International Journal of Impotence Research (1997) 9, 187±192 ß 1997 Stockton Press All rights reserved 0955-9930/97 $12.00 Transurethral Alprostadil with MUSETM (medicated urethral system for erection) vs intracavernous AlprostadilÐa comparative study in 103 patients with erectile dysfunction H Porst Urological Of®ce, Neuer Jungfernstieg 6a, 20354 Hamburg, Germany A comparative study in 103 unselected patients with erectile dysfunction between MUSETM up to 1000 mg and intracavernous Alprostadil (ProstavasinTM)upto20mg provided total response-rates of 43% (MUSETM) vs 70% (ProstavasinTM). Complete rigid erections were reached in 10% (MUSETM) vs 48% (ProstavasinTM). The average end-diastolic ¯ow values in the deep penile arteries ranged between 9.2±9.4 cm/s after MUSETM and 4.5±4.8 cm/s after i.c. Alprostadil con®rming the investigator's assessment, that in the vast majority of patients MUSETM were not able to induce a complete cavernous smooth muscle relaxation. In terms of side effects the reported penile pain/burning-rate after MUSETM was 31.4% compared to 10.6% after i.c. Alprostadil. In addition after MUSETM clinically relevant systemic side-effects like dizziness, sweating and hypotension occurred in 5.8% with syncope in 1%. No circulatory side-effects were encountered after i.c. Alprostadil. Urethral bleeding after MUSETM-application was observed in 4.8%. Due to the superior ef®cacy and lower side-effects self-injection therapy with Alprostadil remains the `Gold Standard' in the management of male impotence. MUSETM should be reserved for a subset of patients suffering from erectile dysfunction. TM Keywords: erectile dysfunction; Alprostadil; Prostaglandin E1; transurethral therapy; MUSE ; self-injection therapy Introduction adenylate cyclase with intracellular accumulation of cAMP and subsequent intracellular calcium decrease, direct stimulation of the maxi K (potas- Alprostadil was proposed for intracavernous injec- sium)-channels resulting in hyperpolarization, in- tion-therapy by Adaikan and Ishii, 1986 in Prague at hibition of the noradrenaline release via presynaptic the Second World Meeting on Impotence.1,2 The EP-receptors at the alpha1 adrenoceptors, resulting publications of its usefulness and safety in larger in a decrease of sympathetic (adrenergic) tone, and patient groups paved the way for a world-wide suppression of Angiotensin II secretion.7±10 Each of acceptance of Alprostadil in self-injection ther- these different pharmacological effects contributes apy.3,4 The high ef®cacy and low side-effect-rates to cavernous smooth muscle relaxation. with priapisms < 1% and ®brotic alterations about Irrespective of the administered vasoactive drug, 1% con®rmed in comprehensive retrospective lit- all published series with self-injection therapy of erature reviews prompted the Clinical Guidelines cavernous bodies reveal relatively high drop out Panel on Erectile Dysfunction of the American rates up to 40±50% in long-term follow up.5 This Urological Association to the statement that Alpros- disadvantage of self-injection therapy is at least tadil (PGE1) monotherapy should be preferred to partly due to the necessity of needle-application as other vasoactive drugs in self-injection therapy.5,6 many patients exhibit needle-phobia. Padma- The convincing ef®cacy of Alprostadil with Nathan et al, 1994 for the ®rst time introduced response-rates (complete rigid erections) of > 70% transurethral application of Alprostadil by means of in large series is attributed to several pharmacolo- MUSETM (Medicated Urethral System for Erection).11 gical properties of the drug: stimulation of the Due to the uncomplicated handling with a ready for use device and the needleless application MUSETM enjoyed great popularity in a very short time and Correspondence: Prof H Porst. was registered in the USA in December 1996. Received 1 August 1997; revised/accepted 22 September 1997 Presently only one comprehensive publication on Transurethral Alprostadil with MUSETM H Porst 188 this subject is available with a follow-up of three months.12 According to this publication, the inves- tigated patients developed erections, which were considered suf®cient for sexual intercourse by several investigators in 65.9% (996 out of 1511) after transurethral Alprostadil up to 1000 mg. With the of®cial approval followed by a tremendous increase of its use in erectile dysfunction critical statements on the promised ef®cacy of MUSETM could be heard which prompted us to compare ef®cacy and safety of transurethral (MUSETM) vs intracavernously injected Alprostadil in the diag- nostic evaluation of male impotence. Table 1 Intracavernous vs transurethral Alprostadil (MUSETM) Materials and methods One hundred and three consecutive patients (51.7 y mean) with chronic erectile dysfunction ( > 6 and all involved patients agreed to participate in the months) underwent a complete diagnostic evalua- trial. tion with patient's history, physical examination including penile