The aim of this study was to assess the efficacy of sildenafil as the first-step tool for erectile dysfunction (ED) in Japanese males. Between March 1999 and March 2003, 281 patients were prescribed five tablets of sildenafil (50 mg) as the first step in the therapeutic management of ED. Of the 281 patients, 206 were evaluable patients. The overall success rate in achieving sexual intercourse in subjects after taking sildenafil was 77.2% (159/206), while 22.8% (47/206) were unsuccessful. The success rates in men with functional ED and organic ED were 91.4% (85/93) and 65.5% (74/113), respectively (P<0.0001). Overall, transient adverse effects of sildenafil occurred in 16 (8%) males. Intolerable adverse effects (edema and dizziness) occurred in only 1% of patients (2/206). Sildenafil citrate may be recommended as the first choice drug for ED because of its high success rate and low invasiveness.
Sildenafil was introduced in March 1999 as an orally active drug for erectile dysfunction (ED) in Japan. The efficacy, safety, minimal invasiveness, and nonspecificity of sildenafil have been reported in the therapeutic management of ED.1 These results have raised the hypothesis that sildenafil can be placed as the first-step therapeutic tool for Japanese males with ED. The aim of this study was to examine this hypothesis.
Between March 1999 and March 2003, 296 patients complaining of ED visited our sexual dysfunction clinic. Of the 296 men, 281 were prescribed five tablets of sildenafil (50 mg) as the first step in the therapeutic management of their ED. ED was diagnosed when the Japanese version of the International Index of Erectile Function 5 (IIEF-5) score was less than 22 as previously described.2, 3 The IIEF had been linguistically validated in 32 languages including Japanese.4 Data on the present illness and the previous history of medication, hospitalization, and surgery were obtained from all patients. No patients were prescribed sildenafil if they had a recent (within the previous 6 months) stroke or myocardial infarction or if they were receiving nitrate therapy. At least 3 months after treatment, the efficacy of the sildenafil was evaluated. When the patients came to our clinic again after taking the five tablets of sildenafil, the efficacy of sildenafil was assessed by a global-efficacy question regarding the patient's satisfaction (‘Did the treatment improve your erections?’), with a response of ‘yes’ (responder) or ‘no’ (nonresponder). Of the 281 patients who were prescribed five tablets of sildenafil (50 mg), 207 (73.7%) came to our clinic again. Of these 207 patients, one had not taken any sildenafil tablets after prescription and was excluded from our analysis, leaving 206 evaluable patients. When subjects did not achieve an erection hard enough for sexual intercourse after taking 50 mg of sildenafil and wanted additional therapies, they underwent intracavernous injections of prostaglandin E1 (PGE1) with color Doppler ultrasonography, or a RidiScan test with sexual stimulation.
Table 1 shows the characteristics of the 206 men. Mean age and standard deviation (s.d.) of the patients were 56.3±13.1 y (range: 19–82). The age distribution of the patients is as follows: teenagers: one 20–29 y: seven 30–39 y: 23, 40–49 y: 25, 50–59 y: 54, 60–69 y: 64, 70–79 y: 28 and over 80 years: 4. Of the 206 men, 113 had associated risk factors for ED as follows; diabetes mellitus in 32 patients, status post pelvic cavity operation in 19, hypertension in 17, benign prostate hyperplasia in 17, psychiatric disease in 13, spinal cord disease in 10, heart disease in seven (arrhythmia six, old myocardial infarction six), hepatic disease in five, respiratory disease in five, and other diseases in 14. Other diseases consisted of hyperlipidemia (n=3), cerebral infarction (n=2), chronic renal failure (n=2), neurogenic bladder dysfunction (n=2), Parkinson's disease (n=1), peptic ulcer (n=1), leukemia (n=1), surgical castration (n=1), and priapism (n=1). Of the 113 men, 26 had more than one disease. We defined these 113 men as having organic ED and the remaining 93 men had functional ED.
Parameters were compared between the responders and nonresponders using the Mann–Whitney U-test. Both univariate and multivariate stepwise logistic regression analyses were performed to determine nonresponders to sildenafil treatment. Statistical significance was set at P<0.05.
The overall success rate in achieving sexual intercourse in subjects after taking 50 mg of sildenafil was 77.2% (159/206), while 22.8% (47/206) were unsuccessful. There was a significant difference in age between responders (mean±s.d.: 54.7±13.8) and nonresponders (62.1±12.0). The success rates in achieving sexual intercourse in men less than 50 y 50–69 y and 70 y or older were 87.5% (49/56), 78.0% (92/118), and 56.3% (18/32), respectively. The success rate in achieving sexual intercourse using 50 mg of sildenafil was associated with age.
The IIEF-5 score ranged from 1 to 21 (6.5±4.7). There was a significant difference in the IIEF-5 score between responders (7.1±4.5) and nonresponders (4.5±4.8). This finding suggests that IIEF-5 before sildenafil treatment may predict the response to sildenafil.
