Objective measures of sleep and dim light melatonin onset in adolescents and young adults with delayed sleep phase disorder compared to healthy controls

Delayed sleep phase disorder is characterized by a delay in the timing of the major sleep period relative to conventional norms. The sleep period itself has traditionally been described as normal. Nevertheless, it is possible that sleep regulatory mechanism disturbances associated with the disorder may affect sleep duration and/or architecture. Polysomnographic data that may shed light on the issue are scarce. Hence, the aim of this study was to examine polysomnographic measures of sleep in adolescents and young adults with delayed sleep phase disorder, and to compare findings to that of healthy controls. A second aim was to estimate dim light melatonin onset as a marker of circadian rhythm and to investigate the phase angle relationship (time interval) between dim light melatonin onset and the sleep period. Data from 54 adolescents and young adults were analysed, 35 diagnosed with delayed sleep phase disorder and 19 healthy controls. Results show delayed timing of sleep in participants with delayed sleep phase disorder, but once sleep was initiated no group differences in sleep parameters were observed. Dim light melatonin onset was delayed in participants with delayed sleep phase disorder, but no difference in phase angle was observed between the groups. In conclusion, both sleep and dim light melatonin onset were delayed in participants with delayed sleep phase disorder. The sleep period appeared to occur at the same circadian phase in both groups, and once sleep was initiated no differences in sleep parameters were observed.     

Prediction of melatonin efficacy by pretreatment dim light melatonin onset in children with idiopathic chronic sleep onset insomnia

Research has shown efficacy of melatonin treatment to advance sleep-wake rhythms in insomnia. In healthy adults, direction and magnitude of the phase shift depends on the timing of administration relative to the phase position of the circadian system. Therefore, in the present study we investigated whether in children with chronic sleep onset insomnia (SOI) efficacy of melatonin treatment in the early evening could be predicted from dim light melatonin onset (DLMO), a phase marker of the circadian system. We combined data of two previously published double blind, randomized, placebo-controlled trials in 110 participants, aged 6-12 years. Sleep was actigraphically estimated, and saliva collected, at baseline and in the third week of a 4-week treatment period with 5 mg melatonin or placebo at 18:00 or 19:00 hours. Primary outcome measures were pre- to post-treatment changes in dim light melatonin onset (DeltaDLMO), sleep onset (DeltaSO), sleep latency (DeltaSL), and total sleep duration (DeltaTSD). Melatonin advanced DLMO with +1:12 h (P < 0.001), SO with +0:42 h (P = 0.004), SL decreased with 25 min (P = 0.019), and TSD did not change significantly, as compared with placebo. In the melatonin-treated group, but not in the placebo-treated group, pretreatment DLMO was significantly related to DeltaDLMO [F(1, 29) = 7.28, P = 0.012] and DeltaSO [F(1, 25) = 7.72, P = 0.010]. The time interval between treatment administration and pretreatment DLMO (INT) was only significantly related to DeltaSO [F(1,26) = 5.40, P = 0.028]. The results suggest that in children with SOI, the efficacy of early evening melatonin to advance sleep onset and endogenous melatonin onset increases the later the pretreatment DLMO is.     

The dim light melatonin onset following fixed and free sleep schedules

The time at which the dim light melatonin onset (DLMO) occurs can be used to ensure the correct timing of light and/or melatonin administration in order to produce desired circadian phase shifts. Sometimes however, measuring the DLMO is not feasible. Here we determined if the DLMO was best estimated from fixed sleep times (based on habitual sleep times) or free (ad libitum) sleep times. Young healthy sleepers on fixed (n=60) or free (n=60) sleep schedules slept at home for 6 days. Sleep times were recorded with sleep logs verified with wrist actigraphy. Half-hourly saliva samples were then collected during a dim light phase assessment and were later assayed to determine the DLMO. We found that the DLMO was more highly correlated with sleep times in the free sleepers than in the fixed sleepers (DLMO versus wake time, r=0.70 and r=0.44, both P<0.05). The regression equation between wake time and the DLMO in the free sleepers predicted the DLMO in an independent sample of free sleepers (n=23) to within 1.5 h of the actual DLMO in 96% of cases. These results indicate that the DLMO can be readily estimated in people whose sleep times are minimally affected by work, class and family commitments. Further work is necessary to determine if the DLMO can be accurately estimated in people with greater work and family responsibilities that affect their sleep times, perhaps by using weekend wake times, and if this method will apply to the elderly and patients with circadian rhythm disorders.     

