A Historical Overview of the Role of Benzodiazepines including Clonazepam in the Treatment of Adult Restless Legs Syndrome and Periodic Limb Movements in Sleep.

In a recent survey of 16,694 people receiving treatment for Restless Legs Syndrome (RLS), approximately 25% were treated with benzodiazepines either singly or in combination with other RLS treatments. Because of the large number of people receiving benzodiazepines for treatment of RLS, we conducted a historical overview of the therapeutic role of benzodiazepines in RLS and its associated condition Periodic Limb Movements in Sleep (PLMS). We found 17 articles on the use of clonazepam in RLS, PLMS, or both, 3 on triazolam and PLMS, 1 on alprazolam and RLS, 1 on temazepam and PLMS, and 1 on nitrazepam and PLMS. The order of benefit of benzodiazepines from the summarized literature is Sleep>RLS>PLMS and arousals > PLMS. Most of the studies on clonazepam employed dosages of 0.5-2.0 mg. Dosages of 3 or 4 mg caused lethargy, somnolence and confusion. An epidemiological study on the therapy of RLS suggests that treatment of RLS with most types of RLS medications including benzodiazepines in combination with other RLS therapies lowers the future cardiovascular risk associated with RLS. The major effect of benzodiazepines is through potentiation of the effect of GABA on the GABA A receptor. Neuroimaging studies suggest that GABA is altered either positively or negatively in various brain regions in RLS and genetic studies suggest that there are alterations in the GABA receptor in RLS. These results suggest that medications with different GABAergic mechanisms such as tiagabine (Gabitril) or others should be investigated in RLS for their possible therapeutic benefit. Highlights: Benzodiazepines are frequently used as therapy in Restless Legs Syndrome (RLS) and Periodic Limb Movements in Sleep. The order of benefit is Sleep>RLS>PLMS and arousals > PLMS. For clonazepam dosages of 0.5 mg-2.0 mg/day are most frequently employed. Benzodiazepines exert their therapeutic effect through GABA-ergic mechanisms.

Sleep improvement with levodopa/carbidopa intestinal gel infusion in Parkinson disease.

BACKGROUND: Sleep disorders are common in patients with advanced Parkinson's disease (PD). Nocturnal akinesia and sleep fragmentation frequently coexist with daytime sleepiness, influencing daytime functioning. Levodopa/carbidopa intestinal gel (LCIG) infusion has been shown to improve motor complications in advanced PD, and preliminary findings suggest that sleep might improve following LCIG infusion. OBJECTIVE: To analyze the impact of LCIG infusion on sleep symptoms and daytime sleepiness in patients with PD. METHODS: Twelve consecutive patients with PD completed the PD-Sleep-Scale-version-2 (PDSS-2) and the Epworth-Sleepiness-Scale (ESS) at baseline and after 2-4 months of LCIG treatment. Activities of daily living, motor symptoms and complications were assessed with the Unified-PD-rating-Scale section II, III, and IV. RESULTS: Nocturnal sleep improved substantially in all patients switched to LCIG infusion. PDSS-2 total score and subscores for 'Disturbed sleep', 'Motor symptoms at night', and 'PD symptoms at night' were significantly reduced. ESS measures of daytime sleepiness also improved. Motor complications and activities of daily living improved significantly with LCIG. CONCLUSION: Subjective measures of sleep quality and daytime sleepiness improve in patients with advanced PD undergoing LCIG infusion. Further studies with a larger number of patients and polysomnographic recordings are needed to confirm the beneficial effect on sleep and clarify the underlying mechanisms.

The influence of the tricyclic antidepressant amitriptyline on periodic limb movements during sleep.

INTRODUCTION: Many antidepressants are associated with periodic limb movements (PLM) during sleep. Although some tricyclic antidepressants, such as amitriptyline, promote sleep and are thus often prescribed as a treatment for sleep disturbances that can accompany depression, it remains unclear whether amitriptyline is associated with PLM. METHODS: 32 healthy males (18-39 years) spent 2 consecutive nights in the sleep lab for polysomnographic recording. During the second night, they received either 75 mg amitriptyline or placebo in a randomized, double-blind, placebo-controlled manner. RESULTS: In subjects receiving amitriptyline but not in subjects receiving placebo, the number of periodic leg movements per h was significantly increased from baseline to intervention night. However, objective polysomnographic sleep parameters (such as the number of awakenings, wake after sleep onset, and sleep efficiency) and subjective sleep perception were not significantly associated with any PLM indices. DISCUSSION: Our findings indicate that amitriptyline can induce or even increase the number of PLM during sleep in healthy subjects. When treating sleep disturbances with amitriptyline, PLM should be considered as a possible cause of insufficient improvement.

Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis.

STUDY OBJECTIVES: Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for treatment. We systematically reviewed the available literature to describe which drug categories are effective in suppressing PLMS, assessing their efficacy through a meta-analysis, when this was possible. METHODS: The review protocol was preregistered on PROSPERO (CRD42021175848), and the systematic search was conducted on and EMBASE (last searched on March 2020). We included original human studies, which assessed PLMS modification on drug treatment with a full-night polysomnography, through surface electrodes on each tibialis anterior muscle. When at least 4 studies were available on the same drug or drug category, we performed a random-effect model meta-analysis. RESULTS: Dopamine agonists like pramipexole and ropinirole resulted the most effective, followed by l-dopa and other dopamine agonists. Alpha2delta ligands are moderately effective as well opioids, despite available data on these drugs are much more limited than those on dopaminergic agents. Valproate and carbamazepine did not show a significant effect on PLMS. Clonazepam showed contradictory results. Perampanel and dypiridamole showed promising but still insufficient data. The same applies to iron supplementation. CONCLUSIONS: Dopaminergic agents are the most powerful suppressors of PLMS. However, most therapeutic trials in restless legs syndrome do not report objective polysomnographic findings, there is a lack of uniformity in presenting results on PLMS. Longitudinal polysomnographic interventional studies, using well-defined and unanimous scoring criteria and endpoints on PLMS are needed. CITATION: Riccardi S, Ferri R, Garbazza C, Miano S, Manconi M. Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis. J Clin Sleep Med. 2023;19(4):811-822.

A 9-year-old female with iron deficiency has severe periodic limb movements while taking mirtazapine for insomnia.

Mirtazapine is a Food and Drug Administration-approved atypical antidepressant used off-label for insomnia. Mirtazapine has been associated with movement disorders in adults. A 9-year-old female was seen in the sleep clinic for symptoms of insomnia, nocturnal awakenings, restless sleep, and growing pains. Mirtazapine was started prior to presentation for severe insomnia. A sleep study showed frequent repetitive leg movements prior to sleep onset as well as significant periodic limb movement disorder with a periodic limb movement index of 25.1/hour. The child was found to have a ferritin level of 23 ng/mL and an iron saturation of 10%. There were concerns that the presence of iron deficiency along with the use of mirtazapine may have contributed to the elevated periodic limb movement index. After starting iron therapy to treat the child's iron deficiency, mirtazapine was weaned off, with further clinical improvements in sleep quality reported. A follow-up sleep study showed a resolution of her periodic limb movement disorder with a periodic limb movement index of 1.4/hour. This is the first pediatric case to describe a sleep-related movement disorder associated with the use of mirtazapine and polysomnographic data to support resolution after discontinuation of mirtazapine along with iron therapy. CITATION: Hawkins M. A 9-year-old female with iron deficiency has severe periodic limb movements while taking mirtazapine for insomnia. J Clin Sleep Med. 2023;19(7):1369-1373.

Evaluation of periodic limb movements in a putative animal model of restless leg syndrome.

Restless leg syndrome (RLS) is a major healthcare burden with increasing prevalence. It has been demonstrated that periodic limb movements (PLM) can occur as an isolated phenomenon, but they are often associated with this syndrome and are the only symptom of this disorder that can be measured electrophysiologically. The aim of this study was to examine the sleep-wake behavior and the presence of limb movement in a rat model of RLS induced by lesioning the A11 dopaminergic nuclei with the neurotoxin 6-hydroxydopamine (6-OHDA). Rats were implanted with electrodes for electrocorticography and electromyography. Sleep recordings were monitored during light/dark periods lasting 12 hours each and were evaluated on days 7, 15, and 28 after injection of the drug or phosphate-buffered saline (PBS). A control group that did not receive any injection was also included. Wakefulness percentages were generated for 4-hour segments of the dark period, yielding the following 3 bins: 7 PM to 11 PM, 11 PM to 3 AM, and 3 PM to 7 PM. Additionally, slow wave sleep, paradoxical sleep, wakefulness, and limb movements were evaluated over the entire 12 hours of the light/dark cycle. All A11-lesioned rats exhibited an increased percentage of wakefulness during the last block of the dark period, as would be expected for an animal model of this syndrome. In addition, at all time points after lesioning, these animals presented increased frequencies of limb movement during both the light and the dark periods. These alterations were reversed by the acute administration of the dopaminergic agonist pramipexole. This animal model strengthens the notion that 6-OHDA-induced A11 lesions can be a valid animal model for RLS and PLM.

