ORIGINAL PAPER
Increased risk of erectile dysfunction among patients with sleep disorders: a nationwide population-based cohort study H.-H. Lin,1 F.-M. Ho,2 Y.-F. Chen,3,4 C.-M. Tseng,1 C.-C. Ho,3 W.-S. Chung3,5,6
1
Department of Management Information Systems, Central Taiwan University of Science and Technology, Taichung, Taiwan 2 Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan 3 Department of Healthcare Administration, Central Taiwan University of Science and Technology, Taichung, Taiwan 4 Department of Health Services Administration, China Medical University, Taichung, Taiwan 5 Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan 6 Department of Health Services Administration, China Medical University, Taichung, Taiwan Correspondence to: Wei-Sheng Chung, MD, PhD, Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare, No. 199, Section 1, San-Min Road, Taichung City 40343, Taiwan Tel.: + 886 4 22294411 Fax: + 886 4 22290020 Email: [email protected]. net Hsuan-Hung Lin and Yung-Fu Chen equally contributed to this work Disclosures All authors declare that they have no conflicts of interest.
846
SUMMARY
What’s known
Aims: Few studies have investigated the relationship between sleep disorders (SD) and erectile dysfunction (ED). Therefore, this study explored whether patients with SD in an Asian population are at an increased risk of developing ED. Methods: This longitudinal nationwide population-based cohort study investigated the incidence and risk of developing ED in 34,548 men newly diagnosed with SD between 2002 and 2008 from the National Health Insurance Research Database. A total of 138,192 controls without SD were randomly recruited from the general population and frequency matched according to age and sex. The follow-up period began from the date of entering the study cohort until the date of an ED event, censoring, or 31 December 2010. We conducted Cox proportional hazard regression analyses to estimate the effects of SD on the risk of ED. Results: The SD cohort had a 2.11-fold adjusted hazard ratio (HR) of subsequent ED development compared with the non-SD cohort [95% confidence interval (CI) = 1.89–2.37]. The incidence of ED increased with age for both cohorts and was higher for the patients in the SD cohort. Compared with the participants without SD or comorbidities, the patients without SD with any comorbidity exhibited a 1.79-fold risk of developing ED (95% CI = 1.54–2.09); the highest risk was for those with both SD and any comorbidity (HR = 3.34, 95% CI = 2.82–3.95). Furthermore, SD patients who had a particular number of comorbidities showed the dose–response effect of developing ED. Conclusion: This nationwide cohort study determined that ED risk evidently increased in SD patients compared with the general population.
Introduction Erectile dysfunction (ED) affects millions of men worldwide and is characterised by the inability to attain or maintain penile erection during sexual activity (1–3). The prevalence of this condition increases with age (4). Feldmen et al. used a self-administered questionnaire as part of the Massachusetts Male Aging Study and reported that ED affects approximately 40% of men at age 40; this rate increases to nearly 70% of men at age 70 (5). Because men with ED may be embarrassed to discuss such information with their physicians, it still remains an under-diagnosed and under-treated condition that impairs quality of life for the individual and potentially for his partner (6). A sleep disorder (SD) is defined as difficulty falling or staying asleep, falling asleep at erratic times, or too much sleep. The association is evident between sleep disorders and comorbidities, such as prior psychiatric
1. Sleep disorders are common for general population in the world. 2. Erectile dysfunction impairs quality of life for the individual and potentially for his partner.
What’s new The patients with sleep disorders exhibited a 2.11fold greater risk of erectile dysfunction than did the people without sleep disorders.
disorders, circulatory diseases, and, gastrointestinal diseases (7). Recent studies have reported that SDs may predispose patients to the risks of cardiovascular and cerebrovascular events (8–10). A high proportion of men with chronic stable coronary artery disease have ED (11), which in turn has been reported to be a predictor of ischemic heart diseases (12,13). However, the relationship between SD and ED remains unclear. Therefore, we explored the association of SD with the development of ED in Taiwan. The results are from a nationwide population-based cohort study assessing the possibilities of the increased risk of ED among SD patients.
Methods Data sources The National Health Insurance (NHI) programme in Taiwan is a single-payer compulsory insurance ª 2015 John Wiley & Sons Ltd Int J Clin Pract, August 2015, 69, 8, 846–852. doi: 10.1111/ijcp.12629
Sleep disorders and erectile dysfunction
system established by the Bureau of National Health Insurance (BNHI) of the Ministry of Health and Welfare, and was launched in 1995. The insurance programme provides healthcare to 99% of the 23.74 million people residing in Taiwan and has a contract with 97% of the hospitals and clinics in Taiwan (14). The National Health Research Institute (NHRI) established and manages the National Health Insurance Research Database (NHIRD), which possesses registration and claims data for one million persons systematically obtained from all insured enrollees. All of the NHI datasets can be interlinked through the deidentification of people, indicating that the NHI reimbursement data are suitable for public academic research. The NHI datasets include information on medical facility registries, as well as details of inpatient orders, ambulatory care, dental services, prescription drugs, services provided by physicians, and registration files with encrypted identification. Diagnoses are coded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). This cohort study was approved by the Ethics Review Board of China Medical University (CMU-REC-101-012).
