- Email: [email protected]
Defining association between sleep apnea syndrome and erectile dysfunction
ADULT UROLOGY
DEFINING ASSOCIATION BETWEEN SLEEP APNEA SYNDROME AND ERECTILE DYSFUNCTION PATRICK E. TELOKEN, ERIC B. SMITH, CHRIS LODOWSKY, THOMAS FREEDOM, AND JOHN P. MULHALL
ABSTRACT Objectives. To conduct a study using validated sexual function and sleepiness inventories to define whether sleep apnea syndrome (SAS) is associated with erectile dysfunction and whether any correlation exists between the severity of SAS and the severity of erectile dysfunction. Previous work has suggested that sleep disorders are associated with erectile dysfunction. Methods. Men presenting to a sleep clinic with symptoms consistent with SAS were given the Epworth Sleepiness Scale and an erectile dysfunction risk factor inventory, the International Index of Erectile Function. A database was constructed and statistical analysis conducted to define the correlation between the two entities. Results. A total of 50 men met the criteria for inclusion. Of the 50 men, 60% had abnormal Epworth Sleepiness Scale scores and 80% of these patients had erectile dysfunction as determined by inventory scores compared with 20% of the men with normal Epworth Sleepiness Scale scores. There were statistically significant differences between men with normal and abnormal sleepiness scores for the total and erectile function domain of the International Index of Erectile Function. The correlation between the severity of the sleepiness and the severity of erectile dysfunction was good (r ⫽ ⫺0.80, P ⫽ 0.012). Conclusions. Men presenting with symptoms consistent with SAS have a significant risk of erectile dysfunction, and the correlation between the severity of sleep apnea and the severity of erectile dysfunction is strong. UROLOGY 67: 1033–1037, 2006. © 2006 Elsevier Inc.
E
rectile dysfunction (ED), defined as the consistent inability to obtain and/or maintain penile erection sufficient for satisfactory sexual relations,1 is associated with a variety of medical, psychologic, and lifestyle risk factors.2 Estimates for ED in the United States range from 20% to 50%, depending on the epidemiologic study.3 It has been demonstrated to have a negative impact on patient selfesteem, quality of life, and interpersonal relationships.4 Many risk factors for ED have been identified, including hypertension, diabetes, dyslipiJ. P. Mulhall is a consultant to Pfizer, Lilly-ICOS, Johnson & Johnson, and Auxilium. From the Department of Urology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; and Department of Urology and Division of Sleep Medicine, Loyola University Medical Center, Stritch School of Medicine, Maywood, Illinois Reprint requests: John P. Mulhall, M.D., Department of Urology, Weill Medical College of Cornell University, New York Presbyterian Hospital, 525 East 68th Street, Starr 900, New York, NY 10021. E-mail: [email protected] Submitted: January 30, 2005, accepted (with revisions): November 15, 2005 © 2006 ELSEVIER INC. ALL RIGHTS RESERVED
demias, vascular disease, and endocrine and neurologic comorbidities.3,5 Previous work has shown that the chronic absence of erections leads to structural alterations in penile erectile tissue, which may contribute to ED.4,6 Furthermore, it has been suggested that nocturnal erections, occurring during REM sleep, may be protective to the penis and help preserve erectile function in men.5 Sleep apnea syndrome (SAS) is also a prevalent disease, affecting an estimated 4% of men between the ages of 30 and 60 years.7 It is characterized by recurring episodes of upper airway obstruction during sleep, and it is usually associated with loud snoring and increased daytime sleepiness.8,9 It results in marked sleep fragmentation and decreased REM sleep. This decrease in REM sleep leads to a decrease in nocturnal erectile activity. Because of this loss of protective erections during REM sleep, some have suggested that SAS may be a risk factor for ED.4,6 Several studies have reported a link between SAS and ED. However, to date, none have used a validated instrument for the assessment of erectile function. This study was undertaken to de0090-4295/06/$32.00 doi:10.1016/j.urology.2005.11.040 1033
TABLE I. Questionnaire data Domain Scores
Entire Group (n ⴝ 50)
ESS >10 (n ⴝ 30)
ESS <10 (n ⴝ 20)
P Value
10 ⫾ 4 49 ⫾ 11 20 ⫾ 6 9⫾3 8⫾2 7⫾3 6⫾2
16 ⫾ 2 44 ⫾ 11 14 ⫾ 4 8⫾4 8⫾2 7⫾3 6⫾2
6⫾2 57 ⫾ 7 29 ⫾ 3 10 ⫾ 2 8⫾3 7⫾3 6⫾1
⬍0.01 ⬍0.01 ⬍0.01 NS NS NS NS
ESS Total IIEF Erectile function Intercourse satisfaction Orgasm Libido Overall satisfaction
KEY: ESS ⫽ Epworth Sleepiness Scale; IIEF ⫽ International Index of Erectile Function; NS ⫽ not significant. P ⬍0.05 was considered statistically significant.
