© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
19
Erectile dysfunction and testosterone deficiency syndrome: the “portal to men’s health”
within 10 years. Men aged 50 to 60 at baseline had a
5.4-
fold increased risk, men aged 60 to 69 had a 2-fold
increased risk, and men over age 70 had a 1.3-fold
increased risk of this outcome. A 2003 study showed
that 67% of men with angiographically proven CAD
had experienced ED an average of 39 months prior
to being diagnosed with CAD.
6
ED may accompany
other undiagnosed diseases. In a United Kingdom
study, among 178 men evaluated at an ED clinic, 65
men (37%) had hyperlipidemia, which was previously
undiagnosed in 46 of the men (71%); 42 men (24%) had
diabetes, which was previously undiagnosed in 6 of
the men (14%); and 35 men (17%) had hypertension,
which was previously undiagnosed in 11 of the men
(31%).
7
Therefore, all physicians, especially primary
care physicians who may have the initial contact with
men with ED need to ask their male patients about
sexual function as part of every routine, yearly physical
check up. The take-home message is that “a man with
ED and no cardiac symptoms is a cardiac (or vascular)
patient until proven otherwise.”
8
Treatments for ED
Treatments for ED have evolved. Fifty years ago
men were desperate for any improvement in sexual
function, whereas now they can expect to have a
return to a normal sex life. Left untreated, ED can
cause emotional distress for the patient and his
partner. Feelings that may result from undiagnosed
or untreated ED include emasculation, depression, low
self-confidence, embarrassment, and guilt or anxiety.
9
ED is one of the most bothersome sexual symptoms.
The Danish Prostate Symptom Score (DAN-PSS) sex
questionnaire
10
examined the “bothersomeness” of
sexual symptoms in men and reported that the most
bothersome sexual symptoms were pain or discomfort
on ejaculation (89%), reduced or absent erections (78%),
and reduced or absent ejaculation (59%).
Pharmaceutical therapies for ED, such as oral
phosphodiesterase-type 5 (PDE-5) inhibitors aim
to increase the production of two key biochemical
mediators involved in achieving an erection: nitric
oxide and cyclic GMP. PDE-5 inhibitors prevent the
breakdownof cGMPand increase nitric oxide and cGMP
levels. Arelativelynormal testosterone level is necessary
as anupstreambiochemical precursor for the production
of nitric oxide. Testosterone replacement therapy, for
the hypogonadal man who is not responding to PDE-5
inhibitors, has been shown to salvage a response in a
significant number of men.
11
By increasing nitric oxide
levels, PDE-5 inhibitors may serve as “endothelial
protectors” or endothelial stimulators.
To determine the best treatment option for a patient
with ED, it is important for the physician to take an
adequate patient history and to identify the onset
time and duration of ED. The physician also needs to
obtain answers to the following questions. Was the
onset of ED gradual or abrupt? Is the ED global or
situational? Did the patient have illness, surgery, or
trauma that may have precipitated the ED? What is
the role and attitude of the patient’s partner(s)? Does
the patient have any associated risk factors for ED such
as diabetes, hypertension, or cardiovascular disease?
Patients and physicians may not distinguish ED
associated with premature ejaculation (PME) versus
PME as a separate entity.
PDE-5 inhibitors
Since the PDE-5 inhibitor sildenafil (Viagra) became
available in 1998, these oral agents have become the
first-line, most common treatments for ED, Table 1.
The three original available agents—sildenafil (Viagra),
vardenafil (Levitra), and tadalafil (Cialis)—are all
well established now. An oral, dissolvable form of
vardenafil, Staxyn, has been recently released. Avanafil
(
Stendra), another oral PDE-5 inhibitor, has been
approved by the FDA. Its “claim to fame” appears to
be rapid onset of action.
On-demand therapy—that is, a PDE-5 inhibitor
taken 30 to 60 minutes before sex—continues to be
the most popular ED treatment method chosen by
patients. Tadalafil has achieved notoriety because
if it is effective for a patient, the average window of
opportunity for sex or repeat sex is up to 36 hours.
This is because tadalafil has a long half-life. Tadalafil
is currently available in a daily, low-dose form (2.5 mg-
5
mg). Once-daily administrationmay benefit patients
who did not respond to or had unwanted side effects
from on-demand tadalafil, or desire more spontaneity,
or have performance anxiety, or were using an on-
demand PDE-5 inhibitor more than twice a week
(
which is more costly).
Daily Cialis has been recently approved for
treatment of ED and the signs and symptoms of
benign prostatic hyperplasia (ED/BPH/LUTS) which
are common and seen frequently as co-problems
in a significant number of middle-aged men—see
“
Emerging Therapies” article by Barkin in this
supplement.
12
Among men with “classical” ED, 30% to 50% of
those who do not initially respond to PDE-5 inhibitors
may respond after they and their partners receive
behavioral counselingabout potential reasons for lack
of a response.
13
Potential reasons for a lack of response
to ED therapy include:
