Dampened circadian amplitude of EEG power in women after menopause.

Postmenopausal women are at high risk of developing sleep-wake disturbances. We previously reported dampened circadian rhythms of melatonin, alertness and sleep in postmenopausal compared with young women. The present study aims to further explore electroencephalography power spectral changes in the sleep of postmenopausal women. Eight healthy postmenopausal women were compared with 12 healthy, naturally ovulating, young women in their mid-follicular phase. Participants followed a regular 8-hr sleep schedule for ≥ 2 weeks prior to laboratory entry. The laboratory visit included an 8-hr baseline sleep period followed by an ultradian sleep-wake cycle procedure, consisting of alternating 1-hr wake periods and nap opportunities. Electroencephalography power spectral analysis was performed on non-rapid eye movement sleep obtained over a 48-hr period. The baseline nocturnal sleep of postmenopausal women comprised lower power within delta and sigma, and higher power within alpha bands compared with that of younger women. During nighttime naps of the ultradian sleep-wake cycle procedure, lower power within delta and sigma, and higher power within beta bands were observed in postmenopausal women. During the ultradian sleep-wake cycle procedure, postmenopausal women presented lower power of delta, theta and sigma (14-15 Hz), undetectable rhythms of delta and theta, and a dampened or undetectable rhythm of sigma (12-15 Hz) power compared with younger women. Our results support the hypothesis of a dampened circadian variation of sleep microstructure in healthy-sleeping postmenopausal women. Circadian changes with aging are potential mechanisms for increased susceptibility to develop sleep disturbances; however, further research is needed to clarify their clinical implications and contribution to insomnia.

Individual metabolomic signatures of circadian misalignment during simulated night shifts in humans.

Misalignment of the daily sleep-wake and fasting-feeding cycles with the endogenous circadian timing system is an inevitable consequence of night shift work and is associated with adverse metabolic health effects. However, a detailed characterisation of the effects of night shifts on 24-h rhythms in the metabolome is missing. We performed targeted metabolomic profiling on plasma samples collected every 2 h from healthy human subjects during two 24-h measurement periods at baseline and on the fourth day of a simulated night shift protocol, in which the habitual sleep-wake cycle was delayed by 10 h. Thirty-two out of the 130 detected metabolites showed a 24-h rhythm both at baseline and during the night shift condition. Among these, 75% were driven by sleep-wake and fasting-feeding cycles rather than by the endogenous circadian clock, showing an average phase delay of 8.8 h during the night shift condition. Hence, the majority of rhythmic metabolites were misaligned relative to the endogenous circadian system during the night shift condition. This could be a key mechanism involved in the increased prevalence of adverse metabolic health effects observed in shift workers. On the individual level, the response to the night shift protocol was highly diverse, with phase shifts of rhythmic metabolite profiles ranging from a 0.2-h advance in one subject to a 12-h delay in another subject, revealing an individual metabolomic signature of circadian misalignment. Our findings provide insight into the overall and individual responses of the metabolome to circadian misalignment associated with night schedules and may thereby contribute to the development of individually tailored strategies to minimise the metabolic impacts of shift work.

Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome.

Misalignment of the endogenous circadian timing system leads to disruption of physiological rhythms and may contribute to the development of the deleterious health effects associated with night shift work. However, the molecular underpinnings remain to be elucidated. Here, we investigated the effect of a 4-day simulated night shift work protocol on the circadian regulation of the human transcriptome. Repeated blood samples were collected over two 24-hour measurement periods from eight healthy subjects under highly controlled laboratory conditions before and 4 days after a 10-hour delay of their habitual sleep period. RNA was extracted from peripheral blood mononuclear cells to obtain transcriptomic data. Cosinor analysis revealed a marked reduction of significantly rhythmic transcripts in the night shift condition compared with baseline at group and individual levels. Subsequent analysis using a mixed-effects model selection approach indicated that this decrease is mainly due to dampened rhythms rather than to a complete loss of rhythmicity: 73% of transcripts rhythmically expressed at baseline remained rhythmic during the night shift condition with a similar phase relative to habitual bedtimes, but with lower amplitudes. Functional analysis revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways. These results show that 4 days of simulated night shifts leads to a loss in temporal coordination between the human circadian transcriptome and the external environment and impacts biological processes related to the adverse health effects associated to night shift work.

Metabolic and cardiovascular consequences of shift work: The role of circadian disruption and sleep disturbances.

