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Alprostadil - transurethral


Clinical bottom line

Transurethral alprostadil has been tested in men with erectile dysfunction at home. All three trials have used enriched enrollment, and data pooling was not possible because of outcomes reported by men, and by attempts. It would appear that over 50% of men who have previously responded to alprostadil can achieve successful intercourse at home with transurethral alprostadil. The NNT calculated on an intention to treat basis was 3.5 (3.1 to 4.0) for one man to achieve successful intercourse at home who would not have done so with placebo. Penile pain was relatively common, but usually described as mild.


Alprostadil is a prostaglandin that can be used to treat erectile dysfunction. There are different methods of using it, by injection into the penis (intracavernosal), by inserting a pellet into the urethra (transurethral), or by a cream or gel applied to the glans penis (topical). This review covers transurethral application, and studies comparing transurethral with intracavernosal injection are dealt with in that section.


Searching was done using PubMed, Medline and the Cochrane Library, up to September 2005. Randomised trials in which alprostadil was compared with placebo were sought. Details of the trials were abstracted and quality scoring done with a 5 point scale. For crossover or partial crossover designs, details of the first phase were used (as a parallel group trial) where possible, and where this was not possible the full crossover data was used.

The outcome sought was patient/partner judgement of satisfactory erections suitable for intercourse, or actual intercourse, at home. Ideally this was on a patient basis, rather than on event basis, which was a secondary outcome. Relative risk and NNT were calculated using standard methods.


Three trials were found in which outcomes at home were measured (Table 1). All used enriched enrollment, whereby the home trial only took place when a man had been shown to respond to alprostadil in clinic with an erection of sufficient rigidity for intercourse.

Table 1: Randomised trials of transurethral alprostadil



Quality score





Adverse events

Hellstrom et al, 1996 Randomised, double blind, crossover, enriched enrollment


68 men with organic erectile dysfunction from previous trial. Age range 27-76 years Placebo and 125, 250, 500 and 1000 µg alprostadil to be used at home Sexual intercourse at home on any dose 8/66 placebo, 26/66 125 µg, 22/66 250 µg, 26/66 500 µg, 33/66 1000 µg, Penile pain in 9-18% of patients with alprostadil but not placebo.
Padma-Nathan et al, 1997 Randomised, double blind, parallel, enriched enrollment


996 men successfully treated in a clinic with alprostadil. Mean age 61 years Alprostadil (125, 250, 500, or 1000 µg) or placebo Intercourse 454/4346 attempts with placebo and 2485/4933 attempts with alprostadil 299/486 men achieved intercourse at least once with alprostadil and 93/511 on placebo Penile pain in 159/486 of men with alprostadil and 17/511 with placebo
Williams et al, 1998 Randomised, double blind, parallel, enriched enrollment


159 men who responded in clinic Alprostadil (125, 250, 500, or 1000 mg) or placebo to be used at home over three months Intercourse Intercourse at least once by 46/67 on alprostadil and 8/73 on placebo Penile pain in 4/78 on alprostadil and 1/81 on placebo

At least half the time a successful erection that allowed intercourse resulted from use of transurethral alprostadil at home in men in whom it had already been shown to work in the clinic. Penile pain was relatively common, but usually described as mild.

Calculating NNTs

We can calculate the NNT for a man to have at least one successful intercourse at home with alprostadil compared with placebo. This can be done on the basis of a per protocol calculation, using the numbers randomised at enriched enrollment. Alternatively, if we accept that those enrolled but not randomised were treatment failures and would have been equally randomised between alprostadil and placebo groups, we can calculate an intention to treat NNT. The calculations are given in Table 2.

Table 2: NNT calculations for transurethral alprostadil at home

Successful intercourse on alprostadil

Successful intercourse on placebo

Relative benefit







(95% CI)

(95% CI)

Per protocol





3.6 (3.0 to 4.4)

2.2 (2.0 to 2.5)

Intention to treat





3.5 (2.9 to 4.3)

3.5 (3.1 to 4.0)

The relative benefit remains the same, but the NNT rises substantially with this calculation, from two men to four men needing to be treated for one to have successful intercourse at home who would not have with placebo.


