Intracavernous Self-Injection of Prostaglandin E1 in the Treatment of Erectile Dysfunction

Intracavernous self-injection of prostaglandin E1 in the treatment of erectile dysfunction

P Kunelius1* and O Lukkarinen1

1Urological Unit, Surgical Clinic, University of Oulu, Finland

In a three-year follow-up study of 69 patients found that erectile dysfunction (ED) impairs many elderly men's life: up to 25% of the men aged 65 y and 80% of those aged 75 y suffer from erectile dysfunction. The most effective non-surgical treatment of ED is intracavernosal pharmacotherapy, and the most common vasoactive agent currently used is prostaglandin E1 (PGE1). The purpose of this study was to assess the long-term outcome of PGE1 treatment and the patients' overall satisfaction with their sexual life. Sixty-nine patients who had started ICI therapy three years earlier were invited to a control examination. The mean age of the patients was 60.5 y. The patients ®lled in a questionnaire, which included questions about the use of PGE1 treatment at home. All the patients evaluated their own satisfaction with their erection, ejaculation, orgasm and libido on a visual analytical scale (VAS, 0 ± 100%). A clinical examination was made, and the penile shaft was examined by ultrasonography. Erection with the home dose of PGE1 was estimated by Rigiscan, and the degree of erection was also estimated clinically (grades 0 ± 5) by a doctor. The most common doses of PGE1 used at home were between 10 and 20 m (58%), 46.4% of the patients had discontinued PGE1 therapy, the mean time of using PGE1 was 23.3 months. The mean coital frequency with PGE1 was 2.8 times per month. 34.8% of the patients (24 out of 69) reported that their own spontaneous erections had improved after the beginning of PGE1 therapy. The most common problem was hematomas in 10.1% of the patients (7 out of 69), which, however, were small and did not cause discontinuation of the therapy. There were three instances of priapism (4.3%), and four patients (5.8%) had ®brosis in ultrasonography. The patients' satisfaction with their erection at home was 67.3% with PGE1. The mean coital frequency with PGE1 therapy was quite low, 2.8 times per month, even though the patients' mean age was only 60.5 y, one reason may be the high price of PGE1 injections. The rate of improvement of spontaneous erections while using PGE1 was quite high, accounting for 34.8% of the patients. Most of the patients who discontinued the PGE1 therapy had a psychogenic etiology. There were no systemic side-effects with PGE1. Only 7.2% of the patients had prolonged pain after the injection, leading to drug discontinuation. It can be concluded that treatment with intracavernous injections of PGE1 is well tolerated and involves only minor problems. The patients' satisfaction with their erections at home with PGE1 therapy was good. Precise determination of the home dose of PGE1 and the teaching of the technique of injection are important at the beginning of this treatment modality.

Keywords: prostaglandin E1; erectile dysfunction; long-term results; self-injection

Introduction dysfunction took place in the 1980s, when the intracavernosal injection therapy was introduced.2 About 70 ± 90% of all impotent patients can be Erectile dysfunction is one of the problems which cured with intracavernosal agents.3±5 The ®rst impair elderly men's life: it has been estimated that vasoactive drug was papaverine hydrochloride, the prevalence of erectile dysfunction at age 40 y is which involved some problems, such as priapism about 4% and increases to 25% by age 65 y and and ®brosis in the penile shaft.6,7 1 to 80% by age 75 y. One of the most signi®- The most common vasoactive agent used nowa- cant improvements in the treatment of erectile days is prostaglandin E1 (PGE1).8 PGE1 is a synthetic prostanoid, which has both vasodilating and relaxing effects on the smooth muscle. PGE1 causes a pharmacologic erection, which is highly *Correspondence: Dr P Kunelius, Urological Unit, Surgical Clinic, University of Oulu, Fin-90220 Oulu, Finland. dose-dependent and therefore has a low rate of 4,5 Received 23 May 1998; accepted in revised form priapism. There have also been only a few cases of 26 September 1998 ®brosis in PGE1 users.2±4 Prolonged pain is quite Long-term results of PGE1 P Kunelius and O Lukkarinen 22 common with PGE1, having been noted in 9.4 ± 34% Bruel and Kjaer). Apart from the clinical examina- of the patients using PGE1 alone. Upon combination tion, the patients underwent an ICI test with their with other drugs (trimix, addition to procaine), the home dose of PGE1. The tumescence and rigidity of incidence of this pain is less.9,10 It has also been erection were determined with a portable monitor recognized that some of the patients recover sponta- (Rigiscan). neous erections suf®ciently to abandon the injec- The degree of erection was also estimated tions.11 ± 13 clinically (grade 0 ± 5) by a doctor. Grade 0 was no Despite the favourable results of intracavernosal response after the injection, Grade 1 was minimal therapy, several studies have shown in the long run tumescence and no rigidity, Grade 2 was moderate that the dropout rate of patients (21 ± 51%) to be tumescence and no rigidity, Grade 3 was full rather high.8,9,13,14 tumescence and no rigidity, Grade 4 was moderate The purpose of this study was to ®nd out how rigidity, but the penis could be bent, and Grade 5 patients with erectile dysfunction who started PGE1 was full rigidity, Grades 4 and 5 are suf®cient for treatment three years ago have managed, what their penetration. The erection induced in the examina- compliance with this treatment was, what compli- tion room was compared to the erection attained at cations occurred during long-term use of PGE1 and home by the patient. what the patients' overall satisfaction with sexual life is like nowadays.

