAS < 30 mm) occurred at ninth and tenth postoperative day. The ultrasound scalpel used as a surgical method in UPPP did not offer significant comprehensive benefits in this study compared to laser-assisted UPPP. Exclusively, postoperative haemorrhage events were minor, paralleling findings of previous studies where ultrasound scalpel had been used for tonsillectomy. We conclude that the ultrasound scalpel is comparable to laser-assisted UPPP.

Transcutaneous carbon dioxide profile during sleep reveals metabolic risk factors in post-menopausal females.

The risks of metabolic syndrome and sleep-disordered breathing increase around the time of the menopause. We have previously shown that features of the nocturnal transcutaneous carbon dioxide (TcCO2) profile are associated with metabolic variables such as cholesterol, glycosylated haemoglobin A1C (GHbA1C) and blood pressure in patients with sleep apnoea. In the present study, we investigated whether these metabolic variables can be predicted using noninvasive TcCO2 measurements during sleep in generally healthy post-menopausal females. 22 post-menopausal females underwent an overnight polygraphic sleep study that involved the continuous monitoring of arterial oxygen saturation (S(a,O2)) and TcCO2. Body composition, GHbA1C, plasma cholesterol and blood pressure were measured prior to the sleep study. Nocturnal TcCO2 features were the most important predictors of lipoprotein cholesterols, triglycerides and blood pressure levels. A longer sleep period and higher TcCO2 levels were linked with lower GHbA1C, and fragmented sleep with lower high-density lipoprotein cholesterol. Neither nocturnal S(a,O2) indices nor the apnoea/hypopnoea index had a predictive power. The results suggest that nocturnal TcCO2 events revealed metabolic risk factors already present in healthy post-menopausal females.

The effect of estrogen plus progestin treatment on sleep: a randomized, placebo-controlled, double-blind trial in premenopausal and late postmenopausal women.

OBJECTIVE: In this prospective randomized, placebo-controlled and double-blind study, the objective was to investigate the effects of estrogen-progestin treatment (EPT) on sleep in pre- and postmenopausal women. DESIGN: Seventeen premenopausal (aged 45-51 years) and 18 postmenopausal (aged 58-70 years) women were studied in a sleep laboratory for two nights (one night for adaptation and one study night) before and after 6 months of treatment with EPT or placebo. During the treatment period, premenopausal women received cyclic EPT or placebo and the postmenopausal women continuous EPT or placebo. Polysomnography and questionnaires were used to evaluate sleep and well-being. RESULTS: At the end of the treatment period, premenopausal women receiving EPT had more awakenings from stage 1 sleep (p = 0.047) and postmenopausal women with EPT had a greater total number of awakenings (p = 0.031) than the corresponding placebo group. Further, sleepiness decreased less in the premenopausal EPT group than in the placebo group (p = 0.031). In postmenopausal women, EPT decreased and placebo slightly increased slow wave activity during the second non-rapid eye movement sleep episode (p = 0.046). CONCLUSIONS: In premenopausal and late postmenopausal women, EPT had only random and marginal effects on sleep. Although the limited findings were mostly unfavorable for EPT, one cannot conclude that EPT deteriorates sleep. Further, neither middle-aged cycling premenopausal women nor older postmenopausal women benefit from estrogen-progestin treatment in terms of their sleep quality.

Parameter estimation of a respiratory control model from noninvasive carbon dioxide measurements during sleep.

A new method for estimating the parameters of a human gas exchange model is presented. Sensitivity analysis is used both to inspect the relative importance of the model parameters and to speed up the par-ameter estimation process. Multistart optimization is used to compensate for the effects of partial and noisy measurements. The validity of the method is first investigated with a test problem for which par-ameter identifiability is shown. The method is then applied to the estimation of sleep-related changes in the respiratory control system from the end-tidal and transcutaneous carbon dioxide measurements on human subjects. The results show that it is possible to gain insight into the behaviour of the rather complex physiological system using only a few noninvasive measurements and tractable computations.

Prolonged spiking in the Emfit sensor in patients with sleep-disordered breathing is characterized by increase in transcutaneous carbon dioxide.

A phenomenon of prolonged spiking in movement sensors, such as static-charge-sensitive bed or Emfit (electromechanical film) sensors, has been connected to an increase in carbon dioxide tension in wakefulness. Spiking is also a common finding in sleep studies. This made us hypothesize that carbon dioxide changes might also happen in sleep during prolonged spiking episodes in Emfit sheet. We examined four different kinds of breathing pattern episodes: normal breathing, episodes of repetitive apnea, episodes of repetitive hypopnea and episodes with prolonged spiking lasting at least 3 min. One hundred and fifteen episodes from 19 polysomnograms were finally admitted to the study according to the protocol. The changes in the transcutaneous carbon dioxide tension (TcCO(2)) were defined for different breathing patterns. During prolonged spiking episodes the TcCO(2) increased significantly and differed statistically from the TcCO(2) changes of normal breathing and periodic breathing patterns (episodes of apnea and hypopnea). The rise in TcCO(2) during prolonged spiking episodes might suggest that prolonged spiking is representing another type of breathing disturbance during sleep differing from periodic breathing patterns. The Emfit sensor as a small, flexible and non-invasive sensor might provide useful additional information about breathing during sleep.

