Preference for oral sildenafil or intracavernosal injection in patients with erectile dysfunction already using intracavernosal injection for > 1 year

Authors


Sae-Chul Kim, Department of Urology, Chung-Ang University, Yongsan Hospital, 65-207, Hangang-Ro 3-Ka, Yongsan-Ku, Seoul 140-757, Korea.
e-mail: saeckim@unitel.co.kr

Abstract

Authors from Seoul describe their experience with patients already on triple therapy by intracavernosal injection who changed to oral sildenafil. Rather surprisingly, they found that patients had had a greater preference than expected for triple therapy, feeling that they had a better quality of erection on intracavernosal injection.

The subject of the effect of renal transplantation on sperm quality and sex hormone levels is discussed by authors from Teheran. They found that sperm morphology and density remained unchanged, but there were significant improvements in sperm mobility. There was also an improvement in hormone levels and sexual function.

OBJECTIVE

To investigate the efficacy and preference for oral sildenafil or intracavernosal injection (ICI) therapy in patients with erectile dysfunction (ED) already using ICI.

PATIENTS AND METHODS

In all, 69 patients with ED (mean age 55.1 years, sd 12.3) on ICI therapy with triple solution (papaverine/phentolamine/prostaglandin-E1) for > 1 year were recruited for the study. Their erection quality, adverse reactions and selection rate of oral sildenafil or ICI as treatment, after using sildenafil for 3 months, and the reasons for their preferences, were compared between the regimens,

RESULTS

Overall, 52 men (75%) responded to sildenafil; of these men, the erection quality with ICI was better than that with sildenafil in 46 (89%) and 16 (31%) preferred ICI as their treatment. Eighteen patients (35%) used each treatment alternately and 18 (35%) used sildenafil exclusively. The main reason given by patients for choosing ICI was a better quality of erection (74%).

CONCLUSION

More patients with ED and using ICI preferred it as their main treatment than was expected, even though they had a good response to oral sildenafil. A better quality of erection with ICI was the reason why experienced patients chose this method, differing from the choice of patients starting treatment for ED.

INTRODUCTION

Intracavernosal injection (ICI) therapy is one of the main medical treatments for erectile dysfunction (ED), with a high efficacy rate despite its high withdrawal rate [1–6]. Recently, oral sildenafil has replaced ICI therapy as the first-line treatment for ED, with clinical trials documenting efficacy and safety in patients of all ages and with ED of various causes and degrees of severity [7–9]; it is also easily administered and not invasive. Many patients who previously used ICI therapy have changed to oral sildenafil and currently ICI remains a second-line treatment for patients who do not respond to oral therapy, although its efficacy rate has not yet been surpassed by any other form of medical therapy.

However, some patients who previously used ICI therapy prefer to continue with it, even though they also have a good erectile response to oral sildenafil. A major reason is that they have already experienced better erections and more rapid and reliable responses with ICI. Although many patients with ED who used ICI therapy have changed to oral sildenafil, and are willing to do so, reports on the efficacy and preference for sildenafil in patients already on ICI are, to our knowledge, few [10]. Consequently, we investigated the preference rate for sildenafil as an ongoing treatment in patients with ED who previously used ICI therapy and showed good erectile responses to oral sildenafil.

PATIENTS AND METHODS

In all, 69 patients with ED (mean age 55.1 years, sd 12.3, range 23–79) who received previous ICI therapy with trimix (a solution of papaverine 18.75 mg/mL, phentolamine 0.625 mg/mL and alprostadil 6.25 µg/mL) for a mean (sd, range) of 3.4  (1.9, 1–7.2) years were recruited for the study. Patients using concomitant treatment with nitrates or nitrites, with significant cardiovascular diseases, e.g. stroke, myocardial infarction and life-threatening arrhythmia, within the previous 6 months, congestive heart failure, unstable angina, resting hypotension (< 90/50 mmHg) or hypertension (> 170/120 mmHg), major haematological, renal, or hepatic disorder, and significant penile deformities, were excluded. The prevalence of associated vascular risk factors included hypertension in 14%, diabetes mellitus in 13% and hypercholesterolaemia in 3%. When recruiting men with cardiovascular diseases, American College of Cardiology and American Heart Association Guidelines were adopted [11].