Body temperature,activity and melatonin profiles in adults with attention‐deficit/hyperactivity disorder and delayed sleep: a case–control study

Irregular sleep–wake patterns and delayed sleep times are common in adults with attention‐deficit/hyperactivity disorder, but mechanisms underlying these problems are unknown. The present case–control study examined whether circadian abnormalities underlie these sleep problems in a naturalistic home setting. We included 12 medication‐naïve patients with attention‐deficit/hyperactivity disorder and delayed sleep phase syndrome, and 12 matched healthy controls. We examined associations between sleep/wake rhythm in attention‐deficit/hyperactivity disorder and circadian parameters (i.e. salivary melatonin concentrations, core and skin temperatures, and activity patterns) of the patients and controls during five consecutive days and nights. Daily bedtimes were more variable within patients compared with controls (F = 8.19, P < 0.001), but melatonin profiles were equally stable within individuals. Dim‐light melatonin onset was about 1.5 h later in the patient group (U = 771, Z = ?4.63, P < 0.001). Patients slept about 1 h less on nights before work days compared with controls (F = 11.21, P = 0.002). The interval between dim‐light melatonin onset and sleep onset was on average 1 h longer in patients compared with controls (U = 1117, Z = ?2.62, P = 0.009). This interval was even longer in patients with extremely late chronotype. Melatonin, activity and body temperatures were delayed to comparable degrees in patients. Overall temperatures were lower in patients than controls. Sleep‐onset difficulties correlated with greater distal–proximal temperature gradient (DPG; i.e. colder hands, r² = ?0.32, P = 0.028) in patients. Observed day‐to‐day bedtime variability of individuals with attention‐deficit/hyperactivity disorder and delayed sleep phase syndrome were not reflected in their melatonin profiles. Irregular sleep–wake patterns and delayed sleep in individuals with attention‐deficit/hyperactivity disorder and delayed sleep phase syndrome are associated with delays and dysregulations of the core and skin temperatures.     

Effects of light exposure and sleep displacement on dim light melatonin onset

The purpose of the study was to induce in two different ways, a phase-angle difference between the circadian pacemaker and the imposed sleep-wake cycle in humans, we intended to: (i) shift the circadian pacemaker by exposure to bright light and keep the timing of the sleep-wake cycle fixed; and (ii) keep the timing of the circadian pacemaker fixed by a constant light-dark cycle and displace sleep. We monitored dim light melatonin onset (DLMO), core body temperature and sleep. DLMO was delayed significantly after 3 days of a 3-h delayed sleep-phase when compared with 3 days of sleep at a normal or 3-h advanced sleep-phase. The shifts in DLMO were not accompanied by shifts in body temperature, changes in waking-up time or by a change in the duration of the first rapid eye movement (REM) sleep episode. Three days of light exposure in the morning or evening resulted in shifts in DLMO of similar magnitude, but this was accompanied by shifts in the rhythm of body temperature, changes in waking-up time and in the duration of the first REM sleep episode. We conclude that the changes observed after light exposure reflect shifts in the circadian pacemaker. In contrast, we propose that the changes observed in DLMO after sleep displacement are not mediated by the circadian pacemaker. These results raise some doubts about the reliability of DLMO as a marker of circadian phase in cases of sleep disturbances. Finally, we initiate a search for changes in sleep that might be responsible for the unexpected effects on DLMO.     

Changes in sleepiness and body temperature precede nocturnal sleep onset: Evidence from a polysomnographic study in young men