Shift work, defined as work occurring outside typical daytime working hours, is associated with an increased risk of various non-communicable diseases, including diabetes and cardiovascular disease. Disruption of the internal circadian timing system and concomitant sleep disturbances is thought to play a critical role in the development of these health problems. Indeed, controlled laboratory studies have shown that short-term circadian misalignment and sleep restriction independently impair physiological processes, including insulin sensitivity, energy expenditure, immune function, blood pressure and cardiac modulation by the autonomous nervous system. If allowed to persist, these acute effects may lead to the development of cardiometabolic diseases in the long term. Here, we discuss the evidence for the contributions of circadian disruption and associated sleep disturbances to the risk of metabolic and cardiovascular health problems in shift workers. Improving the understanding of the physiological mechanisms affected by circadian misalignment and sleep disturbance will contribute to the development and implementation of strategies that prevent or mitigate the cardiometabolic impact of shift work.

Disruption of central and peripheral circadian clocks in police officers working at night.

Working atypical schedules leads to temporal misalignments between a worker's rest-activity cycle and their endogenous circadian system. Several studies have reported disturbed centrally controlled rhythms, but little is known on shift workers' peripheral clocks. Here, we assessed central clock markers, urinary 6-sulfatoxymelatonin and salivary cortisol, and clock gene expression in 2 peripheral clocks, oral mucosa cells and peripheral blood mononuclear cells (PBMCs), in 11 police officers. Before working 7 consecutive nights, officers' centrally controlled rhythms were aligned to a day-oriented schedule. These rhythms were partially realigned to the shifted schedule and dampened after a week working nights. For peripheral clocks at baseline, Period (PER)1-3 and nuclear receptor subfamily 1, group D, member 1 (REV-ERBα) in oral mucosa cells had a significant mRNA peak in the afternoon, whereas in PBMCs, higher PER1-3 expression was observed at 10:00 compared with 19:30. After a week working nights, PER1-3 and REV-ERBα expression in oral mucosa cells lost rhythmicity, and in PBMCs, the morning/evening difference observed at baseline was lost. To our knowledge, this is the first study to demonstrate the disruption of several peripheral clocks in real shift workers. Molecular circadian disturbances are believed to have important clinical implications for the occurrence of shift work-associated medical disorders.-Koshy, A., Cuesta, M., Boudreau, P., Cermakian, N., Boivin, D. B. Disruption of central and peripheral circadian clocks in police officers working at night.

Diurnal and circadian variation of sleep and alertness in men vs. naturally cycling women.

This study quantifies sex differences in the diurnal and circadian variation of sleep and waking while controlling for menstrual cycle phase and hormonal contraceptive use. We compared the diurnal and circadian variation of sleep and alertness of 8 women studied during two phases of the menstrual cycle and 3 women studied during their midfollicular phase with that of 15 men. Participants underwent an ultradian sleep-wake cycle (USW) procedure consisting of 36 cycles of 60-min wake episodes alternating with 60-min nap opportunities. Core body temperature (CBT), salivary melatonin, subjective alertness, and polysomnographically recorded sleep were measured throughout this procedure. All analyzed measures showed a significant diurnal and circadian variation throughout the USW procedure. Compared with men, women demonstrated a significant phase advance of the CBT but not melatonin rhythms, as well as an advance in the diurnal and circadian variation of sleep measures and subjective alertness. Furthermore, women experienced an increased amplitude of the diurnal and circadian variation of alertness, mainly due to a larger decline in the nocturnal nadir. Our results indicate that women are likely initiating sleep at a later circadian phase than men, which may be one factor contributing to the increased susceptibility to sleep disturbances reported in women. Lower nighttime alertness is also observed, suggesting a physiological basis for a greater susceptibility to maladaptation to night shift work in women.

Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans.