All patients received a starting dose of 50 mg of sildenafil; the dose was adjusted to 100 or 25 mg, based on efficacy and tolerability. The efficacy of sildenafil was assessed after patients took it at least four times. A positive response to sildenafil (a good erection) was defined as an erection adequate for satisfactory sexual intercourse, based exclusively on patient reports. Adverse reactions to sildenafil and their severity (mild, moderate, severe) were investigated using a questionnaire. The erection quality, adverse reactions and selection rate of sildenafil or trimix as an ongoing treatment, after using sildenafil for 3 months, and the reasons for the preference, were compared between the regimens, using the International Index of Erectile Function (IIEF) questionnaire. The results were analysed using standard statistical methods, including descriptive statistics, Student's t-test and the chi-square test.

RESULTS

There were good erectile responses to sildenafil in 52 patients (75%); the efficacy rate (86%) of sildenafil in 39 men using a lower dose (< 0.3 mL) of the trimix was significantly higher than in 13 men (53%) using a high dose (≥ 3 mL; P < 0.05). There were no differences in the age distribution, frequency of associated vascular risk factors, duration of ICI therapy, and scores for question 3 and 4 of the IIEF on ICI between those responding or not to sildenafil (Table 1). Among the 52 responders, the erection quality with ICI was better than that with sildenafil in 46 (89%), whereas two (4%) had better erections with sildenafil and four (8%) had similar responses to both.

Table 1. The age distribution, frequency of associated vascular risk factors, duration of ICI therapy, scores for Q3 and Q4 of the IIEF questionnaire on ICI, in those responding or not to sildenafil
 Responding (52)Not responding (15)
Mean (sd) age, years55.9 (9.9)54.3 (13.9)
Vascular risk factors, n
 diabetes mellitus  4  5
 hypertension  5  5
 hypercholesterolaemia  4  3
Mean (sd):
ICI duration, months38.5 (18.6)44.1 (19.8)
IIEF on ICI
Q3  4.94 (0.24)  4.84 (0.49)
Q4  4.96 (0.2)  4.84 (0.49)

The dose of sildenafil ultimately selected in the responders was 100 mg for 37 (71%), 50 mg for 14 (27%) and 25 mg for one (2%). A greater proportion of men using a high dose of trimix solution selected 100 mg of sildenafil than of those using a lower dose, whereas a larger proportion of men using a lower dose of trimix selected 50 mg than of those using a high dose (both P < 0.05) (Table 2).

Table 2. The ultimately selected dose of sildenafil, according to the dose of trimix for ICI in those responding to sildenafil
Trimix
dose, mL
NSildenafil dose, mg
2550100
 < 0.3391 (3)13 (33)28 (65)
0.3–1.013  112
Total5211437

Among the 52 men responding to sildenafil, 18 (35%) selected sildenafil alone for ongoing treatment; another 18 (35%) chose alternate use of each drug and 16 (31%) preferred ICI for their treatment (Table 3). The higher the dose of trimix used, the lower the selection rate for sildenafil (P < 0.05; Table 3). However, of 16 men who remained on ICI monotherapy for their treatment, 10 were those who needed a lower dose (< 0.3 mL) of triple solution. The main reason patients gave for selecting ICI was a better quality of erection (74%) followed by the adverse events of sildenafil (34%), and the rapid (17%) and more reliable (14%) responses to ICI. The main reason given for choosing sildenafil for treatment was easier administration (89%); the side-effects of ICI (22%) and better erections (11%) were minor reasons for preferring sildenafil.

Table 3. The selection rate of sildenafil or ICI as treatment in those responding to sildenafil according to the dose of trimix for ICI
Trimix doseNSildenafil, %ICI, %Alternate, %
< 0.1118 (15)  1 (2)  2 (4)
0.1–< 0.2187 (14)  3 (6)  7 (14)
0.2–< 0.3122 (4)  6 (12)  5 (10)
0.3–< 0.5  71 (2)  3 (6)  3 (6)
0.5–1.0  40  3 (6)  1 (2)
Total5218 (35)16 (31)18 (35)

Of all 69 patients, there were adverse reactions to sildenafil in 20 (29%), with flushing in 12 (17%), rated mild in 10, moderate in one and severe in one. Nine patients had a headache, rated mild by seven, moderate by one and severe by one. Visual disturbance, and dizziness and nasal congestion were reported in two patients (3%), respectively, and palpitation in one other. Two responders to 100 mg of sildenafil discontinued treatment because of severe headache or flushing.