Results Patients and methods The mean home dose of PGE1 was 17.5 mg (4 ± 40 mg). Patients The most common doses of PGE1 used at home were between 10 and 15 mg (33%), 15 ± 20 mg (25%), 5 ± 10 mg (20%), 20 ± 30 mg (16%), under 5 mg (3%) and The primary study population consisted of 95 over 30 mg (3%). Nine patients out of the 69 had patients with ED who had been started on intraca- changed their home dose of PGE1 after they had ®rst vernosal PGE1 medication in the Oulu University been prescribed it three years ago. 46.4% of the Hospital three years previously, all these patients patients (32 out of 69) had discontinued PGE1 were invited to a checkup after the three years. therapy. 84.1% of the patients (58 out of 69) had Twenty-six patients did not attend, and the ®nal found it easy to learn the injection technique, while study population hence consisted of 69 patients. the remaining 15.9% (11 patients) had found it The mean age of the patients was 60.5 y (44 ± 83). All dif®cult at the beginning. The mean time of using patients had erectile dysfunction, a vasculogenic PGE1 was 23.3 months (range 0 ± 48). The mean etiology was found in 30 cases, a psychogenic coital frequency with ICI therapy was 2.8 times per etiology in 31 cases, and a neurologic etiology in month (range 0 ± 8). The mean duration of erection eight cases. The primary examinations consisted of a at home was 58.7 min (range 0 ± 240). Erection began thorough sexual history, a physical examination, within 9.4 min (range 2 ± 20). The injections failed to laboratory tests (hemoglobin, white cells, serum produce a suf®cient erection in 2% of the patients creatinine, serum glucose, serum cholesterol, and after at least ten attempts. 34.8% of the patients (24 serum totaltestosterone), an intracavernous injection out of 69) reported that their own erections test (ICI) with PGE1 (20 mg) and duplex Doppler improved after the introduction of ICI therapy. Most ultrasonography of the penile vessels. of the patients who reported improvement of their own erections had a psychogenic etiology (54.2%, 13 out of 24), while 37.5% (9 out of 24) had a Methods vasculogenic dysfunction and 8.3% (2 out of 24) a neurogenic etiology. The reasons for the discontinuation of therapy are All the patients ®lled in a questionnaire at home and shown in Table 1, loss of ef®cacy and spontaneous this was checked when the patient came for their erections being prominent. The dropout rate was checkup. The questionnaire included several items highest among the patients with vasculogenic pertaining to various aspects of sexual function at dysfunction (56.3%, 18 out of 32) compared to the home and possible problems with PGE1 self-injec- other etiologies (psychogenic 31.3% (10 out of 32) tion. Each patient also evaluated his own satisfac- and neurogenic 12.5% (4 out of 32)). Table 2 shows tion with erection with and without intracavernosal the rates of complications reported by the patients; injection as well as his ejaculation, orgasm and the most common problem was hematomas, which libido on a Visual Analytical Scale (VAS, 0 ± 100%). occurred in 10.1% of the patients (7 out of 69), but A clinical examination was made and the penile were small and did not cause discontinuation of the shaft was examined by ultrasonography (5 MHz, therapy. There were also three cases of priapism Long-term results of PGE1 P Kunelius and O Lukkarinen 23 (4.3%), which occurred at the beginning of the Prolonged pain after the injection has been quite therapy but did not cause any further problems. common with PGE1 alone.3,9 PGE1 has a low risk of Four patients (5.8%) had ®brosis in the penile priapism and local complications, such as penile shaft, which was also determined by ultrasound, the nodules, indurations or ®brosis, during long-term mean size of ®brosis being 1.75 cm (1 ± 2 cm). use. The two year results of PGE1 treatment The patients estimated their libido on a VAS scale presented in the literature involved local complica- (0 ± 100%), and the mean value was 65.3% (5 ± 97). tion rates of 5.6% after one year and an additional The patients' satisfaction with their erections at 3.7% after two years of treatment.16 home without injections was 23.5% (1 ± 92), while In our study, the mean coital frequency with ICI their satisfaction with their erections at home with therapy was quite low, namely 2.8 times per month, PGE1 therapy was 67.3% (0 ± 99). Satisfaction with most of