palpation, determination of serum hormone-, (testosterone, prolactine) and glucose Results levels and pharmacotesting of cavernous bodies. In all patients an intracavernous pharmacotesting Ef®cacy (Table 1 and 2) with Alprostadil was performed up to dosages of 20 mg, in few cases up to 40 mg, respectively, and the Investigator's assessment: Complete rigid erec- results were compared with the outcome of transur- tion (ED-score 5) was obtained in 48% (49 out of ethral application of Alprostadil with MUSETM up to 103) after i.c. Alprostadil and in 10% (10 out of 103) the highest dosage of 1000 mg. All investigations, after MUSETM. Full tumescence with partial rigidity including the drug administrations, were performed (ED-Score 4) occurred in further 22% after i.c. and in by the author himself. The start doses were 500 mg 33% (34 out of 103) after transurethral Alprostadil. TM MUSE or 10 mg PGE1 i.c., respectively, with a wash These numbers indicate a total response rate of 70% out interval of at least 48 h. In responders the (72 out of 103) after i.c. Alprostadil compared to dosages were lowered to 250 mg MUSETM or 5 mg 43% (44 out of 103) after MUSETM. The dosages PGE1, and in non-responders increased to 1000 mg required for ®nal assessment of the highest erection TM MUSE or 20 m PGE1, respectively. Both investiga- score are presented in Table 2. This table empha- tions were combined with a duplex-sonography of sizes the observations that in the majority of patients the penile arteries with determination of the systolic (77%) the high MUSETMdosages of 500 mg (21%) or peak ¯ow velocities as well as the enddiastolic ¯ow in the deep penile arteries. The degree of erection was assessed according to an erection score of 1±5, as it was suggested in the MUSETM studies.12 Patients with an erection score 5 (full rigid erection) and 4 (full tumescence, partial rigidity) were considered as responders. The start of the trial either with intracavernous or with transurethral Alprostadil (MUSETM) was by chance. After each investigation the patients were observed for at least 60 min in the of®ce with blood pressure monitoring in a sitting position and the registration of possible adverse events. At the end of the study each patient was asked upon his estimation which drug was more effective and/or better-tolerated and which drug he would prefer for home use. All patients were informed on the objective of the trial that is to ®nd out the best tolerable and most effective pharmacological treatment for the individual patient Table 2 Intracavernous vs transurethral Alprostadil (MUSETM) Transurethral Alprostadil with MUSETM H Porst 189 Table 3 Intracavernous vs Transurethral Alprostadil (MUSETM) Table 5 Intracavernous vs Transurethral Alprostadil (MUSETM) 1000 mg (56%) were necessary for achievement of the highest ED-score. After i.c. Alprostadil in most patients dosages of 10 mg (28%) and 20 mg (65%) had to be applied in order to reach the highest erection quality. Patients' subjective assessments (Table 3) After termination of the comparative trial 37.9% of the patents estimated i.c. Alprostadil superior and 15.5% inferior to MUSETM. 46.6% of all patients indicated that they were not aware of great differ- Table 6 Intracavernous vs Transurethral Alprostadil (MUSETM) ences in terms of ef®cacy between the both methods with the majority of these patients falling under the non-responder category. than after i.c. Alprostadil (Table 6). Duplex-sonography ®ndings (Table 4 and 5) Systolic peak ¯ow velocities: Whereas after Side-Effects (Table 7) MUSETM-administration the systolic peak ¯ow velo- cities in the dorsal arteries were 55.6 cm/s (left side) and 53.4 cm/s (right side) were somewhat higher After i.c. Alprostadil 3.9% of the patients com- than after i.c. Alprostadil (49.7 and 49.0 cm/s), the plained of severe penile pain and 6.7% of slight ratio was conversely in terms of the deep penile painful sensations during full rigid erections. On the arteries with a slight advantage in favour of i.c. other hand after MUSETM-application in a total of Alprostadil (Table 4 and 5). Concerning the re- 31% painful or burning sensations in the penis or corded enddiastolic ¯ow, which represents an urethra were encountered with additional 2.9% indirect parameter for the degree of the complete- with severe testicle pain. Reddening of the varicose ness of cavernous smooth muscle relaxation, the veins of the lower limbs with simultaneous painful measured values were twice as high after MUSETM sensations occurred in 2.9%. Temporary urethral bleeding after MUSETM-application was observed in 4.8% (5 out of 103) and repeatedly occurred in four of these ®ve patients after further administration during the titration phase. Adverse events of general health conditions attributable to a blood pressure decay, beginning 8±15 min after application and lasting for about 10 min were observed in seven (6.8%) patients with one patient suffering from a short-term syncope.