What is remarkable is that the references found on searching (below) were many. The trials at home with useful outcomes were relatively few, and even these may not be extrapolatable to everyday practice. For instance, in the largest study (Padma-Nathan et al), about one third of the men originally enrolled did not react in the clinic, or for some other reason did not participate in the at-home trial, with a similar proportion with the Williams trial. In these two studies 1155 men entered the at-home trials out of 1760 originally enrolled. This limits the application of these results, though perhaps the intention to treat calculation becomes more useful.

It is interesting also to visit alprostadil in the round, as it were and compare this report with the original report in Bandolier, which was somewhat more enthusiastic in those early days.


Some of the references below (to 2000) might be of interest to some readers. More important is a Cochrane review by Urciuoli and colleagues [1].

  1. R Urciuoli et al. Prostaglandin E1 for treatment of erectile dysfunction. Cochrane Database of Systematic Reviews 2004 issue 2.



Hellstrom WJ, Bennett AH, Gesundheit N et al . A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil. Urology 1996; 48(6):851-6. Include, but enriched enollment
Padma-Nathan H, Hellstrom WJG, Kaiser FE et al. Treatment of men with erectile dysfunction with transurethral alprostadil. The New England Journal of Medicine 1997336; No. 1(1-7). Include, but enriched enrollment
Williams G, Abbou CC, Amar ET et al. Efficacy and safety of transurethral alprostadil therapy in men with erectile dysfunction. MUSE Study Group. Br J Urol 1998; 81(6):889-94. Include, but enriched enrollment
Alprostadil. PRESCRIRE-INT Prescrire-International. 1996; 5(22):34-6. Review
Intracavernous injection of alprostadil for erectile dysfunction. Med Lett Drugs Ther 1995; 37(958):83-4. Summary info of Alprostadil Injection
Intraurethral alprostadil for impotence. Med-Lett-Drugs-Ther 1997; 39:32. Summary information
Vasoactive intracavernous pharmacotherapy for impotence: Papaverine and phentolamine. J-AM-MED-ASSOC Journal-of-the-American-Medical-Association. 1990; 264(6):752-4. Review
Abdallah HM. Comparison of Alprostadil (Caverject) and a combination of vasoactive drugs as local injections for the treatment of erectile dysfunction. INT-UROL-NEPHROL International-Urology-and-Nephrology. 1998; 30(5):617-20. Not an RCT
Althof SE, Turner LA, Levine SB et al. Intracavernosal injection in the treatment of impotence: a prospective study of sexual, psychological, and marital functioning. J Sex Marital Ther 1987; 13(3):155-67. Not an RCT
Alvarez E, Andrianne R, Arvis G et al. The long-term safety of alprostadil (prostaglandin-E-1) in patients with erectile dysfunction. BR-J-UROL British-Journal-of-Urology. 1998; 82(4):538-43. Not an RCT
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Antolin AR, Morales JM, Andres A et al. Treatment of erectile impotence in renal transplant patients with intracavernosal vasoactive drugs. TRANSPLANT-PROC Transplantation-Proceedings. 1992; 24(1):105-6. Not an RCT
Arena F, Peracchia G, Di Stefano C, Cortellini P. PGE1 treatment in erectile dysfunction. ACTA-BIOMED-ATENEO-PARMENSE Acta-Biomedica-de-l'Ateneo-Parmense. 1996; 67(1-2):49-53. Not an RCT