Intravenous iron therapy in the pediatric sleep clinic: a single institution experience.

STUDY OBJECTIVES: Initial reports of intravenous (IV) iron administration have been promising for children with restless legs syndrome, periodic limb movement disorder, and restless sleep disorder. The aim of the current study was to evaluate further the clinical response to IV iron supplementation in children seen in a pediatric sleep clinic. METHODS: We performed a retrospective chart review of children cared for in a single pediatric sleep clinic who also underwent IV iron infusion. Pre and post IV data regarding their sleep symptoms and ferritin levels were abstracted. RESULTS: Overall, 63 pediatric sleep patients underwent IV iron infusion, mostly with ferric carboxymaltose (n = 60), for restless legs syndrome (n = 30), periodic limb movement disorder (n = 22), and restless sleep disorder (n = 17). Of the 59 patients with clinical follow-up, 39 (73%) noted improvement in at least 1 symptom, and 14 (26%) did not notice improvement or noticed worsening symptoms. Of the 59 patients with preinfusion and postinfusion labs, the average ferritin level increased from 21.7 (13.3) to 147.9 (120.9) µg/L, P < .001. Comparing patients who experienced clinical improvement vs those who did not, there were no statistically significant differences in change in ferritin levels (P = .278), sex (P = .452), or age (P = .391). Ferritin change with infusion according to diagnostic subgroups (restless legs syndrome/periodic limb movement disorder/restless sleep disorder) was examined, and no significant differences were noted (F(2,56) = 0.852, P = .432). In terms of immediate adverse reactions to the IV infusion, 7 (11%) experienced at least 1 side effect, with the most common being behavior change (n = 6) or gastrointestinal discomfort (n = 4); no episodes of anaphylaxis or extravasation were noted. CONCLUSIONS: These data provide additional support for the efficacy and safety of IV iron for pediatric restless legs syndrome, periodic limb movement disorder, and restless sleep disorder recalcitrant to oral iron. CITATION: Ingram DG, Al-Shawwa B, DelRosso LM, Sharma M. Intravenous iron therapy in the pediatric sleep clinic: a single institution experience. J Clin Sleep Med. 2022;18(11):2545-2551.

Review of periodic limb movement and restless leg syndrome.

Periodic limb movement (PLM) and Restless leg syndrome (RLS) are types of sleep disorders that are not very well recognized in clinical practice. While RLS is a clinical diagnosis, the diagnosis of PLM is made by polysomnography. They share the same pathophysiology and often respond to the same treatment. To date all the epidemiological studies have reported the prevalence between 2% and 15%. It has recently become known that mild obstructive sleep apnea and upper airway resistance syndrome (UARS) can masquerade as PLM syndrome. New discoveries have been made with regard to genetics and PLM and RLS. Detailed review on this subject should improve the awareness of these disorders, both among general physicians and specialists. Extensive review of journals in the past 20 years was made using Medline search.

Restless Legs Syndrome and Other Common Sleep-Related Movement Disorders.

PURPOSE OF REVIEW: In this article, the different sleep-related movement disorders are discussed with special attention given to restless legs syndrome (RLS). RECENT FINDINGS: The differential diagnosis of sleep-related movement disorders can often be challenging; therefore, it is essential to have accurate information to make a correct diagnosis. This article focuses on RLS, highlighting the change in the paradigm of initial treatment, the role played by iron (pathophysiologic and therapeutic), and how to approach possible complications occurring with long-term treatment. SUMMARY: RLS is one of the most common neurologic conditions, and it is common in clinical practice to find patients experiencing symptoms suggestive of RLS. Neurologists must be careful and thorough in the diagnosis, excluding RLS mimics. The decisions regarding which specific sleep-related movement disorder is present and how it should be treated are important because in certain cases, especially in RLS, adverse effects and long-term complications are frequently reported with the use of certain drugs.

