Oral therapy, because it can be used ‘on
demand’ and without being noticed by the partner, is an ideal form of treatment for
ED, and has now become the firstline therapy.
The available oral agents include yohimbine,
trazodone, phentolamine, apomorphine and more recently, sildenafil, an inhibitor of
cGMP-specific phosphodiesterase type 5. Among these drugs, the best established in terms
of its efficacy and safety is sildenafil, which is currently considered firstline therapy
for patients with ED of all etiologies, except those receiving nitrate drugs (in whom
concomitant administration of sildenafil is contraindicated).
The principal adverse effects of sildenafil are
headache, flushing, dyspepsia, nasal congestion and occasional visual disturbances.
Mostly, these adverse effects are mild and reversible. Caution is necessary in patients
with ischemic heart disease not taking nitrates (which should be considered a relative
contraindication for sildenafil treatment).
The best alternatives to sildenafil would appear to be
apomorphine and phentolamine, and the combination of these drugs with sildenafil may be
promising in resistant cases.
Intracavernosal injection therapy is still a safe and
effective alternative for the treatment of ED, particularly for patients who fail to
respond adequately to oral medication or to MUSE (see below).
Currently, the drug of choice for intracavernosal
injection therapy is alprostadil (prostaglandin E1; PGE1) which acts primarily by
catalyzing the formation of cyclic adenosine monophosphate (cAMP) and causing relaxation
of corporal smooth muscle.
In clinical trials in ED, patient and partner satisfaction rates of
70% or higher have been achieved with alprostadil self-injection therapy. Penile pain is
the most common adverse effect and occurs in about 15 to 23% of patients; prolonged
erections are uncommon (0 to 2% of patients).
Other drugs that have been given via intracavernosal injection
include papaverine and phentolamine, though they are less satisfactory than alprostadil
and are most commonly used in combination with each other, or with alprostadil when mono-
therapy with the latter is not effective or is associated with pain. The addition of
phentolamine to alprostadil speeds the onset of tumescence and permits lower doses of
alprostadil to be used.
Transurethral administration of alprostadil via the MUSEÔ system
(Medicated Urethral System for Erection) has proved a well tolerated treatment for ED, and
is effective in helping patients achieve successful intercourse regardless of age,
underlying etiology, duration of ED, and prior treatment.
The MUSE system administers a medicated pellet containing alprostadil
directly to the urethral mucosa. It may be considered a first-line treatment option in men
with ED who are not willing to use intracavernosal injections or who have failed on oral
medication.
Its most common adverse effect is urethral pain/burning, which is
generally mild or moderate in severity and transient. However, the long-term safety of
MUSEÔ, in particular the risk of penile fibrosis and urethral stricture, need to be more
thoroughly evaluated.
Vacuum constriction devices (VCDs) are a non-invasive method of
treating ED. The vacuum created in the cylinder of a VCD allows blood to flow into the
corpora cavernosa of the penis, leading to tumescence and an erection-like state.
Tumescence is maintained by a constriction ring placed around the base of the penis which
prevents blood from flowing out of the corpora cavernosa. This can be maintained for up to
30 minutes.
Although VCDs have proved effective in providing penile rigidity
sufficient for penetration in about 85% of ED patients (range 66 to 100%), and about 70%
continue to use them long-term, their role in modern day management of ED is that of a
secondary treatment for those who fail to respond to oral or injection therapies or have a
failed prosthesis.
Androgen replacement therapy has only a minor role in ED and is
indicated when sexual dysfunction is accompanied by hypogonadism. However, it should not
be given in the presence of advanced prostatic cancer, breast cancer, polycythemia and
severe cardiac insufficiency.
Where indicated, the three main types of androgens that may be
administered are: (1) orally active agents such as testosterone undecanoate; (2)
injectable preparations such as testosterone enanthate or cypionate or mixed testosterone
esters; and (c) transdermal testosterone delivery systems (scrotal and nonscrotal
patches).
Although preliminary studies defining the risk/benefit ratio of
androgen supple- mentation in healthy older men with low plasma testosterone levels have
been encouraging, long-term studies have yet to confirm this. Major concerns in older men
are the risks of exacerbating cardiovascular disease, predisposing to or accelerating
malignant prostatic disease or benign prostatic hyperplasia (BPH), fluid retention,
increased blood volume, exacerbation of sleep apnea, and possibly gynecomastia.
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