madman
Super Moderator
Sexual dysfunction is a common, almost expected, consequence of autonomic dysfunction. Neurogenic sexual dysfunction may present with decreased erectile rigidity in the male, decreased clitoral and vaginal blood flow/lubrication in the female, or absent or delayed orgasm in either sex. Secondary rapid ejaculation may occur because of decreased erectile rigidity. This focuses on decreased erectile rigidity.
Decreased erectile rigidity, often termed impotence in the past, is defined by an inability to attain sufficient penile hardness for penetrative sex or an inability to maintain erectile rigidity until ejaculation. Loss of erection after ejaculation is normal due to the burst of sympathetic stimulation during ejaculation causing markedly decreased penile corporal artery blood flow. Loss of erectile rigidity before ejaculation, however, often implies neurologic or endovascular dysfunction. Individuals with some types of autonomic dysfunction are markedly more prone to develop decreased erectile rigidity than those without autonomic dysfunction. Of men in the population at large, at age 40, approximately 5% never have penile rigidity sufficient for penetration. By age 70, at least 15% of men experience complete erectile dysfunction while approximately 50% have varying degrees of decreased erectile rigidity. Age and physical health are the most important predictors of the onset of erectile dysfunction. Smoking was the most important lifestyle variable. Erectile dysfunction does not correlate well with male hormone levels.
These figures contrast sharply with the prevalence of decreased erectile rigidity in the autonomic dysfunction population. Patients with Parkinson’s disease and MSA (multiple system atrophy) both have a high rate of decreased erectile rigidity. Decreased rigidity is a common early finding in MSA, while Parkinson's patients usually develop decreased rigidity and other urologic problems such as bladder overactivity later in their disease. Singer et al., in a population of older Parkinson patients, demonstrated that 60% of men were affected compared to 37.5% of age-matched controls. Beck et al.evaluated 62 patients with MSA for impotence. Their data indicate that 96% of the men were impotent and that 37% appeared to have decreased rigidity as the initial symptom of autonomic dysfunction. Other studies have demonstrated similar results.
Mechanism of erection
*Nerves course immediately below the aortic bifurcation into the pelvic plexus. Parasympathetic fibers originate in sacral spinal cord segments 2-4 and join the pelvic plexus. Discrete nerves carrying both sympathetic and parasympathetic fibers innervate the organ of the pelvis. Nonadrenergic noncholinergic (NANC) nerves also follow the pelvic plexus to join the cavernous smooth muscle and secrete nitric oxide(NO) into the corporal artery neuromuscular junction. In 1982 Walsh and Donker demonstrated that nerves coursing posterolateral to the seminal vesicles and prostate and immediately lateral to the membranous urethra continue on to innervate the corpora cavernosa. It is now known that branches of these NANC nerves are the principal innervation of the neuromuscular junction where corporal arterial smooth muscle controls penile blood flow.
Etiology of erectile dysfunction
*The anatomic sites now felt to be the most common cause of decreased erectile rigidity in the general population are the neuromuscular junction where the NANC nerves meet the smooth muscle and the vascular endothelium of the corporal bodies. This is where nitric oxide and cGMP play a critical role in regulating penile blood flow. The typical erectile dysfunction (ED) patient releases less than the normal amount of NO into the neuromuscular junction.
Neuromuscular junction disorders
*Nitric oxide is released from cavernosal nerves causing activation of guanylyl cyclase within the corpus cavernosum. Fig. 119.1 illustrates several steps that, if not functioning properly, could impede erectile function. The generation of nitric oxide by the cavernous nerves and the vascular endothelium appears to be a critical trigger for the erectile mechanism. In particular, NANC nerves innervating cavernosal artery neuromuscular junctions appear to trigger penile engorgement and rigidity. Loss of NANC nerve function can markedly impact the patient’s ability to achieve an erection. NO production by corpora cavernosa endothelium appears to play a critical role in the maintenance of erection.
Neurogenic erectile dysfunction
*Pure neurogenic erectile dysfunction is a frequent cause of erectile failure. Interruption of either somatic or autonomic nerves or their end units may cause erectile dysfunction. These nerves control the flow of blood into and likely out of the corpora cavernosa.