Actimetry-Documented Persistent Periodic Limb Movements During EEG-Confirmed Deep General Anesthesia: A Case Report.

Motor activity during general anesthesia (GA) without neuromuscular blockade is often interpreted as reflecting insufficient anesthesia. Here we present the case of an octogenarian undergoing deep sclerectomy with opioid-sparing electroencephalography (EEG)-guided anesthesia. Periodic leg movements (PLM) appeared during ongoing surgery while the patient's raw EEG displayed a pattern of deep anesthesia, evidenced by burst suppression. Recognizing PLM in the context of opioid-sparing GA is of importance for anesthesiologists, as deep anesthesia is not necessarily associated with a decrease in motor activity.

Determinants of ferritin response to oral iron supplementation in children with sleep movement disorders.

STUDY OBJECTIVES: To identify children who respond to oral iron supplementation as evidenced by increased ferritin levels and to identify factors that correlate with improvement in ferritin levels in those who respond. METHODS: A retrospective chart review of the PLMS/RLS/RSD database at Seattle Children's Hospital was carried out. Data collected included nocturnal polysomnography parameters, age, sex, initial and follow-up ferritin level and date of collection, and presence of restless legs syndrome (RLS), periodic limb movements of sleep (PLMS)/PLM disorder (PLMD), restless sleep disorder (RSD), obstructive sleep apnea (OSA), neurologic, psychiatric, neurodevelopmental, or medical comorbidity. Oral iron therapy was evaluated by side effects (none; constipation; bad taste/nausea), subjective outcome in symptoms (resolved, improved, no change), and adherence to therapy (poor, fair, good). RESULTS: Seventy-seven children were included in this study of whom 42 were classified as responders (increase in ferritin of ≥10 µg/L) and 35 were nonresponders. Age and sex were not different between groups. Adherence was the only significant predictor of an increase in ferritin of ≥10 µg/L. Constipation was seen in 7.1% of responders vs. 45.8% of nonresponders. No change in symptoms was reported in 26.2% of responders vs. 71.4% in nonresponders. A significant correlation was found between treatment duration and ferritin level change in responders but not in nonresponders. CONCLUSIONS: Side effects hinders adherence to oral iron supplementation in children. Responders to oral iron show improvement in ferritin levels and symptoms, while nonresponders show no improvement in ferritin levels despite a long-lasting treatment, at least in part of them.

Children show individual night-to-night variability of periodic limb movements in sleep.

STUDY OBJECTIVE: Several studies have documented the occurrence of significant night-to-night variability of periodic limb movements in sleep (PLMS) in adults.The aim of this study was to investigate the night-tonight variability of PLMS in children. DESIGN AND MEASUREMENTS: Two to 4 nights of polysomnography were performed as part of a multisite, placebo-controlled study investigating the effects of carbidopa/levodopa on attention-deficit/hyperactivity disorder in children who were not taking other medications that impacted the central nervous system. Baseline polysomnograms from all children and endpoint polysomnograms from children who were randomly assigned to a placebo group were scored using International Restless Legs Syndrome Study Group criteria for PLMS. PLMS indexes from 101 sleep studies of 36 children, aged 7 to 12 years, were compared. INTERVENTIONS: N/A. RESULTS: For all 36 children as a group, PLMS index on Night 1 was predictive of PLMS index on Night 2 (odds ratio 7.0, 95% confidence interval 1.4-38.4), suggesting that overall diagnostic classification (PLMS index above or below 5/h) was accurate. In addition, for the 15 children with 5 or more PLMS per hour on either night, there was no significant group difference on Night 1 versus Night 2 for mean PLMS index (10.6 vs 8.5/h, P = 0.92) or chance of having 5 or more PLMS per hour, indicating no first-night effect. When looking at individual data, however, 9 of these 15 children (60%) had PLMS indexes over and under the 5 per hour cutoff on these 2 nights. Of these 15, 10 had clinical diagnoses of restless legs syndrome and 5 of periodic limb movement disorder (PLMD). The PLMS indexes of all children who were medication free for a third and fourth night (n = 7) or just a third night (n = 2) and had not shown a PLMS index of 5 or greater on either of the first 2 nights remained under this threshold. CONCLUSIONS: In this sample of children, considerable individual night-to-night variability of PLMS indexes was observed. This finding has important clinical relevance for the diagnosis of restless legs syndrome and PLMD and may have an impact on future studies that correlate individual PLMS severity with frequently associated symptoms, such as negative affect, fatigue, and inattention. Our data, however, also suggest that individual PLMS variability is random and not likely to skew the group-level analysis of treatment outcome studies.

