Introduction

Obstructive sleep apnea syndrome (OSAS) is defined by repetitive upper airway occlusion, which causes a reduction or cessation of breathing. Recent studies have indicated that the prevalence of OSAS is high and rising continuously, with evidence that up to 10% of men older than 40 years are affected.¹ OSAS is associated with clinical complications, such as daytime somnolence, hypertension, ischemic heart disease and increased risk of stroke.² Furthermore, several reports have suggested a high incidence of erectile dysfunction (ED) among patients with OSAS and a strong correlation among OSAS, ED and quality of life (QOL).^{3, 4}

However, conflicting data exist regarding the relationship between OSAS and ED.^{5, 6} Several studies found a high prevalence of ED in patients with OSAS,^{3, 7, 8} and Fanfulla et al.⁶ suggested that this association may be mediated by hypoxia-induced occult nerve dysfunction. In addition, a 40% improvement in ED has been reported after treating patients with OSAS who had continuous positive airway pressure (CPAP).⁹ However, several studies have contested this apparent relationship. Schiavi et al.⁵ examined 70 men, all of whom underwent four full-night polysomnography studies with assessment of nocturnal penile tumescence, and reported no correlation between sleep apnea and ED.

To date, several studies have reported that OSAS has a significant impact on QOL.^{10, 11} However, most of these did not use scales for OSAS-specific QOL, but instead relied upon general health questionnaires. Thus, we examined the correlation between the severity of OSAS and ED or disease-specific QOL in Korean patients with OSAS. In addition, we identified a reliable polysomnographic parameter that may predict ED in patients with OSAS.

Materials and methods

Subjects

The institutional review board of Seoul National University Hospital approved this case-control study. All participants provided written informed consent before involvement. In total 107 patients evaluated for potential OSAS volunteered to participate in this study. Patients presenting with the following conditions were excluded from this study: chronic or acute psychiatric disorders; cardiovascular diseases, such as hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg); deep vein thrombosis; peripheral vascular disease; connective tissue disorders; metabolic or neurological disorders known to induce peripheral neuropathy or ED (for example, diabetes mellitus) or sleep disorders unrelated to sleep-disordered breathing. If patients were already diagnosed with ED or had undergone therapy with medications that affect erectile function (for example, -blockers or H₂ blockers), they were also eliminated from the study. Of the 107 participants, 78 met the criteria; 19 of them were disqualified because polysomnographic tests were not followed. Thus, the overall study population who completed all requirements was 59 patients.

The experimental group consisted of 32 consecutive male patients with clinical symptoms suggestive of OSAS, including snoring, apnea and daytime sleepiness for at least 1 year. The diagnosis of OSAS was confirmed by an apnea–hypopnea index (AHI) 10 episodes per hour during a full-night polysomnography (PSG). The control group was composed of 27 men with simple snoring and AHI less than 10 on PSG. All of the subjects were men between 20 and 60 years of age. In both groups, basic characteristics, PSG parameters and accompanying disorders were reviewed.

Questionnaires

All subjects were asked to complete three questionnaires, including the Korean versions of the International Index of Erectile Function (KIIEF-5), the Calgary Sleep Apnea Quality of Life Index (SAQLI) and the Epworth Sleepiness Scale (ESS).

The KIIEF-5 consisted of items 15, 5, 13, 4 and 2, in order of importance, which were selected from among 15 items covered in the International Index of Erectile Function (IIEF-15).¹² Each item was related to erection confidence, erection firmness, maintenance frequency, maintenance ability and overall satisfaction. The optimal cutoff score was 21, with corresponding sensitivity and specificity values of 0.97 and 0.91, respectively.¹² Patients with KIIEF-5 score <21 were diagnosed with ED in this study.

