PATHOPHYSIOLOGY OF ERECTILE DYSFUNCTION Neurological diseases

10 PATHOPHYSIOLOGY OF ERECTILE DYSFUNCTION

Age

hyperprolactinemiaNeurological diseases

multiple sclerosis

multiple system atrophy

Parkinson's disease

spinal cord injuryOther

acquired immunodeficiency syndrome (AIDS)

Table 2 Vascular pathophysiology of organic erectile dysfunction

Vascular etiology of erectile dysfunction present in 60% of patients. Small
vessel vascular disease (e.g. diabetes) and large vesselarteriosclerosis
(e.g. hypertension) cause arterial insufficiency/erectile dysfunction; erectile
dysfunction occurs in 25% of men treated forhypertension and 60% of
diabetics

Tobacco alters penile arterial hemodynamics, causing erectile dysfunction in
a high proportion of elderly smokers; pelvic radiation leadsto
fibrosis/stenosis of pelvic arteries and accelerates existing arteriosclerosis;
venous occlusive dysfunction may be due to decreaseddistensibility of
corpora cavernosa or inherent abnormalities in tunica albuginea

Vascular endothelial growth factor may play a role in modulation of normal
vascularity of penile architecture_

or the cavernosal venous system (Figure 29). The etiology of this is obscure,
but is more likely to be a primary disorder ofintracavernosal smooth muscle
than a problem primarily related to the penile veins themselves.

Intracavernosal smooth muscle fibrosis

Full erection depends on achieving complete intracorporeal vasodilatation.
This, in turn, depends on normally functioningcorporeal smooth muscle. Aging
and/or ischemia may result in degeneration of smooth muscle cells, thereby
impairing theability to respond to vasodilator signals. During flaccidity,
the oxygen saturation of the blood within the lacunar spaces is low(40
mmHg). During erection, however, the inflow of arterial blood raises the oxygen
saturation of lacunar blood to >90

mmHg.

The current evidence suggests that the development of intermittent erections
may be an important mechanism formaintaining full oxygenation and, thus,
function of cavernosal smooth muscle. Conditions of low oxygenation promote
theproduction and release of transforming growth factor^. This molecule, in
turn, results in the formation of collagen, with theresultant development of
intracorporeal fibrosis (Figure 30). This may help to explain the physiological
importance of thephenomenon of intermittent nocturnal penile tumescence.
This is an important concept because it suggests that loss oferection due to
any cause may be compounded by loss of cavernosal smooth muscle function and
fibrosis. Clearly, suchconsiderations may have an impact on the timing of
treatment decisions in circumstances such as erectile dysfunctionfollowing
radical prostatectomy.

Failure of intracavernosal neurotransmission

The molecular mechanisms of vasodilatation and vasoconstriction that underlie
erection and detumescence have only recentlybeen elucidated. Bearing in mind
their complexity, it would be surprising if specific abnormalities of
neurotransmission didnot translate into clinical erectile dysfunction. As
yet, however, none have been specifically described, but failure of
NOproduction due to lack of NO synthase or abnormalities of receptor or
second-messenger function may well underlie somecases. More research is
needed in this rapidly evolving area.