The relationship between sleep hygiene, mood, and insomnia symptoms in men with prostate cancer

Insomnia symptoms are commonly experienced by men after prostate cancer (PCa) treatment. Here we explored how sleep hygiene behaviours and psychological symptoms are associated with insomnia symptoms in PCa patients. An online survey was posted on social media and sent to mailing lists of PCa and general cancer organisations. The survey collected information on demographic, sleep hygiene, and psychological symptoms using validated questionnaires. Data from 142 participants were compared based on the absence (age = 68.3 ± 8.9 years) and presence (age = 66.6 ± 9.0 years) of insomnia symptoms. Participants with insomnia symptoms had significantly higher levels of anxiety, depression, fatigue, and sleepiness as well as poorer sleep hygiene than those without insomnia symptoms. Control variables (age, number of comorbidities, and BMI) accounted for 11.9% of the variance in insomnia symptoms. Including treatment history contributed to an additional 1.6% of the variance in insomnia symptoms. Adding sleepiness, fatigue, anxiety, and depressive symptoms to the model explained an additional 44.6% of the variance in insomnia symptoms. Furthermore, including the sleep hygiene item ‘I think, plan, or worry when I am in bed’ and ‘I sleep in an uncomfortable bedroom’ explained an additional 3.6% of the variance in insomnia symptoms. Poor sleep hygiene, fatigue, sleepiness, anxiety, and depressive symptoms were all associated with worse insomnia symptoms in PCa patients. Improving sleep hygiene and treating psychological conditions may potentially help prevent and/or alleviate insomnia symptoms in PCa patients.


Introduction
Men with prostate cancer (PCa) are two to three time more likely to experience insomnia symptoms than men without prostate cancer [1][2][3][4][5]. A recent study also showed that poor sleep is associated with higher odds for having highgrade PCa [6]. Insomnia symptoms are also related to other symptoms in PCa patients, including depression, fatigue, and daytime sleepiness [4,7,8]. Considering that insomnia is associated with poorer psychological outcomes in cancer patients [8,9], it is important to further our understanding of what factors influence insomnia severity in PCa patients in order to improve their quality of life.
Insomnia symptoms among PCa patients can be a result of cancer treatment [3] and tend to be long lasting [10]. Prostatectomy and external beam radiation are often prescribed for localised PCa, but both may lead to urinary symptoms that can ultimately cause a disruption to sleep. A previous study reported that 31.5% of prostatectomy patients experienced insomnia symptoms [2]. In a sample of men who received brachytherapy, radical prostatectomy, or radiation, 32% reported insomnia symptoms, with men who received radiation reporting more severe insomnia [11]. Severe urinary symptoms have been shown to mediate the relationship between insomnia symptoms and receiving radiation therapy alone [3]. Another common treatment for PCa is androgen deprivation therapy (ADT) [12] which can be prescribed for systemic PCa or as an adjuvant therapy to radiation therapy [13]. ADT is associated with significantly worse insomnia symptoms [1,14] which have been attributed to the hot flashes, night sweats, and nocturia that result from deprivation of their gonadal androgens [15,16]. Accordingly, hot flashes, night sweats, and nocturia have also been demonstrated to mediate the relationship between ADT and insomnia symptoms [1,3]. Combined, it is clear that these treatments, while intended to treat disease and prevent recurrence, also come with the potential to negatively impact sleep, which can place these men at risk for poorer physical and mental recovery.
Several other factors may also be associated with insomnia symptoms in PCa patients [17][18][19]. For example, in a sample of 51 PCa patients, depression and cancer-related distress are correlated with insomnia symptoms [19]. In a more recent study with over 3000 PCa patients showed that the presence of psychological symptoms (anxiety and depression), pain, and bowel symptoms were associated with sleep disturbance [18]. In addition, there are data indicating that younger age, higher insomnia symptoms, depression, and anxiety at the start of radiation therapy are all associated with more severe sleep disturbance [17].
Physical activity may also influence sleep. While there are many studies exploring how physical activity programme may alleviate treatment side effects in PCa patients, sleep is rarely assessed. We are only aware of one study that investigated this. Data from a recent randomised clinical trial with 80 PCa patients indicate that patients who exercise intervention programme for 12 weeks had greater sleep improvements than those who did not receive the same intervention [20]. There is evidence from other cancer populations [21][22][23][24] that engaging in a greater physical activity is associated with small improvements in sleep quality. There is also support for a relationship in the opposite direction whereby decreased insomnia symptoms can increase next day physical activity [25,26].
Sleep habits may also influence sleep quality more generally [27]. For example, sleep hygiene, the practice of performing behaviours that may facilitate or hinder sleep, has been studied in a wide variety of populations that may experience sleeping difficulties [27,28]. Poor sleep hygiene, such as using the bed for activities other than sleep and sex as well as alcohol and caffeine consumption, are associated with worse sleep in non-cancer patients [29,30], but the relationship between sleep hygiene practices and insomnia symptoms in PCa patients has not been well investigated. Recent research shows that patients are generally quite willing to improve their sleep hygiene [4]. While sleep hygiene improvement alone is not sufficient to alleviate insomnia symptoms [31,32], sleep hygiene education is often included as a component of cognitive behaviour therapy (CBT) for insomnia [33]. It is important to understand which sleep hygiene behaviours influence the experience of insomnia symptoms in men with PCa as part of a more comprehensive treatment plan.
Here, we aim to further understand how sleep hygiene behaviours are associated with insomnia symptoms in PCa patients. Secondly, we will explore how psychological parameters are associated with insomnia symptoms, because some sleep hygiene behaviours appear to be related to psychological symptoms. For example, some behaviours like thinking and worrying while in bed, or going to bed while feeling distressed may be due to depression or anxiety. Others may relate to fatigue or sleepiness, such as taking prolonged or frequent daytime naps. These psychological variables have been studied previously in PCa patients [34], and may have a bidirectional relationship with insomnia symptoms (as shown in the general population) [35].