Pharyngeal CT studies in patients with mild or severe upper airway obstruction during sleep.

The upper airway cross-sectional areas were studied with pharyngeal computed tomography (CT) at the nasopharyngeal, velopharyngeal, tongue base and hyoid bone levels in 119 consecutively investigated patients with a snoring complaint. According to their findings in an all-night static charge sensitive bed (SCSB) recording, the subjects were divided into four equally sized groups with increasing severity of nocturnal breathing disturbance. The body mass index (BMI) increased and the minimal cross-sectional area at the velopharyngeal level decreased consistently as a function of the severity of nocturnal breathing disturbance. The minimal cross-sectional area at the hyoid bone level showed a biphasic trend, with an initial decrease but a final increase, as the degree of nocturnal breathing disturbance aggravated. The results contradict the idea of gradually increasing anatomical narrowing of the upper airways in general as the nocturnal breathing disturbance exacerbates and support the concept of two anatomically determined entities of partial and complete upper airway obstruction during sleep.

Asymmetry of instructed motor response to auditory stimuli during sleep.

Previous studies have demonstrated that motor activity during sleep is lateralized to the nondominant hand. There are two basic theories concerning this phenomenon: 1) The nondominant hemisphere is nonspecifically more alert or responsive than the dominant one, and 2) the lateralization to the nondominant side is task specific, reflecting the spatially oriented mode of information processing that is responsible for movements during sleep. We examined the motor responses to auditory stimuli during waking and sleep of 10 right-handed healthy subjects, who were instructed to switch off a tone stimulus by pressing a transducer that was attached to each hand. Sleep stage scoring was performed according to Rechtschaffen and Kales's criteria. During wakefulness and in all stages of sleep, with and without alpha activity occurring after stimulus onset, the dominant hand was used more, but during nonrapid eye movement S1 sleep the difference was not statistically significant. When alpha activity was present in the electroencephalogram after stimulus onset, the responses were significantly more lateralized to the right hand than when there was no alpha activity. During an actimetric home recording of both wrists of the subjects, there was an excess of left-sided movements during sleep as compared to waking. The results do not support the idea that the right hemisphere is generally more responsive than the left during sleep. They are, however, in accordance with the hypothesis that spatial information processing is a crucial factor in the nondominant lateralization of spontaneous sleep movements.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Sleep-related disordered breathing during pregnancy in obese women.

STUDY OBJECTIVES: This study was designed to evaluate sleep-related disordered breathing in obese women during pregnancy. Obesity is known to predispose to sleep-related breathing disorders. During pregnancy, obese mothers gain additional weight, but other mechanisms may counteract this effect. DESIGN: A case-control study to compare sleep-related breathing in obese pregnant women (mean prepregnancy body mass index [BMI] > 30 kg/m(2)) with pregnant women of normal weight (mean BMI, 20 to 25 kg/m(2)). SETTING: University teaching hospital with a sleep laboratory. PARTICIPANTS: We recruited 11 obese women (BMI, 34 kg/m(2); mean age 31 years) and 11 control women (BMI, 23 kg/m(2); mean age 32 years). INTERVENTIONS: Overnight polysomnography was performed during early (after 12 weeks) and late (after 30 weeks) pregnancy. MEASUREMENTS AND RESULTS: During pregnancy, obese mothers gained 13 kg and control women gained 16 kg. Sleep characteristics did not differ between the groups. During late pregnancy, the women in both groups slept more poorly and slept in supine position less. During early pregnancy, their apnea-hypopnea indexes (1.7 events per hour vs 0.2 events per hour; p < 0.05), 4% oxygen desaturations (5.3 events per hour vs 0.3 events per hour; p < 0.005), and snoring times (32% vs 1%, p < 0.001) differed significantly. These differences between the groups persisted in the second polysomnography, with snoring time further increasing in the obese. Preeclampsia and mild obstructive sleep apnea were diagnosed in one obese mother. One obese mother delivered a baby showing growth retardation (weight - 3 SD). CONCLUSIONS: We have shown significantly more sleep-related disordered breathing occurring in obese mothers than in subjects of normal weight, despite similar sleeping characteristics.

Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle.

