Rationale for combination therapy of intraurethral prostaglandin E1 and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy

Abstract

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 AE s.d. age, 59 AE 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 m mg 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 m mg of MUSE intraurethrally immediately before intercourse. Independently, either 100 mg of sildenafil citrate or 1000 m mg 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.

Combination therapy for erectile dysfunction: an update review

“…This perhaps points to additional variables involved in therapeutic compliance such as education level, socioeconomic status, medication costs and other psychosocial factors. In a case series of 28 patients, Nehra et al 13 achieved a 100% rate of erections deemed sufficient for penetration with combination treatment after patients failed sildenafil and/or alprostadil monotherapy. Using this regimen, no patients desired a transition to more invasive treatments such as ICI or penile prosthesis implantation.…”

Long-term efficacy and compliance of MUSE for erectile dysfunction following radical prostatectomy: SHIM (IIEF-5) analysis

“…The proposed use of combination therapy will provide an alternative option for many patients who do not accept more invasive treatments such as VCD and intracavernosal injections. 12 Conclusions MUSE can provide good efficacy and compliance in up to 63% of patients. A mean SHIM score of Z16 stratified for a successful and long-term outcome with MUSE therapy.…”

Combining programmed intracavernous PGE1 injections and sildenafil on demand to salvage sildenafil nonresponders

“…15 Recently, the combined use of IC 12 or intraurethral 10,11 PGE1 and the first effective oral PDE-5 inhibitor sildenafil taken together at the time of intercourse has been reported successful in many patients not responding to either single drug. The present data indicate that such a combination can also be effective when the drugs are administered quite separately.…”

“…3,4 They include needle aversion, lack of spontaneity, partner rejection of the procedure, pain, and increased risks of priapism or fibrotic changes in the penis after prolonged use. [5][6][7][8][9] In patients not responding to either type of monotherapy, the combination of both has been tried in order to get additive or synergistic effects, which has been carried out by combining PGE1 delivered either transurethrally 10,11 or by IC injection (as triple agent, mixed with papaverine and phentolamine) 12 with the oral PDE-5 inhibitor sildenafil at 100 mg dose. These studies reported satisfactory results in many patients previously not responding to monotherapy with either drug.…”