Increased Risk of ED Among Patients With Sleep Disorders
Increased Risk of ED Among Patients With Sleep Disorders
Sleep disturbances are common in older adults and previous studies have reported that approximately 25% of the adult population in Taiwan experiences SD. The health effect of SD includes not only impaired quality of life but also increased risk of cardiovascular and cerebrovascular events. Recent studies have also reported that ED may be a sign of cardiovascular disease. However, there are a lack of epidemiologic studies regarding the relationship between SD and ED, with this being the first longitudinal population-based cohort study that investigates an Asian population to determine if SD increases the risk of developing ED, showing that the SD patients exhibited a 2.11-fold greater risk of ED development than did the general population, after we adjusted for age and comorbidities.
The biological processes by which SD increases the risk of ED is unclear. Vascular disease is probably the most common cause of ED, with atherosclerosis being the most common of all vascular causes. Recent studies have reported that sleep disturbance drives inflammation and elevates inflammatory mediators. However, inflammation not only involves endothelial dysfunction but also plays a pivotal role in the accumulation of atherosclerotic plaque in the arteries. Arteriosclerosis reduces the elasticity of arterial walls and therefore allows less blood to travel through corpora cavernosa, resulting in ED.
Fernandez-Mendoza et al. showed that insomnia with an objective short sleep duration increases the risk of incident hypertension and may serve as a useful predictor of the biological severity of incident hypertension. Similar epiphenomena exist between SD and the risk of cardiovascular and cerebrovascular events. Nakazaki et al. indicated that short sleep duration, poor sleep, and insomnia are associated with atherosclerotic risk leading to cardiovascular diseases.
The testosterone levels in plasma peak during sleep and hit a nadir in the aftrernoon. The timing of sleep may play a vital role to modulate the pituitary-gonadal secretary activity, which determines the serum concentration of testosterone. Sleep disturbance including abnormalities of sleep quality, duration, circadian rhythm disruption can lead to a reduction in testosterone levels in plasma. The testosterone therapy may improve erectile function and the response of phosphodiesterase-5 inhibitors in patients with ED and hypogonadism, Therefore, the men with ED and SD may measure their testosterone levels in plasma.
The incidence of ED increased with age at both cohorts, which is consistent with previous studies. The biological mechanism indicates that older men are more likely to have comorbid conditions compared with younger men. In addition, the ageing process and less physical activity regarding older men may also result in increased the risk of ED. The incidence of ED in older adults ≥ 65 years showed a slight decline compared with that of the middle-aged adults in our study, although a possible explanation for the epiphenomenon maybe be related to our ED diagnosis based on patients seeking treatment with their physician rather than based on a questionnaire survey in previous studies. Men older than 65 years may feel ashamed to seek treatment for sexual problems. Gott et al. indicated that a significant proportion of older people who experience sexual problems do not seek treatment for these conditions.
Although comorbid diseases were more likely to be prevalent in SD patients compared with the non-SD cohort, SD still remains the independent risk factor for the development of ED after we adjusted for covariates. Moreover, the SD patients coexisting with any comorbid condition exhibited a multiplicative risk of developing ED compared with non-SD individuals who had no comorbid diseases. Furthermore, the SD patients who had a particular number of comorbidities showed the dose–response effect of developing ED, and the ED-free rate was also significantly lower for the SD cohort compared with that for the non-SD cohort. These results are relatively robust because several multivariable model analyses were used for assessing the increased risk of ED development.
Several limitations must be considered when interpreting these findings. First, the NHIRD does not provide detailed lifestyle information such as body mass index, physical activity levels, socioeconomic status, or daily alcohol consumption, and laboratory results namely testosterone levels, all of which were potentially limiting factors in this study. Second, the lack of drug-treatment data, such as those on antihypertensive therapy and the use of antihistamines, may have influenced the primary outcomes of this study. Third, the primary outcome, ED, was based on a patient's clinical visit and physician diagnosis, which may have caused us to underestimate the ED incidence. Finally, healthcare claims data may contain potential misclassification bias of primary outcomes, whereas the auditing reviews conducted by BNHI can help minimise diagnostic uncertainty and misclassification.
This study is the first to provide epidemiologic data to address the association between SD and ED, and its strength is in providing a large sample size for an Asian population to investigate the relationship between SD and the increased risk of subsequent ED events. Each NHI beneficiary is assigned a unique personal identification number; therefore, every participant can be traced in NHIRD records throughout the follow-up period. Moreover, the ED diagnosis of the study was obtained from physicians rather than self-reported from the participants.
In conclusion, our nationwide population-based cohort study examining 34,548 SD patients with a follow-up period of approximately 250,000 person-years determined that SD patients are at a 2.11-fold increased risk of developing ED, compared with the general population. These findings highlight the importance of a multidisciplinary approach to managing the potential risk factors of developing ED among SD patients; however, future studies on the biological mechanisms of SD and their effect on ED are warranted.