Sleep-associated movement disorders and heart failure.

Sleep-associated movement disorders are a broad group of sleep disorders characterized by involuntary movements that may disrupt sleep. Relatively little is known about the clinical consequences of sleep-associated movement disorders on cardiovascular health. Because these disorders manifest mostly during sleep, recognizing a movement disorder can be particularly difficult. Nevertheless, patients can have frequent arousals and suffer from similar sleep deprivation, fragmentation, and autonomic disruption as occurs in sleep-disordered breathing. Subsequently, these disorders may have a serious impact on daytime function and perception of health in patients with chronic heart failure.

[Sleep-related movement disorders]. / Søvnrelaterte bevegelsesforstyrrelser.

BACKGROUND: Restless legs syndrome is a common cause of sleep problems; the condition is often associated with periodic limb movement during sleep. The syndrome is probably under-diagnosed and under-treated. MATERIAL AND METHODS: The article is based on literature identified through a search in PubMed, a review of international recommendations and our own clinical experience. RESULTS: The restless leg syndrome is common, with a prevalence of about 10 %. Many of these patients are affected by sleep disturbances and have periodic limb movement during sleep (PLMS). Restless legs and the associated sleep disturbances can be effectively treated with dopaminagonists. Because of the augmentation risk, the lowest necessary dose should be maintained. PLMS also occurs in other sleep disorders. Periodic limb movement disorder (PLMD) is defined as PLMS combined with sleep disturbances and/or sleepiness during daytime without a known cause. The clinical relevance of PLMD for sleep disturbances is not clear. INTERPRETATION: The restless legs syndrome is a common cause of sleep disturbance; good treatment options are available.

Magnesium supplementation for the treatment of restless legs syndrome and periodic limb movement disorder: A systematic review.

Magnesium supplementation is often suggested for restless legs syndrome (RLS) or period limb movement disorder (PLMD) based on anecdotal evidence that it relieves symptoms and because it is also commonly recommended for leg cramps. We aimed to review all articles reporting the effects of magnesium supplementation on changes in RLS and/or PLMD. We conducted a systematic search looking for all relevant articles and then two reviewers read all article titles and abstracts to identify relevant studies. Eligible studies were scored for their quality as interventional trials. We found 855 abstracts and 16 of these could not be definitively excluded for not addressing all aspects of our research question. Seven full-text articles were unlocatable and one was ineligible which left eight studies with relevant data. One was a randomised placebo-controlled trial, three were case series and four were case studies. The RCT did not find a significant treatment effect of magnesium but may have been underpowered. After quality appraisal and synthesis of the evidence we were unable to make a conclusion as to the effectiveness of magnesium for RLS/PLMD. It is not clear whether magnesium helps relieve RLS or PLMD or in which patient groups any benefit might be seen.

Images: Identification and Effect of Periodic Limb Movements in End-Stage Renal Disease.

None: Sleep disorders are prevalent in patients with end-stage renal disease (ESRD). In those patients on nocturnal dialysis, it is important to perform objective sleep assessment during regular dialysis. We present the case of a man on continuous cycler peritoneal dialysis with disabling fatigue and moderate restless legs syndrome (RLS). Actigraphy demonstrated excessive nocturnal movement. Unattended home polysomnography, performed during his regular peritoneal dialysis, confirmed frequent nocturnal periodic limb movements with disturbed sleep. Treatment with low dose pramipexole led to improved RLS and marked improvement in his energy. Clinicians caring for patients with ESRD should have a low threshold for objective sleep assessment given that sleep disorders are common, disabling and eminently amenable to treatment.

Improvement of Parasomnias After Treatment of Restless Leg Syndrome/ Periodic Limb Movement Disorder in Children.

