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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
hypertension, low high-density lipoprotein (HDL)
levels, hypogonadism, smoking (in men with heart
disease or hypertension), high levels of anger and
dominance, and depression.
2
Complete ED was
prevalent in 44% of men with treated heart disease,
25%of menwith treated hypertension, and 17%of men
with treated diabetes. This study suggested that there
was a relationship between hypogonadism and ED,
and it demonstrated common vascular comorbidities
that were prevalent in the men with ED.
Nitric oxide, the main vasodilator produced by the
endothelial cells that line blood vessels is released in
response to pharmacological stimuli such as bradykinin
and acetylcholine or physiological stimuli such as
increased shear stress in blood vessel walls. In healthy
endothelium, low levels of nitric oxide are continuously
released to keep blood vessels dilated. Nitric oxide
has three other effects. It exerts an antithrombotic
effect by inhibiting platelet aggregation. It exerts an
anti-inflammatory effect by preventing the adhesion
of white blood cells (leukocytes) to the endothelium.
Lastly, it exerts an anti-atherosclerotic effect by reducing
the oxidation of low-density lipoprotein (LDL)
cholesterol, the proliferation of smooth muscle cells,
and decreasing the expression of adhesion molecules
that would attract cholesterol.
Endothelial dysfunction, erectile dysfunction
and cardiovascular disease
Endothelial dysfunction, where there is a reduced
dilation response of blood vessels (which can be due
to decreased production of nitric oxide by endothelial
cells), is one of the most common causes of ED. Risk
factors for endothelial dysfunction and ED are similar.
Risk factors associatedwith endothelial dysfunction
include hypercholesterolemia, hypertension, increasing
age, male gender, diabetes mellitus, tobacco use,
hereditary predisposition, and hyperhomocysteinemia.
Risk factors associated with ED include diabetes
mellitus (3.72-fold increased risk), drug intake (3.71),
peripheral vascular disease (2.44), tobacco use (2.41),
hypercholesterolemia (1.71), hypertension (1.69), and
coronary artery disease (CAD, 1.61), while the risk
from increasing age and hereditary predisposition
are unknown.
4
Since there is such a large overlap of the risk factors
associated with endothelial dysfunction and ED, it is
important for physicians to ask questions concerning
the symptoms and signs of endothelial dysfunction
when men present with ED, and vice versa.
A recent study of 133 men with type 2 diabetes
suggests that ED may be a marker for vascular
disease.
5
The study found a strong, independent
association between ED and silent CAD. One-third
of patients with silent CAD had ED, whereas only 5%
of patients without silent CAD had ED. The study
concluded that ED could be a potential predictor of
silent CAD.
Another study compared 30 men with a mean
age of 46 years who had Doppler-proven ED and no
clinical evidence of cardiovascular disease versus
27 age-matched healthy men (controls).
6
There was
a significantly increased risk of vascular disease in
the men with ED, again suggesting that ED can be
a signal of vascular disease. Compared with the
healthy controls, men with ED exhibited significantly
lower brachial artery flow-mediated, endothelium
dependent and independent vasodilatation, suggesting
the presence of a peripheral vascular abnormality in
the nitric oxide pathway.
Another study concluded that ED may be an early
marker for cardiovascular disease, surfacing long
before the discovery of CAD.
7
In this study of 300 men
with angiographically-documented CAD, 147 men
(49%) had ED. Among the 147 men with coexisting ED
and CAD, the onset of ED preceded CAD symptoms
in 97 patients (66%).
Diagnosingandmanagingerectiledysfunction
The first step in diagnosing ED is to obtain a complete
patient history and perform a physical examination.
Information from the patient history should identify
the time of onset of ED as well as any precipitating
factors such as illness, accident, surgery, or trauma. The
physician also needs to obtain answers to the following
questions. Was the onset of ED gradual or fairly
abrupt? Does the patient have any associated diabetic,
neurologic, or other medical conditions that would
predispose him to having ED? Is the ED situational
or global? Is the ED associated with premature
ejaculation or is premature ejaculation the primary
patient symptom? (Some patients do not realize the
difference between the two conditions). Does the
patient have difficulty obtaining or maintaining an
erection? Does the patient smoke or drink alcohol?
Does the patient take recreational or medical drugs?
What are his dietary habits? Does he exercise? The
physical examination should confirm that the patient
has normal secondary sex characteristics with a normal
penis and testicles.
Management of ED should be initiated by the
primary care physician (PCP). After diagnosing ED,
the first management step is to counsel the patient
about modifying reversible causes such as smoking,
3
Erectile dysfunction and hypogonadism (low testosterone)