Arielly J, Weinberg D, Eliraz A, Adam M, El Hanani BI, Eisenkraft S. Intracavernous auto-injection of prostaglandin E-1 for diagnosis and treatment of erectile dysfunction. HAREFUAH Harefuah. 1994; 126(7):369-73+428. Hebrew, no translation
Austoni E, Bellorofonte C, Mantovani F. Improved results with intracavernous vasoactive drug infusion following new surgical techniques for vasculogenic impotence. WORLD-J-UROL World-Journal-of-Urology. 1987; 5(3):182-9. Not an RCT
Bechara A, Casabe A, Cheliz G, Romano S, Fredotovich N. Prostaglandin E1 versus mixture of prostaglandin E1, papaverine and phentolamine in nonresponders to high papaverine plus phentolamine doses [see comments]. J Urol 1996; 155(3):913-4. Laboratory setting, not home RCT
Bechara A, Casabe A, Cheliz G, Romano S, Rey H, Fredotovich N. Comparative study of papaverine plus phentolamine versus prostaglandin E1 in erectile dysfunction [see comments]. J Urol 1997; 157(6):2132-4. No placebo group
Beretta G, Zanollo A, Portalupi W. PGE1- Intracavernous injections in the treatment of erectile pathology. ARCH-ITAL-UROL-NEFROL-ANDROL Archivio-Italiano-di-Urologia-Nefrologia-Andrologia. 1991; 63(4):481-5. Not an RCT
Bischoff A. Alprostadil-alfadex in erectile dysfunction. PHARM-ZTG Pharmazeutische-Zeitung. 1997; 142(47):48. Narrative Review
Bucher A, Mrstik Ch, Stogermayer F. Therapeutic effect of PGE-1 in the treatment of erectile dysfunction. AKTUEL-UROL Aktuelle-Urologie. 1990; 21(1):17-8. Not an RCT
Buvat J, Amar E, Cambau O, Desvaux P, Gout A, Leriche A. Double-blind multicenter study comparing Alprostadil Alfadex with moxisylyte chlorhydrate in patients with chronic erectile dysfunction. ANDROLOGIE Andrologie. 1998; 8(2):204-12. No placebo group and duplicate of below
Buvat J, Costa P, Morlier D, Lecocq B, Stegmann B, Albrecht D. Double-blind multicenter study comparing alprostadil alpha-cyclodextrin with moxisylyte chlorhydrate in patients with chronic erectile dysfunction [see comments]. J Urol 1998; 159(1):116-9. No placebo group and duplicate of below
Buvat J, Lemaire A, Herbaut Buvat M. Intracavernous pharmacotherapy: Comparison of Moxisylyte and prostaglandin E1. ANDROLOGIE Andrologie. 1996; 6(4):406-14. No placebo group and duplicate of above
Buvat J, Lemaire A, Herbaut Buvat M. Intracavernous pharmacotherapy: comparison of Moxisylyte and prostaglandin E1. Int J Impot Res 1996; 8(2):41-6. Not an RCT
Buvat J, Lemaire A, Marcolin G, et al. Intracavernous injection of papaverine (ICIP). Assessment of its diagnostic and therapeutic value in 100 impotent patients. WORLD-J-UROL World-Journal-of-Urology. 1987; 5(3):150-5. Not an RCT
Chen JK, Hwang TI, Yang CR. Comparison of effects following the intracorporeal injection of papaverine and prostaglandin E1. Br J Urol 1992; 69(4):404-7. No placebo group
Coker C, Bettocchi C, Pryor J. Caverject, a new licensed prostaglandin preparation for use in erectile dysfunction. J-ANDROL Journal-of-Andrology. 1994; 15(6 SUPPL.):71S. Abstract
Colli E, Calabro A, Gentile V, Mirone V, Soli M. Alprostadil sterile powder formulation for intracavernous treatment of erectile dysfunction. Eur Urol 1996; 29(1):59-62. Laboratory setting, not home RCT
Costabile RA, Spevak M, Fishman IJ et al. Efficacy and safety of transurethral alprostadil in patients with erectile dysfunction following radical prostatectomy. J Urol 1998; 160(4):1325-8. Retrospective subgroup analysis
Delle Rose A, Stomaci N, Pironti M, Raugei A, Lenzi R. Impotence due to pelvic trauma: Treatment with papaverine and PGE-1. ACTA-UROL-ITAL Acta-Urologica-Italica. 1992; 6(SUPPL. 4):27-8. Not an RCT
