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.
Background
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
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.
Results
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
|
Study |
Design |
Quality score |
Patients |
Treatment |
Outcome |
Result |
Adverse events |
| Hellstrom et al, 1996 | Randomised, double blind, crossover, enriched enrollment |
2 |
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 |
3 |
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 |
3 |
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 |
NNT |
|||
| Condition |
Number/Total |
Percent |
Number/Total |
Percent |
(95% CI) |
(95% CI) |
| Per protocol |
345/553 |
62 |
101/584 |
17 |
3.6 (3.0 to 4.4) |
2.2 (2.0 to 2.5) |
| Intention to treat |
345/856 |
40 |
101/885 |
10 |
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.
Comment
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.
References
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].
- R Urciuoli et al. Prostaglandin E1 for treatment of erectile dysfunction. Cochrane Database of Systematic Reviews 2004 issue 2.
|
Reference |
Notes |
| 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 |
| Amar E, Kobelinsky M, Khoury R et al. [Treatment of sexual impotency by intra-cavernous injections of prostaglandin E1. Report of 180 patients]. Prog Urol 1993; 3(6):971-8. | Not an RCT |
| 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 |
| Ponchietti R, Raugei A, Benaim G, Vici I. Prosthesis or intracavernous pharmacotherapy for the restoration of erectile function in patients with spinal cord injury. ACTA-UROL-ITAL Acta-Urologica-Italica. 1990; 4(6 SUPPL. 1):277-9. | No placebo |
| Porst H. The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience. J Urol 1996; 155(3):802-15. | Review |
| 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 |
| Soli M, Brunocilla E, D'Amato G et al. Intracavernous prostaglandin E-1 in the diagnosis and therapy of impotence. ACTA-UROL-ITAL Acta-Urologica-Italica. 1991; 5(3):227-9. | Not an RCT |
| Valdevenito R, Melman A. Intracavernous self-injection pharmacotherapy program: analysis of results and complications. Int J Impot Res 1994; 6(2):81-91. | Not an RCT |
| 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 |
| Vanderschueren D, Heyrman RM, Keogh EJ et al . A study in patients with erectile dysfunction comparing different formulations of prostaglandin E1. Alprostadil Study Group. J Urol 1995; 154(5):1744-7. | Formulation study |
| Vardi Y, Lidgi S, Moskovitz B, Levin RD. Intracavernous pharmacotherapy for treatment and evaluation of impotence. HAREFUAH Harefuah. 1991; 121(7-8):223-5+280. | Hebrew, no translation |
| 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 |