Recent research unveiled a circadian regulation of the immune system in rodents, yet little is known about rhythms of immune functions in humans and how they are affected by circadian disruption. In this study, we assessed rhythms of cytokine secretion by immune cells and tested their response to simulated night shifts. PBMCs were collected from nine participants kept in constant posture over 24 h under a day-oriented schedule (baseline) and after 3 d under a night-oriented schedule. Monocytes and T lymphocytes were stimulated with LPS and PHA, respectively. At baseline, a bimodal rhythmic secretion was detected for IL-1ß, IL-6, and TNF-α: a night peak was primarily due to a higher responsiveness of monocytes, and a day peak was partly due to a higher proportion of monocytes. A rhythmic release was also observed for IL-2 and IFN-γ, with a nighttime peak due to a higher cell count and responsiveness of T lymphocytes. Following night shifts, with the exception of IL-2, cytokine secretion was still rhythmic but with peak levels phase advanced by 4.5-6 h, whereas the rhythm in monocyte and T lymphocyte numbers was not shifted. This suggests distinct mechanisms of regulation between responsiveness to stimuli and cell numbers of the human immune system. Under a night-oriented schedule, only cytokine release was partly shifted in response to the change in the sleep-wake cycle. This led to a desynchronization of rhythmic immune parameters, which might contribute to the increased risk for infection, autoimmune diseases, cardiovascular and metabolic disorders, and cancer reported in shift workers.

An algorithmic approach to the management of insomnia in patients with schizophrenia.

BACKGROUND: Insomnia is an important problem in patients with schizophrenia and is an emerging area of interest for researchers. We propose a treatment algorithm that synthesizes the various psychological and pharmacological interventions for insomnia in this population. METHODS: Our selective literature review incorporates English language articles from 4 medicine databases through May 2016. Selected articles discuss risk factors and treatments for insomnia, as well as comorbid sleep disorders that coexist in this population. RESULTS: Various lifestyle factors and comorbid sleep disorders may predispose patients with schizophrenia to insomnia. Cognitive-behavioral therapy for insomnia shows promising results in treating insomnia in patients with schizophrenia spectrum disorders. Additionally, studies of eszopiclone and melatonin have yielded significant results in short-term trials that evaluated both subjective and objective insomnia symptoms. CONCLUSIONS: We have summarized the relevant literature regarding the treatment of insomnia in this patient population and propose an algorithm comprising 6 sequential steps, beginning with the assessment of sleep complaints and medication adherence. This is followed by a targeted treatment of any co-occurring sleep disorders, and ends with psychoeducation, cognitive-behavioral therapy, and pharmacotherapy. This algorithm provides a detailed guideline to improve the assessment and therapeutic intervention for managing insomnia among patients with schizophrenia.

Glucocorticoids entrain molecular clock components in human peripheral cells.

In humans, shift work induces a desynchronization between the circadian system and the outside world, which contributes to shift work-associated medical disorders. Using a simulated night shift experiment, we previously showed that 3 d of bright light at night fully synchronize the central clock to the inverted sleep schedule, whereas the peripheral clocks located in peripheral blood mononuclear cells (PBMCs) took longer to reset. This underlines the need for testing the effects of synchronizers on both the central and peripheral clocks. Glucocorticoids display circadian rhythms controlled by the central clock and are thought to act as synchronizers of rodent peripheral clocks. In the present study, we tested whether the human central and peripheral clocks were sensitive to exogenous glucocorticoids (Cortef) administered in the late afternoon. We showed that 20 mg Cortef taken orally acutely increased PER1 expression in PBMC peripheral clocks. After 6 d of Cortef administration, the phases of central markers were not affected, whereas those of PER2-3 and BMAL1 expression in PBMCs were shifted by ∼ 9.5-11.5 h. These results demonstrate, for the first time, that human peripheral clocks are entrained by glucocorticoids. Importantly, they suggest innovative interventions for shift workers and jet-lag travelers, combining synchronizing agents for the central and peripheral clocks.

Interindividual variability in coherence between self-reported alertness and performance in shift workers.

OBJECTIVES: Evidence indicates that self-reported measures of alertness do not always reflect performance impairments. The present study aims to explore whether subjective and objective measures of vigilance vary in the same direction in individuals working nights. METHODS: A total of 76 police officers participated to a month-long observational study. They worked either a 2 or 3-shift system during which they self-reported alertness and completed a psychomotor vigilance task several times a day. RESULTS: A reduction in alertness and reaction speed was observed with time awake. At the group level, changes in alertness and reaction speed with time awake were positively correlated during night shifts only. In 63.6% of the officers, changes were coherent between both variables. The other officers reported that their alertness dropped (25.5%) or improved (10.9%) whereas their performance changed in the opposite direction. CONCLUSION: Significant interindividual variability exists in self-appraisal vigilance impairment due to night shift work.

Circadian Adaptation of Melatonin and Cortisol in Police Officers Working Rotating Shifts.