fine the incidence of ED using the International Index of Erectile Dysfunction (IIEF) in men with SAS documented using a validated instrument. MATERIAL AND METHODS This study was a collaboration between urology and sleep medicine, in concordance with approval by the ethics committee of the respective institutions. The study population consisted of men presenting to the sleep clinic for initial evaluation with symptoms consistent with sleep apnea as defined by a sleep specialist (T.F.). Patients who had a history of ED and/or had sought prior evaluation for ED from a physician were excluded. The diagnosis of SAS was determined from the clinical history and completion of the Epworth Sleepiness Scale (ESS). Each patient was given an ED risk factor inventory assessing the presence of vascular comorbidities, the IIEF, and the ESS. The ESS is a self-administered questionnaire that provides a measurement of the subject’s general level of daytime sleepiness. It assesses the likelihood of dozing during eight different activities (scored 0 to 3, the higher the score the greater the chance of dozing). For scores of more than 10, the ESS has been shown to have the capability to distinguish normal subjects from patients with SAS.9 In this study, an ESS score greater than 10 was considered to be supportive of the sleep specialist’s diagnosis of SAS. The IIEF is divided into five domains (erectile function, intercourse satisfaction, orgasm, sex drive, and overall satisfaction). The erectile function domain consists of six questions (questions 1 to 5 and 15) and has a maximal score of 30 and a minimal score of 6. Each question is scored on a 5-point Likert scale, with 5 representing the best function. A score of less than 26 is indicative of ED.2 Furthermore, the degree of ED can be estimated from the score, with scores of 17 to 25 representing mild ED, 11 to 16 moderate ED, and 10 or less severe ED.2 Statistical analysis was performed comparing the IIEF scores of patients with an ESS score of 10 or less and patients with an ESS score of greater than 10 using the Mann-Whitney U test. Pearson correlation coefficients were calculated for the relationship between the ESS and IIEF scores.
for the entire group was 48 ⫾ 10 years, and the mean duration of sleep problems was 2.5 ⫾ 1.5 years. No significant difference existed for either of these parameters between those patients with normal and abnormal ESS scores. The baseline risk factor profile of the entire group included hypertension (55%), hyperlipidemia (40%), diabetes (10%), and cigarette smoking (50%). No statistically significant difference was found in the incidence of hypertension, diabetes, or hyperlipidemia between those with normal and those with abnormal ESS scores. No patient was using erectogenic medication or any medication for sleep disorders at enrollment and questionnaire completion. The two groups were compared using the results of the total IIEF score and each individual IIEF domain (erectile function, intercourse satisfaction, orgasmic function, sex drive, and overall satisfaction). These data are summarized in Table I. Of the 30 patients with an ESS score of greater than 10, 24 (80%) had ED as determined by an erectile function domain score of less than 26. This compares with only 4 (20%) of 20 of those with a normal ESS score. This difference was statistically significant (P ⬍0.01). The average total IIEF score was 44 ⫾ 11 for those with an abnormal ESS score and 57 ⫾ 7 for those with a normal ESS score (P ⬍0.01). The differences in the rest of the domain scores were not significantly different between the two groups. The strongest correlation was noted between an abnormal ESS score and an abnormal erectile function domain score, with a Pearson correlation coefficient (r) of ⫺0.80 (P ⫽ 0.0012; Fig. 1). In addition, the Pearson correlation coefficient for the total IIEF score was statistically significant (r ⫽ ⫺0.62, P ⫽ 0.011).