Participants
We recruited men with PCa who accessed an online survey through a link posted by PCa support groups and organisations on their social media. The participant information sheet indicated that the survey was open to all men who had been diagnosed with PCa, even if they had not received any PCa treatment. The survey was approved by the University of Otago Human Ethics Committee (Health) (H18/078) and built using the Research Electronic Data Capture (RED-Cap). The survey link generated from REDCap was then distributed to support groups and organisations who were contacted via email. This survey took approximately 45 min to complete. Once the person had consented to the study, they could then access the questionnaires.
The survey was active from August 2018 to May 2019. Within this period, those surveys which were only partially completed were excluded from the analysis. In this study, 442 people accessed the survey link, and 218 consented to the study. From this, 76 were removed because of substantial missing data. The final number of participants for the analyses in this paper was 142 and these included participants with few missing data.

Demographic
Demographic information including age, ethnicity, location, income, education, relationships status, job, comorbidities, and PCa treatment history was collected by self-report.

Insomnia Severity Index
Current insomnia symptoms (i.e. past 2 weeks) were assessed using the Insomnia Severity Index (ISI) [36]. This questionnaire asks about difficulty falling asleep, staying asleep, problems with waking too early, and satisfaction with current sleep pattern. In addition, the ISI also includes questions on how worried one is about their current sleep quality, how noticeable they think it is to others, and how much their potential sleep problems interfere with their daily functioning. Each item was rated on a scale from 0 to 4, with a higher score indicating more severe insomnia symptoms. The cut-off scores for no, mild, moderate, and severe insomnia symptoms were 0-7, 8-14, 15-21, and 22-28, respectively. The internal consistency in our sample was α = 0.90.

Sleep hygiene
The Sleep Hygiene Index [37] was used to measure how frequently the participant engaged in 13 behaviours that may potentially affect their quality of sleep. For example, it asks about frequency of getting out of bed and into bed at different times each day, or using alcohol, tobacco, or caffeine within 4 h of going to bed. Each item was rated on a 5-point scale, with a higher score indicating worse sleep hygiene. The answer options range from 'never' to 'always'. The internal consistency in our sample was α = 0.74.

Anxiety
Anxiety symptoms during the last 2 weeks were measured by the Generalised Anxiety Disorder (GAD-7) screening questionnaire [38]. This measure asks about the frequency of seven behaviours related to anxiety, covering worry, irritability, and trouble relaxing during the last 2 weeks. Each item was measured on a scale 0-3 with a higher total score indicating more severe anxious symptoms. The internal consistency in our sample was α = 0.92.

Depression
Depressive symptoms during the past weeks were measured using the Center for Epidemiologic Studies Depression (CES-D) Scale [39]. This questionnaire assessed the frequency of 20 depressive symptoms like being sad, lonely, and loss of appetite within the last week. Each question was measured on a scale of 0-3 with a higher total score indicating more severe depressive symptoms. The internal consistency in our sample was α = 0.89.

Fatigue
Fatigue levels were measured using the Brief Fatigue Inventory (BFI) [40]. This scale assessed the level of fatigue as well as how fatigue had interfered with participant's functioning across a variety of parameters within the past 24 h. This included the level of fatigue at that moment, generally in the last 24 h and the worst level experienced in the previous 24 h. Each item was measured on a scale of 0-10, with a higher score indicating a higher level of interference. The internal consistency in our sample was α = 0.96.