Study participants We selected male patients with newly identified sleep disorders as the SD cohort, including nonorganic sleep disorders and sleep disturbances diagnosed by physicians (ICD-9-CM codes 307.4 and 780.5) from January 2002 to December 2008. The date of SD diagnosis was used as the index date and patients with a history of ED before the index date were excluded. The comparison cohort comprised randomly selected patients without a history of SD and ED, frequency matched according to sex, age, and index date. Four persons were assigned to the comparison cohort for each SD patient.
Outcome measures The primary outcome was newly diagnosed ED (ICD-9-CM code 607.84) reported in the medical records. The follow-up person-years were determined by calculating the interval between the index date and the date on which any of the following first occurred: the date of ED diagnosis, date of withdrawal from the NHI programme, date of death, or 31 December 2010.
9-CM code 428), ischemic heart disease (ICD-9-CM codes 410-414), and depression (ICD-9-CM codes 296.2, 296.3, 300.4, 311).
Statistical analysis All statistical analyses were performed using SPSS 17.0 software (SPSS Inc., Chicago, IL, USA). The proportionate distribution of demographic characteristics and comorbidities between the SD patients and non-SD participants were compared and tested using the chi-squared test, and the mean age of both cohorts was measured and tested using a t-test. The follow-up person-years were used to estimate the incidence density rates of ED. The incidence rate ratios (IRRs) of the SD cohort to the non-SD cohort and 95% confidence intervals (CIs) were calculated based on the demographic statuses and comorbidities of the patients. The IRRs were determined using the Poisson assumption. Overall age- and comorbidityspecific incidence of ED for both SD and non-SD cohorts was assessed and Cox proportional hazard regression analysis was used to estimate the hazard ratios (HRs) with 95% CIs of ED development in the SD cohort; the results were then compared with those of the non-SD cohort. The incidence rates and the HRs for the interaction between SD and comorbidity on the development of ED were also measured. To assess the difference in the ED-free rates between the two cohorts, the Kaplan–Meier analysis and log-rank test were also applied. All of these tests were performed at the 2-tailed significance level of 0.05.
Results Demographic characteristics and comorbidity in SD patients and non-SD individuals Eligible study participants included 34,548 patients in the SD cohort and 138,192 individuals in the comparison cohort. The proportion of age stratification was the same in both cohorts, with the mean age of the participants being 48.9 15.8 years. SD patients exhibited a significantly greater proportion of prevalent comorbid diseases than did the comparison cohort (Table 1). The mean follow-up time was 7.21 years for the SD cohort and 7.46 years for the non-SD cohort (data not shown).
Covariates and comorbid diseases
Comparison of incidence and hazard ratios of ED between SD patients and comparison cohort
Age stratification was categorised into ≤ 34 years, 35–44 years, 45–54 years, 55–64 years, and ≥ 65 years. The included comorbidities were diabetes (ICD-9-CM code 250), congestive heart failure (ICD-
Compared with the comparison cohort, the SD patients displayed greater incidence rates of ED (18.9 vs. 8.33 per 10,000 person-years), with an adjusted HR of 2.11 (95% CI = 1.03–1.73), after we
ª 2015 John Wiley & Sons Ltd Int J Clin Pract, August 2015, 69, 8, 846–852
847
848
Sleep disorders and erectile dysfunction
Table 1 Demographic characteristics and comorbidity in patient with and without sleep disorders
Sleep disorders
Variable
Age ≤ 34 35–44 45–54 55–64 ≥ 65 Age, mean (SD)* Comorbidity Diabetes Ischemic heart disease Congestive heart failure Depression
No N = 138,192
Yes N = 34,548
n (%) 28,404 (20.6) 30,720 (22.2) 30,284 (21.9) 20,524 (14.9) 28,260 (20.4) 48.9 (15.8)
n (%) 7101 (20.6) 7680 (22.2) 7571 (21.9) 5131 (14.9) 7065 (20.4) 48.9 (15.8)
1.0
13,180 (9.54) 9561 (6.92) 1952 (1.41) 2018 (1.46)
4256 (12.32) 3795 (10.98) 804 (2.33) 2396 (6.94)
< < <
Increased risk of erectile dysfunction among patients with sleep disorders: a nationwide population-based cohort study H.-H. Lin,1 F.-M. Ho,2 Y.-F. Chen,3,4 C.-M. Tseng,1 C.-C. Ho,3 W.-S. Chung3,5,6
1
Department of Management Information Systems, Central Taiwan University of Science and Technology, Taichung, Taiwan 2 Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan 3 Department of Healthcare Administration, Central Taiwan University of Science and Technology, Taichung, Taiwan 4 Department of Health Services Administration, China Medical University, Taichung, Taiwan 5 Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan 6 Department of Health Services Administration, China Medical University, Taichung, Taiwan Correspondence to: Wei-Sheng Chung, MD, PhD, Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare, No. 199, Section 1, San-Min Road, Taichung City 40343, Taiwan Tel.: + 886 4 22294411 Fax: + 886 4 22290020 Email: [email protected]. net Hsuan-Hung Lin and Yung-Fu Chen equally contributed to this work Disclosures All authors declare that they have no conflicts of interest.
