NEUROGENIC CAUSES

AN ATLAS OF ERECTILE DYSFUNCTION 11

NEUROGENIC CAUSES

The dependence of normal erectile and ejaculatory function on intact neural
pathways to and from the brain has already beenmentioned. Not surprisingly a
considerable number of neurological disorders may result in erectile dysfunction
(Table 3).Those involving the central nervous system include cerebrovascular
accidents, Parkinson's disease and multiple sclerosis.Damage or degeneration
of peripheral nerves supplying the corpora also results in erectile dysfunction.
Examples includediabetic neuropathy, cauda equina lesions due to a prolapsed
intervertebral disk, and iatrogenic neural injury during
abdominoperineal resection of the rectum. The unusual, but interesting,
disorder known as multiple system atrophy ischaracterized by degeneration of
both the sympathetic and parasympathetic central and peripheral autonomic
neurons, as wellas of Onuf's nucleus in the sacral spinal cord (Figure 31).
The result is progressive and disabling ortho static hypotension,urinary
incontinence and erectile dysfunction, together with ejaculatory failure.

ENDOCRINOLOGICAL CAUSES

Testosterone secreted from the Leydig cells of the testes under the influence
of luteinizing hormone (LH) is necessary fornormal male sexuality and sexual
function (Table 4). Medications such as luteinizing hormone-releasing hormone
(LHRH)agonists or stilbestrol, which lower circulating testosterone, result
in loss of libido and in erectile dysfunction. Patients whoare hypogonadal
as a result of pituitary or testicular dysfunction frequently suffer from
erectile dysfunction, which respondsto treatment with exogenous androgens.
More contentious is the suggestion that waning testosterone levels in men of
middleage and beyond (Figure 32), the socalled 'male menopause', are a
frequent cause of erectile dysfunction and, therefore,boosting serum
testosterone levels has therapeutic benefits (Table 5). However, there is some
evidence from experimentalanimal models that androgens are necessary for the
support of intracavernosal smooth muscle function and maintenance ofNO
synthase levels. Exogenous androgens are certainly capable of enhancing the
libido, which is an important component ofsexuality.

Dihydrotestosterone (DHT), the potent androgenic metabolite of testosterone
produced by the enzyme 5a-reductase, iscrucial for the normal development of
the male external genitalia, seminal vesicles and prostate, but is not essential
for eitherthe libido or erectile function. Compounds such as finasteride,
which inhibit the activity of 5a-reductase type II, result inshrinkage of
the prostate by 20-30%, but have been reported to cause erectile dysfunction in
only around 3-5% of patients.However, in the 4-year placebo-controlled study
of finasteride recently reported by McConnell and colleagues, nearly 14%
ofpatients taking the active drug experienced some form of sexual
dysfunction.

Prolactin, which is released from the pituitary gland, acts as an inhibitory
factor in male sexual function.Hyperprolactinemia, either idiopathic or,
less commonly, the result of a tumor such as a pituitary prolactinoma (Figure
33), isassociated with erectile dysfunction, as is the more common entity of
idiopathic hyperprolactinemia. Correction of the raisedprolactin levels
using bromocriptine may sometimes restore potency in such patients.

Table 3 Neurogenic pathophysiology of organic erectile dysfunction

Diabetes, alcoholism/vitamin deficiencies contribute to somatic/autonomic
neuropathyDemyelinating diseases (e.g. multiple sclerosis) decrease penile
sensation

Aging elevates sensory thresholds to vibratory/electrical stimulation

Pelvic/retroperitoneal surgery (e.g. radical prostatectomy) may damage the
autonomic nervous system controlling the physiology ofpenile
erection/ejaculation_

Table 4 Endocrinological pathophysiology of organic erectile
dysfunctionLow testosterone levels associated with decreased libido

Decline in nitric oxide synthase activity in castrated animals reversed by
androgen supplementationNitric oxide synthase mRNA increases with androgen
supplementation

Hypogonadism may be due to primary testicular failure, decreased secretion of
gonadotropin releasing hormone (e.g.

hyperprolactinemia), or alterations in steroid hormone protein binding (e.g.
alcoholism, liver failure)_

Table 5 Age-related pathophysiology of organic erectile dysfunction

Cellular senescence alters collagen content in corpora cavernosa/tunica
albuginea, leading to venous occlusive dysfunction/decreasedneuronal
transmission to cavernosal smooth muscle

Aging alters endothelial function, leading to decreased basal nitric oxide
release and up-regulation of basal endothelin-1

Reproductive aging in animals impairs neurogenic erectile response: increase
in latency period to attain an erection/decrease in maximalintracavernosal
pressure; loss of function integrity of endoluminal structures; imbalance in
expression of vasoconstricting/vasorelaxingmodulators of penile
erection/decrease in nitric oxide synthase/increase in endothelin-1 levels_