Original Article

Vascular and Endovascular Surgery

1-5
Erectile Dysfunction in Peripheral Vascular ª The Author(s) 2020
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Disease: Endovascular Revascularization as DOI: 10.1177/1538574420952923
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a Potential Therapeutic Target

Kapila S. Benaragama, MBBS, MRCS1 ,

Aminder A. Singh, MBBS, MRes, MRCS2 , Tahani Taj, MBBS1,
Julian Hague, FRCR1, Jonathan R. Boyle, MD, FRCS2, and
Toby Richards, MD, FRCS1

Abstract
Introduction: Erectile dysfunction (ED) affects more than 150 million men worldwide, with deleterious effects on quality of life.
ED is known to be associated with ischemic heart disease but the impact of ED in patients with peripheral arterial disease (PAD) is
unknown. We assessed the prevalence and severity of ED in patients with PVD. Methods: Following ethical approval, sequential
male patients diagnosed with PAD over a 1-year period following diagnosis of intermittent claudication. The patient demographics
and comorbidities were recorded, with the International Index of Erectile Function (IIEF-5) questionnaire used to grade severity
of ED. Computed tomographic angiography and severity of stenosis in the proximal vessels and internal pudendal arteries were
correlated using a modified Bollinger Matrix scoring system. Results: 60 patients were recruited, most (77.2%) reported erectile
dysfunction (52.5% severe, 22.5% moderate). Patients with severe ED were more likely to have 2 or more comorbidities (P ¼
.009). 86.7% with severe ED had bilateral internal pudendal artery stenosis with a mean modified Bollinger score of 17.6. 35.5% of
moderate ED patients had bilateral internal pudendal stenosis with a mean Bollinger score of 11.75. There was significant dif-
ference in overall scores between moderate and severe erectile dysfunction (p< 0.05), thus indicating a potential link between ED
severity and extent of vessel stenosis. Conclusion: There is a substantial burden of clinically significant ED among patients with
PAD. This study suggests ED should be discussed with all PAD patients and ED may precede a PAD diagnosis. There is scope for
endovascular revascularization as a treatment option for ED secondary to arterial insufficiency.

Keywords
erectile dysfunction, peripheral arterial disease, endovascular, stenting, angioplasty

