madman
Super Moderator
5.1 Introduction
In the past few decades, our knowledge of the role that sleep exerts on many aspects of health has expanded significantly. Disordered sleep has been shown to negatively impact cardiometabolic health, diminish psychomotor performance, and affect multiple other physiological functions that are pertinent to men’s health. Disordered sleep may be restricted or insufficient (decreased total sleep time), misaligned to the endogenous circadian rhythm (as may be seen in night-shift workers), or disrupted (as occurs with nocturia or obstructive sleep apnea). Insufficient, misaligned, and disrupted sleep has distinct effects on sleep architecture. Since each sleep stage serves specific physiological functions, insufficient, misaligned, and disrupted sleep could differentially influence different aspects of andrological and metabolic health. Conceptualizing this requires an understanding of normal sleep architecture.
The adult human sleep cycle is 90–120 minutes in duration. Sleep cycles are divided into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Each stage of sleep can be recognized by characteristic electrophysiological features: specific waveforms and frequencies of brain activity on electroencephalogram (EEG), rolling or saccadic eye movements detected by electrooculogram, and skeletal muscle activity revealed by electromyography. NREM sleep contributes to 75–80% of total sleep time and is itself subdivided into three stages: N1, N2, and N3. N1 generally progresses to N3 as sleep deepens and waveform frequencies slow on the EEG. Stage 3 NREM sleep, also known as slow-wave sleep (SWS), typically occurs during the first one-third of the night and is believed to be the most restorative type of sleep that underpins important metabolic processes, including restoring insulin sensitivity [1, 2]. During SWS, cerebral blood flow and metabolism are reduced. There is also increased secretion of growth hormone during SWS [1]. In contrast, REM sleep contributes to 20–25% of the total time spent in sleep, and REM cycles progressively lengthen as the night progresses [3]. REM sleep is required for memory consolidation and for a sleep-related increase in systemic testosterone exposure [4]
Restricting sleep decreases total sleep time, but SWS tends to be maintained, so metabolic processes dependent on SWS such as insulin sensitivity may also be relatively preserved. Circadian misalignment of sleep may advance (initiating sleep earlier) or delay sleep (initiating sleep later). When sleep is advanced, SWS and REM are reduced. When sleep is delayed, N2 decreases, SWS is preserved, and REM sleep increases [5]. Disrupted sleep interrupts normal sleep architecture by interfering with the orderly progression of the sleep stages. Causes of disrupted sleep include environmental (e.g., light, noise, and bed partner movements) and pathologic (e.g., nocturia and OSA) factors. OSA may sometimes disrupt REM sleep in particular, when the collapsibility risk from reduced upper airway muscular tone is predominant. Accordingly, a reduction in systemic testosterone exposure with REM-associated OSA would be expected.
*This chapter focuses on the effects of common causes of disordered sleep on andrological health, emphasizing well-established surrogates such as semen parameters for male fertility and circulating testosterone concentrations for hypogonadism.
5.2 Insufficient Sleep
Some causes of insufficient sleep include lifestyle and environmental factors, such as shift work, noise, prolonged working hours, and jet lag; other causes include sleep disorders such as insomnia and other medical conditions [3]. Insufficient sleep is linked to increased mortality, andrological and cardiovascular disease, and metabolic disorders including diabetes mellitus. Interventional studies investigating the effects of restricting sleep reveal worsened insulin resistance and increased blood pressure, especially nocturnal blood pressure [8].
*5.2.1 Effect on Reproductive Health
5.3 Misaligned Sleep
Common causes of misaligned sleep include jetlag (fast trans-meridian travel) and certain work schedules (night and alternating shift work).
*5.3.1 Effect on Reproductive Health
5.4 Disrupted Sleep
Many medical conditions disrupt sleep. Perhaps the most common cause is obstructive sleep apnea (OSA). Nocturia, due to prostatic problems or diuretic use, is also a common cause. Other causes include poorly controlled asthma, heart failure, and gastroesophageal reflux disease.
*5.4.1 Effects on Reproductive Health
*5.4.2 Testosterone Replacement Therapy and Obstructive Sleep Apnea
Testosterone therapy is widely believed to induce or worsen sleep apnea, but the evidence that underpins this relationship is weak [37]. Nevertheless, two randomized controlled trials do show that testosterone therapy can acutely induce sleep-disordered breathing.
Two other randomized, placebo-controlled, parallel-group studies have partly filled this gap in knowledge by investigating the effect of longer-term replacement dose and more steady-state testosterone therapy on sleep-disordered breathing [49, 50].
*Overall, studies show some evidence that the initiation of testosterone therapy might induce or worsen OSA, but any effects are moderate in size and may not persist. Nevertheless, the Endocrine Society has made, for now, a prudent recommendation to avoid initiating testosterone therapy in those with untreated severe OSA [37].
5.5 Conclusion
Disordered sleep can be categorized as insufficient, misaligned, or disrupted. Epidemiological data have established a relationship between disordered sleep and increased mortality, cancer, cardiovascular disease, insulin resistance, and type 2 diabetes mellitus. This review shows that disordered sleep also affects andrological health: insufficient sleep decreases testosterone, whereas circadian misalignment due to shift work or simulated shift work schedule per se does not. Disrupted sleep due to obstructive sleep apnea is associated with lower systemic testosterone concentrations, although this may be due to concomitant adiposity. Preliminary data suggest the possibility that male fertility and semen parameters may also be impacted by sleep duration, but the impacts of circadian misalignment and/or disrupted sleep on fertility have not yet been studied comprehensively. In any case, sleep should be prioritized and valued to promote overall health, including andrological well-being. Methods to minimize deleterious effects of shift work and to promote CPAP adherence remain important research priorities.