Discussion
Sleep disturbances are common in older adults and previous studies have reported that approximately 25% of the adult population in Taiwan experiences SD. The health effect of SD includes not only impaired quality of life but also increased risk of cardiovascular and cerebrovascular events. Recent studies have also reported that ED may be a sign of cardiovascular disease. However, there are a lack of epidemiologic studies regarding the relationship between SD and ED, with this being the first longitudinal population-based cohort study that investigates an Asian population to determine if SD increases the risk of developing ED, showing that the SD patients exhibited a 2.11-fold greater risk of ED development than did the general population, after we adjusted for age and comorbidities.
The biological processes by which SD increases the risk of ED is unclear. Vascular disease is probably the most common cause of ED, with atherosclerosis being the most common of all vascular causes. Recent studies have reported that sleep disturbance drives inflammation and elevates inflammatory mediators. However, inflammation not only involves endothelial dysfunction but also plays a pivotal role in the accumulation of atherosclerotic plaque in the arteries. Arteriosclerosis reduces the elasticity of arterial walls and therefore allows less blood to travel through corpora cavernosa, resulting in ED.
Fernandez-Mendoza et al. showed that insomnia with an objective short sleep duration increases the risk of incident hypertension and may serve as a useful predictor of the biological severity of incident hypertension. Similar epiphenomena exist between SD and the risk of cardiovascular and cerebrovascular events. Nakazaki et al. indicated that short sleep duration, poor sleep, and insomnia are associated with atherosclerotic risk leading to cardiovascular diseases.
The testosterone levels in plasma peak during sleep and hit a nadir in the aftrernoon. The timing of sleep may play a vital role to modulate the pituitary-gonadal secretary activity, which determines the serum concentration of testosterone. Sleep disturbance including abnormalities of sleep quality, duration, circadian rhythm disruption can lead to a reduction in testosterone levels in plasma. The testosterone therapy may improve erectile function and the response of phosphodiesterase-5 inhibitors in patients with ED and hypogonadism, Therefore, the men with ED and SD may measure their testosterone levels in plasma.
The incidence of ED increased with age at both cohorts, which is consistent with previous studies. The biological mechanism indicates that older men are more likely to have comorbid conditions compared with younger men. In addition, the ageing process and less physical activity regarding older men may also result in increased the risk of ED. The incidence of ED in older adults ≥ 65 years showed a slight decline compared with that of the middle-aged adults in our study, although a possible explanation for the epiphenomenon maybe be related to our ED diagnosis based on patients seeking treatment with their physician rather than based on a questionnaire survey in previous studies. Men older than 65 years may feel ashamed to seek treatment for sexual problems. Gott et al. indicated that a significant proportion of older people who experience sexual problems do not seek treatment for these conditions.
Although comorbid diseases were more likely to be prevalent in SD patients compared with the non-SD cohort, SD still remains the independent risk factor for the development of ED after we adjusted for covariates. Moreover, the SD patients coexisting with any comorbid condition exhibited a multiplicative risk of developing ED compared with non-SD individuals who had no comorbid diseases. Furthermore, the SD patients who had a particular number of comorbidities showed the dose–response effect of developing ED, and the ED-free rate was also significantly lower for the SD cohort compared with that for the non-SD cohort. These results are relatively robust because several multivariable model analyses were used for assessing the increased risk of ED development.
Several limitations must be considered when interpreting these findings. First, the NHIRD does not provide detailed lifestyle information such as body mass index, physical activity levels, socioeconomic status, or daily alcohol consumption, and laboratory results namely testosterone levels, all of which were potentially limiting factors in this study. Second, the lack of drug-treatment data, such as those on antihypertensive therapy and the use of antihistamines, may have influenced the primary outcomes of this study. Third, the primary outcome, ED, was based on a patient's clinical visit and physician diagnosis, which may have caused us to underestimate the ED incidence. Finally, healthcare claims data may contain potential misclassification bias of primary outcomes, whereas the auditing reviews conducted by BNHI can help minimise diagnostic uncertainty and misclassification.
This study is the first to provide epidemiologic data to address the association between SD and ED, and its strength is in providing a large sample size for an Asian population to investigate the relationship between SD and the increased risk of subsequent ED events. Each NHI beneficiary is assigned a unique personal identification number; therefore, every participant can be traced in NHIRD records throughout the follow-up period. Moreover, the ED diagnosis of the study was obtained from physicians rather than self-reported from the participants.
In conclusion, our nationwide population-based cohort study examining 34,548 SD patients with a follow-up period of approximately 250,000 person-years determined that SD patients are at a 2.11-fold increased risk of developing ED, compared with the general population. These findings highlight the importance of a multidisciplinary approach to managing the potential risk factors of developing ED among SD patients; however, future studies on the biological mechanisms of SD and their effect on ED are warranted.