the patients said they had no problem with ejaculation was 61.5% (11 ± 100) and that with the injection in the beginning (84.1%). The mean orgasm 66.5% (7 ± 99). dose of PGE1 was 1.75 mg. Many studies have The ICI test was done with the home dose of shown that the most frequently used initial dose PGE1. The erection was determined with the has been 20 mg of PGE1. Erection began in normal Rigiscan device. The mean maximal rigidity at the time, that is 9.4 min, and its duration was about one tip of the penis was 56.6% and at the base of the hour, which is less than reported previously.3,5,15 penis 53.3% (0 ± 994). The degree of erection was Almost all instances of intercourse succeeded at estimated clinically by a doctor as follows: Grade 1 home with PGE1. At work, the Rigiscan measure- 3.5%, Grade 2 10.5%, Grade 3 36.8%, Grade 4 45.6% ment with the home dose of PGE1 also showed the and Grade 5 3.5%. erection to be fairly good (the mean maximal rigidity The patients also estimated their erection them- was 53.5% at the base and 56.6% at the tip of the selves. 52.6% of the patients said their erection at penis). work was worse than at home, while 40.4% said Increased sympathetic activity may inhibit the their erection was the same as at home, and 7% said cavernosal smooth muscle relaxation providing a their erection was better at work than at home. good erection. In our study, the majority of patients did not have equally good erections at work (52.6%) than at home. There were no systemic side-effects with PGE1. Discussion Only 7.2% of the patients had prolonged pain after the injection, leading to drug discontinuation by 5.8% of the patients, this is less than in most other PGE1 treatment is the most common mode of ICI- studies where PGE1 has been used alone. When therapy in erectile dysfunction nowadays, the PGE1 is used in combination with other drugs as effectiveness of PGE1 has been proved in several triple-drug therapy (papaverine, phentolamine and 3,5,15 studies. There have been only minor problems PGE1 solution) or with procaine, the incidence of with PGE1 treatment as reported in the literature. pain could be less.5,8,10,14,17 ± 19 Priapism occurred only in three cases, which were all seen at the Table 1 Reasons for dropping out among 69 patients who began beginning of the treatment; Priapism was a relatively intracavernosal home therapy common complication in papaverine users, but after PGE1 treatment it has become rare.7,20 Reason for dropping out Number Fibrosis was seen in 5.8% of the patients and led Loss of ef®cacy 9 (13%) to drug discontinuation in 4.3%. However, the mean Illness of wife 2 (2.9%) size of ®brosis was small (1.75 cm): it has been Wife disapproved of treatment 2 (2.9%) Spontaneous erections 8 (11.6%) noticed that there is less ®brosis in PGE1 users than Did not get a new prescription 2 (2.9%) in papaverinee users and penile scarring is also less Fibrosis in the penile shaft 3 (4.3%) extensive than in papaverinee therapy.6,15 Pain after injection 4 (5.8%) The improvement of spontaneous erections in the Total 32 (46.4%) men using intracavernous injections has been reported in several studies.8,11 ± 13 In our study, 34.8% of the patients (24 out of 69) reported improvement of their own erections after PGE1 Table 2 Reported complications by the patients with PGE1 therapy. This was the reason for the discontinuation of PGE1 therapy by eight patients (11.6%). A Complication Number majority of the patients who discontinued PGE1 Loss of ef®cacy 3 (4.3%) therapy had a psychogenic etiology. This may be Hematoma 7 (10.1%) one reason for the high dropout percentage (46.4%), Pain after injection 5 (7.2%) which has also been seen in other studies,8,9,14 Fibrosis 4 (5.8%) Priapism 3 (4.3%) another reason may be the high price of PGE1 therapy. Long-term results of PGE1 P Kunelius and O Lukkarinen 24 It can be concluded that treatment with intraca- 8 Gerber GS, Levine LA. Pharmacological erection program vernous injections of PGE1 is well tolerated and has using prostaglandin E1. J Urol 1991; 146: 786 ± 789. only minor problems. The patients' satisfaction with 9 Govier FE, et al. Experience with triple-drug therapy in a pharmacological erection program. J Urol 1993; 150: their erection at home was good. The reasons why 1822 ± 1824. many patients fail to continue their PGE1 therapy in 10 Schramek P, Plas EG, Hubner WA. 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