DISCUSSION

Several studies and clinical trials have confirmed the efficacy and safety of sildenafil for treating ED of various causes, with a response rate of ≈ 70%[7,8]. The overall efficacy rate of sildenafil in the present study was 75%, which is comparable with the results of other clinical trials. In a study of the effectiveness of sildenafil and patient preference in a group of impotent men on ICI, Hatzichristou et al.[10] reported that the relative efficacy of sildenafil in those on alprostadil only and on a triple solution (papaverine, phentolamine and alprostadil) was 86% and 43%, respectively. The overall efficacy rate of sildenafil was 75%, similar to the present result. The higher efficacy rate of sildenafil in the present study for patients on ICI with trimix can be explained by our uniform use of trimix for ICI therapy regardless of the severity of ED, whereas Hatzichritou et al. used the combined solution only for patients with more severe ED, and those not responding to 20 µg alprostadil.

In an American flexible-dose study of sildenafil the ultimate dose selection was 100 mg in 75% of patients, 50 mg in 23% and 25 mg in 2%[8]. Similarly, in worldwide flexible-dose studies, 60% of patients selected a 100-mg, 30% a 50-mg and 10% a 25-mg dose [12]. The ultimate dose selected by the present responders to sildenafil was within this range. The dose of vasoactive agents a patient requires reflects the degree of underlying haemodynamic and corporal smooth muscle impairment. Consequently, the response rate for sildenafil was significantly lower in men using a high dose of trimix. Likewise, a larger proportion of men using a high dose of trimix selected 100 mg of sildenafil than of those using a lower dose of trimix.

Among the sildenafil responders, 35% preferred sildenafil for their treatment, 35% chose each treatment alternately and 31% preferred ICI alone. However, Hatzichristou et al. reported that 64% of sildenafil responders ultimately preferred to continue with oral sildenafil, 33% elected to return to ICI and only 3% chose to use each treatment alternatively. Of 16 sildenafil responders in the present study who preferred ICI alone for their treatment, 10 were those who needed a lower dose of triple solution. The main reason for the higher preference for ICI in the present patients, either as monotherapy or alternated with sildenafil, was related to the better erections with ICI, and a more reliable and rapid response. Intracavernosal vasoactive agents have a direct relaxing effect on cavernosal smooth muscle independently of sexual desire, whereas oral sildenafil only provokes an erection response in association with sexual stimulation. Therefore, the indirect mechanism of the action of sildenafil may be more easily biased than the direct action of ICI and result in different responses even in the same individual, especially in men with significant psychological inhibition. That the higher the dose of combined solution used, the lower the selection rate of sildenafil, even though they were able to obtain an erection on oral sildenafil, may be attributed to the better and more reliable erectile response from ICI than sildenafil in men with greater impairment of erection haemodynamics and corporal smooth muscle.

Long-term follow-up studies of patients receiving ICI therapy have shown withdrawal rates of ≈ 70% within 5 years. The reasons for discontinuing therapy were fear of injection needles, difficulties in use, pain during injection, and failure to coincide with patient and partner desires for more spontaneous erections [5,6]. However, as most patients who discontinue ICI therapy do so within the initial few months to a year [4], the disadvantages of ICI were least likely to produce false-positive results in the present study, considering that the patients had been using ICI for > 1 year.

The most common adverse events of sildenafil were flushing and headache, followed by abnormal vision and dizziness, and comparable with those reported in other clinical studies [7,8].

In conclusion, more patients than expected with ED and using ICI preferred ICI as their treatment, either as monotherapy or as an alternating treatment with sildenafil, even though they had good responses to oral sildenafil. Better erections with ICI, and a reliable and rapid response, make experienced users choose ICI, differing from those with no previous experience.

Abbreviations
ICI

intracavernosal injection

ED

erectile dysfunction

IIEF

International Index of Erectile Function.

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