Severe obstructive sleep apnoea syndrome and erectile dysfunction: a prospective randomised study to compare sildenafil vs nasal continuous positive airway pressure
A high incidence of erectile dysfunction (ED) among patients with obstructive sleep apnea syndrome (OSAS) has been reported, with a strong correlation among OSAS, ED and quality of life (QOL), it has been estimated that 10 to 60% of patients with OSAS suffer from ED. In this prospective, randomized trial we have investigated 82 consecutive men with ED who had been referred to the outpatient clinic for sleep disorders and proved to suffer from severe OSAS (AHI>30 events / hour). Aim of this study was to evaluate and compare the efficacy of sildenafil versus CPAP lonely in men with ED and severe OSAS.
Materials and Methods
This prospective, randomized unsponsored clinical trial included 82 consecutive men with ED who had been referred to the outpatient clinic for sleep disorders and proved to suffer from OSAS. Inclusion criteria was a severe OSAS as defined per apnoea/hypopnoea index (AHI) more than 30 events per hour as evidenced by recent polysomnography (performed <6 months earlier). Exclusion criteria included: known ED treated with medication or intracavernous injections, blood hypertension (systolic blood pressure above 160mmHg; diastolic blood pressure above 100mmHg), use of nitrates, diabetes mellitus, vascular diseases (deep vein thrombosis, peripheral vascular disease, Raynaud’s disease, vasculitis syndromes), mild and moderate OSAS (AHI<30 events per hour), peripheral neuropathic disease, prostate cancer, pelvic trauma history, renal transplantation, aortic aneurysm, spinal cord injury, endocrine disturbances, penile deformity current alcohol or drug abuse, and medications that could affect erection (eg, beta blockers, H2 blockers). All recruited patients were randomized in 2 main treatment groups: group 1 (41 men) was treated with sildenafil 100 mg (1 hour before sexual intercourse) without CPAP, and group 2 (41 men) was treated with only nasal CPAP during night time sleep. Both groups were evaluated with the same questionnaires (International Index of Erectile Function-EF domain; Sex Encounter Profile; Erectile Dysfunction Inventory Treatment Satisfaction) after 3-months treatment.
Under sildenafil, 312/536 (58.2%) of attempted intercourses were successful compared to 156/512 (30.4%) under CPAP. The number of attempts reported by patients under sildenafil was slightly higher than patients under CPAP (mean: 13.0 vs. 12.4; p=0.1995), but with a significant higher successful report (mean: 7.6 and 3.8; p<0.0001). Moreover, the mean number of successful attempts per week was 2.9 in the sildenafil group, which was significantly higher than the 1.7 successful attempts per week in the CPAP group (p<0.0001).
The mean IIEF-EF domain scores were significantly increased in both groups compared to baseline (26.3 vs 15.8, p<0.0001 in sildenafil group; and 18.7 vs 15.4, p<0.0001 in CPAP group). When the mean IIEF-EF domain scores were compared a significantly higher score was reported in sildenafil treatment group than the CPAP group (p<0.0001).
Overall, 12 of 41 men (29%) were satisfied with CPAP treatment for ED, whereas 28 of 41 men (68%) were satisfied with sildenafil. Satisfaction with treatment was significantly higher among the patients under sildenafil than that in the CPAP group (p = 0.0015). The corresponding partners’ confirmed these data satisfaction rates that were absolutely equal to those reported by the patients (29% with CPAP and 68% with sildenafil). Therapeutic satisfaction was clearly superior among the partners of sildenafil treated patients compared to the CPAP group (p = 0.0006). The analytical assessment of answers to EDITS given by patients and their partners revealed that partners gave a different evaluation of treatment satisfaction. However this difference was not statistically significant, the satisfaction scores reported by patients and partners with sildenafil were significantly higher to that achieved with CPAP.
In this study, we investigated only patients with severe OSAS and ED. Since our purpose was to study only severe OSAS patients with related ED, a strict enrolment selection was performed. In order to collect only subjects with severe OSA as main cause of ED, patients with the most frequently ED related comorbidities (e.g. blood hypertension, diabetes, etc.) were excluded.
CPAP therapy was advised routinely in all these cases. Patel et al. reported with CPAP a significant improvement in objective and subjective measures of sleepiness in patients with OSAS with ED. Whether the improvement was due to the CPAP effectiveness of or because all patients had severe OSAS, it remains unclear. In the study by Perimenis et al. sildenafil increased CPAP effectiveness in patients with mild OSAS when compared with CPAP alone.
Our study is, to date, the only trial that has investigated the PDE5 inhibitors in patients with severe OSAS. This study shows that severe OSAS is strongly associated with ED. In our study, we reported a high overall response rate to sildenafil 100 mg treatment compared with previous studies in the literature. The results obtained in our study are correlated to the selection of enrolled patients, which provided strict exclusion criteria. The high response rate to sildenafil in fact is due to the exclusion of major diseases responsible for ED (blood hypertension, diabetes mellitus, peripheral vascular and neuropathic disease, prostate cancer, spinal cord injury, endocrine disturbances, current alcohol or drug abuse, and medications that could affect erectile function). The direct smooth muscle relaxation in the penile arteries and corpora cavernosa achieved by sildenafil may explain the higher effectiveness of this treatment compared to CPAP. The higher efficacy of sildenafil may thus explain the greater number of intercourse attempts, reflecting the patients strengthened self-confidence.
Even though overall satisfaction with treatment was significantly higher among the patients under sildenafil than that in the CPAP group, about one third (32%) of patients were not satisfied even with the more effective treatment. These data suggest that there is still no specific treatment for erectile dysfunction related to OSAS, and combination therapy (CPAP and sildenafil), as previously reported in the literature does not seem to achieve significantly higher satisfaction rates. We conclude a different therapeutic mode should be studied further.
Treatment of ED in OSAS is still controversial and varies according to its principal cause, but the cause of OSA related ED remains unclear. Consequently, without defining the cause of ED, many drugs such as sildenafil have been used for treatment. This study confirms that severe OSAS is strongly associated with ED. CPAP and sildenafil 100 mg are safe and effective therapies in OSA related ED patients. In the present study sildenafil proved to be more effective than CPAP as it resulted in a significantly higher rate of successful attempts for intercourse and higher IIEF-EF domain scores. Moreover, we reported a high overall response rate to sildenafil 100 mg treatment compared with previous studies in the literature, due to severe criteria of patient enrollment.
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