RESULTS A total of 50 patients met all inclusion criteria and represented the study population. The patients were stratified into those with abnormal ESS scores (ESS score greater than 10) and those with normal scores (ESS score of 10 or less). Of the 50 patients, 30 (60%) had abnormal ESS scores. The mean age 1034
COMMENT Both ED and SAS affect millions of men. Both diseases have a significant negative impact on patients’ quality of life and interpersonal relationships. The correlates of ED are well-known. Men who have diabetes, hypertension, hyperlipidemia, UROLOGY 67 (5), 2006
FIGURE 1. Graphic representation of correlation between Epworth Sleepiness score and IIEF erectile function domain score.
cardiovascular disease, lower urinary tract symptoms associated with benign prostate hyperplasia, or endocrinopathies or have undergone radical pelvic surgery have an increased incidence of ED compared with men without these conditions. Schmidt and Wise,10 in 1981, were the first to note a relationship between ED and SAS. They analyzed 15 consecutive patients with secondary ED. Seven (46%) had varying degrees of abnormal nocturnal penile tumescence. All nocturnal penile tumescence measurements of this group, except for the circumference change at the glans, were significantly lower than in patients with psychogenic impotence or normal men.10 A prevalence study by Hirshkowitz et al.11 that analyzed 1025 men with ED showed that 91.3% of them had an Apnea Index of 5 or more suggesting a sleep disorder. Seftel et al.12 found a correlation between ED complaints or a diagnosis of organic ED and snoring. However, in a logistic regression model that included age, snoring, and preexisting conditions, only age, depression, and a history of hypercholesterolemia varied significantly between those with and without ED.12 Margel et al.13 recently evaluated 209 men with SAS and demonstrated an association between the severity of ED, as determined by the IIEF scores, and the respiratory disturbance index on polysomnography. The use of polysomnography rendered the information in their report not readily clinically applicable to the sleep physician or urologist who has more ready access to questionnaires. The predictive factors for ED in patients with SAS include age, morning tiredness, and the respiratory disturbance index.13 Karacan and Karatas6 demonstrated in a small study that ED improves in one third of patients with SAS after treatment with continuous positive airway pressure. Li et al.14 showed that patients with ED treated with continuous positive airway pressure had a significant improvement compared with conUROLOGY 67 (5), 2006
trols. Perimenis et al.15 compared sildenafil 100 mg before intercourse with continuous positive airway pressure during nighttime sleep for men with ED and SAS. After a 12-week treatment period, the IIEF score was significantly greater in the sildenafil group.15 Moreland16 first introduced the concept that cavernosal hypoxia is deleterious to erectile tissue structure and function. His study demonstrated that cavernosal tissue exposed to chronically low levels of oxygen upregulates fibrogenic cytokines, leading to collagenization and fibrosis of tissue.16 The decreased REM sleep associated with SAS results in fragmentation of sleep and a decrease in the number of nocturnal erections. Chronic absence of nocturnal erectile activity may lead to cavernosal hypoxia, and it is likely that the loss of these erections contributes to ED in these men. A standardized technique and normative values for NPT (number of episodes and degree of tumescence and rigidity), although extensively studied and published, have not been well established.17 However, most men with functional erections obtain three to six erections per night that are at least 60% rigid and 10 minutes in duration.18 It should be noted that measurable tumescence changes do not always correlate with penile rigidity sufficient for vaginal penetration.19 Sleep disorders adversely affect NPT without, in many cases, affecting awake physiologic performance (normal erections or normal erections with vascular stimulants). Using the IIEF, our data indicate that men with SAS have a significant chance of having ED and that a correlation exists between the severity of sleep apnea and ED (Table II and Fig. 1). Thus, 80% of men with the diagnosis of SAS had IIEF erectile function domain scores of less than 26, indicative of ED. The IIEF is a robust instrument that has been used extensively in ED analyses and currently represents the reference standard questionnaire for the assessment of erectile function.2,20,21 With regard to the use of the ESS, comparing the Multiple Sleep Latency Test, the Maintenance of Wakefulness Test, and the ESS, the receiver operator characteristic curves have demonstrated that the ESS is the most discriminating test.22 On the basis of the scores of 72 normal subjects selected by strict criteria derived from a detailed sleep questionnaire that screened out those with most sleep disorders, including insomnia and snoring or sleep-disordered breathing, a normative reference range of 0 to 10 was defined.23 Another study with a sample of 188 normal subjects suggested that the normative reference range may be 0 to 11.24 In the current study, in men with a clinical suspicion of SAS, we used an ESS score of 10 as the 1035
TABLE II. Pearson coefficients for correlation between ESS and IIEF domain scores IIEF Total ESS P value
Erectile Function
⫺0.62* 0.01
⫺0.88* 0.012
Intercourse Satisfaction
Orgasm
Sex Drive
Overall Satisfaction
⫺0.2 0.06
⫺0.12 0.24
⫺0.10 0.11
0.0 0.9
Abbreviations as in Table I. * Statistically significant correlation.
