| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Genitourinary Imaging |
1 From the Department of Radiology, Assaf-Harofeh Medical Center, Sackler School of Medicine, Tel Aviv University, Zerifin, Israel 70300 (L.C.); Departments of Urology (R.K.) and Radiology (J.S.), Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Radiology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (A.B.); and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (J.S., R.G.S.). Received September 4, 2004; revision requested November 10; revision received December 1; accepted January 12, 2005. Address correspondence to L.C. (e-mail: lcopel{at}gmail.com).
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
|---|
MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Thirteen consecutive patients (age range, 22–77 years; mean, 60.4 years) with erectile dysfunction were evaluated with clinical assessment and cavernosal duplex ultrasonography (US). The patients were examined at two sessions 3 weeks apart. First, each patient received 100 mg of sildenafil citrate orally and was examined 60 minutes later without any sexual stimulation. Each patient then underwent repeat clinical and duplex US assessment after audiovisual sexual stimulation. Three weeks later, the patients underwent identical clinical evaluation and duplex US after intracavernosal injection of a commercially available combination of papaverine, prostaglandin E1, and phentolamine. Clinical and duplex US data (ie, peak systolic velocity [PSV]) were examined by using the Wilcoxon signed rank test for matched pairs.
RESULTS: At rest, the overall mean cavernosal artery PSV was 1.08 cm/sec and remained unchanged after intake of sildenafil without any audiovisual stimulation, with no clinical evidence of erection. With the addition of audiovisual sexual stimulation, eight (62%) of 13 patients had penile congestion or erection, and six (46%) had a PSV greater than 25 cm/sec. With intracavernosal injection of the combination of three drugs, all 13 patients achieved congestion or erection, and 10 (77%) had a PSV greater than 25 cm/sec. Both clinical and duplex US responses to intracavernosal injection were significantly greater than they were to sildenafil with audiovisual sexual stimulation (P = .04 and .003, respectively).
CONCLUSION: Oral sildenafil with audiovisual sexual stimulation led to a significant clinical response and increment in blood flow in the cavernosal arteries. However, more patients responded to intracavernosal injection of the combination of three drugs than to sildenafil, and the clinical response was significantly better.
© RSNA, 2005
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
|---|
Intracavernosal injection of vasoactive substances is a well-established treatment for erectile dysfunction as well (6,7). Drugs for use with intracavernosal injection include papaverine, prostaglandin E1, and phentolamine (6,7). These substances may be administrated as a single drug or in combination, with reported efficacy rates of up to 94% (6,8).
We hypothesized there would be no statistically significant difference between the clinical response to sildenafil and intracavernosal injection of vasoactive agents. Thus, the purpose of our study was to prospectively evaluate the clinical response and hemodynamic changes in the cavernosal arteries after oral administration of sildenafil without and with audiovisual sexual stimulation and to compare those responses with responses from intracavernosal injections of vasoactive agents.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
|---|
Ultrasonography and Treatment
All ultrasonographic (US) examinations were performed by a single radiologist (L.C.) with 4 years of experience in Doppler US. A single urologist (R.K.) with 3 years of experience in diagnosing and treating erectile dysfunction performed all intracavernosal injections and clinical assessments.
The anatomic and vascular changes in the cavernosal arteries of the penis were evaluated with duplex US, because it has already been documented in the literature to be highly accurate for assessing patients with erectile dysfunction (9–12). Patients were examined in a semidark room in the supine position, with the penis placed passively on the abdomen. Gray-scale and Doppler US examinations were performed on the ventral surface of the penis at the level of the penile-scrotal junction. All examinations were performed by using an Acuson 128 XP scanner (Acuson, Mountain View, Calif) with a 7.0-MHz linear-array transducer with optimized gain settings. Initially and prior to any treatment regimen, gray-scale scanning of the penis was performed to document any structural deformity or fibrotic plaques. For optimal gray-scale images, magnification was used and the gain was changed dynamically for maximal contrast between the arteries and the surrounding cavernosal tissue.
This was followed by Doppler US assessment of the cavernosal arteries to determine the peak systolic velocity (PSV) and end-diastolic velocity (EDV) within each cavernosal artery. PSVs and EDVs were obtained at the center of the vessel lumen by using the smallest window possible at a standardized angle of 60°. Both color and spectral Doppler US were optimized for the detection of low-velocity flow, with the scale set to measure flow in the cavernosal arteries and adjusted dynamically to prevent aliasing. When flow velocity measurements differed between the two arteries in a patient, the average flow between both arteries was recorded and used for the purpose of this study.
