COMPARISON OF LONG-TERM OUTCOMES OF PENILE PROSTHESES AND INTRACAVERNOSAL INJECTION THERAPY

Purpose

Intracavernosal injection therapy is one of the most popular therapies for erectile dysfunction today. Yet, most clinicians consider intracavernosal injection a palliative treatment for erectile dysfunction because of the high patient initiated dropout rate. In contrast, penile prostheses appear to offer a more permanent cure for erectile dysfunction. We compare the long-term outcomes of both therapies in contemporaneously treated patients and determine the reasons for failure of each.

Materials and Methods

Telephone survey and chart review was conducted on the first 115 patients treated with intracavernosal injection and 65 patients undergoing insertion of a penile prosthesis during the same period at our institution. Mean patient age was 57 and 60 years, respectively, and mean followup of all patients was 5.4 years (range of 3.3 to 16).

Results

An equal percentage of patients were lost to followup in both groups, including 19% of the intracavernosal injection group and 18% of the penile prosthesis group. Of the intracavernosal injection patients 6 (6%) died during followup and 10 (19%) of the prosthetic patients died (p <0.05). At the time of contact only 41% of the patients were still using intracavernosal injection. In contrast, 70% of the patients were still sexually active with the prosthesis (p <0.01). Mean duration of use of the penile prosthetics was 63 months compared to 37 months for intracavernosal injection (p <0.001). The most common reasons for discontinuing intracavernosal injection were inadequate erections (16 cases), lack of spontaneity (14), side effects (12), lack of partner (10), loss of sexual interest (6) and spontaneous return of normal erections (4). More than half of the patients (61%) who discontinued intracavernosal injection remain sexually active with other therapies, including penile prosthesis in 11, vacuum devices in 4, vascular surgery in 1 and oral medication in 1, and 14 without any therapy. We could not identify any significant clinical parameters that would accurately predict which patients most benefited by the long-term use of intracavernosal injection therapy. In contrast, only 6 patients discontinued use of the implant because of complications (infection, erosion and malfunction) and 7 for reasons independent of the implant (that is lack of partner, loss of sexual interest and co-morbidity).

Conclusions

Intracavernosal injection serves as only a palliative therapy for the majority of patients with erectile dysfunction but there exists a core group who derives long-term satisfaction with its use. The majority of patients who discontinue intracavernosal injection remain sexually active yet do not progress to more invasive or effective therapies. The reason for discontinuing therapies for erectile dysfunction is often unrelated to the actual therapeutic modality. Our findings suggest that further improvements in intracavernosal injection therapy and the development of alternative methods of delivery of vasoactive agents will have only a limited impact on the overall outcome of therapy for erectile dysfunction and that increased attention to issues separate from the erection is warranted.     

Assessment of the immediate and long-term effects of pharmacologically induced penile erections in the treatment of psychogenic and organic impotence

Thirty-eight patients with predominantly organic and 29 with psychogenic impotence had intracavernosal injections of a combination of 30 mg papaverine and 1 mg phentolamine on at least one occasion. An immediate increase in length and penile rigidity resulted in all subjects. Eighteen of the organic patients subsequently developed spontaneous erections for periods ranging from 1 week to 1 month. Nineteen of the 24 patients in the psychogenic group had spontaneous erections, five for at least 4 months and 14 for 2 to 8 weeks. Increasing the dose was of benefit only to organic patients who initially had a poor response. Three of eight patients with a poor immediate response to pharmacologically induced penile erections (PIPE) were found to have venous incompetence. PIPE is therefore of value in the diagnosis and treatment of organic and psychogenic impotence.     

Effects of intracavernosal trazodone hydrochloride: animal and human studies

Trazodone hydrochloride is an oral antidepressant agent which has been associated with the improvement of erections in impotent men and the development of prolonged erections or priapism in potent men. An in vivo study in animal and human subjects was performed to gain experience with the effect of intracavernosal trazodone. In the anesthetized New Zealand White rabbit, intracavernosal trazodone or its major metabolite m-chlorophenylpiperazine (m-CPP) produced full penile erection in 76% and 84% of animals studied respectively with doses ranging from one to 15 mg. On the other hand, intracavernosal administration of five mg. papaverine resulted in a prolonged erection in 90% of animals studied. In 13 selected volunteer patients, intracavernosal trazodone caused tumescence but not full penile erection with corporal body pressures of 28.2 +/- 5.8 mm. Hg. Intracavernosal papaverine or papaverine and phentolamine in these subjects resulted in significantly higher corporal body pressures of 58 +/- 18 mm. Hg (p less than .05). Intracavernosal administration of alpha adrenoceptor agonists but not normal saline resulted in complete detumescence of trazodone- or m-CPP-induced prolonged erection in the animal studies. Intracavernosal trazodone results in erectile activity that appears in part based on its local alpha blocking activity but like other intracavernosal alpha-blocking agents is not as effective in initiating penile erections as are intracavernosal agents that directly induce smooth muscle relaxation.     