STUDY OBJECTIVES: Previous studies have shown that non-rapid eye movement (NREM) sleep parasomnias commonly coexist with restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in children, leading to speculation that RLS/PLMD may precipitate or worsen parasomnias. However, there are limited data about the effect of the treatment of RLS/PLMD on parasomnias in children. Hence, we performed this study to determine whether the treatment of RLS/PLMD with oral iron therapy is associated with improvement of parasomnias in children. METHODS: A retrospective database was created for children with RLS/PLMD who were treated with iron therapy. These participants were followed for at least 1 year at Cincinnati Children's Hospital Medical Center. All participants had ferritin level testing and were treated with iron therapy. In addition, all participants underwent polysomnography before starting iron therapy for RLS/PLMD except for one participant who was already on iron but required a higher dose. Most participants underwent polysomnography after iron therapy. RESULTS: A total of 226 participants were identified with the diagnosis of RLS/PLMD. Of these, 50 had parasomnias and 30 of them were treated with iron therapy. Of the 30 participants, RLS symptoms improved in 15 participants (50%) and resolution of parasomnias was noted in 12 participants (40%) participants after iron therapy. Repeat polysomnography after iron therapy was performed in 21 participants (70%). After iron therapy, there was a significant decrease in periodic limb movement index (17.2 ± 8.8 [before] versus 6.7 ± 7.3 [after] events/h, P < .001). In addition, there were significant decreases in PLMS (24.52 ± 9.42 [before] versus 7.50 ± 7.18 [after] events/h, P < .0001), PLMS-related arousals (4.71 ± 1.81 [before] versus 1.35 ± 1.43 [after] events/h, P < .0001), and total arousals (11.65 ± 5.49 [before] versus 8.94 ± 3.65 [after] events/h, P < .01) after iron therapy. CONCLUSIONS: Parasomnias are common in our cohort of children with RLS/PLMD. Iron therapy was associated with a significant improvement in periodic limb movement index, RLS symptoms, and resolution of a significant proportion of NREM sleep parasomnias, suggesting that RLS/PLMD may precipitate NREM sleep parasomnia.

Defining the boundaries of the response of sleep leg movements to a single dose of dopamine agonist.

STUDY OBJECTIVES: To define which leg movements (LM) associated with restless legs syndrome (RLS) respond to dopamine-agonist treatment and verify if they fall within current diagnostic criteria for periodic LM during sleep (PLMS). DESIGN: Single-blind placebo-controlled study. SETTINGS: Sleep laboratory. PATIENTS: 43 consecutive untreated patients with idiopathic restless legs syndrome. INTERVENTIONS: Patients underwent clinical and neurophysiological evaluation, hematological screening, and 2 consecutive full-night polysomnographic studies. Before the second polysomnographic study, all patients were randomized to receive 0.25 mg of pramipexole or placebo. MEASUREMENTS AND RESULTS: LM parameters such as duration, amplitude, interval, and periodicity were analyzed. Compared to placebo, pramipexole significantly (P < 0.01) reduced PLMS while increasing sleep efficiency. Specifically we observed a significant (P < 0.01) reduction in LM ranging 2-4 s in duration and with intermovement interval of 6-46 s and a significant decrease in the periodicity of motor events. No effect of pramipexole was observed on isolated LM. CONCLUSIONS: These results support a heterogeneous basis for LM in RLS patients; while isolated LM do not respond to pramipexole treatment, most, but not all, PLMS classified by means of the current criteria do. Further studies with different pramipexole doses or dopamine agonists with different receptor-binding preference are warranted to better define the borders of dopamine response of PLMS.

Effects of hormone therapy with estrogen and/or progesterone on sleep pattern in postmenopausal women.

OBJECTIVE: To investigate the effects of estrogen and progesterone on sleep in postmenopausal women. METHOD: The 33 participants were randomly assigned to an estrogen or placebo group after undergoing clinical and hormonal assessments and a polysomnogram, and they underwent the same tests again after 12 weeks. Then, while still taking estrogen or placebo, they all received progesterone for another 12 weeks and underwent a final polysomnogram. RESULTS: Estrogen plus progesterone was more effective than estrogen alone in decreasing the prevalence of periodic limb movement (PLM) (8.1% vs 2.8%), hot flashes (14.2% vs 0%), and bruxism (11.1% vs 0%) at night, or somnolence and attention difficulty during the day. The prevalences of breathing irregularities, arousal from sleep, anxiety, and memory impairment were decreased in both groups following progesterone treatment. CONCLUSION: While not significantly affecting sleep quality, hormone therapy decreased the prevalence of arousal in both groups and that of PLM in the group treated with estrogen plus progesterone.