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Clinical and sonographic assessment of the side effects of intracavernous injection of vasoactive substances


The objective of this study is to evaluate the side effects of intracavernous vasoactive agents on clinical and sonographic basis. Two groups of patients were included, group I included 168 ED patients trained on self-injection therapy using one of the three protocols. Protocol A: papaverine; protocol B: PGE1; and protocol C: trimix (papaverine, phentolamine and PGE1). Patients were followed up clinically, sonographically and by laboratory investigations for 6 months to evaluate the occurrence of side effects. Group II included 21 patients presenting to our department for the first time with a complication of intracavernous injection pharmacotherapy (ICI) initiated elsewhere. In all, 168 patients of group I completed the study. Patients on papaverine had the highest incidence of complications concerning prolonged erection, subcutaneous hematoma and penile fibrosis. Postinjection penile pain was observed more with groups B and C than group A. No systemic side effects were reported. Duplex ultrasound was beneficial in detecting mild clinically impalpable fibrosis. In total, 10 patients of group II presented with prolonged erection, seven with penile fibrosis, three with cavernositis and one with intracavernous needle breakage. We conclude that although ICI therapy is an effective second-line treatment option, patients on a self-injection program should be followed up both clinically and sonographically both at the initiation phase and on regular follow-up visits.


The use of intracavernous injection pharmacotherapy (ICI) helped resolve a great deal of frustration on the part of the patient as well as the physician treating patients with organic impotence.1,2 However several complications have been reported. Early complications include pain, hematoma formation, syncope and prolonged erections. Late complications include fibrosis occurring in 1.9–16%.3,4

The aim of this work is to assess the side effects of intracavernous injection of vasoactive drugs on clinical and sonographic basis.

Patients and methods

Two groups were included in this study from the Andrology Department, Cairo University. Group I included 168 ED patients of more than a year with previous failed trials at oral medical treatment. Group II included 21 patients presenting to our department for the first time with of one of the complications of ICI received elsewhere. Physical examination including general and local genital examination was performed before initiating ICI therapy and at bimonthly intervals.

Patients' age ranged from 40 to 60 y with a mean of 48.23±7.32 y. The mean duration of ED was 1.5±0.3 y.

Duplex ultrasound evaluation

Dynamic duplex study was carried out using color ultrasound machine with a 7.5 MHz linear array transducer with a color flow mapping capability (Esaote Biomedica AU3, Italy).

Self-injection training

Patients underwent an average of two office sessions of intracavernous injection. In the first session, a test dose of the vasoactive substance was injected into the lateral corpus through a 30-gauge needle fixed on a tuberculin syringe. The injection technique was demonstrated and explained to the patient with special emphasis on the sterile technique and the firm compression of 5 min after the injection. If the erection achieved was judged to be inadequate, a booster injection was used to double the dose. In the second session, patients performed the injection themselves in the office and the dose was adjusted.

Intracavernous medication

Group A (59 patients) received 30–60 mg of papaverine. Group B (56) patients received 10–20 μg of PGE1. Group C (53 patients) received 0.5–1 ml of trimix solution (10 mg papaverine+0.4 mg phentolamine+10 μgPGE1).

Patients were advised to use the intracavernous injection one to two times per week 15 min before sexual intercourse.


Clinical, laboratory and duplex ultrasound follow-up was performed at 1, 3 and 6 months of therapy.

Basic laboratory investigations included blood sugar, CBC, urine analysis, SGOT, SGPT and serum creatinine.

Statistical analysis

Statistical analysis of data was performed using Pearson's χ2 test to compare quantitative variables among different classification groups.


Complications of ICI among patients in different groups are illustrated in Table 1. Table 2 demonstrates the relation between risk factors and penile fibrosis.

Table 1 Complications of ICI among patients in different groups
Table 2 Relation between risk factors and penile fibrosis

Penile pain occurring during self-injection therapy occurred significantly more with PGE1 than with papaverine (P<0.05). Table 1 also shows that penile fibrosis detected clinically and sonographically was significantly higher in the papaverine group than trimix group (P<0.05).