Penile response to intracavernosal vasoactive intestinal polypeptide alone and in combination with other vasoactive agents

Intracavernosally injected vasoactive intestinal polypeptide (VIP) (2 micrograms and 4 micrograms) resulted in penile tumescence even in men with predominantly organic impotence. Papaverine and phentolamine were successful in inducing erections in all subjects studied but the addition of VIP to this combination improved the erectile response further. A combination of papaverine and VIP produced penile rigidity similar to that with papaverine and phentolamine. While intracavernosal VIP alone produced disappointing penile responses, its combination with papaverine potentiated the response to this drug, probably by increasing venous outflow resistance.     

Sildenafil improves sleep-related erections in hypogonadal men: evidence from a randomized, placebo-controlled, crossover study of a synergic role for both testosterone and sildenafil on penile erections

To study the effects of sildenafil on human sleep-related erections according to the state of androgenization, we evaluated the effects of sildenafil on sleep-related erections in hypogonadal men before and during testosterone replacement treatment and in control subjects. We enrolled 24 hypogonadal men and 24 healthy men as a control group. All hypogonadal subjects had very low testosterone levels (<200 ng/dL [6.9 nmol/L]) [corrected] All subjects underwent nocturnal penile tumescence and rigidity monitoring (NPTRM) for 3 consecutive nights and were randomly assigned to consume either 50 mg of sildenafil or placebo 1 hour before bedtime on the second or third night of nocturnal penile monitoring. The hypogonadal subjects were tested twice, first without replacement treatment (H-T) and then after at least 6 months of testosterone replacement therapy (H+T). The subjects of the control group (C) were tested once. The following parameters of sleep-related erections were analyzed: total number of valid erections, total duration of both rigidity greater than or equal 70% and increase in penile circumference greater than or equal 30 mm, maximum rigidity, and maximum increase in penile circumference. NPTRM parameters were reduced in hypogonadal men before testosterone treatment (H-T+P) when compared with control subjects taking placebo (C+P). NPTRM parameters after testosterone (H+T+P) and sildenafil (H-T+S) administration were similar to that of control subjects taking placebo (C+P). When the statistical analysis was restricted to the hypogonadal men before testosterone treatment, sildenafil alone significantly increased NPTRM parameters when compared with placebo (H-T+S vs H-T+P). Testosterone restored normal erections when administered to hypogonadal subjects (H+T+P vs H-T+P); in hypogonadal men, however, the combined treatment (sildenafil plus testosterone) resulted in the maximum positive effect on NPTRM parameters. When the increase from baseline was analyzed, the effects of testosterone plus sildenafil were greater than the sum of the effects of each drug used alone. In conclusion, sildenafil administered at bedtime improves sleep-related erections in hypogonadal men, suggesting that the nitric oxide pathway may be pharmacologically enrolled and enhanced despite low serum testosterone. Furthermore, these data strongly support the idea of a synergic effect on sleep-related erections of sildenafil and testosterone.     

2 years' experiences with cavernosal autoinjection therapy

Between February 1985 and January 1987, 186 patients with erectile dysfunction were selected for cavernosal autoinjection therapy (CAT). After more than 4800 protocolled autoinjections and 10-230 CAT/pt., no cavernous fibrosis, penile deviation or cavernitis occurred. The only serious side effects were prolonged erections in about 10% during diagnostic and less than 1% during therapeutic use. These prolonged erections could be easily treated by puncture and aspiration of corpora cavernosa or intracavernosal injection of Metaraminol.     