Recent research has shown a close temporal relationship between the nocturnal decrease in rectal core temperature and the initiation of sleep. However, there is not yet a clear temporal relationship between changes in peripheral and core temperatures and nocturnal sleep onset. We recorded body temperatures in 14 adult males (age±SEM=22.1±0.6 y), who attended the sleep laboratory for an adaptation night and two counterbalanced experimental sessions. Subjects self-selected lights-out on one experimental night (the Habitual Sleep condition). To determine the relationship between body temperature changes and sleep onset, lights out was delayed until after 01.00 hours on the other experimental night (Delayed Sleep condition). Individual datasets in both conditions were expressed relative to the time of sleep onset in the Habitual Sleep condition only, so that they were aligned at identical clock times. Saliva samples confirmed that mean dim light melatonin onset (DLMO) occurred at 00.10±00.16 hours in the Delayed Sleep condition, which was after habitual sleep onset at 23.44±00.08 hours. Rectal core temperature (Tc) decreased significantly over time only in the Habitual Sleep condition ( P < 0.01). For the 20 min before habitual sleep onset, Delayed Sleep Tc was on average 0.1°C higher than Tc in the Habitual Sleep condition ( P < 0.01). The greater decline in Habitual Sleep Tc was associated with significantly increased peripheral hand and foot skin temperatures before sleep (both P < 0.05). Subjective sleepiness measures were higher in the Habitual Sleep onset condition from 150 min prior until sleep onset ( P < 0.01). From these results it is reasonable to infer that a sequence of thermoregulatory and sleep propensity changes occur before, but are associated with habitual sleep onset, as the changes are significantly attenuated if sleep is delayed.     

An experimental study of adolescent sleep restriction during a simulated school week: changes in phase,sleep staging,performance and sleepiness

This laboratory study investigated the impact of restricted sleep during a simulated school week on circadian phase, sleep stages and daytime functioning. Changes were examined across and within days and during a simulated weekend recovery. Participants were 12 healthy secondary school students (six male) aged 15–17 years [mean = 16.1 years, standard deviation (SD) = 0.9]. After 2 nights with 10 h (21:30–07:30 hours), time in bed was restricted to 5 h for 5 nights (02:30–07:30 hours), then returned to 10 h time in bed for 2 nights (21:30–07:30 hours). Saliva was collected in dim light on the first and last sleep restriction nights to measure melatonin onset phase. Sleep was recorded polysomnographically, and the Psychomotor Vigilance Task (PVT) and Karolinska Sleepiness Scale were undertaken 3‐hourly while awake. Average phase delay measured by melatonin was 3 h (SD = 50 min). Compared to baseline, sleep during the restriction period contained a smaller percentage of Stages 1 and 2 and rapid eye movement (REM) and a greater percentage of Stage 4. PVT lapses increased significantly during sleep restriction and did not return to baseline levels during recovery. Subjective sleepiness showed a similar pattern during restriction, but returned to baseline levels during recovery. Results suggest that sustained attention in adolescents is affected negatively by sleep restriction, particularly in the early morning, and that a weekend of recovery sleep is insufficient to restore performance. The discrepancy between sleepiness ratings and performance may indicate a lack of perception of this residual impairment.     

Day-time melatonin administration: Effects on core temperature and sleep onset latency

Significant hypothermic and hypnotic effects have been reported for melatonin at a wide range of doses. It has been suggested that this decrease in core temperature (Tc) following melatonin administration may mediate the observed increase in sleepiness. To test this, melatonin was administered to young adults during the day, and the concurrent effects on Tc and sleep onset latency (SOL) were recorded. Sixteen healthy males received either a 5 mg oral formulation of melatonin or placebo at 14.00 hours. Core temperature was recorded continuously. Sleep onset latency to stage 1 (SOL1) and stage 2 (SOL2) were recorded using an hourly multiple sleep latency test (MSLT). Compared with placebo, melatonin significantly decreased Tc 1.5 h after administration for 6 h. Between 15.00 and 18.00 hours, the drop in Tc was associated with a concurrent decrease in SOL1 and SOL2. Following administration mean SOL1 and SOL2 were reduced by 40 and 25%, respectively. In this study, daytime melatonin administration produced a significant decrease in Tc with a corresponding decrease in SOL. Taken together, these data are not inconsistent with the suggestion that melatonin may facilitate sleep onset via a hypothermic effect. In addition, this study provides support for the idea that melatonin may play a role in regulating circadian and/or age-related variations in sleep/wake propensity. From a practical perspective, exogenous melatonin may be useful in the treatment of sleep disorders associated with increased nocturnal Tc.     