Sleepiness
Sleepiness was measured by the Epworth Sleepiness Scale (ESS) [41]. This questionnaire asks the respondent to reflect on their 'usual' likelihood of falling asleep in different daytime situations (e.g. when reading, talking to someone, or sitting after lunch). Each item was measured on a scale from 0 to 3, with a higher score indicating a higher chance of dozing. The internal consistency in our sample was α = 0.79.

Data analyses
These data were analysed using SPSS statistics software (IBM version 25). Demographic data were summarised based on the presence (≥ 8) or absence (< 8) of insomnia symptoms, using descriptive statistics. A distribution of ISI scores of our participants was also presented. We compared the sleep hygiene score as well as fatigue, daytime sleepiness, depressive and anxiety symptoms of our participants based on whether they experienced insomnia symptoms, using an independent samples t-test. In addition, we performed hierarchical multiple regression analyses on our sample to determine whether sleep hygiene behaviours were associated with insomnia symptoms. For this analysis, we controlled for variables which are associated with increased risk of insomnia symptoms: ADT treatment history [1], age [42], BMI [43], and number of comorbidities [44]. In step 1, control variables (age, BMI, number of comorbidities) were entered. In step 2, treatment history (prostatectomy, external beam radiation, ADT) was entered. In step 3, the total sleepiness (ESS), anxiety (GAD-7), depressive symptoms score (CES-D), and fatigue (BFI) were added. In step 4, various sleep hygiene behaviours were step-wise entered into the model. p < 0.05 was considered significant. Table 1 summarises the demographic characteristics of participants in our study, based on their ISI score. None of the demographic variable significantly differed between participants with and without insomnia symptoms. Among participants with insomnia symptoms (n = 84, 59.2%), the most common comorbidities (depression, heart attack, and circulation problems) had prevalence rates of 13.6%, 13.9%, and 12.8% respectively. The most common treatments were prostatectomy (n = 51, 60.7%), radiation therapy (n = 35, 41.7%), and ADT (n = 35, 41.7%). Thirty participants provided their ADT duration data (22.9 ± 18.6 months).
In addition, Table 3 shows how sleep hygiene behaviours are associated with insomnia symptoms in our sample. The control variables (age, number of comorbidities, BMI) accounted for 11.9% of the variance in insomnia symptoms. The addition of treatment (prostatectomy, external beam radiation, ADT) history contributed to an additional 1.6% of the variance in insomnia symptoms. When scores for anxiety, depression, fatigue, and sleepiness were added, an additional 44.6% of the variance was accounted for. When the sleep hygiene items were added in step-wise method, only two items contributed to additional 3.6% of the variance in insomnia symptoms. These were 'I think, plan, or worry when I am in bed' (β = 0.185, p = 0.035) and 'I sleep in an uncomfortable bedroom' (β = − 0.135, p = 0.047).

Discussion
Insomnia is common among PCa patients due to either psychological distress or treatment side effects. In this study, we show that insomnia symptoms are associated with various psychological (anxiety, depression, fatigue, sleepiness) as well as lifestyle (sleep hygiene) factors in the PCa population. These findings stress that PCa patients also experience concurrent psychological symptoms in addition to insomnia symptoms. Treating insomnia symptoms in this patient population may potentially alleviate other psychological symptoms [45][46][47]. While insomnia requires a multi-modal treatment to manage it, our finding also suggests the importance of including sleep hygiene education for insomnia management in PCa patient population.
In our study, 60% of participants had at least mild insomnia symptoms (≥ 8 ISI score). This is consistent with Gonzalez et al. [1] who reported that 59% of PCa patients had ≥ 8 ISI score at 1 year after receiving ADT. Furthermore, our findings are in line with Maguire et al. [18] who reported that 19% of patients endorsed 'quite a bit' or 'very much' trouble sleeping during the last week, which is similar to the 21.3% of our sample which reported moderate or severe sleep problems. Other published research has reported lower estimates of insomnia symptom prevalence. Savard et al. [2] found that 29.4%% of men who received prostatectomy had ≥ 8 ISI score. Similarly, Savard et al. [3] also showed that 41.9% of patients who received ADT as an adjuvant therapy to radiation therapy reported ≥ 8 ISI score. Differences in treatments received might explain these differences, with receipt of ADT being associated with higher insomnia severity. Regardless, the presence of insomnia suggests that this symptom should be assessed for and appropriately managed.
Patients who had more severe insomnia symptoms reported significantly higher presence anxiety and depressive symptoms. While there is some evidence in the general population to support a causal relationship between insomnia and mood disturbance [48,49], it is likely that there are also other confounding factors at play. For example, a wide range of PCa treatment side effects can also affect sleep such as hot flashes and urinary symptoms [1]. Furthermore, these side effects may also augment psychological symptoms that are present. These data therefore stress the importance of assessing and treating a variety of factors that may be of a detriment to a patients sleep.
Cognitive Behavioral Therapy for Insomnia (CBT-I) remains the first-line intervention in cancer patients [33,50] and the general population [51]. One component of CBT-I is sleep hygiene education. Our data supports the notion that behavioural adjustment may potentially help patients sleep better such as by avoiding going to bed while being distressed [52]. However, sleep hygiene improvement alone may not be sufficient as patients may have additional problems they face that affect their sleep (e.g. treatment side effects). For example, many PCa patients experience depression and anxiety [34], both of which are associated with insomnia symptoms in our sample. Thus, clinicians may need to manage these symptoms too.
Coincidentally, some sleep hygiene behaviours that were associated with insomnia symptoms appear to be related to anxiety-related behaviours, e.g. worrying or being distressed in bed. There are two possible explanations for this; that insomnia symptoms are causing more stress and worry around bedtime, or that stress and worry around bedtime are causing insomnia symptoms [53,54]. In the general population, there is a bi-directional relationship between anxiety and insomnia [35]. Such a relationship may also be present in the PCa population. Healthcare providers may need to work with patients to identify their source of anxiety and psychological distress, and plan how to best work together with patients in addressing these problems so they can have less anxiety or distress while in bed.
We also found that insomnia symptoms are related to sleepiness and fatigue. This is likely because insufficient sleep may be leaving the patient fatigued and having excessive daytime sleepiness, as also has been shown in other cancer population [21]. This finding is consistent with data from a previous study [4], where both daytime sleepiness and fatigue were elevated in participants with severe insomnia symptoms. Our data also suggest that treating insomnia symptoms in these patients is important to reduce fatigue and daytime sleepiness. Such a treatment may potentially improve patients' daytime functioning and work productivity.