Relation of sexual dysfunction to hormone levels, diseases and drugs used in andrological patients

In 169 patients visiting our department complaining of sexual dysfunction, the medical history was taken using a semistructured interview. A clinical investigation and a hormone analysis were added. The age of patients, hormone values, and items of the interview were collected into a common database. The items were categorized as either dichotomous (yes/no) or ordinal. Statistical analysis was performed using regression analysis with the aim to generate hypotheses of relations. An increase of FSH levels and a decrease of testosterone levels with age occurred. None of the relations of hormone levels or diseases to symptoms of sexual dysfunction produced odds ratios (OR) statistically significant different from 1. However, the risk of having a reduced libido and reduced morning erections was lower in psychoneurological diseases, the risk of reduced arousal and libido was lower in men with diabetes mellitus, but the risk of reduced morning erections was higher in these men. The testosterone levels were not associated with the risk of having reduced penile rigidity, duration of erection, arousal and sexual libido, reduced morning erections and the ability to masturbate. Smoking was not associated with reduced arousal, libido and morning erections. However, a significant increase of testosterone levels with number of cigarettes used was observed. We conclude that sexual dysfunction in patients visiting an andrological department for diagnosis and treatment is mostly not associated to any single evaluable factor.     

Sex therapy for the penile prosthesis recipient

In conclusion, the evidence for technical success of the penile prosthesis is clear, but more detailed follow-up studies suggest that a large minority of patients and partners fail to achieve sexual satisfaction. If the goal of surgery is to restore sexual frequency, variety, and pleasure to optimal levels, an integrated treatment program that incorporates sex therapy may be more successful than implantation alone. The type of sex therapy required depends on the risk factors present for postsurgery sexual dissatisfaction. A majority of patients can benefit from several sessions of brief sexual counseling preoperatively, with routine follow-up at 3 and 6 months after surgery to identify problems in resuming sex successfully. I also would point out that an integrated treatment approach is just as applicable to home intracavernosal injection programs. Including sex therapy in the package might reduce the large drop-out rates currently being seen and might decrease the risk of misuse of these medications.     

Nocturnal tumescence: a parameter for postoperative erectile integrity after nerve sparing radical prostatectomy

PURPOSE: The exact process and time required for rehabilitation of erectile function after nerve sparing prostatectomy remain unclear to date. Different theories of the pathophysiology of postoperative erectile dysfunction are currently being discussed. In a prospective study we performed recordings of nocturnal penile tumescence and rigidity during the acute phase after nerve sparing radical prostatectomy, ie in the first night after removal of the catheter, to assess the organic penile integrity. MATERIALS AND METHODS: In 27 patients with local prostate carcinoma who had been sexually active before the intervention, we performed unilateral or bilateral nerve sparing radical prostatectomy. Preoperative sexual function of all patients was evaluated by the International Index of Erectile Function-5 questionnaire. On the day of catheter removal (postoperative day 7 to 14) an NPTR recording was performed on the following night with an erectometer (RigiScan). RESULTS: All patients had a preoperative IIEF score greater than 18. After removal of the catheter 25 of 27 patients (93%) showed 1 to 5 nocturnal rigidity increases by greater than 70% for at least 10 minutes. In a control group of 4 patients who underwent radical prostatectomy without nerve sparing, no nocturnal erections were recorded. CONCLUSIONS: NPTR recording during the acute phase after nerve sparing radical prostatectomy showed residual erectile function as early as the first night after catheter removal. These results are significant for selecting adequate pharmacological treatment for optimal therapy and rehabilitation of satisfactory erections and sexual function. In cases of early nocturnal tumescence, application of a PDE5 inhibitor can support successive organ rehabilitation. However, if tumescence does not occur, penile injection therapy is recommended.     

Objective double-blind evaluation of erectile function with intracorporeal papaverine in combination with phentolamine and/or prostaglandin E1.

We performed a double-blind, crossover study using objective measurements to compare maximum rigidity and duration of erections with papaverine hydrochloride in combination with phentolamine mesylate and/or prostaglandin E1. The rationale for the protocol was to combine a smooth muscle relaxant (papaverine) with either or both vasodilating agents (phentolamine and prostaglandin E1) commonly used for injection therapy. The 7 volunteer patients with organic impotence documented by abnormal nocturnal penile tumescence testing were injected with 0.5 to 1.0 ml. papaverine (30 mg./ml.) in combination with phentolamine (0.5 mg./ml.) and/or prostaglandin E1 (5 micrograms./ml.). Each patient received 2 injections on each of 2 testing dates; injection 2 was given after tumescence resulting from injection 1 had subsided completely. The medications were given in a randomized, counterbalanced order following double-blind procedures. Patients evaluated the erections subjectively. In addition, the RigiScan device was used to measure maximum rigidity and duration of erections. All patients observed increased duration of erections with both combinations containing prostaglandin E1. Analysis of RigiScan measurements showed no statistically significant differences for maximum rigidity (p greater than 0.1) but significantly greater duration of erections with papaverine plus prostaglandin E1, and papaverine plus phentolamine plus prostaglandin E1 compared to papaverine plus phentolamine (p less than 0.001). There was no statistical difference in rigidity or duration of erections between papaverine plus prostaglandin E1 and papaverine plus phentolamine plus prostaglandin E1. No patient reported significant penile pain with any of the injections. We conclude that the combination of papaverine and prostaglandin E1 produces erections of longer duration than papaverine plus phentolamine and that no additional benefit is gained by adding phentolamine to a combination of papaverine and prostaglandin E1. Further studies are in progress to define optimal dose response curves for papaverine and prostaglandin E1 as individual agents and in combination.     