Misalignment of behavior and circadian rhythms due to night work can impair sleep and waking function. While both simulated and field-based studies suggest that circadian adaptation to a nocturnal schedule is slow, the rates of adaptation in real-world shift-work conditions are still largely unknown. The aim of this study was to evaluate the extent of adaptation of 24-h rhythms with 6-sulfatoxymelatonin (aMT6s) and cortisol in police officers working rotating shifts, with a special attention to night shifts. A total of 76 police officers (20 women; aged 32 ± 5.4 years, mean ± SD) from the province of Quebec, Canada, participated in a field study during their 28- or 35-day work cycle. Urine samples were collected for ~32 h before a series of day, evening, and night shifts to assess circadian phase. Before day, evening, and night shifts, 60%-89% of officers were adapted to a day schedule based on aMT6 rhythms, and 71%-78% were adapted based on cortisol rhythms. To further quantify the rate of circadian adaptation to night shifts, initial and final phases were determined in a subset of 37 officers with suitable rhythms for both hormones before and after 3-8 consecutive shifts (median = 7). Data were analyzed with circular and linear mixed-effects models. After night shifts, 30% and 24% of officers were adapted to a night-oriented schedule for aMT6s and cortisol, respectively. Significantly larger phase-delay shifts (aMT6s: -7.3 ± 0.9 h; cortisol: -6.3 ± 0.8 h) were observed in police officers who adapted to night shifts than in non-adapted officers (aMT6s: 0.8 ± 0.9 h; cortisol: 0.2 ± 1.1 h). Consistent with prior research, our results from both urinary aMT6s and cortisol midpoints indicate that a large proportion of police officers remained in a state of circadian misalignment following a series of night shifts in dim-light working environments.

A shot in the dark: the impact of online visibility on the search for an effective sleep app.

STUDY OBJECTIVES: Dictated by consumer ratings and concealed algorithms, high levels of online visibility are granted to certain sleep apps on mainstream modes of app selection. Yet, it remains unclear to what extent these highly visible apps are evidence-based. The objectives of this review were to identify and describe the apps with the greatest online visibility when searching for a sleep app and to assess the claimed and actual research associated with them. METHODS: A keyword search was conducted in Google Play and Google search. Titles of the most visible apps were retrieved. App descriptions were examined to identify research claims made about app effectiveness on sleep and other health-related outcomes. A follow-up search on PubMed and Google Scholar was conducted to verify claims. RESULTS: The keyword search identified 53 highly visible apps. Examination of app store descriptions found that no reference to research was made for the majority of apps (n = 45, 84.9%). Published research studies were available for just three apps, with most studies evaluating app impact on non-sleep related outcomes. There was some evidence to attesting to the effectiveness of two apps in improving sleep. CONCLUSIONS: This review demonstrates how, when carrying out a typical search for a sleep app, information about the evidence base for the majority of highly visible apps is not available. Results highlight the need for the improvement of mainstream modes of app selection in terms of better consumer-app specificity and increased transparency regarding the access to information about the evidence base for apps.

Dopamine and light: dissecting effects on mood and motivational states in women with subsyndromal seasonal affective disorder.

BACKGROUND: Despite evidence that bright light can improve mood, the neurobiology remains poorly understood. Some evidence implicates the catecholamines. In the present study, we measured the effects of transiently decreasing dopamine (DA) synthesis on mood and motivational states in healthy women with mild seasonal mood changes who were tested in either bright or dim light. METHODS: On 2 test days, participants slept overnight in a light-controlled room. On the morning of each session, half of the participants awoke to gradual increases of bright light, up to 3000 lux, and half to dim light (10 lux). For all participants, DA was reduced on 1 of the test days using the acute phenylalanine/tyrosine depletion (APTD) method; on the other day, they ingested a nutritionally balanced control mixture (BAL). Beginning 4 hours postingestion, participants completed subjective mood questionnaires, psychological tests and a progressive ratio breakpoint task during which they worked for successive units of $5. RESULTS: Thirty-two women participated in our study. The APTD lowered mood, agreeableness, energy and the willingness to work for monetary reward. The effects on energy and motivation were independent of light, while the effects on mood and agreeableness were seen in the dim condition only, being prevented by bright light. LIMITATIONS: Acute phenylalanine/tyrosine depletion might affect systems other than DA. The sample size was small. CONCLUSION: These results suggest that increased DA function may be responsible for some of the beneficial effects of light, while adding to the evidence that the neurobiology of mood and motivational states can be dissociated.

The Effect of Night Shifts on 24-h Rhythms in the Urinary Metabolome of Police Officers on a Rotating Work Schedule.