Introduction
Erectile dysfunction (ED) is defined as a “persistent inability to
attain and maintain an erection sufficient to permit satisfactory
sexual performance.”1 It is estimated over 152 million men
worldwide have experienced erectile dysfunction, and it is pre-
dicted that this figure will rise to 322 million by 2025.2,3 ED
can significantly impact on all aspects of health-related quality
of life and is not necessarily linked to its impact on sexual
performance.4 The National Institute for Health and Clinical
Excellence (NICE) recommend first line treatment with
phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil,
or vardenafil), regardless of the suspected cause of ED.5 How-
ever, up to 50% of men have an inadequate response to PDE-5
therapy.6
The etiology of ED is multi-factorial and thought to be a
complex interplay of multiple pathophysiological mechanisms
in which atherosclerosis and endovascular dysfunction may
play a key role.7 Symptoms of ED often precede those of
coronary artery disease,8 and treatment for cardiac risk factors
shows a significant improvement in erectile function in clinical
trials.9 Meta-analyses have linked ED to increased risk of cor-
onary artery disease, stroke and all-cause mortality.10,11 The
presence of ED could be an early indicator of atherosclerosis in
different arterial beds and hence it is clinically relevant.12 This
has led to the formation of the artery size hypothesis where it is
postulated that atherosclerosis initially causes symptomatic
occlusion of smaller vessels before larger vessels are
affected.13 This would mean that the same common disease
1
University College London Hospitals NHS Foundation Trust, London, UK
2
Cambridge Vascular Unit, Cambridge University Hospitals NHS Trust,
Cambridge, UK
Corresponding Author:
Kapila S. Benaragama, University College London Hospitals NHS Foundation
Trust, 250 Euston Road, London NW1 2PG, UK.
Email: shanka.benaragama@nhs.net
2 Vascular and Endovascular Surgery XX(X)
process may affect smaller vessels supplying the penis before
larger vessels are affected, leading to symptoms of ED before
those of coronary artery disease (CAD) or peripheral arterial
disease (PAD). Population based studies have suggested ED is
associated with a high atherosclerotic burden arterial beds such
as the carotid arteries but not in lower extremities.14 Current
guidelines recommend screening for all patients presenting
with erectile dysfunction for cardiovascular and PAD,1 how-
ever a reciprocal recommendation for patients presenting with
PAD is not currently present. If the artery size hypothesis holds
true this may mean that those who already have PAD may also
have a high prevalence of ED. Pilot studies have suggested
endovascular intervention could play an important role in ED
management with up to 40% of PAD patients having arterial
lesions amenable to angioplasty with or without stenting.15
Wang et al. demonstrated clinically significant improvement
in erectile function in 60% of their cohort with isolate penile
artery stenosis.16 Hence imaging techniques to accurately diag-
nose ED could aid endovascular treatment strategies.
The primary outcome of this study was to assess the pre-
valence and severity of ED in patients with PAD. Secondary
outcomes included assessing the link between ED and co-
morbidities, as well as elucidating any links between the sever-
ity of ED and the extent of stenosis of relevant arteries.
Methods
Patient Identification
A cross-sectional study was undertaken. 60 male patients with
recently diagnosed PAD were sequentially recruited from vas-
cular outpatient clinic over a 1-year period (a total of 72 were
asked to participate of whom 12 declined). Exclusion criteria
were history of urological or surgical interventions or chemor-
adiotherapy for pelvic or abdominal malignancies.
Initial Questionnaire
Participants completed a 2-part questionnaire. An initial ques-
tionnaire elicited patient demographics, co-morbidities, smok-
ing, awareness of current ED treatment modalities and any
previous treatment use. Co-morbidities assessed included:
hypertension, diabetes mellitus, hypercholesterolemia,
ischemic heart disease, peripheral vascular disease, obesity and
depression. Age, ethnicity, marital status, smoking status and
current sexual activity were also assessed along with treatment
options such as sildenafil, penile injections, vacuum pumps and
prostheses. Patients were also asked if they had previously
discussed ED with a medical professional. The standardized
International Index of Erectile Function (IIEF-5) questionnaire
was used to obtain a cumulative score for severity of ED for
each participant. Total scores range from 1-25, with a lower
score associated with a greater severity of ED. Scores of 1-7
indicated severe ED, 8-15 moderate ED, 15-21 mild ED.
Computed Tomographic Angiography and Vessel
Stenosis Assessment
Patients were scanned during normal working hours so that
glyceryl trinitrate (GTN) could be administered by a radiologist
pre-scan if required. The protocol for scanning was:
1. The abdominal angiography protocol is selected from
the scanner
2. Scan coverage is from bifurcation of aorta to cover the
whole of pelvis (to ensure coverage of prostate)
3. Three phase imaging (pre-contrast, arterial and venous
phases)
4. MRI is simultaneously booked
A detailed analysis of proximal pelvic arteries, primarily the
internal iliac and internal pudendal arteries, was performed by a
single blinded vascular interventional radiologist in order to
identify any potential links between the severity of erectile
dysfunction and vessel stenosis. To grade the extent of vessel
stenosis, a modified Bollinger matrix scoring system was
used.17,18 In this scoring system, vessels were assessed for the
degree of lumen stenosis with percentage stenosis categorized
into 6 levels, ranging from 0-24% through to 100%. A higher
score indicates a more severe lesion and the score only takes
into account the single most severe lesion. The presence of
diffuse stenosis and the use of stenting was assessed, as well
as those with bilateral internal pudendal stenosis, which may
correlate with erectile dysfunction as the internal pudendal
directly supplies the penis.19 These were identified as having
a score of 1 or more in both left and right internal pudendal
vessels, and a combined internal pudendal score was calculated
where bilateral stenosis was present.
Demographic data including those on comorbidities was
accrued using a patient questionnaire and confirmed with elec-
tronic medical records. Overweight was defined as a body mass
index  25. This was analyzed to establish any correlation
between the prevalence of 2 or more comorbidities and the
level of ED severity using a chi-squared test. The data was
assessed to identify any significant differences between all
patients and those with erectile dysfunction using a student
t-test. A p value <0.05 was considered significant. CT angio-
gram data was analyzed using a 2-tailed T-test to identify any