A SURGICAL ALGORITHM FOR THE TREATMENT OF PEYRONIE''S DISEASE

Purpose

When conservative treatment of Peyronie's disease fails, the optimal surgical approach is not well defined. Multiple factors, including penile rigidity, degree of curvature, shaft narrowing with hinge effect and erectile response to vasoactive penile injections, indicate that no single approach is likely to solve the problem in all patients.

Materials and Methods

A surgical algorithm was developed for the treatment of Peyronie's Disease based on our previous surgical experience, which was used prospectively in 103 consecutive men. Penile straightening without prosthesis was offered to patients with adequate rigidity for coitus. Specifically, for mild to moderate curvature less than 60 degrees without hourglass or hinge effect deformity the less complicated tunica albuginea plication procedure was performed. For those men with more severe, complex curvature greater than 60 degrees and/or significant hourglass or hinge effect deformity plaque incision or partial excision with dermal grafting was offered to limit shaft shortening and to reconstruct a shaft with normal caliber to provide optimal axial support during intromission. For men with poor sexually induced erections and/or inadequate response to intracavernosal pharmacotherapy penile prosthesis placement was recommended to provide adequate straightening and rigidity.

Results

Of 22 patients who underwent plication procedures 91% remained potent and the penis remained straight postoperatively. Of 52 patients who underwent an incision or partial excision and grafting procedure, 48 had dermal grafts with the penis remaining straight in 94% and 75% remaining potent postoperatively. A total of 29 patients received a prosthesis with the penis remaining straight in 93% who were sexually active postoperatively. During the follow up period (mean 22.3 months) there have been no mechanical device failures.

Conclusions

Surgical outcome was optimized with this algorithm, which correlates surgical complexity to the underlying severity of the penile deformity and erectile capacity.     

Effects of moxonidine and metoprolol in penile circulation in hypertensive men with erectile dysfunction: results of a pilot study

Centrally acting (moxonidine) and peripherally acting (metoprolol) sympatholytic agents might have different actions upon penile circulation in hypertensive men with erectile dysfunction. A total of 11 nonsmoking, hypertensive but otherwise healthy men with erectile dysfunction were studied after 8 weeks on moxonidine monotherapy (0.4 mg per day, increased to 0.6 mg if needed) and then after 8 weeks of metoprolol monotherapy (100 mg per day, increased to 200 mg if needed) in a crossover design. At the end of each treatment phase, the subjects were asked about their subjective erectile capacity (nocturnal and coital erections), and resting and stimulated (after intracavernosal injection of a mixture of alprostadil and phentolamine) penile deep artery diameters and systolic peak velocities were measured by color Doppler ultrasonography. There were no significant differences in blood pressure after either therapy. The change from earlier antihypertensive therapy, moxonidine produced significant subjective amelioration of sexual dysfunction in 9/11 of the men (< or = 0.001), whereas 9/11 returned to impaired dysfunction after crossover to metoprolol treatment. Resting and stimulated deep penile diameters and peak systolic velocities were higher after moxonidine treatment compared with metoprolol (diameters: < or = 0.004, < or = 0.0001; velocities: < or = 0.008, < or = 0.038). The centrally acting sympatholytic agent moxonidine seems to improve erectile function both subjectively and objectively and has a better effect on penile circulation compared with the peripherally acting sympatholytic agent metoprolol.     