Shift workers face an increased risk of metabolic health problems, but the direct metabolic response to working nights is not fully understood. The aim of this study was to investigate the effect of night shifts on the 24-h urinary metabolome of shift workers. Eleven police officers working rotating shifts completed two 24-h laboratory visits that took place before and after they worked 7 consecutive nights. Sleep and meals were scheduled on a day schedule in the first visit and then on a night schedule (i.e., sleep and meals shifted by approximately 12 h) in the second visit. Targeted metabolomic analysis was performed on urine samples collected throughout these laboratory visits. Differential rhythmicity analysis was used to compare 24-h rhythms in urinary metabolites in both conditions. Our results show that on the day schedule, 24-h rhythms are present in the urinary levels of the majority of metabolites, but that this is significantly reduced on the night schedule, partly due to loss of organic acid rhythmicity. Furthermore, misalignment of 24-h metabolite rhythms with the shifted behavioral cycles in the night schedule was observed in more than half of the metabolites that were rhythmic in both conditions (all acylcarnitines). These results show that working nights alters the daily rhythms of the urinary metabolome in rotating shift workers, with the most notable impact observed for acylcarnitines and organic acids, 2 metabolite classes involved in mitochondrial function. Further research is warranted to study how these changes relate to the increased metabolic risks associated with shift work.

The circadian variation of sleep and alertness of postmenopausal women.

STUDY OBJECTIVES: Several factors may contribute to the high prevalence of sleep disturbances occurring in postmenopausal women. However, the contribution of the circadian timing system to their sleep disturbances remains unclear. In the present study, we aim to understand the impact of circadian factors on changes of sleep and alertness occurring after menopause. METHODS: Eight healthy postmenopausal women and 12 healthy young women in their mid-follicular phase participated in an ultradian sleep-wake cycle procedure (USW). This protocol consisted of alternating 60-min wake periods and nap opportunities for ≥ 48 h in controlled laboratory conditions. Core body temperature (CBT), salivary melatonin, self-reported alertness, and polysomnographically recorded sleep were measured across this procedure. RESULTS: In both groups, all measures displayed a circadian variation throughout the USW procedure. Compared to young women, postmenopausal women presented lower CBT values, more stage N1 and N2 sleep, and number of arousals. They also showed a reduced amplitude of the circadian variation of melatonin, total sleep time (TST), sleep onset latency (SOL), stage N3 sleep, and alertness levels. Postmenopausal women fell asleep faster and slept more during the biological day and presented higher alertness levels during the biological night than young women. CONCLUSION: These results support the hypothesis of a weakened circadian signal promoting sleep and wakefulness in older women. Aging processes including hormonal changes may be main contributors to the increased sleep-wake disturbances after menopause.

Exploratory study of the effects of sex and hormonal contraceptives on alertness, fatigue, and sleepiness of police officers on rotating shifts.

Study Objectives: This exploratory study assessed the impact of sex and hormonal contraceptives (HC) use on the homeostatic and diurnal variation of alertness, fatigue, sleepiness, psychomotor performance, and sleep behavior in police officers working rotating shifts. Methods: A total of 56 men and 20 women (6 using, 11 not using, and 3 with unknown use of HC) participated in an observational study throughout a month-long work cycle. Participants wore an actigraph, filled out a sleep and work log, answered questionnaires (Samn-Perelli, KSS, Visual Analogue Scales), and completed 5-min Psychomotor Vigilance Tasks (PVT) according to an ecological momentary assessment approach. Linear mixed-effects models were used to analyze the effects of group (men, women, and HC use), time awake, and time of day on the dependent variables. Results: Self-reported parameters and performance significantly varied with time awake and time of day. Women were more fatigued and sleepier than men, when considering both time awake and time of day. Compared to men, women using HC were more fatigued, less alert, and sleepier. Women had less attention lapses than men after 7 and 17 h awake, although no main effect of HC was detected. Conclusions: Women tended to rate themselves as more fatigued than men, especially when using HC. Surprisingly, psychomotor performances of women were sometimes better than those of men. This exploratory study indicates that sex and HC are important factors to consider in occupational medicine.

Disturbance of the Circadian System in Shift Work and Its Health Impact.