cutoff for its diagnosis. Using this cutoff, we have demonstrated that the correlation between the severity of sleepiness and ED is good (Fig. 1). Although the results of this study have corroborated the findings of previous studies, we used validated instruments to confirm the association between SAS and ED. One of the limitations was that the analysis was conducted on a small population, which deprived us of the ability to conduct more robust statistical methods, such as multivariate analysis. Another limitation is the absence of data on baseline patient body mass index and serum testosterone levels. The single most important risk factor for sleep apnea is obesity.25,26 Sleep apnea also causes reversible neuroendocrine dysfunction in men, manifested by decreased plasma testosterone levels. This neuroendocrine dysfunction is related to the severity of the sleep apnea, as indicated by the nadir levels of arterial oxygen desaturation and the rate of desaturation episodes.27 Information on both of these factors would have strengthened our study work and helped to shed light on the mechanisms by which the two conditions are associated. CONCLUSIONS These data indicate that men presenting with symptoms suggestive of SAS have a high chance of having ED, and that the correlation between the severity of sleep apnea and the severity of ED is strong. REFERENCES 1. Recommendations of the 1st International Consultation on Erectile Dysfunction, in Jardin A, Wagner G, et al (Eds): Erectile Dysfunction. Plymouth, UK, Health Publications, 2000, pp 711–726. 2. Rosen RC, Riley A, Wagner G, et al: The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 49: 822– 830, 1997. 3. Rosen RC, Fisher WA, Eardley I, et al: The multinational Men’s Attitudes to Life Events and Sexuality (MALES) study: I. Prevalence of erectile dysfunction and related health concerns in the general population. Curr Med Res Opin 20: 607– 617, 2004. 4. Schiavi RC, Mandeli J, Schreiner-Engel P, et al: Aging, sleep disorders, and male sexual function. Biol Psychiatry 30: 15–24, 1991. 5. Hirshkowitz M, Karacan I, Gurakar A, et al: Hypertension, erectile dysfunction, and occult sleep apnea. Sleep 12: 223–232, 1989. 1036
6. Karacan I, and Karatas M: Erectile dysfunction in sleep apnea and response to CPAP. J Sex Marital Ther 21: 239 –247, 1995. 7. Young T, Palta M, Dempsey J, et al: The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328: 1230 –1235, 1993. 8. van Houwelingen KG, van Uffelen R, and van Vliet AC: The sleep apnoea syndromes. Eur Heart J 20: 858 – 866, 1999. 9. Johns MW: A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 14: 540 –545, 1991. 10. Schmidt HS, and Wise HA II: Significance of impaired penile tumescence and associated polysomnographic abnormalities in the impotent patient. J Urol 126: 348 –352, 1981. 11. Hirshkowitz M, Karacan I, Arcasoy MO, et al: Prevalence of sleep apnea in men with erectile dysfunction. Urology 36: 232–234, 1990. 12. Seftel AD, Strohl KP, Loye TL, et al: Erectile dysfunction and symptoms of sleep disorders. Sleep 25: 643– 647, 2002. 13. Margel D, Cohen M, Livne PM, et al: Severe, but not mild, obstructive sleep apnea syndrome is associated with erectile dysfunction. Urology 63: 545–549, 2004. 14. Li F, Feng Q, Zhang X, et al: [Treatment for erectile dysfunction patients with obstructive sleep apnea syndrome by nasal continual positive airway pressure]. Zhonghua Nan Ke Xue 10: 355–357, 2004. 15. Perimenis P, Karkoulias K, Markou S, et al: Erectile dysfunction in men with obstructive sleep apnea syndrome: a randomized study of the efficacy of sildenafil and continuous positive airway pressure. Int J Impot Res 16: 256 –260, 2004. 