The SAQLI identifies conditions or factors that are specific to patients with sleep apnea, and it was designed as a measure of clinical outcomes in sleep apnea studies.^{13, 14} All items that had an influence on the QOL of these patients were identified. The SAQLI consists of 35 questions organized into four domains: daily function, social interactions, emotional function and symptoms. Because the fifth and sixth domains examined treatment-related symptoms, we used the sum of first four domains as a parameter for QOL. The SAQLI has a high degree of internal consistency, face validity (as determined by both content experts and patients) and construct validity, as shown by its positive correlation with the the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the improvement of scores in patients who had successfully completed a 4-week trial of CPAP.^{13, 14}

The ESS is a simple, self-administered questionnaire that is shown to provide a measurement of the subject's general level of daytime sleepiness.¹⁵ Subjects are asked to rate on a scale of 0–3 how likely they would doze off or fall asleep in the eight situations, based on their usual way of life in recent times. In patients with OSAS, ESS scores were significantly correlated with the respiratory disturbance index and the minimum oxygen saturation level.¹⁵

Polysomnography

We used an Embla N 7000 (Embla, Reykjavik, Iceland) and standard electrodes and sensors. Electroencephalography electrodes were applied at C3/A2, O1/A2 and O2/A1, and two electrooculography electrodes were applied at the sides of both eyes to record horizontal and vertical eye movements. Submental electromyography electrodes were applied at the submentalis muscles, and electromyograms of both anterior tibialis muscles were used to analyze limb movements during sleep. Strain gauges were used to record chest and abdominal respiratory movements, and nasal pressure canulas were used to record airflow. Arterial oxygen saturation was measured using pulse oximeters applied to the index finger. On the basis of criteria established by Rechtschaffen and Kales,¹⁶ we scored every 30-s epoch of the nocturnal polysomnogram. Apnea was defined as the complete cessation of airflow for at least 10 s, whereas hypopnea was defined as a substantial reduction in airflow (>50%) for at least 10 s or a moderate reduction in airflow (>30%) for at least 10 s with electroencephalographic arousal or oxygen desaturation (4%). The AHI was defined as the total number of apneas and hypopneas per hour of sleep.

Statistical analysis

Descriptive statistics were first performed; each value was expressed as the means.d. Continuous variables were analyzed using Student's t-test if the data were normally distributed. Otherwise, the Mann-Whitney U-test was used. Categorical variables were compared using the ²-test with Yates correction. If a value in a cell was less than 5, the Fisher's exact test was used. Odds ratio and corresponding 95% confidence interval (CI) were also calculated. Simple linear regression was performed for the correlation study. A P-value of <0.05 was considered statistically significant. All statistical analysis was performed using the statistical software package SigmaStat for Windows SPSS 12.0 (SPSS, Chicago, IL, USA).

Results

Patient characteristics, including age, body mass index (BMI), basic PSG parameters and KIIEF-5, SAQLI and ESS scores were summarized in Table 1. BMI, AHI, longest apnea, lowest oxygen saturation, ESS score and SAQLI score were significantly worse in patients with OSAS. No statistical difference was observed in the KIIEF-5 scores between groups.

Table 1 - Comparison of baseline variables between the OSAS and non-OSAS groups.

Full table

Regarding ED, 19 of 32 (59.3%) patients with OSAS had ED, compared to only 8 of 27 (29.6%) control patients. The proportion of patients with ED in the OSAS group was significantly higher than in the control group with an odds ratio of 3.471 (95% CI, 1.171–10.286).

We also found that the lowest oxygen saturation level was more closely related to the KIIEF-5 and SAQLI scores than to AHI (Table 2). ED showed no significant association with AHI; however, it was strongly associated with the lowest oxygen saturation level. When the cutoff value for the lowest oxygen saturation level to predict ED was set at 77%, its positive predictive value was 88.9% (sensitivity=70.4%, specificity=62.0%; Table 3). When this cutoff value was applied to our study subjects, the patients with the lowest saturation <77% showed a much higher proportion of ED (88.9%, Table 4).

Table 2 - Correlation between primary polysomnographic parameters and KIIEF-5 or SAQLI.

Full table

Table 3 - Cutoff value for the lowest oxygen saturation to predict erectile dysfunction.

Full table

Table 4 - Proportion of patients with erectile dysfunction below the cutoff value for lowest oxygen saturation.