Table 2 demonstrates a significant increase in the development of penile fibrosis among diabetic patients than nondiabetic patients completing the study (P<0.05).

Of 21 patients in group II, 10 presented with prolonged erections due to papaverine, seven with penile fibrosis or penile deviation, three with cavernositis and one with intracavernous needle breakage. Four of the 10 patients (with prolonged erection) received their injection at radiology centers during duplex studies. Six other patients received the injection at private clinics by specialized doctors and two patients received the injection at a pharmacy.

Within group II, patients with prolonged erections were managed accordingly.12 Patients presenting with penile fibrosis were using papaverine as their IC agent and were managed accordingly.13 Three patients presented to our department complaining of painful penile swellings occurring after ICI. After clinical, laboratory and sonographic evaluation, the diagnosis of postinjection cavernositis associated with uncontrolled elevated blood sugar was reached. The patients were treated with i.v. antibiotics and drainage of the abscesses. Penile fibrosis was observed weeks after subsidence of the acute condition. A 43-y-old patient presented to our department complaining of intracavernous painful small swelling after ICI. The patient noticed that after his last ICI, a part of the needle was missing. Plain X-ray on the penis confirmed the diagnosis of an intracavernous broken needle tip. Successful surgical extraction of the broken needle was performed by directly incising at the site of the needle tip as imaged by X-ray.


In the present era of effective oral drug therapy for ED, ICI therapy remains an effective second-line treatment option. In group 1 our data concerning prolonged erections during initial testing were in agreement with the work carried out by other workers.5,6 Although the dose of IC agent was properly adjusted, prolonged erections still occurred during home therapy. Lomas and Jarow7 investigated this issue and concluded that it may be related to the etiology of ED, as patients with psychogenic or neurogenic impotence were at greater risk than those with vasculogenic impotence. Serels and Melman8 explained this situation by the presence of added sexual stimulation at home, which could not be attained during ICI test. This may imply decreasing the dose for home therapy. Pain following ICI of PGE1 postinjection is the most frequently reported adverse effect of this IC agent. This type of pain usually starts 15 min after injection and may last for up to 6 h. In our study, it occurred more frequently with patients on home therapy with PGE1 and trimix than with patients using papaverine alone (P<0.05).

Penile fibrosis occurring with papaverine was statistically higher than that occurring with either PGE1 or trimix (P<0.05). This may be due to the relative acidity of papaverine hydrochloride (pH=5). A significant association was found between penile fibrosis and diabetes mellitus (P<0.05). This may be explained by the fact that diabetes mellitus produces microangiopathy of the small blood vessels, leading to defective oxygenation to the cavernous tissue and subsequently helping in fibrosis development.9 Most fibrotic nodules occur in patients who inject themselves frequently (multiple microtraumas to the corporeal tissue) and those who do not compress the injection site for a sufficient time with the subsequent development of intracavernous hematoma.5

Bazzocchi et al10 reported a benefit of the use of penile color Doppler ultrasound in assessing prolonged erections and penile fibrosis. In our study, penile ultrasound proved helpful in demonstrating subclinical penile fibrosis, its actual site and size. The determination of the size and extent of penile fibrosis (even prior to ICI treatment) can help during long-term follow-up in the assessment of the effect of the vasoactive agent administered and also in evaluating the treatment of fibrosis given, for example, tamoxifen and vitamin E. Liver enzymes were either not elevated or only mildly elevated in all patients. This was in agreement with other workers, suggesting that only patients with a history of alcohol abuse or liver disease receiving papaverine as intracavernous injection should LFTs (liver functions tests) be obtained before initiating treatment and at 6-month intervals.11

Self-injection therapy in the era of effective oral drug therapy in the treatment of ED still has an important role. This necessitates that side effects of intracavernous pharmacotherapy must be properly diagnosed and managed. It also shows the need for much safer intracavernous agents with less invasive delivery systems.


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Correspondence to H M Ghanem.

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Moemen, M., Hamed, H., Kamel, I. et al. Clinical and sonographic assessment of the side effects of intracavernous injection of vasoactive substances. Int J Impot Res 16, 143–145 (2004).

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  • intracavernous injection
  • side effects

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