16. Moreland RB: Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the Society for the Study of Impotence. Int J Impot Res 10: 113–120, 1998. 17. Kessler WO: Nocturnal penile tumescence. Urol Clin North Am 15: 81– 86, 1988. 18. Levine LA, and Carroll RA: Nocturnal penile tumescence and rigidity in men without complaints of erectile dysfunction using a new quantitative analysis software. J Urol 152: 1103–1107, 1994. 19. Wein AJ, Fishkin R, Carpiniello VL, et al: Expansion without significant rigidity during nocturnal penile tumescence testing: a potential source of misinterpretation. J Urol 126: 343–344, 1981. 20. Rosen RC, Cappelleri JC, and Gendrano N III: The International Index of Erectile Function (IIEF): a state-of-thescience review. Int J Impot Res 14: 226 –244, 2002. 21. Rosen RC, Cappelleri JC, Smith MD, et al: Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 11: 319 –326, 1999. 22. Johns MW: Sensitivity and specificity of the Multiple Sleep Latency Test (MSLT), the Maintenance of Wakefulness Test and the Epworth Sleepiness Scale: failure of the MSLT as a gold standard. J Sleep Res 9: 5–11, 2000. UROLOGY 67 (5), 2006
23. Johns M, and Hocking B: Daytime sleepiness and sleep habits of Australian workers. Sleep 20: 844 – 849, 1997. 24. Parkes JD, Chen SY, Clift SJ, et al: The clinical diagnosis of the narcoleptic syndrome. J Sleep Res 7: 41–52, 1998. 25. Laitinen LA, Anttalainen U, Pietinalho A, et al: Sleep apnoea: Finnish National guidelines for prevention and treatment 2002–2012. Respir Med 97: 337–365, 2003.
UROLOGY 67 (5), 2006
26. Santamaria JD, Prior JC, and Fleetham JA: Reversible reproductive dysfunction in men with obstructive sleep apnoea. Clin Endocrinol (Oxf) 28: 461– 470, 1988. 27. Grunstein RR, Handelsman DJ, Lawrence SJ, et al: Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy. J Clin Endocrinol Metab 68: 352–358, 1989.
1037
DEFINING ASSOCIATION BETWEEN SLEEP APNEA SYNDROME AND ERECTILE DYSFUNCTION PATRICK E. TELOKEN, ERIC B. SMITH, CHRIS LODOWSKY, THOMAS FREEDOM, AND JOHN P. MULHALL
ABSTRACT Objectives. To conduct a study using validated sexual function and sleepiness inventories to define whether sleep apnea syndrome (SAS) is associated with erectile dysfunction and whether any correlation exists between the severity of SAS and the severity of erectile dysfunction. Previous work has suggested that sleep disorders are associated with erectile dysfunction. Methods. Men presenting to a sleep clinic with symptoms consistent with SAS were given the Epworth Sleepiness Scale and an erectile dysfunction risk factor inventory, the International Index of Erectile Function. A database was constructed and statistical analysis conducted to define the correlation between the two entities. Results. A total of 50 men met the criteria for inclusion. Of the 50 men, 60% had abnormal Epworth Sleepiness Scale scores and 80% of these patients had erectile dysfunction as determined by inventory scores compared with 20% of the men with normal Epworth Sleepiness Scale scores. There were statistically significant differences between men with normal and abnormal sleepiness scores for the total and erectile function domain of the International Index of Erectile Function. The correlation between the severity of the sleepiness and the severity of erectile dysfunction was good (r ⫽ ⫺0.80, P ⫽ 0.012). Conclusions. Men presenting with symptoms consistent with SAS have a significant risk of erectile dysfunction, and the correlation between the severity of sleep apnea and the severity of erectile dysfunction is strong. UROLOGY 67: 1033–1037, 2006. © 2006 Elsevier Inc.
