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Phentolamine for erectile dysfunction

 

Clinical bottom line

There is limited information about the oral or intracavernosal use of phentolamine, alone or in combination with intracavernosal papaverine. Effect seem to be shown, but on such small numbers of patients (137 men) that it would be unwise to extrapolate from these results. For intracavernosal phentolamine plus papaverine the NNT was 2.1 (1.6 to 3.2) in 93 men in trials conducted in the 1980s. There was one case of priapism.


Searching

Searching was done using PubMed, Medline and the Cochrane Library, up to September 2005. Randomised trials in which phentolamine 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

Placebo-controlled trials

Searching unearthed three papers from 1987. One examined oral phentolamine at three doses compared to placebo in 40 men. On these small numbers the only sensible conclusion was that there was an apparent effect (Table 1).

Two studies on intracavernosal phentolamine plus papaverine showed larger effects in somewhat more men. Overall 23/47 men (49%, 95% CI 35-63%) achieved erections adequate for intercourse with the combination. In contrast, 1/47 men (2%, 95% CI 0-6%) achieved the same outcome with saline placebo. These were the same men in crossover trials. The relative benefit was 16 (3.2 to 77) and the NNT was 2.1 (1.6 to 3.2) (Table 1).

Table 1: Randomised trials of oral or intracavernosal phentolamine alone or in combination with papaverine

Study

Design

Quality score

Patients

Treatment

Outcome

Result

Adverse events

Oral phentolamine
Becker et al, 1999 Randomised, double blind study

2

44 men with erectile dysfunction for less than three years. Mean age 50 years 20, 40, 60 mg oral phentolamine or placebo Full erection adequate for intercourse at home 2/10 placebo, 3/10 20 mg. 5/10 40 mg and 4/10 60 mg phentolamine One minor adverse event with 60 mg phentolamine
Intracavernosal phentolamine plus papaverine
Kiely et al, 1987 Randomised, double blind, crossover

2

18 impotent men Intracavernosal 30 mg papaverine plus 1 mg phentolamine, for one injection Penile size and rigidity, plus sexual satisfaction over four weeks 11/18 has spontaneous erections with normal intercourse with combination, 1/18 with placebo No adverse reactions
Gasser et al, 1987 Randomised, double blind, crossover

3

30 men with impotence. Mean age 61 years Intracavernosal 30 mg papaverine plus 0.5 mg phentolamine for six injections Erections suitable for sexual intercourse at home 12/29 with combination, 0/29 with placebo One case of transient priapism (26 hours), and mild reactions at injection site

Active controlled trials

Two randomised active controlled trials were found. One [4] compared intracavernous sodium nitroprusside with papaverine phentolamine in 42 men, and measured penile rength, cuircumference and hardness, and found no majhor differences.

Another randomised open-label study compared 123 men given sildenafil (25-100 mg) with 119 men given oral phentolamine 40 mg, to a maximum of one table daily, for eight weeks. Efficacy was assesed using IIEF questionaire at baseline and end of the study, together with global questions about efficacy.

The results for sildenafil was much better than those for phentolamine in these men, who had an average age of 55 years and average duration of erectile dysfunction of more than three years. The average number of successful attepmpts per week was much higher (3.1) for sildenafil than for phentolamine (1.7), and other outcomes also were much better (Figure 1).

Figure 1: Comparison of oral sildenafil with oral phentolamine

Comment

There really isn't a great weight of evidence here, with 40 men on oral phentolamine and 48 using an intracavernosal combination in placebo-controlled trial. The one active controlled trial comparing oral phentolamine with oral sildenafil was open, but large, and showed phentolamine to be significantly less effective. Phentolamine has also been used with intracavernosal VIP.