Derouet H, Weirauch A, Bewermeier H. [Prostaglandin E1 (PGE1) in diagnosis and long-term therapy of erectile dysfunction]. Urologe A 1996; 35(1):62-7. Not an RCT
Earle CM, Keogh EJ, Wisniewski ZS et al. Prostaglandin E1 therapy for impotence, comparison with papaverine. J Urol 1990; 143(1):57-9. Not double blind / no placebo
Engel JD, McVary KT. Transurethral alprostadil as therapy for patients who withdrew from or failed prior intracavernous injection therapy. Urology 1998; 51(5):687-92. Retrospective subgroup analysis
Fessler B. Alprostadil: Intracavernous self-injection in the treatment of erectile dysfunction. DTSCH-APOTH-ZTG Deutsche-Apotheker-Zeitung. 1996; 136(30):30. Review
Floth A, Schramek P. Intracavernous injection of prostaglandin E1 in combination with papaverine: enhanced effectiveness in comparison with papaverine plus phentolamine and prostaglandin E1 alone. J Urol 1991; 145(1):56-9. No placebo group
Garceau RJ, Zhang IX, Jen L. Dose-response studies of intracavernous injection therapy with alprostadil in Asian and Australian men with erectile dysfunction. CURR-THER-RES-CLIN-EXP Current-Therapeutic-Research-Clinical-and-Experimental. 1996; 57(1):50-61. Not RCT at home
Godschalk M, Gheorghiu D, Chen J, Katz PG, Mulligan T. Long-term efficacy of a new formulation of prostaglandin E1 as treatment for erectile failure [see comments]. J Urol 1996; 155(3):915-7. Not an RCT
Godschalk MF, Chen J, Katz PG, Mulligan T. Prostaglandin E1 as treatment for erectile failure in elderly men. J Am Geriatr Soc 1994; 42(12):1263-5. Not an RCT
Godschalk MF, Chen J, Katz PG, Mulligan T. Treatment of erectile failure with prostaglandin E1: a double-blind, placebo-controlled, dose-response study. J Urol 1994; 151(6):1530-2. Not RCT at home
Ishii N, Watanabe H, Irisawa C et al. [Studies on male sexual impotence. Report 18. Therapeutic trial with prostaglandin E1 for organic impotence]. Nippon Hinyokika Gakkai Zasshi 1986; 77(6):954-62. Not an RCT
Kattan S. Double-blind randomized crossover study comparing intracorporeal prostaglandin E1 with combination of prostaglandin E1 and lidocaine in the treatment of organic impotence. Urology 1995; 45(6):1032-6. No placebo
Kattan S, Collins JP, Mohr D. Double-blind, cross-over study comparing prostaglandin E1 and papaverine in patients with vasculogenic impotence. Urology 1991; 37(6):516-8. No placebo
Kawanishi Y, Kimura K, Iriguchi H et al. [Double-blind trial of oral prostaglandin E1 on impotence]. Nippon Hinyokika Gakkai Zasshi 1992; 83(10):1655-61. Japanese, no translation
Kovalev VA, Koroleva SV. [A trial of the use pf prostaglandin E1 (Edex, Caverject) for the diagnosis and treatment of erectile dysfunction]. Urol Nefrol Mosk 1997; (2):41-4. Not an RCT
Lee LM, Stevenson RW, Szasz G. Prostaglandin E1 versus phentolamine/papaverine for the treatment of erectile impotence: a double-blind comparison. J Urol 1989; 141(3):549-50. Not an RCT
Lemaire A, Buvat J. [Erectile response to intracavernous injection of linsidomine in 38 impotent patients. Comparison with prostaglandin E1]. Prog Urol 1998; 8(3):388-91. No placebo
Lenk S, Schonherr G, Korner I. Intracavernous injection therapy in erectile dysfunction. Z-UROL-NEPHROL Zeitschrift-fur-Urologie-und-Nephrologie. 1990; 83(10):539-46. Not an RCT