846
SUMMARY
What’s known
Aims: Few studies have investigated the relationship between sleep disorders (SD) and erectile dysfunction (ED). Therefore, this study explored whether patients with SD in an Asian population are at an increased risk of developing ED. Methods: This longitudinal nationwide population-based cohort study investigated the incidence and risk of developing ED in 34,548 men newly diagnosed with SD between 2002 and 2008 from the National Health Insurance Research Database. A total of 138,192 controls without SD were randomly recruited from the general population and frequency matched according to age and sex. The follow-up period began from the date of entering the study cohort until the date of an ED event, censoring, or 31 December 2010. We conducted Cox proportional hazard regression analyses to estimate the effects of SD on the risk of ED. Results: The SD cohort had a 2.11-fold adjusted hazard ratio (HR) of subsequent ED development compared with the non-SD cohort [95% confidence interval (CI) = 1.89–2.37]. The incidence of ED increased with age for both cohorts and was higher for the patients in the SD cohort. Compared with the participants without SD or comorbidities, the patients without SD with any comorbidity exhibited a 1.79-fold risk of developing ED (95% CI = 1.54–2.09); the highest risk was for those with both SD and any comorbidity (HR = 3.34, 95% CI = 2.82–3.95). Furthermore, SD patients who had a particular number of comorbidities showed the dose–response effect of developing ED. Conclusion: This nationwide cohort study determined that ED risk evidently increased in SD patients compared with the general population.
Introduction Erectile dysfunction (ED) affects millions of men worldwide and is characterised by the inability to attain or maintain penile erection during sexual activity (1–3). The prevalence of this condition increases with age (4). Feldmen et al. used a self-administered questionnaire as part of the Massachusetts Male Aging Study and reported that ED affects approximately 40% of men at age 40; this rate increases to nearly 70% of men at age 70 (5). Because men with ED may be embarrassed to discuss such information with their physicians, it still remains an under-diagnosed and under-treated condition that impairs quality of life for the individual and potentially for his partner (6). A sleep disorder (SD) is defined as difficulty falling or staying asleep, falling asleep at erratic times, or too much sleep. The association is evident between sleep disorders and comorbidities, such as prior psychiatric
1. Sleep disorders are common for general population in the world. 2. Erectile dysfunction impairs quality of life for the individual and potentially for his partner.
What’s new The patients with sleep disorders exhibited a 2.11fold greater risk of erectile dysfunction than did the people without sleep disorders.
disorders, circulatory diseases, and, gastrointestinal diseases (7). Recent studies have reported that SDs may predispose patients to the risks of cardiovascular and cerebrovascular events (8–10). A high proportion of men with chronic stable coronary artery disease have ED (11), which in turn has been reported to be a predictor of ischemic heart diseases (12,13). However, the relationship between SD and ED remains unclear. Therefore, we explored the association of SD with the development of ED in Taiwan. The results are from a nationwide population-based cohort study assessing the possibilities of the increased risk of ED among SD patients.
Methods Data sources The National Health Insurance (NHI) programme in Taiwan is a single-payer compulsory insurance ª 2015 John Wiley & Sons Ltd Int J Clin Pract, August 2015, 69, 8, 846–852. doi: 10.1111/ijcp.12629
Sleep disorders and erectile dysfunction
system established by the Bureau of National Health Insurance (BNHI) of the Ministry of Health and Welfare, and was launched in 1995. The insurance programme provides healthcare to 99% of the 23.74 million people residing in Taiwan and has a contract with 97% of the hospitals and clinics in Taiwan (14). The National Health Research Institute (NHRI) established and manages the National Health Insurance Research Database (NHIRD), which possesses registration and claims data for one million persons systematically obtained from all insured enrollees. All of the NHI datasets can be interlinked through the deidentification of people, indicating that the NHI reimbursement data are suitable for public academic research. The NHI datasets include information on medical facility registries, as well as details of inpatient orders, ambulatory care, dental services, prescription drugs, services provided by physicians, and registration files with encrypted identification. Diagnoses are coded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). This cohort study was approved by the Ethics Review Board of China Medical University (CMU-REC-101-012).