References

  1. AJ Becker et al. Oral phentolamine as treatment for erectile dysfunction. Journal of Urology 1998 159: 1214-1216.
  2. TC Gasser et al. Intracavernous self-injection with phentolamine and papaverine for the treatment of impotence. Journal of Urology 1987 137: 678-680.
  3. EA Kiely et al. Penile function following intracavernosal injection of vasoactive agents or saline. British Journal of Urology1987 59: 473-476.
  4. F Ugarte et al. Comparison of the efficacy and safety of sildenafil citrate (Viagra) and oral phentyolamine for the treatment of erectile dysfunction. International Journal of Impotence Research 2002 14 Suppl 2: S48-S53.
  5. Q Fu et al. A clinical comparative study on effects of intracavernous injection of sodium nitroprusside and papaverine/phentolamine in erectile dysfunction patients. Asian Journal of Urology 2000 2: 301-303.

Other references to 2000

Reference

Notes

Becker AJ, Stief CG, Machtens S et al. Oral phentolamine as treatment for erectile dysfunction. J Urol 1998; 159(4):1214-6.
RCT
Gasser TC, Roach RM, Larsen EH, Madsen PO, Bruskewitz RC. Intracavernous self-injection with phentolamine and papaverine for the treatment of impotence. J Urol 1987; 137(4):678-80.
RCT
Kiely EA, Ignotus P, Williams G. Penile function following intracavernosal injection of vasoactive agents or saline. Br J Urol 1987; 59(5):473-6.
RCT
 
