18, NUMBER 6
Evaluating erectile dysfunction:
Oral sildenafil versus intracavernosal injection of papaverine
BOBBY VISWAROOP, ANTONISAMY B.,
Background. Intracavernosal injection
of vasoactive drugs is an established method of evaluating erectile dysfunction.
However, it is invasive and may be associated with pain and priapism. We investigated
the use of oral sildenafil as a possible substitute for intracavernosal agents.
Methods. Men with erectile dysfunction were randomized
into two groups of 25 each. One group of 25 men received injection papaverine
initially followed by oral sildenafil, and another 25 received oral sildenafil
followed by injection papa-verine. Genital self-stimulation was used in both
the groups. Penile length and circumference as well as angle of erection, before
and after each medication, were recorded. Two days later, the intervention arms
were crossed over. Subjective responses were obtained. The effect of medication
on each outcome variable was studied by using analysis of variance models in
relation to patient, period and medication.
Results. There was statistically significant improvement
from the baseline value in both the arms, i.e injection papaverine and oral
sildenafil (p<0.001, p<0.001, respectively) for both penile length and
circumference. No significant difference was observed between the two medications
in the outcome measures.
Conclusion. Oral sildenafil was as
effective as injection papaverine in evaluating erectile dysfunction.
Natl Med J India 2005;18:299–301
Erectile dysfunction (ED) is a common clinical
problem affecting men of all ages.1,2 Evaluation
of ED was the terrain of psychotherapists before the 1980s. Since the introduction
of papaverine in 1982 by Virag,3 testing
by intracavernosal injection of pharmacological agents became a well accepted
procedure in the evaluation of ED.4 While age is
a definite risk factor for ED,5 to our surprise, a majority of men attending
our clinic are young and unmarried. We use intracavernosal agents routinely
in these men to demonstrate their erectile
power and, at the same time, to reassure them. However, injections are painful
and associated with fear, anxiety, risk of extravasation and priapism.6 Prostaglandins,
though freely available, are expensive. Oral therapy is preferred to invasive
medical or surgical therapies as demonstrated in studies done before the availability
of oral drugs.7,8 Sildenafil is an established
oral therapy for ED.9 It has also been shown to be useful as a second-line testing
agent along with colour
Doppler ultrasound (CDU).10–12 We aimed to
assess whether oral sildenafil was as useful as injectable papaverine in the
evaluation of men with ED.
Fifty men between 21 and 65 years of age who presented to our outpatient clinic
at the Christian Medical College, Vellore, with a history of ED irrespective
of aetiology, marital status and duration of ED were recruited for the study.
Men in whom the use of either sildenafil or papaverine was contraindicated were
excluded. All patients had at least a one month history of ED. A sexual function
questionnaire was used to record the medical and sexual history. All patients
underwent a detailed physical examination followed by focused vascular and neurological
examinations. Biochemical investigations (lipid profile, serum testosterone,
prolactin, follicle-stimulating hormone and luteinizing hormone) were done when
We used a cross-over study design. The sample size was calculated with 80% power
of detecting a treatment benefit of 0.75 cm in length and the within-subject
variance of the difference in mean length between the two periods of 3.34 cm,
based on the two-sided test, with a significance level of 5% and also with an
assumption of no carry-over effect.
|Table I. Improvement in parameters in each medication arm
as compared to the baseline
||Baseline – papaverine (95% CI)
||Baseline – sildenafil (95% CI)
||–4.27 (–4.79 to –3.75)
||–3.95 (–4.44 to –3.46)
||–2.52 (–2.81 to –2.09)
||–2.17 (–2.39 to –0.81)
|Values in parentheses are SD unless otherwise
stated p value based on paired t test
|Table II. Comparison of outcome between injection papaverine
and oral sildenafil
||Difference (95% CI)
||0.32 (–0.52 to 1.16)
||0.35 (–0.17 to 0.87)
|Angle of erection
||–0.20 (–7.49 to 7.09)
|Values are mean (SD) unless otherwise stated
*adjusted for subject, period and sequence effect using analysis
Twenty-five subjects received injection papaverine initially
followed by oral sildenafil and another 25 received oral
sildenafil followed by injection papaverine,
the order of medication being randomized by a computer programme. The two
arms were separated by a wash-out period of 2 days. Injection
papaverine 30 mg (intracavernosal)
and sildenafil 50 mg (oral) were used in both the groups. All patients performed
genital self-stimulation. Measurements were taken by the same observer 5 minutes
after injec-tion and 30 minutes after oral sildenafil. The dorsal length of
the penis (from the symphysis pubis to the tip of the penis) and circumference
(measured 1 cm proximal to the coronal sulcus) as well as its angle as described
by Wespes et al.,13 before and after each medication,
were measured. Penile rigidity was evaluated by digital examination.
