Alprostadil - intracavernosal

Clinical bottom line

Intraurethral alprostadil works, though there is not a large evidence-base from randomised trials. It is associated with penile pain, and with prolonged erections occasionally. It will not be a first-line treatment choice.

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 article looks at intracavernosal application.

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

Four randomised trials were found, one with a placebo comparison, two comparing intracavernosal with transurethral alprostadil, and one a comparison with sildenafil. The trials were small, and varied in their outcomes, which often included laboratory as well as clinical results.

Table 1: Randomised trials of intracavernosal alprostadil

Study	Design	Quality score	Patients	Treatment	Outcome	Result	Adverse events
Linet et al. NEJM 1996 334: 873-877 USA	Randomised, double-blind single dose study of various doses of alprostadil or placebo	R=1 DB=2 WD=1 Total=4	Men with erectile dysfunction	1 2.5 µg (n=57) 2 5 µg (n=60) 3 10 µg (n=62) 4 20 µg (n=58) 5 placebo (n=59)	Penile rigidity estimated clinically or by plethysmography	Dose response, with 28% of men with full rigidity at top two doses	Five men had prolonged erections, lasting more than four hours in two
Shokeir et al. BJU International 1999 83: 812-815 Saudi Arabia	Randomised comparison of intracavernosal and intraurethral alprostadil, for 3 months at home	R=1 DB=0 WD=1 Total=2	Men with mostly organic erectile dysfunction, mean age 55 years	1 20 µg IC (n=30) 2 500 µg or 1000 µg IU (n=30)	Erectile assessment scale and sexual intercourse at home	At least one intercourse 1 87% 2 53% Percent of use leading to intercourse 1 85% 2 55%	Dropout rate 1 67% 2 17% Urogenital pain 1 47% 2 7%
Shabsigh et al. Urology 2000 55: 109-113 USA	Randomised open label crossover study over six months	R=1 DB=0 WD=1 Total=3	Men with erectile dysfunction for six months, mean age 59 years	1 up to 40 µg IC 2 up to 1000 µg IU 111 initially 95 underwent laboratory tests 68 used treatments at home	Various laboratory and clinical outcomes	Patient preference at home was 1 69% 2 16%	At home use - penile pain 1 34% 2 25% Prolonged erection 1 3% 2 0%
Mancini et al. Int J Impot Res 2004 16: 8-12 USA	Randomised open label crossover study over a month	R=1 DB=0 WD=1 Total=3	Men with vasculogenic or nonvasculogenic erectile dysfunction, treated separately, mean age 55-60 years	Group size of 10-12 men, treated daily with oral sildenafil 25 mg, 1-3 times weekly with 5-20 µg 1-3 times a week, or placebo	IIEF scores	Sildenafil and alprostadil significantly increased IIEF scores (to 21 with sildenafil), with much greater response than placebo	No details

These trials tell us that while intracavernosal alprostadil works, and probably works better than transurethral alprostadil, it is associated with high levels of penile pain, and some prolonged erections.

Comment

Intracavernosal injection of alprostadil will not be the first treatment choice for all men with erectile dysfunction. It will be useful for some men in which other treatments do not work.