Lewis RW, Porst H. Transurethral alprostadil with MUSE registered (medicated urethral system for erection) vs intracavernous alprostadil - A comparative study in 103 patients with erectile dysfunction (multiple letters) [1]. INT-J-IMPOTENCE-RES International-Journal-of-Impotence-Research. 1998; 10(1):61-2. Letter
Linet OI, Neff LL. Intracavernous prostaglandin E1 in erectile dysfunction. Clin Investig 1994; 72:139-49. Review
Linet OI, Ogring FG. Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. The New England Journal of Medicine 1996; 334(No. 14):873-7. Not RCT at home
Lipshultz LI. Injection therapy for erectile dysfunction. NEW-ENGL-J-MED New-England-Journal-of-Medicine. 1996; 334(14):913-4. Review
Lui - Int J Impotence Res, 1990 (2/suppl2) 147-50 No placebo
Mahmoud KZ, el Dakhli MR, Fahmi IM, Abdel Aziz AB. Comparative value of prostaglandin E1 and papaverine in treatment of erectile failure: double-blind crossover study among Egyptian patients. J Urol 1992; 147(3):623-6. No placebo group
Martin Du Pan R. Use of intracavernous injections of papaverine and prostaglandin in the study and treatment of erectile impotence. REV-MED-SUISSE-ROMANDE Revue-Medicale-de-la-Suisse-Romande. 1989; 109(4):291-8. Review
Martinez Pineiro L, Cortes R, Cuervo E, Lopez Tello J, Cisneros J, Martinez Pineiro JA. Prospective comparative study with intracavernous sodium nitroprusside and prostaglandin E1 in patients with erectile dysfunction. Eur Urol 1998; 34(4):350-4. No placebo group
Martinez Pineiro L, Lopez Tello J, Alonso Dorrego JM, Cisneros J, Cuervo E, Martinez Pineiro JA. Preliminary results of a comparative study with intracavernous sodium nitroprusside and prostaglandin E1 in patients with erectile dysfunction [see comments]. J Urol 1995; 153(5):1487-90. No placebo group (and may not be double blind)
McMahon CG. An attempt to standardize the pharmacological diagnostic screening of vasculogenic impotence with prostaglandin E1. Int J Impot Res 1995 Jun;7(2):83-90 Updated reference not yet obtained
McVary KT, Polepalle S, Riggi S, Pelham RW. Topical prostaglandin E1 SEPA gel for the treatment of erectile dysfunction [see comments]. J Urol 1999; 162(3 Pt 1):726-30; discussion 730-1. Not an RCT
Milewczyk P, Marcyniak M, Maj K, el Rabti AM. [Use of prostaglandin E1 for treatment of erectile dysfunction]. Ginekol Pol 1998; 69(7):598-602. Polish, no translation
Norwood P C, Kaiser F E, Nolten W E et al. Treatment of chronic erectile dysfunction with transurethral alprostadil in diabetic and nondiabetic men. Diabetologia 1997; 40:A591 DE. Abstract
Pagano F, Calabro A, Ostardo E et al. Prostaglandin E1 in the study of erectile impotence. BASI-RAZION-TER Basi-Razionali-della-Terapia. 1990; 20(5):387-90. Not an RCT
Palmieri A, Imbimbo C, Fabrizio F, Lamberti F, Mirone V, Lotti T. Intracavernous drug therapy: Results with a variety of pharmacological agents. ACTA-UROL-ITAL Acta-Urologica-Italica. 1992; 6(1):49-50. Not an RCT
Peterson CA, Bennett AH, Hellstrom WJ et al. Erectile response to transurethral alprostadil, prazosin and alprostadil-prazosin combinations. J Urol 1998; 159(5):1523-7; discussion 1527-8. Not RCT at home
Plumb JM, Guest JF. Cost-effectiveness of Viridal Duo compared to MUSE and Viagra in the treatment of erectile dysfunction in the UK - A preliminary model. J-MED-ECON Journal-of-Medical-Economics. 1999; 2(65-83):65-83. Review