Limitations
The limitations of this study include the fact that the majority of the patients were Caucasian, with a university education and high household income. Therefore, these data may not be fully representative of the wider PCa population. Furthermore, our data were collected online, so they In the first block, age, body mass index (BMI), and number of comorbidities were entered. In the second block, treatment history (prostatectomy, external beam radiation, ADT) was entered (1 = yes, 0 = no). For the third block, the total score for sleepiness (ESS), anxiety (GAD-7), depressive symptoms (CES-D), and fatigue (BFI) was entered. In the fourth block, items from the Sleep Hygiene Index were step-wise entered into the model. ps < .05 are indicated in bold may not reflect those patients who are not internet users. In addition, the self-report nature of the data may influence the accuracy, as we cannot confirm the survey data with clinical data. However, we attempt to minimise this by using validated questionnaires and by seeking help from cancer organisations to post our questionnaires. In addition, 60% of our participants have at least mild insomnia symptoms, suggesting that our survey may have been biased towards patients with insomnia even though the study was not advertised to recruit for men experiencing this symptom. Our survey did not include a control group as well (men of comparable age with no diagnosis of PCa) but insomnia is well known to increase with ageing [55]. Unfortunately, we also did not collect information on time since cancer diagnosis or detailed information about the prostatectomy or radiation therapy; all of which may potentially affect sleep. While our regression analyses do not show association of ADT experience with insomnia symptoms, this does not exclude the possibility that ADT worsens insomnia symptoms as already shown in the literature [1,56]. The discrepancy may be due to the cross-sectional nature of our study design, where patients are at various stages after their cancer treatment. Our team is currently conducting a follow-up study using actigraphy and hormonal measurements to further support the data presented in this paper. These follow-up data will give objective confirmation on sleep-wake parameters and the actual hormonal profiles of the patients.

Clinical implications
Our study has important clinical implications for the quality of life of PCa patients as many experience insomnia symptoms after receiving treatment. As stated above, treating insomnia symptoms in this patient population is likely to involve multiple approaches. CBT-I remains the treatment recommended for improving insomnia in cancer patients [33,50]. Furthermore, our data support the importance of integrating sleep hygiene education in CBT for PCa patients. Mindfulness therapy could be another potential treatment for insomnia in PCa patients as psychological factors appear to be common predictors for insomnia [57,58]. We are not aware of any studies that have investigated either therapy solely in PCa patients. However, their efficacies have been proven in breast cancer patients [59], and warrants exploration in PCa patient population.

Conclusion
In conclusion, our findings support the fact that poor sleep hygiene and psychological symptoms are associated with insomnia symptoms in PCa patients. These data emphasise the complexity of insomnia symptoms in PCa patients, and suggest that their treatment will likely require multiple approaches. In addition, the sleep hygiene education component of CBT-I is likely to be important for ensuring that patients are engaging in behaviours that facilitate their sleep. Future studies could explore interventions such as CBT-I or mindfulness for alleviating insomnia symptoms in PCa patients. PCa patients generally endorse both strategies, and those with high insomnia symptoms are more likely to use CBT-I than those with low insomnia symptoms [4].