Normal hemodynamic parameters do not always predict the presence of a rigid erection: a quantitative assessment of functional erectile impairment

The purpose was to assess objectively and quantitatively the hemodynamic status and the degree of functional erectile impairment in a group of impotent patients. A clinical study was designed, incorporating pharmacocavernosometry (to evaluate arterial and veno-occlusive function) with axial buckling forces and penile geometry measurements in a group of impotent patients. The pressure gradient between the intracavernosal pressure associated with the presence of penile axial rigidity and the equilibrium intracavernosal pressure was calculated (axial rigidity gradient, ARG); such methodology allowed a quantitative characterization of functional impairment, as ARG expresses the intracavernosal pressure increase necessary to achieve axial rigidity and therefore potency. Penile geometry characteristics were also expressed by calculating the penile aspect ratio (diameter/length, D/L). In 83 consecutive patients tested (mean age 42.89+/-9.96), rigidity occurred at intracavernosal pressures between 50 and 100 mm Hg. A conversely proportional relation was noticed between penile aspect ratio values and the intracavernosal pressure associated with rigidity values, clearly demonstrating the important functional role of penile geometry. ARG demonstrated a wide range of values (3-69 mm Hg), reflective of the severity of the erectile dysfunction on each patient. Half (50.6%) of the patients had ARG values < or =20 mm Hg, indicative of minimal and minimal-to-moderate erectile impairment, while 20.48% had ARG between 21-30 and 28.92% >30 mm Hg, indicative of moderate and severe erectile dysfunction (ED) respectively. In all, 6% of the study group, all of them with primary ED, ARG <20 mm Hg had normal hemodynamics, but low penile aspect ratio values indicating that penile geometry may be the cause of insufficient rigidity. Hemodynamic integrity is the most critical, but not the only determinant of penile rigidity, as erectile impairment may be noticed in patients with normal arterial inflow and corporal veno-occlusive function. In such cases, unfavorable penile geometry should be considered as the possible etiological factor of impotence.     

Usefulness of power Doppler ultrasonography in evaluating erectile dysfunction

OBJECTIVE: To evaluate deep penile arterial flow after an intracavernosal injection with papaverine in patients with erectile dysfunction (ED). PATIENTS AND METHODS: Twenty patients with ED were evaluated using power Doppler ultrasonography with a linear probe (8 MHz). Diagnostic tests were undertaken after an intracavernosal injection with 40 mg papaverine. The peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI) were analysed. RESULTS: After injecting papaverine, seven patients had a normal erection and appropriate waveform patterns; their mean PSV was 30.7 cm/s, the EDV 4.42 cm/s and the RI 0.85. There was tumescence and elongation of the penis with no rigidity in eight patients; their mean PSV was 23.9 cm/s, the EDV 7.34 cm/s and the RI 0.72. There was no erection in five patients. The abnormal flow values showed insufficient arterial vessels in a quarter of the men, venous leakage in 15% and mixed ED in 20%. CONCLUSION: The power Doppler technique allows the accurate location and evaluation of deep penile arteries. Vascular pathology may be differentiated after an intracavernosal injection with a vasomotor agent. Recognising the pathological pattern assists in choosing the best method of treatment.     

Effects of sildenafil on nocturnal penile tumescence and rigidity in normal men: randomized,placebo-controlled,crossover study

We studied the effects of sildenafil on sleep-related erections in 44 adult healthy men not affected by erectile dysfunction (mean age +/- SD: 39.3 +/- 10.5 years). No subjects were administered any medication the first night, but all were randomly administered sildenafil 50 mg or placebo the second night and vice versa the third night. Sildenafil and placebo were administered 1 hour before bedtime. The following parameters of sleep-related erections, after taking sildenafil or placebo, were analyzed: total number of valid erections, total duration of rigidity more than or equal to 70% of a tightening force of 2.8 N applied by the recording device, total duration of increase in penile circumference more than or equal to 30 mm, maximum rigidity, mean of maximum rigidity, and maximum increase of tumescence. Apart from the maximum increase of tumescence, all the parameters analyzed were significantly higher after sildenafil than after placebo administration during the first 4 hours of monitoring in all subjects (n = 44) (study 1). All the parameters were significantly higher after sildenafil than after placebo administration during the whole 8 hours of monitoring in 25 of 44 subjects (study 2A) who slept at least 8 hours. Comparing both the first and the second 4 hours in the 25 of 44 subjects who slept at least 8 hours (study 2B), all the parameters were significantly higher after sildenafil than after placebo administration, apart from maximum rigidity and mean of maximum rigidity during the first 4 hours. Our data suggest that sildenafil, administered at bedtime, is efficacious in improving sleep-related erections in normal men, indirectly confirming that the nitric oxide pathway is crucial in the physiology of erections during sleep. The effect of sildenafil is prolonged up to 8-9 hours after its administration.     