E
rectile dysfunction (ED), defined as the consistent inability to obtain and/or maintain penile erection sufficient for satisfactory sexual relations,1 is associated with a variety of medical, psychologic, and lifestyle risk factors.2 Estimates for ED in the United States range from 20% to 50%, depending on the epidemiologic study.3 It has been demonstrated to have a negative impact on patient selfesteem, quality of life, and interpersonal relationships.4 Many risk factors for ED have been identified, including hypertension, diabetes, dyslipiJ. P. Mulhall is a consultant to Pfizer, Lilly-ICOS, Johnson & Johnson, and Auxilium. From the Department of Urology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; and Department of Urology and Division of Sleep Medicine, Loyola University Medical Center, Stritch School of Medicine, Maywood, Illinois Reprint requests: John P. Mulhall, M.D., Department of Urology, Weill Medical College of Cornell University, New York Presbyterian Hospital, 525 East 68th Street, Starr 900, New York, NY 10021. E-mail: [email protected] Submitted: January 30, 2005, accepted (with revisions): November 15, 2005 © 2006 ELSEVIER INC. ALL RIGHTS RESERVED
demias, vascular disease, and endocrine and neurologic comorbidities.3,5 Previous work has shown that the chronic absence of erections leads to structural alterations in penile erectile tissue, which may contribute to ED.4,6 Furthermore, it has been suggested that nocturnal erections, occurring during REM sleep, may be protective to the penis and help preserve erectile function in men.5 Sleep apnea syndrome (SAS) is also a prevalent disease, affecting an estimated 4% of men between the ages of 30 and 60 years.7 It is characterized by recurring episodes of upper airway obstruction during sleep, and it is usually associated with loud snoring and increased daytime sleepiness.8,9 It results in marked sleep fragmentation and decreased REM sleep. This decrease in REM sleep leads to a decrease in nocturnal erectile activity. Because of this loss of protective erections during REM sleep, some have suggested that SAS may be a risk factor for ED.4,6 Several studies have reported a link between SAS and ED. However, to date, none have used a validated instrument for the assessment of erectile function. This study was undertaken to de0090-4295/06/$32.00 doi:10.1016/j.urology.2005.11.040 1033
TABLE I. Questionnaire data Domain Scores
Entire Group (n ⴝ 50)
ESS >10 (n ⴝ 30)
ESS <10 (n ⴝ 20)
P Value
10 ⫾ 4 49 ⫾ 11 20 ⫾ 6 9⫾3 8⫾2 7⫾3 6⫾2
16 ⫾ 2 44 ⫾ 11 14 ⫾ 4 8⫾4 8⫾2 7⫾3 6⫾2
6⫾2 57 ⫾ 7 29 ⫾ 3 10 ⫾ 2 8⫾3 7⫾3 6⫾1
⬍0.01 ⬍0.01 ⬍0.01 NS NS NS NS
ESS Total IIEF Erectile function Intercourse satisfaction Orgasm Libido Overall satisfaction
KEY: ESS ⫽ Epworth Sleepiness Scale; IIEF ⫽ International Index of Erectile Function; NS ⫽ not significant. P ⬍0.05 was considered statistically significant.
fine the incidence of ED using the International Index of Erectile Dysfunction (IIEF) in men with SAS documented using a validated instrument. MATERIAL AND METHODS This study was a collaboration between urology and sleep medicine, in concordance with approval by the ethics committee of the respective institutions. The study population consisted of men presenting to the sleep clinic for initial evaluation with symptoms consistent with sleep apnea as defined by a sleep specialist (T.F.). Patients who had a history of ED and/or had sought prior evaluation for ED from a physician were excluded. The diagnosis of SAS was determined from the clinical history and completion of the Epworth Sleepiness Scale (ESS). Each patient was given an ED risk factor inventory assessing the presence of vascular comorbidities, the IIEF, and the ESS. The ESS is a self-administered questionnaire that provides a measurement of the subject’s general level of daytime sleepiness. It assesses the likelihood of dozing during eight different activities (scored 0 to 3, the higher the score the greater the chance of dozing). For scores of more than 10, the ESS has been shown to have the capability to distinguish normal subjects from patients with SAS.9 In this study, an ESS score greater than 10 was considered to be supportive of the sleep specialist’s diagnosis of SAS. The IIEF is divided into five domains (erectile function, intercourse satisfaction, orgasm, sex drive, and overall satisfaction). The erectile function domain consists of six questions (questions 1 to 5 and 15) and has a maximal score of 30 and a minimal score of 6. Each question is scored on a 5-point Likert scale, with 5 representing the best function. A score of less than 26 is indicative of ED.2 Furthermore, the degree of ED can be estimated from the score, with scores of 17 to 25 representing mild ED, 11 to 16 moderate ED, and 10 or less severe ED.2 Statistical analysis was performed comparing the IIEF scores of patients with an ESS score of 10 or less and patients with an ESS score of greater than 10 using the Mann-Whitney U test. Pearson correlation coefficients were calculated for the relationship between the ESS and IIEF scores.