The various non-standard schedules required of shift workers force abrupt changes in the timing of sleep and light-dark exposure. These changes result in disturbances of the endogenous circadian system and its misalignment with the environment. Simulated night-shift experiments and field-based studies with shift workers both indicate that the circadian system is resistant to adaptation from a day- to a night-oriented schedule, as determined by a lack of substantial phase shifts over multiple days in centrally controlled rhythms, such as those of melatonin and cortisol. There is evidence that disruption of the circadian system caused by night-shift work results not only in a misalignment between the circadian system and the external light-dark cycle, but also in a state of internal desynchronization between various levels of the circadian system. This is the case between rhythms controlled by the central circadian pacemaker and clock genes expression in tissues such as peripheral blood mononuclear cells, hair follicle cells, and oral mucosa cells. The disruptive effects of atypical work schedules extend beyond the expression profile of canonical circadian clock genes and affects other transcripts of the human genome. In general, after several days of living at night, most rhythmic transcripts in the human genome remain adjusted to a day-oriented schedule, with dampened group amplitudes. In contrast to circadian clock genes and rhythmic transcripts, metabolomics studies revealed that most metabolites shift by several hours when working nights, thus leading to their misalignment with the circadian system. Altogether, these circadian and sleep-wake disturbances emphasize the all-encompassing impact of night-shift work, and can contribute to the increased risk of various medical conditions. Here, we review the latest scientific evidence regarding the effects of atypical work schedules on the circadian system, sleep and alertness of shift-working populations, and discuss their potential clinical impacts.

Sleep of Healthcare Workers During the COVID-19 Pandemic and the Role of Atypical Work Schedules: A Scoping Review.

The COVID-19 pandemic has negatively impacted the well-being of healthcare workers (HCWs). HCWs are highly exposed to shift work and their work schedules have been subject to increasing unpredictability since the start of the pandemic. This review aims to: (1) map the studies providing information about factors associated with sleep characteristics in HCWs working in the context of the COVID-19 pandemic during the first and second waves and (2) examine the state of the evidence base in terms of the availability of information on the influence of atypical work schedules. A literature search was performed in PubMed. Studies containing information about factors (demographic; psychological; occupational; COVID-19-specific; work schedule; lifestyle; medical; or other) associated with various sleep characteristics among HCWs working in the context of the COVID-19 pandemic were included. Particular attention was paid to the availability of information on the role of atypical work schedules on HCW sleep. Fifty-seven articles met the inclusion criteria. Most studies were reports of quantitative cross-sectional surveys using self-report measures. Associations between female sex, frontline HCW status, psychological factors, and poorer sleep were observed. Six studies included a measure of shift work in their analyses, 5 of which reported an association between shift work status and sleep. A wide range of factors were investigated, with female sex, frontline HCW status, and psychological factors repeatedly demonstrating associations with poorer sleep. Sleep was predominantly measured in terms of self-reported sleep quality or insomnia symptoms. Few studies investigated the influence of atypical work schedules on HCW sleep in the context of the COVID-19 pandemic. Research on this topic is lacking in terms of reliable and consistent measurements of sleep outcomes, longitudinal data, and knowledge about the influence of covariates such atypical work schedules, comorbidity, and medical history on HCW sleep.

How effective are Fatigue Risk Management Systems (FRMS)? A review.

OBJECTIVE: Fatigue Risk Management Systems (FRMS) are a data-driven set of management practices for identifying and managing fatigue-related safety risks. This approach also considers sleep and work time, and is based on ongoing risk assessment and monitoring. This narrative review addresses the effectiveness of FRMS, as well as barriers and enablers in the implementation of FRMS. Furthermore, this review draws on the literature to provide evidence-based policy guidance regarding FRMS implementation. METHODS: Seven databases were drawn on to identify relevant peer-reviewed literature. Relevant grey literature was also reviewed based on the authors' experience in the area. In total, 2129 records were screened based on the search strategy, with 231 included in the final review. RESULTS: Few studies provide an evidence-base for the effectiveness of FRMS as a whole. However, FRMS components (e.g., bio-mathematical models, self-report measures, performance monitoring) have improved key safety and fatigue metrics. This suggests FRMS as a whole are likely to have positive safety outcomes. Key enablers of successful implementation of FRMS include organisational and worker commitment, workplace culture, and training. CONCLUSIONS: While FRMS are likely to be effective, in organisations where safety cultures are insufficiently mature and resources are less available, these systems may be challenging to implement successfully. We propose regulatory bodies consider a hybrid model of FRMS, where organisations could choose to align with tight hours of work (compliance) controls. Alternatively, where organisational flexibility is desired, a risk-based approach to fatigue management could be implemented.