Erectile dysfunction following treatment of prostate cancer: new insights and therapeutic options

Prostate cancer remains the most common cancer in adult men. Its treatment usually results in compromised or absent erectile function. This article will review the treatment options available to resume sexual activity following prostate cancer therapy and will focus on non-surgical treatment options. In addition, intracavernosal injection therapy has been shown to enhance recovery of spontaneous, unassisted erections when started shortly after nerve-sparing radical prostatectomy. Most recently, oral treatment with sildenafil citrate begun shortly after surgery was shown in a placebo-controlled trial to encourage return of normal erections. Presumably this occurs by promoting nocturnal erections which appear to prevent the permanent neurovascular damage to the penis following radical prostate surgery.     

EFFECT OF THE SELECTIVE PHOSPHODIESTERASE TYPE 5 INHIBITOR SILDENAFIL ON ERECTILE FUNCTION IN THE ANESTHETIZED DOG

Purpose

The effects of sildenafil, a highly selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, on erectile function in the anesthetized dog were evaluated.

Materials and Methods

In pentobarbital-anesthetized dogs, increases in intracavernosal pressure in the corpus cavernosum and penile blood flow were induced by pelvic nerve stimulation over a frequency range of 1 to 16 hertz. The effects of increasing doses of sildenafil on electrically stimulated intracavernosal pressure, penile blood flow, blood pressure, and heart-rate were evaluated. In parallel experiments, the effects of the nitric oxide synthase inhibitor N omega-Nitro-L-Arginine (L-NOArg) on these same parameters also were assessed.

Results

The effects of nerve stimulation on intracavernosal pressure and blood flow to the penis were blocked by L-NOArg, 0.1-3 mg./kg., in a dose-related manner, confirming the important role of nitric oxide in producing erections. Sildenafil, 1-100 micro g./kg administered intravenously, had no direct effect on intracavernosal pressure but potentiated the increase in intracavernosal pressure induced by nerve stimulation. This potentiation occurred at sildenafil plasma concentrations consistent with its relaxation effect on isolated human cavernosal tissue and its inhibition of phosphodiesterase type 5 in vitro. Sildenafil had no significant effect on blood pressure or heart rate.

Conclusions

By inhibiting cyclic guanosine monophosphate-specific phosphodiesterase type 5, sildenafil augments the neuronal mechanism responsible for penile erection. This mechanism explains the significant improvements reported in the rigidity and duration of erections seen in patients with erectile dysfunction who have been treated with oral sildenafil.     

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

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 filled 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 fibrosis 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.     

Rationale for combination therapy of intraurethral prostaglandin E(1) and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy

Corpus cavernosum smooth muscle relaxation and hence penile erection are regulated in part by increases in smooth muscle synthesis of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). The object of this study was to determine 30-month follow-up results in motivated patients desiring noninvasive medical therapy using sildenafil citrate (Viagra) in combination with intraurethral prostaglandin E(1) (PGE(1)) (Medicated Urethral System for Erection [MUSE]). Twenty-eight patients (mean +/- s.d. age, 59 +/-7.3 y; 17 who had undergone radical prostatectomy and 11 who had a diagnosis of organic erectile dysfunction) were included in this study. Detailed history taking and physical examinations were performed and vascular risk factors noted. In these patients, treatment with either 100 mg of sildenafil citrate and/or 1000 microg of MUSE had failed. None of these patients desired intracavernosal injection. Duplex Doppler ultrasonography after redosing was carried out on all patients. Dynamic infusion corpus cavernosography/cavernosometry was obtained in 17 of 28 patients, and combination therapy was initiated using 100 mg of sildenafil citrate orally 60 min before intercourse and 500 microg of MUSE intraurethrally immediately before intercourse. Independently, either 100 mg of sildenafil citrate or 1000 microg of MUSE was not efficacious in inducing an erection sufficient for vaginal penetration in any of the 28 patients. After initiating a combination therapy, at 30 months, all 28 patients were reporting erections sufficient for vaginal penetration, with 3.6 intercourse episodes per month. None of the patients crossed over to intracavernosal therapy or penile prosthesis. During therapy, eight of 28 patients reduced the dose of sildenafil citrate to 50 mg. Combination therapy with MUSE and sildenafil may be more efficacious in the salvage of patients who desire noninvasive therapy but in whom single-treatment modalities fail. Although both cAMP- and cGMP-mediated vasodilation can lead to penile erection, combining therapies that incorporate both pathways may succeed when single therapies fail.