Home versus laboratory assessments of melatonin production and melatonin onset in young adults complaining of a delayed sleep schedule

Recent evidence points toward an association between higher non‐visual sensitivity to light and a later circadian phase in young adults complaining of a delayed sleep schedule. Light exposure in the evening may therefore induce a larger suppression of melatonin production in these individuals, which might: (a) bias home estimates of melatonin onset; and (b) decrease sleep propensity at bedtime. In this study, we compared home and laboratory melatonin onsets and production in sleep‐delayed and control participants, using saliva samples collected in the 3 hr preceding habitual bedtime. The mean light intensity measured during saliva sampling at home was ~10 lux in both groups. Melatonin suppression at home was significant, averaging 31% and 24% in sleep‐delayed and control individuals, respectively. Group difference in melatonin suppression was not significant. Estimates of melatonin onset were on average 27 min later at home than in laboratory conditions, with no group difference. Looking specifically at sleep‐delayed participants, there was no correlation between non‐visual sensitivity to light and home–laboratory differences in melatonin onsets. However, higher light sensitivity was associated with greater melatonin suppression in the hour before habitual bedtime. Greater melatonin suppression before bedtime was also associated with a later circadian phase. These results indicate that the validity of home estimates of melatonin onset is similar in sleep‐delayed and in control individuals. Results also suggest that increased non‐visual sensitivity to light could impact melatonin secretion in sleep‐delayed individuals and contribute to a late bedtime by delaying circadian phase and decreasing sleep propensity.     

Chronotype is associated with the timing of the circadian clock and sleep in toddlers

Chronotype is a construct reflecting individual differences in diurnal preference. Although chronotype has been studied extensively in school‐age children, adolescents and adults, data on young children are scarce. This study describes chronotype and its relationship to the timing of the circadian clock and sleep in 48 healthy children aged 30–36 months (33.4 ± 2.1 months; 24 males). Parents completed the Children's Chronotype Questionnaire (CCTQ) ~2 weeks before the start of the study. The CCTQ provides three measures of chronotype: midsleep time on free days, a multi‐item morningness/eveningness score and a single item chronotype score. After 5 days of sleeping on their habitual schedule (assessed with actigraphy and sleep diaries), children participated in an in‐home salivary dim light melatonin onset assessment. Average midsleep time on free days was 1:47 ± 0:35, and the average morningness/eveningness score was 26.8 ± 4.3. Most toddlers (58.4%) were rated as ‘definitely a morning type’ or ‘rather morning than evening type’, while none (0%) were rated as ‘definitely evening type’. More morning types (midsleep time on free days and morningness/eveningness score, respectively) had earlier melatonin onset times (r = 0.45, r = 0.26), earlier habitual bedtimes (r = 0.78, r = 0.54), sleep onset times (r = 0.80, r = 0.52), sleep midpoint times (r = 0.90, r = 0.53) and wake times (r = 0.74, r = 0.34). Parent ratings using the single‐item chronotype score were associated with melatonin onset (r = 0.32) and habitual bedtimes (r = 0.27), sleep onset times (r = 0.33) and sleep midpoint times (r = 0.27). Morningness may best characterize circadian preference in early childhood. Associations between chronotype and circadian physiology and sleep timing suggest adequate validity for the CCTQ in this age group. These findings have important implications for understanding the marked variability in sleep timing during the early years of life.     

Circadian period and the timing of melatonin onset in men and women: predictors of sleep during the weekend and in the laboratory

Sleep complaints and irregular sleep patterns, such as curtailed sleep during workdays and longer and later sleep during weekends, are common. It is often implied that differences in circadian period and in entrained phase contribute to these patterns, but few data are available. We assessed parameters of the circadian rhythm of melatonin at baseline and in a forced desynchrony protocol in 35 participants (18 women) with no sleep disorders. Circadian period varied between 23 h 50 min and 24 h 31 min, and correlated positively (n = 31, r_s = 0.43, P = 0.017) with the timing of the melatonin rhythm relative to habitual bedtime. The phase of the melatonin rhythm correlated with the Insomnia Severity Index (n = 35, r_s = 0.47, P = 0.004). Self‐reported time in bed during free days also correlated with the timing of the melatonin rhythm (n = 35, r_s = 0.43, P = 0.01) as well as with the circadian period (n = 31, r_s = 0.47, P = 0.007), such that individuals with a more delayed melatonin rhythm or a longer circadian period reported longer sleep during the weekend. The increase in time in bed during the free days correlated positively with circadian period (n = 31, r_s = 0.54, P = 0.002). Polysomnographically assessed latency to persistent sleep (n = 34, r_s = 0.48, P = 0.004) correlated with the timing of the melatonin rhythm when participants were sleeping at their habitual bedtimes in the laboratory. This correlation was significantly stronger in women than in men (Z = 2.38, P = 0.017). The findings show that individual differences in circadian period and phase of the melatonin rhythm associate with differences in sleep, and suggest that individuals with a long circadian period may be at risk of developing sleep problems.     