Of the 159 patients who achieved successful intercourse using 50 mg of sildenafil, 74 (46.5%) had risk factors for ED, while 39 of 47 (83.0%) who could not achieve intercourse with sildenafil had risk factors for ED. The success rates in achieving sexual intercourse in men with functional ED and organic ED were 91.4% (85/93) and 65.5% (74/113), respectively (Table 2). The success rates in achieving sexual intercourse using 50 mg of sildenafil in men with or without diabetes mellitus or a history of pelvic cavity operation were 56.3% (18/32), 81.0% (141/174), 42.1% (8/19), and 80.7% (151/187), respectively (P=0.002 and P<0.0001, respectively). In patients with or without hypertension, the success rates in achieving sexual intercourse using 50 mg of sildenafil were 52.9% (9/17) and 79.4% (150/189), respectively (P=0.007). Patients without hepatic disease achieved successful sexual intercourse in 78.6% of cases (158/201), while patients with hepatic disease achieved successful sexual intercourse in 20.0% (1/5) (P=0.001). In the remaining diseases, there was no significant difference in success rate. Upon univariate logistic regression analysis, age, status of post pelvic cavity operation, diabetes mellitus, hypertension, and liver dysfunction were statistically significant predictors for the nonresponders to sildenafil. By multivariate stepwise logistic regression analysis, status of post pelvic cavity operation was the best independent predictor for the nonresponders to sildenafil treatment, followed in order by, diabetes mellitus, hypertension, and age (≥70 y old) (Table 2).
Overall, adverse effects of sildenafil were flushing in nine of 206 cases (4.3%), visual disturbance in three (1.4%), headache in two (1.0%), edema in one (0.5%), and dizziness in one (0.5%). Two patients stopped taking sildenafil because of adverse effects (edema and dizziness).
Of the 47 nonresponders, 25 received additional therapies after RidiScan test or intracavernous injection of PGE1, and achieved an erection hard enough for sexual intercourse. Of them, 11 received 75 or 100 mg of sildenafil (75 mg: one, 100 mg: 10), six used a penile constriction band with sildenafil 50 or 100 mg (50 mg: five, 100 mg: one), six received intracavernous injection with PGE1 (one used PGE1 with 100 mg of sildenafil), and two used a vacuum constriction device (VCD). Although one used a VCD with 100 mg of sildenafil and intracavernous injection with PGE1, he failed to achieve sexual intercourse. The remaining 21 nonresponders did not want any additional therapy.
The total number of men with ED in Japan is estimated to be over 9.8 million. This number is approximately three times higher than 10 y ago.5, 6 The number of elderly men (≥65 y old) is predicted to rise until 2050,7 and ageing is associated with ED.8 In addition, the risk of ED increases with cardiac disease, diabetes mellitus, chronic renal failure, and hypertension in middle-aged men in Japan.9 Furthermore, since patients have been able to take sildenafil citrate since 1999 in Japan, the number of patients who consult a doctor for ED has also increased.10 Advertizing and increased knowledge regarding ED has become available that would increase the number of men requesting treatment. Therefore, the increase in number of men with ED is expected to continue.
In the present study, we prescribed five tablets of sildenafil (50 mg) as the first therapeutic tool for Japanese patients with ED since the introduction of sildenafil in 1999 in Japan. We evaluated the effect of sildenafil citrate when patients came to our clinic again after having taken it five times. Since the more times the patients took it, the higher the intercourse success rate was,11 we prescribed five tablets of 50 mg sildenafil for patients without any contraindications at the first visit. The successful intercourse rate with sildenafil citrate 50 mg at our clinic (77.2%) was similar to those of other reports (61–82%).12, 13 Although the sildenafil citrate success rate was lower in patients with organic ED (65.5%) than in those with functional ED (91.4%), a success rate of approximately 70% was maintained. In addition, only 1% of patients (2/206) stopped taking sildenafil due to intolerable adverse effects in this study. Tan14 reported that sildenafil should be considered the first-line management for ED when considering economic cost. Therefore, sildenafil citrate may be the first choice drug because of its high success rate, low adverse effects, low invasiveness and applicability for functional as well as organic ED.
Based on multivariate logistic regression analysis, status of post pelvic cavity surgery, diabetes mellitus, hypertension, and patient's age (70 y or older) were independent predictors for nonresponders to sildenafil treatment. Radical surgery for colorectal cancer, prostate cancer, and bladder cancer was associated with a high incidence of ED.15 ED may be caused by interference with the neural pathways and blood supply to the cavernous body. Diabetes mellitus is one of the main systematic diseases causing ED. Diabetes may cause ED through its vascular, neurogenic, endothelial, psychogenic, and androgenal dysfunction.16 Hypertension may cause arterial stenosis and decreased arterial flow to the cavernous body and cause ED.16 In an in vitro study, ageing selectively affected endothelium-mediated nitric oxide release from cholinergenic stimulation.17 Therefore, pelvic surgery, diabetes mellitus, hypertension, and ageing were associated with poor response to sildenafil treatment. There, however, is a limitation in our study because of a small number with risk factors and we need a further study with a larger number.
In the present study, 19 of 45 (42%) patients who failed to achieve intercourse after taking sildenafil citrate did not want to take additional therapies probably because of their invasiveness and complexity. Low invasiveness and less complexity are therefore necessary when choosing the additional options. Success with sildenafil citrate was reported to depend on the dose.18 Therefore, an increase in dose is the easiest next step in Japan. Sildenafil citrate is allowed to be taken in doses up to 50 mg. A total of 13 patients were treated with sildenafil at these levels (75–100 mg) according to previous report,18 and 11 of them achieved successful intercourse.
In conclusion, it is recommended that sildenafil citrate (50 mg) may be the first choice drug for ED because of its high success rate, very low intolerable adverse effects, and low invasiveness. Other oral agents with a different pharmacological activity from sildenafil for sildenafil-resistant ED are needed.
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Ochiai, A., Naya, Y., Soh, J. et al. Efficacy of sildenafil as the first-step therapeutic tool for Japanese patients with erectile dysfunction. Int J Impot Res 17, 339–342 (2005) doi:10.1038/sj.ijir.3901318
- erectile dysfunction
- sildenafil citrate
- Japanese male
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