Study participants We selected male patients with newly identified sleep disorders as the SD cohort, including nonorganic sleep disorders and sleep disturbances diagnosed by physicians (ICD-9-CM codes 307.4 and 780.5) from January 2002 to December 2008. The date of SD diagnosis was used as the index date and patients with a history of ED before the index date were excluded. The comparison cohort comprised randomly selected patients without a history of SD and ED, frequency matched according to sex, age, and index date. Four persons were assigned to the comparison cohort for each SD patient.
Outcome measures The primary outcome was newly diagnosed ED (ICD-9-CM code 607.84) reported in the medical records. The follow-up person-years were determined by calculating the interval between the index date and the date on which any of the following first occurred: the date of ED diagnosis, date of withdrawal from the NHI programme, date of death, or 31 December 2010.
9-CM code 428), ischemic heart disease (ICD-9-CM codes 410-414), and depression (ICD-9-CM codes 296.2, 296.3, 300.4, 311).
Statistical analysis All statistical analyses were performed using SPSS 17.0 software (SPSS Inc., Chicago, IL, USA). The proportionate distribution of demographic characteristics and comorbidities between the SD patients and non-SD participants were compared and tested using the chi-squared test, and the mean age of both cohorts was measured and tested using a t-test. The follow-up person-years were used to estimate the incidence density rates of ED. The incidence rate ratios (IRRs) of the SD cohort to the non-SD cohort and 95% confidence intervals (CIs) were calculated based on the demographic statuses and comorbidities of the patients. The IRRs were determined using the Poisson assumption. Overall age- and comorbidityspecific incidence of ED for both SD and non-SD cohorts was assessed and Cox proportional hazard regression analysis was used to estimate the hazard ratios (HRs) with 95% CIs of ED development in the SD cohort; the results were then compared with those of the non-SD cohort. The incidence rates and the HRs for the interaction between SD and comorbidity on the development of ED were also measured. To assess the difference in the ED-free rates between the two cohorts, the Kaplan–Meier analysis and log-rank test were also applied. All of these tests were performed at the 2-tailed significance level of 0.05.
Results Demographic characteristics and comorbidity in SD patients and non-SD individuals Eligible study participants included 34,548 patients in the SD cohort and 138,192 individuals in the comparison cohort. The proportion of age stratification was the same in both cohorts, with the mean age of the participants being 48.9 15.8 years. SD patients exhibited a significantly greater proportion of prevalent comorbid diseases than did the comparison cohort (Table 1). The mean follow-up time was 7.21 years for the SD cohort and 7.46 years for the non-SD cohort (data not shown).
Covariates and comorbid diseases
Comparison of incidence and hazard ratios of ED between SD patients and comparison cohort
Age stratification was categorised into ≤ 34 years, 35–44 years, 45–54 years, 55–64 years, and ≥ 65 years. The included comorbidities were diabetes (ICD-9-CM code 250), congestive heart failure (ICD-
Compared with the comparison cohort, the SD patients displayed greater incidence rates of ED (18.9 vs. 8.33 per 10,000 person-years), with an adjusted HR of 2.11 (95% CI = 1.03–1.73), after we
ª 2015 John Wiley & Sons Ltd Int J Clin Pract, August 2015, 69, 8, 846–852
847
848
Sleep disorders and erectile dysfunction
Table 1 Demographic characteristics and comorbidity in patient with and without sleep disorders
Sleep disorders
Variable
Age ≤ 34 35–44 45–54 55–64 ≥ 65 Age, mean (SD)* Comorbidity Diabetes Ischemic heart disease Congestive heart failure Depression
No N = 138,192
Yes N = 34,548
n (%) 28,404 (20.6) 30,720 (22.2) 30,284 (21.9) 20,524 (14.9) 28,260 (20.4) 48.9 (15.8)
n (%) 7101 (20.6) 7680 (22.2) 7571 (21.9) 5131 (14.9) 7065 (20.4) 48.9 (15.8)
1.0
13,180 (9.54) 9561 (6.92) 1952 (1.41) 2018 (1.46)
4256 (12.32) 3795 (10.98) 804 (2.33) 2396 (6.94)
< < <