for the entire group was 48 ⫾ 10 years, and the mean duration of sleep problems was 2.5 ⫾ 1.5 years. No significant difference existed for either of these parameters between those patients with normal and abnormal ESS scores. The baseline risk factor profile of the entire group included hypertension (55%), hyperlipidemia (40%), diabetes (10%), and cigarette smoking (50%). No statistically significant difference was found in the incidence of hypertension, diabetes, or hyperlipidemia between those with normal and those with abnormal ESS scores. No patient was using erectogenic medication or any medication for sleep disorders at enrollment and questionnaire completion. The two groups were compared using the results of the total IIEF score and each individual IIEF domain (erectile function, intercourse satisfaction, orgasmic function, sex drive, and overall satisfaction). These data are summarized in Table I. Of the 30 patients with an ESS score of greater than 10, 24 (80%) had ED as determined by an erectile function domain score of less than 26. This compares with only 4 (20%) of 20 of those with a normal ESS score. This difference was statistically significant (P ⬍0.01). The average total IIEF score was 44 ⫾ 11 for those with an abnormal ESS score and 57 ⫾ 7 for those with a normal ESS score (P ⬍0.01). The differences in the rest of the domain scores were not significantly different between the two groups. The strongest correlation was noted between an abnormal ESS score and an abnormal erectile function domain score, with a Pearson correlation coefficient (r) of ⫺0.80 (P ⫽ 0.0012; Fig. 1). In addition, the Pearson correlation coefficient for the total IIEF score was statistically significant (r ⫽ ⫺0.62, P ⫽ 0.011).
RESULTS A total of 50 patients met all inclusion criteria and represented the study population. The patients were stratified into those with abnormal ESS scores (ESS score greater than 10) and those with normal scores (ESS score of 10 or less). Of the 50 patients, 30 (60%) had abnormal ESS scores. The mean age 1034
COMMENT Both ED and SAS affect millions of men. Both diseases have a significant negative impact on patients’ quality of life and interpersonal relationships. The correlates of ED are well-known. Men who have diabetes, hypertension, hyperlipidemia, UROLOGY 67 (5), 2006
FIGURE 1. Graphic representation of correlation between Epworth Sleepiness score and IIEF erectile function domain score.
cardiovascular disease, lower urinary tract symptoms associated with benign prostate hyperplasia, or endocrinopathies or have undergone radical pelvic surgery have an increased incidence of ED compared with men without these conditions. Schmidt and Wise,10 in 1981, were the first to note a relationship between ED and SAS. They analyzed 15 consecutive patients with secondary ED. Seven (46%) had varying degrees of abnormal nocturnal penile tumescence. All nocturnal penile tumescence measurements of this group, except for the circumference change at the glans, were significantly lower than in patients with psychogenic impotence or normal men.10 A prevalence study by Hirshkowitz et al.11 that analyzed 1025 men with ED showed that 91.3% of them had an Apnea Index of 5 or more suggesting a sleep disorder. Seftel et al.12 found a correlation between ED complaints or a diagnosis of organic ED and snoring. However, in a logistic regression model that included age, snoring, and preexisting conditions, only age, depression, and a history of hypercholesterolemia varied significantly between those with and without ED.12 Margel et al.13 recently evaluated 209 men with SAS and demonstrated an association between the severity of ED, as determined by the IIEF scores, and the respiratory disturbance index on polysomnography. The use of polysomnography rendered the information in their report not readily clinically applicable to the sleep physician or urologist who has more ready access to questionnaires. The predictive factors for ED in patients with SAS include age, morning tiredness, and the respiratory disturbance index.13 Karacan and Karatas6 demonstrated in a small study that ED improves in one third of patients with SAS after treatment with continuous positive airway pressure. Li et al.14 showed that patients with ED treated with continuous positive airway pressure had a significant improvement compared with conUROLOGY 67 (5), 2006