Full table

Discussion

In this study, the proportion of ED was markedly higher among patients with OSAS than in the control group. The KIIEF-5 score did not differ between the OSAS and control groups, which were based on AHI. In fact, AHI itself was not significantly related to the KIIEF-5 score; instead, the lowest oxygen saturation level showed a significant association with the KIIEF-5 and SAQLI scores. Taken together, these findings suggest that the patient's lowest oxygen saturation level is a more reliable parameter rather than AHI to predict ED in patients with OSAS. In the previous studies, the lowest oxygen saturation was also used to assess the severity of sleep-disordered breathing, and used as a predictive indicator of ED.^{3, 17}

Although the mechanism underlying this correlation between OSAS and ED is unclear, previous studies have proposed that recurrent intermittent hypoxemia and increased sympathetic activation, primarily at the termination of apneic events, increases the frequency of ED in patients with OSAS.^{18, 19} Initially, OSAS was examined as one of the causes underlying intermittent failure to transport the full complement of nasal nitric oxide (NO) to the lung with each breath.²⁰ Although further study should be conducted to investigate the relationship between NO and OSAS, the impairment of the vasoprotective function of NO as a result of respiratory disturbances during nighttime sleep may explain the association between OSAS and ED.²¹

Testosterone has been proposed as another linking factor between ED and hypoxia, though it is controversial. Köhler et al.²² reported that androgen deficiency was quite common in men with ED. Because sleep apnea is more prevalent in men and testosterone is known to affect sleep apnea and chemosensitivity, explaining why ED is more common in patients with OSAS based on testosterone levels alone is difficult. Stewart et al.²³ reported that androgen blockade had no clinically significant effect on sleep, sleep-disordered breathing or chemosensitivity in patients with moderate to severe sleep apnea, which was contrary to the hypothesis that reduced androgen activity would influence sleep-disordered breathing and respiratory control.

Sleep fragmentation itself, irrespective of intermittent hypoxia, is known to influence similar physiological consequences, including sympathetic activation. Regarding sleep architecture in our study, patients with OSAS had significantly longer total sleep time (P=0.016) and lower proportion of stages 3 and 4 (P=0.028) than those without OSAS. However, both the OSAS and control groups were similar in terms of sleep and rapid eye movement latency (P=0.575 and 0.559, respectively). Our linear regression analysis revealed no statistical significances among KIIEF-5 score and other sleep parameters that indicate the degree of sleep fragmentation (Table 2).

Numerous reports have noted an association between OSAS and QOL, but these studies produced conflicting results, particularly in terms of improved QOL after surgical intervention or CPAP.^{3, 24, 25} In addition, these studies relied upon general health questionnaires, such as SF-36 and the Satisfaction With Life Scale to evaluate QOL. Therefore, the results did not address issues related specifically to OSAS, such as marital problems, increased divorce rates, depression or poor job performance. Herein, we assessed health-related QOL issues that are specific to patients with OSAS using the Calgary SAQLI. Our results demonstrate for the first time that the disease-specific QOL was significantly compromised in Korean patients with OSAS compared to subjects without OSAS.

We diagnosed ED in patients with OSAS based on the patient's KIIEF-5 score. However, a previous study determined that the sensitivity and specificity of the KIIEF-5 cutoff value were 97 and 91%, respectively, indicating that this questionnaire is sufficient to identify patients with ED. Furthermore, it is not realistic to expect all patients with OSAS to complete the KIIEF-5 in the ear, nose and throat (ENT) outpatient clinic or to consult a sexologist, demonstrating why a reliable polysomnographic predictor for ED is necessary. Thus, the notion that the lowest oxygen saturation is a clinical indicator for ED screening is plausible with regard to its close correlation with the KIIEF-5 score, though it cannot be concluded in the present study. The cutoff value of the lowest oxygen saturation to predict ED was calculated with a value of 77% (positive predictive value=88.9%, sensitivity=70.4% and specificity=62.0%).

In conclusion, clinicians should consider the possibility of sexual dysfunction and necessity of consultation when their male patients with OSAS showed the lowest oxygen saturation levels lower than 77%. Additional studies are necessary to discover the mechanism of ED in OSAS, especially the role of desaturation.

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Acknowledgements

We thank Dr W Flemons for his permission to translate the Calgary Sleep Apnea Quality of Life Index (SAQLI) into Korean and to use it in this study. The authors have no financial or other potential conflicts of interest to declare.