Aging young sleep: a test of the phase advance hypothesis of sleep disturbance in the elderly

SUMMARY  With aging, the phase relationship between sleep and body core temperature is altered such that the temperature minimum occurs substantially earlier in the major nocturnal sleep period. The sleep maintenance difficulties that often accompany normal aging are generally assumed to be associated with this age-related change in the phase angle between sleep and temperature. To test this notion, we used timed exposure to bright light to reproduce in healthy young adults a similar phase relationship between temperature and sleep, to determine if such a manipulation would induce the same fragmented nocturnal sleep commonly observed in individuals over 65 years of age. Seven young adults were exposed to morning bright light for 3 consecutive days following a baseline night. Bright light exposure caused a 97 min phase advance of the fitted temperature minimum when compared with baseline. Significant declines in several measures of sleep quality were associated with the phase advance, including wakefulness after initial sleep onset (WASO), sleep efficiency and number of stage changes. Yet, the severity of sleep disturbance exhibited by these subjects did not approach that exhibited by most elderly subjects. The findings suggest that while chronophysiological changes appear to be strongly associated with the tendency to awaken in the early morning, they cannot account entirely for the severity of sleep disturbance frequently observed in older subjects.     

A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome

OBJECTIVE: The effects of exogenous melatonin on sleep, daytime sleepiness, fatigue, and alertness were investigated in 22 patients with delayed sleep phase syndrome whose nocturnal sleep was restricted to the interval from 24:00 to 08:00 hours. This study was a randomized, double-blind, placebo-controlled crossover trial. Subjects received either placebo or melatonin (5 mg) daily for 4 weeks, underwent a 1-week washout period, and then were given the other treatment for an additional 4 weeks. Patients could take the melatonin between 19:00 and 21:00 hours, which allowed them to select the time they felt to be most beneficial for the phase-setting effects of the medication. METHODS: Two consecutive overnight polysomnographic recordings were performed on three occasions: at baseline (before treatment), after 4 weeks of melatonin treatment, and after 4 weeks of placebo treatment. RESULTS: In the 20 patients who completed the study, sleep onset latency was significantly reduced while subjects were taking melatonin as compared with both placebo and baseline. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time), but there was a significant decrease in total sleep time while patients were taking placebo. Melatonin did not result in altered scores on subjective measures of sleepiness, fatigue, and alertness, which were administered at different times of the day. After an imposed conventional sleep period (from 24:00 to 08:00), subjects taking melatonin reported being less sleepy and fatigued than they did while taking placebo. CONCLUSIONS: Melatonin ameliorated some symptoms of delayed sleep phase syndrome, as confirmed by both objective and subjective measures. No adverse effects of melatonin were noted during the 4-week treatment period.     

Evening administration of melatonin and bright light: Interactions on the EEG during sleep and wakefulness

Both the pineal hormone melatonin and light exposure are considered to play a major role in the circadian regulation of sleep. In a placebo- controlled balanced cross-over design, we investigated the acute effects of exogenous melatonin (5 mg p.o. at 20.40 hours) with or without a 3-h bright light exposure (5000 lux from 21.00 hours–24.00 hours) on subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in healthy young men. The acute effects of melatonin, bright light and their interaction were measured on the first day (treatment day), possible circadian phase shifts were assessed on the post-treatment day. On the treatment day, the evening rise in subjective sleepiness was accelerated after melatonin and protracted during bright light exposure. These effects were also reflected in specific changes of EEG power density in the theta/alpha range during wakefulness. Melatonin shortened and bright light increased sleep latency. REMS latency was reduced after melatonin administration but bright light had no effect. Slow-wave sleep and slow-wave activity during the first non-rapid eye movement (NREMS) episode were suppressed after melatonin administration and rebounded in the second NREMS episode, independent of whether light was co-administered or not. Self rated sleep quality was better after melatonin administration whereas the awakening process was rated as more difficult after bright light. On the post-treatment day after evening bright light, the rise in sleepiness and the onset of sleep were delayed, independent of whether melatonin was co-administered or not. Thus, although acute bright light and melatonin administration affected subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in a additive manner, the phase shifting effect of a single evening bright light exposure could not be blocked by exogenous melatonin     

Effects of vitamin D on ovary in DHEA-treated PCOS rat model: A light and electron microscopic study