trols. Perimenis et al.15 compared sildenafil 100 mg before intercourse with continuous positive airway pressure during nighttime sleep for men with ED and SAS. After a 12-week treatment period, the IIEF score was significantly greater in the sildenafil group.15 Moreland16 first introduced the concept that cavernosal hypoxia is deleterious to erectile tissue structure and function. His study demonstrated that cavernosal tissue exposed to chronically low levels of oxygen upregulates fibrogenic cytokines, leading to collagenization and fibrosis of tissue.16 The decreased REM sleep associated with SAS results in fragmentation of sleep and a decrease in the number of nocturnal erections. Chronic absence of nocturnal erectile activity may lead to cavernosal hypoxia, and it is likely that the loss of these erections contributes to ED in these men. A standardized technique and normative values for NPT (number of episodes and degree of tumescence and rigidity), although extensively studied and published, have not been well established.17 However, most men with functional erections obtain three to six erections per night that are at least 60% rigid and 10 minutes in duration.18 It should be noted that measurable tumescence changes do not always correlate with penile rigidity sufficient for vaginal penetration.19 Sleep disorders adversely affect NPT without, in many cases, affecting awake physiologic performance (normal erections or normal erections with vascular stimulants). Using the IIEF, our data indicate that men with SAS have a significant chance of having ED and that a correlation exists between the severity of sleep apnea and ED (Table II and Fig. 1). Thus, 80% of men with the diagnosis of SAS had IIEF erectile function domain scores of less than 26, indicative of ED. The IIEF is a robust instrument that has been used extensively in ED analyses and currently represents the reference standard questionnaire for the assessment of erectile function.2,20,21 With regard to the use of the ESS, comparing the Multiple Sleep Latency Test, the Maintenance of Wakefulness Test, and the ESS, the receiver operator characteristic curves have demonstrated that the ESS is the most discriminating test.22 On the basis of the scores of 72 normal subjects selected by strict criteria derived from a detailed sleep questionnaire that screened out those with most sleep disorders, including insomnia and snoring or sleep-disordered breathing, a normative reference range of 0 to 10 was defined.23 Another study with a sample of 188 normal subjects suggested that the normative reference range may be 0 to 11.24 In the current study, in men with a clinical suspicion of SAS, we used an ESS score of 10 as the 1035
TABLE II. Pearson coefficients for correlation between ESS and IIEF domain scores IIEF Total ESS P value
Erectile Function
⫺0.62* 0.01
⫺0.88* 0.012
Intercourse Satisfaction
Orgasm
Sex Drive
Overall Satisfaction
⫺0.2 0.06
⫺0.12 0.24
⫺0.10 0.11
0.0 0.9
Abbreviations as in Table I. * Statistically significant correlation.
cutoff for its diagnosis. Using this cutoff, we have demonstrated that the correlation between the severity of sleepiness and ED is good (Fig. 1). Although the results of this study have corroborated the findings of previous studies, we used validated instruments to confirm the association between SAS and ED. One of the limitations was that the analysis was conducted on a small population, which deprived us of the ability to conduct more robust statistical methods, such as multivariate analysis. Another limitation is the absence of data on baseline patient body mass index and serum testosterone levels. The single most important risk factor for sleep apnea is obesity.25,26 Sleep apnea also causes reversible neuroendocrine dysfunction in men, manifested by decreased plasma testosterone levels. This neuroendocrine dysfunction is related to the severity of the sleep apnea, as indicated by the nadir levels of arterial oxygen desaturation and the rate of desaturation episodes.27 Information on both of these factors would have strengthened our study work and helped to shed light on the mechanisms by which the two conditions are associated. CONCLUSIONS These data indicate that men presenting with symptoms suggestive of SAS have a high chance of having ED, and that the correlation between the severity of sleep apnea and the severity of ED is strong. REFERENCES 1. Recommendations of the 1st International Consultation on Erectile Dysfunction, in Jardin A, Wagner G, et al (Eds): Erectile Dysfunction. Plymouth, UK, Health Publications, 2000, pp 711–726. 2. Rosen RC, Riley A, Wagner G, et al: The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 49: 822– 830, 1997. 3. Rosen RC, Fisher WA, Eardley I, et al: The multinational Men’s Attitudes to Life Events and Sexuality (MALES) study: I. Prevalence of erectile dysfunction and related health concerns in the general population. Curr Med Res Opin 20: 607– 617, 2004. 4. Schiavi RC, Mandeli J, Schreiner-Engel P, et al: Aging, sleep disorders, and male sexual function. Biol Psychiatry 30: 15–24, 1991. 5. Hirshkowitz M, Karacan I, Gurakar A, et al: Hypertension, erectile dysfunction, and occult sleep apnea. Sleep 12: 223–232, 1989. 1036
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