Patients were reviewed two hours after medication for evidence of priapism
or untoward effects. The subjective response to and side-effects of medication
were obtained. Improvement in para-meters from the baseline in each medication
arm was compared using a paired t test. The mean and standard deviation of
parameters between the two medication arms are presented. An analysis of variance
model was also fitted, containing terms for the main effects of medication,
period, carry-over, subject within sequence (order of randomization of medication).14 The
effect of carry-over was removed if it was non-significant at the 10% level;
the main model which was then fitted included terms for subject, period
Of the 50 men, 33 were married (66%), 16 were bachelors (32%) and one was
divorced (2%). The mean (SD) age was 30 (10.2) years. Thirty had psychogenic
and 20 had some contributing medical conditions (6 had diabetes mellitus,
3 had hypertension, 2 abused alcohol, 4 had a depressive illness and were
3 had anxiety neurosis and 1 each had cerebrovascular accident and neuropathy).
The mean (SD) penile length was 7.71 (1.26) cm at baseline, but improved in
the papaverine arm by 4.27 cm (11.98 [2.40] cm) and in the sildenafil arm
by 3.95 cm (11.66 [2.20] cm). The difference in penile length was significant
both the arms (p<0.001, p<0.001 respectively; Table I). The mean penile
circumference was 7.50 (1.07) cm at baseline and improved with papaverine by
2.52 cm (10.02 [1.5] cm) and with sildenafil by
2.17 cm (9.67 [1.39] cm). There was a statistically significant improvement
with both the medications compared with the baseline penile circumference
p<0.001, respectively; Table I).
After adjusting for the subject, period and sequence effects, the outcome
between the two arms was compared (Table II). The improvement in outcome variables,
i.e length, circumference and angle of erection was similar with papaverine
and sildenafil (p values 0.45, 0.19, 0.96, respectively).
Subjective parameters, when analysed, showed that 20 of the 50 men (40%) favoured
the oral drug over injection, compared with 24 men (48%) who favoured the injection.
Three men (6%) scored equally for both the medications and 3 (6%) had no response
to either. Five men had priapism (10%) following injection; of them, 3 required
a corporal wash. Following sildenafil, 2 had headache (4%), 1 had blurring
of vision (2%) and 1 had dyspepsia (2%).
The 1993 National Institutes of Health (NIH) Consensus Panel1 defined ED,
a relatively common problem affecting men of all ages, as ‘the inability to achieve
and/or maintain an erection sufficient for satisfactory sexual activity’.
In the Massachusetts Male Aging Study (MMAS),2 52%
of subjects had some degree of ED and 35% of men aged 40–70 years reported moderate to complete impotence.
ED was found to be an age-dependent disorder with a prevalence ranging from 0.1%
at 20 years of age to 75% at 80 years.15 Invasive
and non-invasive methods have been used to understand the mechanism of erection
and its alteration in illness.
Nocturnal penile tumescence (NPT) was considered the first diagnostic test
in the impotent male and is based on the change in penile diameter during sleep.16
The device to measure this is sophisticated, expensive, requires at least 2
in a sleep laboratory and includes polysomnographic monitoring to rule out
a sleep disorder.17 The NPT methodology has been
criticized because of its failure
to include adequate measurements of both circumference and rigidity.18
Pharmacological testing agents not only indicate the presence or absence of
organic conditions, but are also predictors of the therapeutic response. The
for pharmacological testing should be one that will cause full but not prolonged
erection. Unfortunately, there is no ideal drug available, nor are the criteria
for erectile response defined.19 Papaverine and
prostaglandins have been used extensively, but are associated with side-effects
such as priapism, pain and
ecchymosis. Audiovisual sexual stimulation (AVSS) has been used to distinguish
between organic and psychogenic causes of ED. Slob et al.20 reported
the use of AVSS in conjunction with NPT and an erectiometer, and concluded
may be useful as an initial screening test.
A literature review revealed inconsistent data regarding the erectogenic capacity
of AVSS without pharmacological testing agents. Cahill et al.21 were unable
to obtain any meaningful response in 25 patients and Fouda et al.22 found
response to AVSS alone in 6.6% of their patients. Moreover, AVSS does not usually
result in ejaculation and some patients may have a cultural or moral aversion
Genital stimulation is usually involved in foreplay and is more physiological.23 The
main argument against the use of sildenafil in the experimental setting was
the lack of sexual stimulation. We use tactile stimulation routinely in
along with intra-cavernosal injections. We decided to test this hypothesis
in addition to assessing objectively the role of sildenafil in the evaluation
ED. Rigiscan, rigidometer and snap gauge can be used to evaluate rigidity but
such equipment adds to the cost of evaluation.24
We found that oral sildenafil is as effective as papaverine. The subjective
and objective responses were highly corroborative. Though the onset of erections
was delayed, their duration and quality were comparable. Adverse effects were
seen in only 8% of men; all these effects were mild and none of the men had
The response in men who had had no prior sexual encounter was also favourable.
In summary, oral sildenafil was as effective as injection papa-verine in evaluating
ED. We recommend the use of oral sildenafil with genital self-stimulation as
an office procedure in the evaluation of ED, especially in young men with psychogenic
We thank Mr Samson, male nurse, for his assistance in maintaining the records
and Mr Ramesh, our secretary, for help in preparing this manuscript.
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Christian Medical College, Dr Ida Scudder Road, Vellore
Tamil Nadu, India
Bobby Viswaroop, Ganesh GopalakrIshnan Department of Urology
Antonisamy B. Department of Biostatistics
Correspondence to Ganesh GopalakrIshnan; email@example.com