MUSE (medicated urethral system for erections; Vivus, Menlo Park, CA) has been available for the treatment for erectile dysfunction since January 1997. This form of therapy is novel because the active medication, alprostadil (synthetic prostaglandin E1), a potent vasodilator, is admininstered and absorbed intraurethrally. In contrast, Caverject (Upjohn-Pharmacia, Kalamazoo, MI) represents the same medication at a much lower dose injected directly into the corporal bodies. The U.S. patent for MUSE refers to its unique application system for intraurethral delivery. This intraurethral route of therapy was first described in 1993.[22] MUSE is available in 4 doses: 125 m g, 250 m g, 500 m g, and 1000 m g, which cost approximately $20-25 per application. As of July 1998, MUSE accounts for about <1% of prescriptions written for the treatment of erectile dysfunction.

The application of MUSE, a peripheral initiator of erections, is simple and straight-forward.(figure 1) After the patient urinates to lubricate the urethra, he places the stem end of the applicator approximately 3.2 cm in the urethra. To disperse the 3-6 mm alprostadil pellet, he depresses the applicator button and gently rolls the penis. Men who do not achieve good rigidity of the penis with prior applications may find that the ACTISä band applied around the shaft of the penis may help augment the subsequent erection. The alprostadil pellet is rapidly absorbed by the corpus spongiosum within 10 minutes of application and then disseminated to the corpora cavernosa by vascular communications between these distinct compartments of the penis. The alprostadil functions as a corporal and arterial smooth muscle relaxant, leading to an increased arterial inflow into the sinusoidal spaces of the cavernous bodies and a compression of the trabecular smooth muscle against the emissary veins. This mechanism results in a decreased venous outflow and the maintenance of the rigidity of an erection.

Clinically, the rapid absorption of alprostadil is evidenced by the onset to erection in 7 minutes. Erections typically are maximal about 22-24 minutes after administration, then completely detumesce by 64-79 minutes after application. With a half-life of several minutes and extensive pulmonary metabolism, clearance is rapid and plasma levels are nearly undetectable.

In a multi-center, placebo-controlled study sponsored by VIVUS and involving 996 men, 65.9% had grade 4-5 erections judged to be "sufficient" for intercourse during in-office testing.[23] Of those men who responded in the clinic, 64.9% were able to have intercourse at least once during home application. Erections were scored on the Erection Assessment Scale which ranges from 0-5, with 4=erection sufficient for intercourse (i.e. "stuffable") and 5=full ridigity (i.e. "stickable"). Regardless of the cause of erectile dysfunction and the age of the patient, MUSE was significantly more efficacious than placebo. Hellstrom et al reported similar findings.[24]

When examining the responses per dose administered, however, only 48.8% of men using the highest dose of 1000 m g had a grade 4 or 5 erection.[23](figure 2) 12.3% of men using the 125 m g dose were able to develop similar quality erections. Werthman and Rajfer using an erection scale of rigid, full, and poor had more disappointing results, reporting that only 7% of men had well-sustained, rigid erections.[25] Another 30% had erections, but with only partial rigidity. These same men developed rigid and full erections using intracavernous injections 49% and 40% of the time, respectively. Another comparative study by Porst concluded that due to superior efficacy and lower side-effects, self-injection therapy with alprostadil remains the 'Gold Standard' in the management of male impotence, and that MUSE should be reserved for a subset of patients suffering from erectile dysfunction.[26] Only 10% of men had rigid erections with MUSE in this study.

In contrast, a subgroup of 95 men for whom intracavernous injections were "not effective" stated that MUSE resulted in an erection sufficient for intercourse.[27] Fifty-eight percent of men of these "not effective" men had an erection sufficient for intercourse after MUSE application in the clinic, and 47% of these men reported successful intercourse after home administration. Such studies suggest that men should not be discouraged or excluded from trying MUSE if intracavernous injections, which are considered more potent, fail. The efficacy of MUSE was consistent regardless of a number of factors including duration and cause of erectile dysfunction, age of the patient, history of previous therapy.

Adverse effects include penile and perineal discomfort, minor urethral trauma, and hypotension. Local pain in the penis (36%), urethra (13%), and testes (5%) was typically mild and self-limited. This discomfort, seen with PGE-1 intracavernous injections also, is likely an inherent effect of PGE-1 because of its pain-sensitizing activity.. The pain is manifested as a delayed aching beginning 5-10 minutes after application and often lasting up to several hours. Because of the small, but significant risk of hypotension (3.3%), MUSE should be initially tested in the office. Priapism, defined as a rigid erection lasting ³ 6 hours, was reported in only 0.1% of applications. Only 7% of men discontinued MUSE because of adverse events. The efficacy and safety studies led to its FDA approval for the treatment of erectile dysfunction in December 1997.

We do not advocate the use of MUSE in men trying to establish a pregnancy, although alprostadil does not appear to have any effect on in vitro sperm motility, viability, or membrane integrity.[28] While the concentration of PGE-1 in the semen is slightly higher after MUSE administration, this increase was not significant. The effects of the PGE-1 did, however, cause vaginal burning or itching in 5.8% of female partners versus 0.8% in the placebo group.

Dosing of MUSE should be guided by the results in figure 2. The significant increase in efficacy appears at the 500 mcg dose. With in-office testing, we have been starting men with spinal cord injury at 125 mcg; psychogenic impotence or men <50 of age with no identifiable cause at 250 mcg; and clearly evident organic dysfunction, post-radical prostatectomy, and men >50 years of age at 500 mcg.

In summary, MUSE remains a first-line therapy for erectile dysfunction treatment. The main advantages of MUSE are the avoidance of needles and the ease of application. By avoiding needles as with intracavernous injections, the risk of penile fibrosis, generally in the range of 3-7%, but as high as 23%, may be minimized.[29] The drawbacks include its cost of $20-$25 per application and relative lack of efficacy in producing rigid hard erections.