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Porst H. [Transurethral alprostadil administration with MUSE ("Medicated Urethral System for Erection"). Current overview and personal experiences]. Urologe A 1998; 37(4):410-6. Review and trial with no placebo
Porst H. Transurethral alprostadil with MUSE (medicated urethral system for erection) vs intracavernous alprostadil--a comparative study in 103 patients with erectile dysfunction [see comments]. Int J Impot Res 1997; 9(4):187-92. Not an RCT
Porst H, Buvat J, Meuleman E, Michal V, Wagner G. Intracavernous Alprostadil Alfadex--an effective and well tolerated treatment for erectile dysfunction. Results of a long-term European study. Int J Impot Res 1998; 10(4):225-31. Not an RCT
Porst H, Van Ahlen H, Block Th et al. Intracavernous self-injection of prostaglandin E-1 in the therapy of erectile dysfunction. VASA-J-VASC-DIS Vasa-Journal-of-Vascular-Diseases. 1989; 18(SUPPL. 28):50-6. Not an RCT
Ravnik-Oblak - Int J Impotence Res, 1990 (2) 143-50 Not an RCT
Robinson PK. An observational study of prostaglandin E-1: comparing trial and maintenance dose. Urol Nurs 1994; 14(3):76-8. Not an RCT
Sahu MA, Ayyaz M, Chaudhry Z. Intracavernous injections of papaverine and phentolamine for treatment of impotence. J-COLL-PHYS-SURG-PAK Journal-of-the-College-of-Physicians-and-Surgeons-Pakistan. 1997; 7(3):102-4. Not available in Uk
Sarosdy MF, Hudnall CH, Erickson DR, Hardin TC, Novicki DE. A prospective double-blind trial of intracorporeal papaverine versus prostaglandin E1 in the treatment of impotence. J Urol 1989; 141(3):551-3. No placebo
Schilling H, Kimont H G. Therapy of erectile dysfunction with alprostadil. UROLOGE-AUSG-B Urologe-Ausgabe-B. 1999; 39(5):432-4. Not an RCT
Schramek P, Waldhauser M. Dose-dependent effect and side-effect of prostaglandin E1 in erectile dysfunction. Br J Clin Pharmacol 1989; 28(5):567-71. Not RCT at home
Shokeir AA, Alserafi MA, Mutabagani H. Intracavernosal versus intraurethral alprostadil: a prospective randomized study. BJU Int 1999; 83(7):812-5. No placebo
Soderdahl DW, Thrasher JB, Hansberry KL. Intracavernosal drug-induced erection therapy versus external vacuum devices in the treatment of erectile dysfunction. Br J Urol 1997; 79(6):952-7. No placebo
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Van Deventer CP, Meuleman EJH, Bierkens PB, Sabbe BGC, Smals AGH. Experience with intracavernous autoinjection for treatment of erectile dysfunction. NED-TIJDSCHR-GENEESKD Nederlands-Tijdschrift-voor-Geneeskunde. 1993; 137(8):408-12. Not an RCT
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von Heyden B, Donatucci CF, Marshall GA, Brock GB, Lue TF. A prostaglandin E1 dose-response study in man [see comments]. J Urol 1993; 150(6):1825-8. Single blind
Wetterauer U, Kopperman U, Bischoff Rea. Intraindividual comparison of papaverine-phentolamine combination versus prostaglandin E1 in intracavernous injection therapy for erectile dysfunction. Int. J. Impotence Res. 1990; 2(suppl 2):238-9. No placebo
Williams G, Abbou C C, Amar ET et al. The effect of transurethral alprostadil on the quality of life of men with erectile dysfunction, and their partners. BR-J-UROL British-Journal-of-Urology. 1998; 82(6):847-54. QoL study
Willke RJ, Yen W, Parkerson GR Jr, Linet OI, Erder MH, Glick HA. Quality of life effects of alprostadil therapy for erectile dysfunction: results of a trial in Europe and South Africa. Int J Impot Res 1998; 10(4):239-46. Not an RCT