Self-Injection Therapy

The demonstration by Virag in 1982 that intracavernous injection of papaverine produced a fully-rigid erection in normal males, introduced a new route of administration in the clinical management of pharmacologic agents for the treatment of erectile failure. Intracavernous injection of a vasoactive agent that readily produces erection has greatly simplified the multidisciplinary diagnostic investigations and management of erectile dysfunction (ED). Three groups of drugs are presently used for self-injection therapy worldwide, or at least in some parts of the world. These include papaverine, alpha-adrenoceptor blocking agents such as phentolamine or moxisylyte, and prostaglandin E1 (PGE1). These compounds have proven to be effective in all etiologies of erectile failure such as psychogenic, neurogenic or vasculogenic impotence.

Other agents that have been investigated for their suitability in self-injection therapy, but never reached the stage of official approval or even off-label use, comprise calcium channel blocking agents, vasoactive intestinal polypeptide, ketanserin, histamine, P-adrenergic agonists, nitric oxide donors (linsidomine or sodium nitroprusside) etc. Generally speaking, compounds that were able to relax the smooth muscle cells of both the penile arteries and the cavernous tissue, subsequently resulting in blood engorgement of the cavernous sinusoidal spaces, with activation of the veno-occlusive mechanism through compression of the subtunical veins, may be principally considered for self-injection therapy in erectile dysfunction (ED).

Up to 1998, self-injection therapy was the only effective pharmacologic treatment in erectile dysfunction and was considered a first-line option in this indication. But with the launch of sildenafil (Viagra ®) intracavernous self-injection therapy became generally a second-line option for the majority of erectile dysfunction patients, with the exception of those men in whom phosphodiesterase-5 (PDE-5) inhibitors were contraindicated, or turned out to be ineffective. In the following, the essential features of those compounds are described, which are either approved and/or mostly used, even in off-label use, for self-injection therapy.

Alprostadil (PGE1 — Caverject, Edex, Viridal)


Alpha-adrenoceptor blockers

Drug combinations for self-injection therapy

Technique and complications of self-injection therapy

Special populations/features with self-injection therapy

Patients on anticoagulants

According to the literature and my own experience, self-injection therapy can be performed even in men on warfarin or phenprocoumon-containing anticoagulants, without increasing the risk of bleeding/ ecchymosis.

Transplant patients

The literature does not show any increased risk with self-injection therapy in patients who have received kidney or heart transplants.


Both in the literature and in own patient populations, erectile dysfunction patients with diabetes are revealed at increased risk of fibrosis and painful sensations with self-injection therapy.

Trans(intra)urethral Therapy

Transurethral alprostadil (PGE1) with MUSE ® (Medicated Urethral System for Erection)

A new alprostadil preparation using transurethral application with a small single-use applicator was introduced in 1994, and later on developed as MUSE ® (Medicated Urethral System for Erection) for market approval in US, 1996 (VIVUS, USA) followed by many other countries worldwide. Although the transurethral application route seemed at first glance to be preferable to self-injection therapy the outcome and especially direct comparative trials to intracavernously-applied alprostadil (Caverject ®, Edex ®, Viridal ®), revealed a distinct inferiority of MUSE ®.

Typical frequent side effects of MUSE ® are penile/urethral pain between 25 and 43%, and urethral bleeding (around 5%). Infrequently reported adverse events are dizziness with fall in blood pressure (1-5%), and even the occurrence of syncope between 0.4 and 3%.

Of importance for achieving the best efficacy with MUSE ® and avoidance of bleeding is a correct technical application, i.e. to insert MUSE ® directly upon micturition with the urethra still being moist. The efficacy of MUSE ® may be enhanced by simultaneous application of a constriction bandage on the base of the penis to avoid quick drainage of the medication through the penile veins. Successful salvage of non-responders to mono therapy either with sildenafil or MUSE ® using a combination of both methods was reported by several authors. At present transurethral alprostadil therapy with MUSE ® must be considered a niche therapy in erectile dysfunction (ED). The main indications of MUSE ® are patients, non-responsive to PDE-5 inhibitors due to damage of the autonomic penile nerve supply after pelvic surgery or trauma (RRP, cystectomy).

Transurethral route used with other compounds

Transurethral application with other compounds such as lyophilized liposomal PGE1 (LLPGE) or PGE2 was investigated several times, but then abandoned, and never reached the stage of market approval.

Topical Therapies in Erectile Dysfunction

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