We investigated the cardiovascular responses to acute hypercapnia during the menstrual cycle. Eleven female subjects with regular menstrual cycles performed hypercapnic rebreathing tests during the follicular and luteal phases of their menstrual cycles. Ventilatory and cardiovascular variables were recorded breath by breath. Serum progesterone and estradiol were measured on each occasion. Serum progesterone was higher during the luteal [50.4 +/- 9.6 (SE) nmol/l] than during the follicular phase (2.1 +/- 0.7 nmol/l; P < 0.001), but serum estradiol did not differ (follicular phase, 324 +/- 101 pmol/l; luteal phase, 162 +/- 71 pmol/l; P = 0.61). The systolic blood pressure responses during hypercapnia were 2.0 +/- 0.3 and 4.0 +/- 0.5 mmHg/Torr (1 Torr = 1 mmHg rise in end-tidal PCO2) during the follicular and luteal phases, respectively, of the menstrual cycle (P < 0.01). The diastolic blood pressure responses were 1.1 +/- 0.2 and 2.1 +/- 0.3 mmHg/Torr during the follicular and luteal phases, respectively (P < 0.002). Heart rate responses did not differ during the luteal (1.7 +/- 0.3 beats.min-1.Torr-1) and follicular phases (1.4 +/- 0.3 beats.min-1.Torr-1; P = 0.59). These data demonstrate a greater pressor response during the luteal phase of the menstrual cycle that may be related to higher serum progesterone concentrations.

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.

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.

Ventilatory response to isocapnic hyperoxia.

Breathing O2 for up to 1 h has been shown to either not influence or slightly increase (6-13%) minute ventilation. However, end-tidal PCO2 was not kept constant in these experiments. In nine healthy men, we studied the ventilatory, blood pressure, and heart rate responses to 30 min of normobaric hyperoxia (50% O2) at isocapnic conditions. Hyperoxia led to a 60% increase in mean minute ventilation (P = 0.002), largely due to an increase in mean tidal volume from 0.66 +/- 0.04 (SE) to 0.88 +/- 0.05 liter (P = 0.007). Fifteen minutes after the termination of hyperoxia, minute ventilation was still increased (P = 0.02) compared with baseline, although it was reduced compared with hyperoxia (P = 0.02). Arterial blood gas analyses in six subjects before and during hyperoxia showed an increase in arterial PO2 and O2 saturation but no change in arterial PCO2 or pH. Hyperoxia induced no changes in arterial blood pressure or heart rate. We conclude that 1) isocapnic hyperoxia stimulates respiration markedly, an effect that is approximately five times higher than previously measured; 2) the increase in ventilation induced by hyperoxia does not affect arterial blood pressure and heart rate; and 3) in experiments using hyperoxia, its effect on breathing and subsequently on PCO2 has to be taken into account.

Effect of different levels of hyperoxia on breathing in healthy subjects.

We have recently shown that breathing 50% O2 markedly stimulates ventilation in healthy subjects if end-tidal PCO2 (PETCO2) is maintained. The aim of this study was to investigate a possible dose-dependent stimulation of ventilation by O2 and to examine possible mechanisms of hyperoxic hyperventilation. In eight normal subjects ventilation was measured while they were breathing 30 and 75% O2 for 30 min, with PETCO2 being held constant. Acute hypercapnic ventilatory responses were also tested in these subjects. The 75% O2 experiment was repeated without controlling PETCO2 in 14 subjects, and in 6 subjects arterial blood gases were taken at baseline and at the end of the hyperoxia period. Minute ventilation (VI) increased by 21 and 115% with 30 and 75% isocapnic hyperoxia, respectively. The 75% O2 without any control on PETCO2 led to 16% increase in VI, but PETCO2 decreased by 3.6 Torr (9%). There was a linear correlation (r = 0.83) between the hypercapnic and the hyperoxic ventilatory response. In conclusion, isocapnic hyperoxia stimulates ventilation in a dose-dependent way, with VI more than doubling after 30 min of 75% O2. If isocapnia is not maintained, hyperventilation is attenuated by a decrease in arterial PCO2. There is a correlation between hyperoxic and hypercapnic ventilatory responses. On the basis of data from the literature, we concluded that the Haldane effect seems to be the major cause of hyperventilation during both isocapnic and poikilocapnic hyperoxia.

The effect of short-term estrogen replacement therapy on cognition: a randomized, double-blind, cross-over trial in postmenopausal women.

OBJECTIVE: To evaluate the effect of estrogen replacement therapy on cognitive functioning. METHODS: The study consisted of two 3-month treatment periods, one with estrogen and one with the placebo, in random order, separated by a 1-month wash-out period. The study group comprised 70 healthy postmenopausal women, aged 47-65 years, with previous hysterectomy. Sixty-two women completed the study. Cognitive speed and accuracy, attention, and memory were evaluated. Serum estradiol (E2) and FSH levels were controlled at the end of the estrogen, placebo, and wash-out periods. RESULTS: Most of the cognitive tests correlated with age: older women were slower and made more errors than younger women. Estrogen replacement therapy was not superior to the placebo in any test of cognitive performance. In two out of ten visual detection tasks, recognition thresholds were longer with estrogen than with the placebo (P < .001 and P = .004). On the most demanding test of working memory, the reaction times (P = .045) and error rates (P = .043) differed between treatments, yet this finding proved to be an effect of learning rather than treatment. There was no correlation between cognitive performance and serum E2 levels. CONCLUSION: Cognitive performance decreased with age. Short-term estrogen replacement therapy did not provide any advantage over the placebo in terms of improving the performance.

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.

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.

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.