All patients underwent clinical and US evaluation before and after the administration of two types of pharmacologic stimulus: First, the patients were given 100 mg of sildenafil citrate (Viagra; Pfizer) orally without and with audiovisual sexual stimulation. At a second session, they received an intracavernous injection of a combination of 5 mg papaverine, 5 µg prostaglandin E1, and 0.25 mg phentolamine, which was prepared in the pharmaceutical department at Hadassah Hebrew University Medical Center (Jerusalem, Israel) from its generic drugs. All intracavernosal injections were performed by one urologist (R.K.) with 3 years of experience with intracavernosal injections. Treatment regimens were separated by a 3-week interval, with no treatment for erectile dysfunction during the interval to ensure findings at clinical assessment and US were solely the result of the currently administrated treatment plan.
At each of the two sessions, semiquantitative clinical grading of an erection was performed prior to and sequentially after the administration of the treatment regimen as follows: score of 0 = flaccidity; score of 1 = tumescence, mild engorgement of the penis with inadequate rigidity for vaginal penetration; score of 2 = congestion, partial erection that still enables minimal compression or bending of the penis with moderate external compression; and score of 3 = full erection, complete stiffness of the penis. Full erection or congestion was considered sufficient for sexual intercourse. The semiquantitative clinical grading of erection was performed by one urologist (R.K.) with 3 years of experience in diagnosing and treating erectile dysfunction.
Specifically, in the sildenafil protocol after baseline evaluation, a second clinical and US evaluation of the penis was performed 1 hour after the administration of sildenafil, with no additional audiovisual sexual stimulation. A 1-hour delay was chosen because the peak plasma concentration of sildenafil is known to occur at this time (13). This was followed by an audiovisual sexual stimulus, given that sildenafil has been documented to require a direct sexual stimulus for maximum effectiveness (14–17). The audiovisual stimulus consisted of 15 minutes of private continuous visualization of an erotic film. After 15 minutes and with the patient still receiving the audiovisual stimulus, clinical and US evaluations were again performed thereafter at 5-minute intervals for a total of 20 minutes. Hence, the sildenafil regimen consisted of clinical and US evaluation of the penis five times after baseline and over a 95-minute period.
The intracavernosal injection protocol included baseline clinical and US assessment followed by sequential assessments at 1, 5, 10, 15, and 20 minutes after administration of 0.25 mL of the combination of three drugs injected directly into the corpora cavernosa.
US criteria for defining a normal response to either treatment regimen included any cavernosal artery PSV equal to or more than 25 cm/sec and an EDV of less than 5 cm/sec (9,18,19). Clinically, full erection (score of 3) or congestion (score of 2) was considered a successful endpoint for both regimens.
Statistical Analysis
Comparison of the clinical response between sildenafil without audiovisual stimulation, sildenafil with audiovisual stimulation, and intracavernosal injection of the combination of three drugs was performed by using the Wilcoxon signed rank test for matched pairs. For all 13 patients, the mean PSV occurring as a result of sildenafil without audiovisual stimulation, sildenafil with audiovisual stimulation, and intracavernosal injection of the combination of three drugs was also assessed for differences by using the Wilcoxon signed rank test for matched pairs. Differences were considered significant when the P value was less than .05. Statistical analysis was performed with commercial software (KaleidaGraph Synergy, version 3.6; Reading, Pa).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
|---|
Combination of Papaverine, Prostaglandin E1, and Phentolamine
At rest, before the intracavernosal injection of the combination of three drugs, the mean PSV was 0.69 cm/sec ± 1.70 (range, 0–5 cm/sec), which did not differ from the baseline US measurements obtained 3 weeks earlier, prior to the administration of sildenafil (P = .37). The clinical score (0 in all patients) was also identical to the previously obtained baseline score. Significant (P < .001) changes were documented following intracavernosal injection of the combination of three drugs; the mean PSV increased to 47.08 cm/sec ± 36.91 (range, 19–164 cm/sec), and the mean EDV was less than 5 cm/sec in all patients. Clinical assessment revealed significant (P < .001) increase in erectility from 0 to 2.46 ± 0.52.
Intrapatient Comparison
When each patient was considered independently and intracavernosal injection of the combination of three drugs was compared to sildenafil administration with audiovisual stimulation, the combination of three drugs caused a significantly higher increase in PSV (P = .003). With the combination of three drugs, 10 (77%) of 13 patients achieved a PSV greater than 25 cm/sec, while this occurred in only six (46%) of 13 patients with sildenafil and audiovisual stimulation. Of note, all of the latter six patients had a PSV greater than 25 cm/sec with the combination of three drugs as well (Figs 1, 2).
|
|
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
|---|
With both regimens of treatment, we found good correlation between clinical assessment and PSV. Seventeen (81%) of 21 examinations with a clinical score of 2 or 3 (congestion or full erection) also had a PSV greater than 25 cm/sec. These findings are indirectly supported by previous studies correlating untreated erectile dysfunction and Doppler US, where a PSV below 25 cm/sec was associated with erectile dysfunction and lower PSVs correlated with an increased likelihood of inadequate erection (9,12,18).