Vasoactive intracavernous pharmacotherapy for impotence: Papaverine and phentolamine. J-AM-MED-ASSOC Journal-of-the-American-Medical-Association. 1990; 264(6):752-4.
Review
Allen RP, Engel RM, Smolev JK, Brendler CB. Objective double-blind evaluation of erectile function with intracorporeal papaverine in combination with phentolamine and/or prostaglandin E1. J Urol 1992; 148(4):1181-3.
No Placebo
Blum MD, Bahnson RR, Porter TN, Carter MF. Effect of local alpha-adrenergic blockade on human penile erection. J Urol 1985; 134(3):479-81.
RCT, but 8 patients 2 controls
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
Bodner DR, Lindan R, Leffler E, Kursh ED, Resnick MI. The application of intracavernous injection of vasoactive medications for erection in men with spinal cord injury.: J-Urol. 310-1987;1987.
Not RCT
Dembe K, Jasik M, Piechna K. [Evaluation of clinical usefulness of direct drug injections for increasing local circulation, into cavernous bodies of the penis for treatment of erection impotence in patients with diabetes mellitus]. Pol Tyg Lek 1994; 49(1-3):19-20.
Polish
Notes: Medline Apr'2000 Original Title: Ocena przydatnosci klinicznej wstrzykniec do cial jamistych lekow zwiekszajacych miejscowy przeplyw naczyniowy w leczeniu impotencji erekcyjnej u chorych na cukrzyce.
No Placebo
Dinsmore WW, Alderdice DK. Vasoactive intestinal polypeptide and phentolamine mesylate administered by autoinjector in the treatment of patients with erectile dysfunction resistant to other intracavernosal agents. Br J Urol 1998; 81(3):437-40.
Not RCT
Dinsmore WW, Gingell C, Hackett G et al. Treating men with predominantly nonpsychogenic erectile dysfunction with intracavernosal vasoactive intestinal polypeptide and phentolamine mesylate in a novel auto-injector system: a multicentre double-blind placebo-controlled study. BJU Int 1999; 83(3):274-9.
See VIP
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
Gerstenberg TC, Metz P, Ottesen B, Fahrenkrug J. Intracavernous self-injection with vasoactive intestinal polypeptide and phentolamine in the management of erectile failure. J-UROL Journal-of-Urology. 1992; 147(5):1277-9.
Not RCT
Graul A, Castaner J. Phentolamine Mesilate. Treatment of erectile dysfunction. DRUGS-FUTURE Drugs-of-the-Future. 1998; 23(7):725-8.
Review
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
Keogh EJ, Watters GR, Earle CM et al. Treatment of impotence by intrapenile injections. A comparison of papaverine versus papaverine and phentolamine: a double-blind, crossover trial. J Urol 1989; 142(3):726-8.
No placebo
Lakin MM, Montague DK, VanderBrug Medendorp S, Tesar L, Schover LR. Intracavernous injection therapy: analysis of results and complications. J Urol 1990; 143(6):1138-41.
Not 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 RCT
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 RCT
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
Palmieri A, Imbimbo C, Caggiano S et al. Combinations in intracorporeal pharmacotherapy: Comparison between phentolamine and ketanserin. ACTA-UROL-ITAL Acta-Urologica-Italica. 1992; 6(SUPPL. 4):449-50.
Probably not an RCT - (no placebo)
Pettirossi O, Serenelli G. Intracavernous injection of papaverine phentolamine and phenoxybenzamine. ACTA-UROL-BELG Acta-Urologica-Belgica. 1988; 56(2):211-9.
Not RCT
Porst H. [Prostaglandin E1 in erectile dysfunction]. Urologe A 1989; 28(2):94-8.
Not RCT
Rozsahegyi J, Rusz A. Intracavernous injection pharmacotherapy of erectile dysfunction. LEGE-ARTIS-MED Lege-Artis-Medicine. 1997; 7(3):154-60.
Probably not an RCT - (no placebo)
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 UK
Sandhu D, Curless E, Dean J et al. A double blind, placebo controlled study of intracavernosal vasoactive intestinal polypeptide and phenotolamine mesylate in a novel auto-injector for the treatment of non-psychogenic erectile dysfunction. Int J Impot Res 1999; 11(2):91-7.
See VIP
Segenreich E, Israilov S, Shmueli J, Simon D, Baniel J, Livne P. Combinations of vasoactive agents by penile injection for erectile dysfunction. HAREFUAH Harefuah. 1998 MAY 01; 134(9):692-4+750-751.
Not RCT
Shenfeld O, Hanani J, Shalhav A, Vardi Y, Goldwasser B. Papaverine-phentolamine and prostaglandin E1 versus papaverine-phentolamine alone for intracorporeal injection therapy: a clinical double-blind study. J Urol 1995; 154(3):1017-9.
No placebo
Sidi AA, Cameron JS, Dykstra DD, Reinberg Y, Lange PH. Vasoactive intracavernous pharmacotherapy for the treatment of erectile impotence in men with spinal cord injury. J Urol 1987; 138(3):539-42.
Not RCT
Sogari PR, Teloken C, Souto CA. Atropine role in the pharmacological erection test: study of 228 patients [see comments]. J Urol 1997; 158(5):1760-3.
No placebo
Stief CG, Wetterauer U. Erectile responses to intracavernous papaverine and phentolamine: comparison of single and combined delivery. J Urol 1988; 140(6):1415-6.
Not RCT
Szasz G, Stevenson RW, Lee L, Sanders HD. Induction of penile erection by intracavernosal injection: a double-blind comparison of phenoxybenzamine versus papaverine-phentolamine versus saline. Arch Sex Behav 1987; 16(5):371-8.
Does not say randomised
Thon WF, Hartmann U, Engelmann U et al. Efficacy and safety of intracavernous self-injection with a papaverine/phentolamine mixture. UROLOGE-AUSG-A Urologe-Ausgabe-A. 1993; 32(6):466-9.
Not 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 RCT
Waldhauser M, Schramek P. Efficiency and side effects of prostaglandin E1 in the treatment of erectile dysfunction. J Urol 1988; 140(3):525-7.
No placebo
Wehnert J, Kramer J, Weller J, Leike S. [Intracavernous injection of vasoactive substances in the treatment of erectile dysfunction]. Z Urol Nephrol 1988; 81(2):73-8.
Not RCT
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, Mulcahy MJ, Kiely EA. Impotence: Treatment by autoinjection of vasoactive drugs. BR-MED-J British-Medical-Journal. 1987; 295(6598):595-6.
Not RCT
Zorgniotti AW. Experience with buccal phentolamine mesylate for impotence. Int J Impot Res 1994; 6(1):37-41.
Single blind