Aim: The aim of this study was to investigate the effects of vitamin D treatment on ovary in experimentally designed polycystic ovary syndrome of female rats using light and electron microscopic techniques. Methods: Twenty-four female pre-pubertal rats were divided into control, DHEA and DHEA+Vit.D groups. In DHEA group, the PCOS rat model was developed by 6mg/kg/day dehydroepiandrosterone administration as subcutaneously injections. In DHEA+Vit.D group, 6 mg/kg/day DHEA and 120ng/100g/week 1,25(OH)2D3 was performed simultaneously. Controls were injected with vehicle alone. At the end of the 28 days, blood samples were collected and the ovarian tissues were taken for histological examinations. Results: FSH, LH levels, LH/FSH ratio, and testosterone levels showed a significant increase in DHEA group when compared with the control group. Moreover, these measurements were lower in the treatment group than the DHEA group. In DHEA group, increased number of atretic follicles and cystic follicles were seen with light microscopic analysis. Cystic follicles with attenuated granulosa cell layers and thickened theca cell layers and lipid accumulation in interstitial cells were observed by electron microscope. It is observed that atretic and cystic follicles were decreased as a result of vitamin D treatment. Conclusion: Our results indicate the curative role of vitamin D treatment on the androgen excess in PCOS rat model which causes abnormalities in ovarian morphology and functions. Vitamin D has positive effects on the hormonal and structural changes observed in PCOS, but it has been concluded that long-term use may be more beneficial.     

A hyper-ferritinemia syndrome evolving in recurrent macrophage activation syndrome,as an onset of amyopathic juvenile dermatomyositis: A challenging clinical case in light of the current diagnostic criteria

Juvenile dermatomyositis is an immune-mediated inflammatory multi-system disease involving mainly striated muscles and skin. Typical dermatological features are fundamental to establish the diagnosis, especially whenever the myopathy is very mild or absent, as it occurs in the form called as amyopathic juvenile dermatomyositis. Sometimes, systemic rheumatic diseases can develop a hyperferritinemia syndrome characterized by hemophagocytosis, namely macrophage activation syndrome, which represents a severe and life-threatening complication. Here, we describe a complex clinical history characterized by a hyper-ferritinemia syndrome after infectious mononucleosis, leading to recurrent episodes of macrophage activation syndrome. Finally, the late onset of several skin changes brought to a diagnosis of amyopathic juvenile dermatomyositis.     

Insomnia related to postmenopausal syndrome and hormone replacement therapy: sleep laboratory studies on baseline differences between patients and controls and double-blind,placebo-controlled investigations on the effects of a novel estrogen-progestogen combination (Climodien,Lafamme) versus estrogen alone

Differences in sleep and awakening quality between 51 insomniac postmenopausal syndrome patients and normal controls were evaluated. In a subsequent double-blind, placebo-controlled, comparative, randomized, three-arm trial (Climodien 2/3 = estradiol valerate 2 mg + the progestogen dienogest 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P), the effects of 2 months of hormone replacement therapy were investigated, followed by a 2-month open-label phase in which all patients received Climodien 2/2 (EV 2 mg + dienogest 2 mg = regimen A*). Polysomnography at baseline demonstrated significantly deteriorated sleep initiation and maintenance, increased S1 and decreased S2 in patients. Subjective sleep and awakening quality, well-being, morning drive, wakefulness, memory and reaction time performance were deteriorated too. Treatment with both regimen A and regimen EV induced a moderate, although nonsignificant, improvement in the primary efficacy variable wakefulness during the total sleep period compared with baseline, while under placebo no changes occurred. Secondary efficacy variables concerning sleep initiation and maintenance, and sleep architecture showed similar findings. The apnea and apnea-hypopnea indices improved significantly under regimen A, compared with both baseline and placebo. Subjective sleep and awakening quality improved significantly after regimen A and EV compared with baseline, with the drug-induced changes being superior to those induced by placebo. In the open-label phase, subjective sleep quality improved further, significantly in the former regimen A group. Awakening quality, somatic complaints and morning thymopsyche did not yield any significant findings. Concerning morning noopsychic performance, memory improved significantly after regimen A compared with baseline, fine motor activity after regimen EV. Reaction time performance increased with all three compounds. In conclusion, Climodien significantly improved subjective sleep quality, the apnea and apnea-hypopnea indices of insomniac postmenopausal syndrome patients, while it only marginally improved variables concerning objective sleep and awakening quality.