Authors of many recent articles have focused on the clinical effectiveness of sildenafil versus that of intracavernosal injection, without any hemodynamic correlation. In a multicenter study comprising 134 patients, 89.6% (60 of 67) of patients in a group who had no clinical response to treatment with sildenafil showed clinical improvement after intracavernosal injection treatment with a synthetic derivate of prostaglandin E1 (25). In another study (26), clinical response was assessed with patient interviews and a patient self-administrated sexual questionnaire. During the study period of 4 months, 44 (29.9%) of 147 patients known to clinically respond to intracavernosal injection showed no response to sildenafil, while 53 (36.1%) patients who responded to both treatment regimens had a higher clinical response to intracavernosal injection.
In our study, we not only found significant differences in the clinical response between intracavernosal injection and sildenafil with audiovisual stimulation but also in changes in PSVs in the cavernosal arteries. Significantly more patients had erection or congestion and a higher PSV with use of intracavernosal injection than with use of sildenafil. Because our study group of 13 patients was the same for both regimens and all other variables were constant, our results indicate that intracavernosal injection is more likely to cause improvement in a patient's erectile dysfunction compared with sildenafil with audiovisual stimulation, and this improvement is the direct result of a greater increase in cavernosal arterial flow.
We do point out that our findings that intracavernosal injection for erectile dysfunction is associated with a significantly greater hemodynamic response compared with sildenafil may in part be due to our use of a combination of three vasoactive drugs (papaverine, prostaglandin E1, and phentolamine). Authors of several studies (27,28) have reported that mixtures of stimulating drugs for intracavernosal injection (papaverine, prostaglandin E1, and phentolamine) were significantly more potent than a single drug with respect to clinical response.
Further, other investigators (22,23) actually concluded that sildenafil is comparable to intracavernosal injection of only prostaglandin E1 or papaverine when assessing for a hemodynamic response. For example, in the study by Basar et al (22), no significant differences in PSV and EDV were found between oral sildenafil citrate, intracavernosal injection of prostaglandin E1, and intracavernosal injection of papaverine. The results of a recent study (24) resemble our findings. Similar to our findings, the differences in PSV were significantly higher after injection of papaverine than after oral administration of sildenafil in impotent patients with normal Doppler US findings (P < .001). Therefore, it is likely that our mixture of vasoactive drugs for intracavernosal injection likely had a synergistic effect on cavernosal arterial flow.
Another possible explanation for the clinical and US differences we found between sildenafil and intracavernosal injection may be related to patient anxiety. The test-induced anxiety might have been higher with sildenafil since it was the first examination performed. Patient anxiety is an important factor that can affect both clinical and Doppler US results. However, it has been documented that patients are understandably more comfortable using sildenafil compared with intracavernosal injection (22) and that intracavernosal injection can increase adrenergic tension, causing a decrease in erection (29).
We found no clinical response or significant change in PSV in response to oral administration of sildenafil without sexual stimulation when compared with the resting state. These results are totally in accord with the mechanism of action of sildenafil (16,17). High levels of cyclic guanine monophosphate, which cause cavernosal artery vasodilatation and subsequent erection, are facilitated by nitric oxide release that is a direct result of sexual stimulation (16,17). Sildenafil facilitates an erection because it blocks phosphodiesterase 5, which disassembles cyclic guanine monophosphate (14,15). Hence, without local release of nitrous oxide, sildenafil should have no effect on cavernosal artery hemodynamics, as was found in our study.
Although we have a small group of patients, each patient served as his own control. By doing this, we excluded the possibility that the differences found can result from different patient groups. By comparing each patient specifically to himself, we were able to show that hemodynamic and the resultant clinical effects of intracavernosal injection of the combination of papaverine, prostaglandin E1, and phentolamine on the cavernosal arteries appear to be superior to those of sildenafil, regardless of the risk factors for erectile dysfunction.
Our study had limitations. First, we evaluated only a small group of patients, and second, our study was not double blinded because of the inherent differences in treatment regimens.
In conclusion, oral sildenafil with audiovisual sexual stimulation led to a significant clinical response and increment in blood flow in the cavernosal arteries. However, more patients responded to intracavernosal injection of the combination of three drugs than to sildenafil, and the clinical response was significantly better. Thus, patients who do not have an apparent response to sildenafil may still respond to intracavernosal injection with combination of papaverine, prostaglandin E1, and phentolamine.
|
FOOTNOTES |
|---|
Abbreviations: EDV = end-diastolic velocity • PSV = peak systolic velocity
Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, L.C., R.K., A.B.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, L.C., R.K.; clinical studies, L.C., R.K., A.B., J.S.; statistical analysis, L.C.; and manuscript editing, all authors
|
References |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| RADIOLOGY | RADIOGRAPHICS | RSNA JOURNALS ONLINE |