significant difference in stenosis scores between those with
moderate and with severe erectile dysfunction.
Results
Demographic Data and Prevalence of ED
There was no significant difference in mean age between those
who self-reported ED (66 years) and those that did not report
ED (65 years). 45% of all respondents who completed the IIEF-
5 questionnaire reported they were currently sexually active
(Table 1). This was in comparison to 46% of those with self-
reported ED. 77% of all respondents self-reported erectile dys-
function of which 55% were found to have severe ED (Table
Benaragama et al
Table 1. International Index of Erectile Function (IIEF-5) Results.
IIEF-5 results Total n ¼ 60
Sexually active 26 (43%)
Erectile dysfunction 44 (73%)
Considered treatment 28 (47%)
Discussed treatment 15 (25%)
1). Only 37% of respondents had previously discussed ED with
health professionals. 71% had discussed with their GP, 57%
with a hospital doctor and 14% with a nurse. However, 73% of
patients with ED had heard of at least 1 treatment option, 64%
would consider using or more treatment options and 43% had
previously tried at least 1 treatment.
The presence of comorbidities was investigated in all
respondents and in those with established ED (Table 2). The
prevalence of 2 or more comorbidities was significantly higher
in patients with erectile dysfunction (P ¼ .009).
Imaging Analysis
Of those patients with severe ED, 87% also had bilateral inter-
nal pudendal artery stenosis. This is in comparison with those
with moderate ED, of whom 50% were assessed to have bilat-
eral stenosis.
Using the modified Bollinger matrix scoring system, the
average cumulative scores of all vessels were calculated for
patients with either moderate or severe ED. Of a theoretical
maximum score of 30 (indicating severe stenosis in all ana-
lyzed vessels), the average cumulative score for patients with
moderate ED was 11.75, with a mean of 17.6 for patients with
severe disease (Figure 1). This corresponded to a statistically
significant difference (p < .05).
Discussion
This study suggests there is a substantial burden of erectile
dysfunction among patients with PAD. We report a 77% ED
rate which is substantially higher than reported in similar stud-
ies.14,15 Almost half of patients with self-reported ED were
sexually active—a proportion similar to that of all patients.
Furthermore, the majority of this ED is severe, indicating that
this is a clinically significant issue that may have a substantial
impact on patients’ quality of life.4,20 The subject of erectile
dysfunction is under-explored with patients, with only 37%
reporting a previous discussion with a health professional and
the majority of these discussions (71%) being with a general
practitioner. Coupling this with the high prevalence of ED
among patients with PAD, it is clear that opportunities being
missed to discuss this sensitive topic.
The correlation between the severity of ED and the preva-
lence of 2 or more comorbidities supports current theories of a
complex interaction of pathophysiological mechanisms leading
to erectile dysfunction.7 The comorbidities assessed in these
patients—ischemic heart disease, high cholesterol, diabetes
3
Table 2. Patient Characteristics.
Characteristics Total n ¼ 60
Patient characteristics
Age – y 65.7
Comorbidity
Ischemic heart disease 14 (23%)
Dyslipidemia 31 (52%)
Diabetes mellitus 20 (33%)
Overweight 14 (23%)
Smoking
Current 22 (37%)
mellitus, obesity and smoking—are all conditions known to
accelerate atherosclerosis.21,22 The higher incidence of these
conditions in severe ED patients would agree with the theory of
atherosclerosis and vessel stenosis being a leading factor in the
etiology of ED. The link between ED and CAD is well estab-
lished.7 ED manifests earlier in patients with undiagnosed
CAD and suggests the presence of this condition can predict
future CAD diagnosis.23 As CAD and PAD share similar etiol-
ogy, the connection between ED and PAD is now well
accepted.14,15 This study confirms a high prevalence of ED in
PAD patients and suggests that healthcare professionals treat-
ing PAD should consider exploring issues around ED in men.
ED may similarly predict a future PAD diagnosis in patients,
and we should be mindful of this when managing ED patients.
It increases the importance of risk factor identification and
modification in ED patients to aid reduction in incidence of
CAD and PAD and hence all-cause mortality.
Identification of flow limiting lesions relevant to ED and
treatment with endovascular stenting shown to significantly
improve erectile function.16,24,25 A meta-analysis by Doppala-
pudi et al. reported a 63.2% clinical success of angioplasty with
or without stenting for ED.26 The commonest vessel targeted
was the internal pudendal artery (43.7%) but the iliac and
penile arteries were also treated. These promising results sug-
gest further research in this field is warranted to delineate
exactly which patient populations would benefit from endovas-
cular management of ED.
Limitations
Given the relatively small sample size of the study, greater
numbers of participants would help to support to this conclu-
sion. Furthermore, prevalence of comorbidities between all
levels of ED severity—including mild as well as moderate or
severe ED—should be assessed to assess the trend of increasing
prevalence with increasing severity.
ED has several other causes other than vascular dysfunction.
We did not control for these in the present study and other
factors may have influenced results. We did not assess for
venous outflow obstruction within this patient population and
this will be explored in future work.
4 Vascular and Endovascular Surgery XX(X)

Figure 1. a) Average scores for stenosis in analyzed vessels in both moderate and severe ED. Almost all the vessels have a higher score in severe
ED. b) Difference in average combined internal pudendal score for moderate and severe ED (P < .05 2-tailed t-test).

Conclusion
This pilot study suggests a high prevalence of ED in PAD
patients. Based on the results, there is a compelling potential
for a further larger series powered to investigate links between
comorbidities and ED severity. Currently, there is scope for
confirming the efficacy of endovascular treatment for ED to
improve symptomology.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
ORCID iDs
Kapila S. Benaragama https://orcid.org/0000-0002-8131-4153
Aminder A. Singh https://orcid.org/0000-0002-9099-4162
Review Board and Ethical Approval
University College London Hospital NHS Trust. The study is classi-
fied under clinical audit, performance review and service evaluation
sections of the UCL Research and Ethics committee exception criteria
hence no formal ethical committee approval was needed. However,
Internal Review Board (IRB) approval from hospital clinical research,
audit and governance department was obtained for written consent,
data collection, analysis & publication.
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