In the past few decades, our knowledge of the role that sleep exerts on many aspects of health has expanded significantly. Disordered sleep has been shown to negatively impact cardiometabolic health, diminish psychomotor performance, and affect multiple other physiological functions that are pertinent to men’s health. Disordered sleep may be restricted or insufficient (decreased total sleep time), misaligned to the endogenous circadian rhythm (as may be seen in night-shift workers), or disrupted (as occurs with nocturia or obstructive sleep apnea). Insufficient, misaligned, and disrupted sleep has distinct effects on sleep architecture. Since each sleep stage serves specific physiological functions, insufficient, misaligned, and disrupted sleep could differentially influence different aspects of andrological and metabolic health. Conceptualizing this requires an understanding of normal sleep architecture.
The adult human sleep cycle is 90–120 minutes in duration. Sleep cycles are divided into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Each stage of sleep can be recognized by characteristic electrophysiological features: specific waveforms and frequencies of brain activity on electroencephalogram (EEG), rolling or saccadic eye movements detected by electrooculogram, and skeletal muscle activity revealed by electromyography. NREM sleep contributes to 75–80% of total sleep time and is itself subdivided into three stages: N1, N2, and N3. N1 generally progresses to N3 as sleep deepens and waveform frequencies slow on the EEG. Stage 3 NREM sleep, also known as slow-wave sleep (SWS), typically occurs during the first one-third of the night and is believed to be the most restorative type of sleep that underpins important metabolic processes, including restoring insulin sensitivity [1, 2]. During SWS, cerebral blood flow and metabolism are reduced. There is also increased secretion of growth hormone during SWS [1]. In contrast, REM sleep contributes to 20–25% of the total time spent in sleep, and REM cycles progressively lengthen as the night progresses [3]. REM sleep is required for memory consolidation and for a sleep-related increase in systemic testosterone exposure [4]
Restricting sleep decreases total sleep time, but SWS tends to be maintained, so metabolic processes dependent on SWS such as insulin sensitivity may also be relatively preserved. Circadian misalignment of sleep may advance (initiating sleep earlier) or delay sleep (initiating sleep later). When sleep is advanced, SWS and REM are reduced. When sleep is delayed, N2 decreases, SWS is preserved, and REM sleep increases [5]. Disrupted sleep interrupts normal sleep architecture by interfering with the orderly progression of the sleep stages. Causes of disrupted sleep include environmental (e.g., light, noise, and bed partner movements) and pathologic (e.g., nocturia and OSA) factors. OSA may sometimes disrupt REM sleep in particular, when the collapsibility risk from reduced upper airway muscular tone is predominant. Accordingly, a reduction in systemic testosterone exposure with REM-associated OSA would be expected.
*This chapter focuses on the effects of common causes of disordered sleep on andrological health, emphasizing well-established surrogates such as semen parameters for male fertility and circulating testosterone concentrations for hypogonadism.
5.2 Insufficient Sleep
Some causes of insufficient sleep include lifestyle and environmental factors, such as shift work, noise, prolonged working hours, and jet lag; other causes include sleep disorders such as insomnia and other medical conditions [3]. Insufficient sleep is linked to increased mortality, andrological and cardiovascular disease, and metabolic disorders including diabetes mellitus. Interventional studies investigating the effects of restricting sleep reveal worsened insulin resistance and increased blood pressure, especially nocturnal blood pressure [8].
*5.2.1 Effect on Reproductive Health
5.3 Misaligned Sleep
Common causes of misaligned sleep include jetlag (fast trans-meridian travel) and certain work schedules (night and alternating shift work).
*5.3.1 Effect on Reproductive Health
5.4 Disrupted Sleep
Many medical conditions disrupt sleep. Perhaps the most common cause is obstructive sleep apnea (OSA). Nocturia, due to prostatic problems or diuretic use, is also a common cause. Other causes include poorly controlled asthma, heart failure, and gastroesophageal reflux disease.
*5.4.1 Effects on Reproductive Health
*5.4.2 Testosterone Replacement Therapy and Obstructive Sleep Apnea
Testosterone therapy is widely believed to induce or worsen sleep apnea, but the evidence that underpins this relationship is weak [37]. Nevertheless, two randomized controlled trials do show that testosterone therapy can acutely induce sleep-disordered breathing.
Two other randomized, placebo-controlled, parallel-group studies have partly filled this gap in knowledge by investigating the effect of longer-term replacement dose and more steady-state testosterone therapy on sleep-disordered breathing [49, 50].
*Overall, studies show some evidence that the initiation of testosterone therapy might induce or worsen OSA, but any effects are moderate in size and may not persist. Nevertheless, the Endocrine Society has made, for now, a prudent recommendation to avoid initiating testosterone therapy in those with untreated severe OSA [37].
5.5 Conclusion
Disordered sleep can be categorized as insufficient, misaligned, or disrupted. Epidemiological data have established a relationship between disordered sleep and increased mortality, cancer, cardiovascular disease, insulin resistance, and type 2 diabetes mellitus. This review shows that disordered sleep also affects andrological health: insufficient sleep decreases testosterone, whereas circadian misalignment due to shift work or simulated shift work schedule per se does not. Disrupted sleep due to obstructive sleep apnea is associated with lower systemic testosterone concentrations, although this may be due to concomitant adiposity. Preliminary data suggest the possibility that male fertility and semen parameters may also be impacted by sleep duration, but the impacts of circadian misalignment and/or disrupted sleep on fertility have not yet been studied comprehensively. In any case, sleep should be prioritized and valued to promote overall health, including andrological well-being. Methods to minimize deleterious effects of shift work and to promote CPAP adherence remain important research priorities.