Endocrine disorders
*Testosterone plays a permissive role in erectile function. However, the amount of androgen necessary for normal erectile function is relatively low. Androgen replacement (testosterone cypionate 200 mg q 2-3 weeks or daily topical testosterone preparations) is expected to induce the return of erectile function in patients with very low (<200 ng/mL) or undetectable serum total testosterone concentration due to true primary or secondary hypogonadism. These patients are relatively uncommon, however. More commonly, the patient with decreased erectile rigidity will have normal or decreased free or total testosterone levels often diagnosed as adult-onset hypogonadism. Testosterone replacement rarely restores erectile function in those with mildly decreased serum testosterone levels (225-300 ng/mL) and should not be routinely given for that indication. Testosterone supplementation is never indicated for patients with normal circulating androgen levels.
The most common endocrine disorder affecting erectile ability is diabetes mellitus. The most important effect diabetes has on erectile ability appears to relate to the loss of function of long autonomic nerves. Erection is partially mediated by efferent parasympathetic cholinergic neural stimuli. Loss of long cholinergic neurons results in interruption of the efferent side of the erectile reflex arc. Diabetes also appears to produce dysfunction of the neuromuscular junction at the level of arterial smooth muscle in the penile corpora cavernosa. Studies have indicated markedly decreased acetylcholine and nitric oxide concentrations in the trabeculae of the corpora cavernosa in diabetics. These
findings probably represent a combination of neural loss and neuromuscular junction dysfunction.
Medical and surgical treatment
*Current medical therapy is based on the inhibition of phosphodiesterase type-5 (PDE-5). Fig. 119.1 illustrates that cGMP is broken down to inactive 50-GMP by PDE5. Sildenafil, vardenafil, avanafil, and tadalafil competitively inhibit PDE-5 breakdown of cGMP by binding to the catalytic domain of PDE-5 and thereby increasing cGMP concentration. The use of a PDE-5 inhibitor results in improved erectile rigidity even in patients with decreased nitric oxide production or cGMP synthesis. Generally, 60% of patients overall and 80% with ED due to spinal cord injury respond to PDE-5 inhibition.
*Autonomic dysfunction may progress to a point where NANC nerves produce little or no NO. At that point, PDE-5 inhibitors are no longer effective. Other therapeutic interventions may be used including pharmacologic injection of prostaglandin E-1 or other agents intothe penile corporal body, intraurethral delivery of prostaglandin E-1, vacuum erection devices, and inflatable penile implants. Patients who have good performance status should be offered urologic referral if initial medical therapy fails to achieve adequate penile rigidity.
Decreased erectile rigidity, often termed impotence in the past, is defined by an inability to attain sufficient penile hardness for penetrative sex or an inability to maintain erectile rigidity until ejaculation. Loss of erection after ejaculation is normal due to the burst of sympathetic stimulation during ejaculation causing markedly decreased penile corporal artery blood flow. Loss of erectile rigidity before ejaculation, however, often implies neurologic or endovascular dysfunction. Individuals with some types of autonomic dysfunction are markedly more prone to develop decreased erectile rigidity than those without autonomic dysfunction. Of men in the population at large, at age 40, approximately 5% never have penile rigidity sufficient for penetration. By age 70, at least 15% of men experience complete erectile dysfunction while approximately 50% have varying degrees of decreased erectile rigidity. Age and physical health are the most important predictors of the onset of erectile dysfunction. Smoking was the most important lifestyle variable. Erectile dysfunction does not correlate well with male hormone levels.
These figures contrast sharply with the prevalence of decreased erectile rigidity in the autonomic dysfunction population. Patients with Parkinson’s disease and MSA (multiple system atrophy) both have a high rate of decreased erectile rigidity. Decreased rigidity is a common early finding in MSA, while Parkinson's patients usually develop decreased rigidity and other urologic problems such as bladder overactivity later in their disease. Singer et al., in a population of older Parkinson patients, demonstrated that 60% of men were affected compared to 37.5% of age-matched controls. Beck et al.evaluated 62 patients with MSA for impotence. Their data indicate that 96% of the men were impotent and that 37% appeared to have decreased rigidity as the initial symptom of autonomic dysfunction. Other studies have demonstrated similar results.
Mechanism of erection
*Nerves course immediately below the aortic bifurcation into the pelvic plexus. Parasympathetic fibers originate in sacral spinal cord segments 2-4 and join the pelvic plexus. Discrete nerves carrying both sympathetic and parasympathetic fibers innervate the organ of the pelvis. Nonadrenergic noncholinergic (NANC) nerves also follow the pelvic plexus to join the cavernous smooth muscle and secrete nitric oxide(NO) into the corporal artery neuromuscular junction. In 1982 Walsh and Donker demonstrated that nerves coursing posterolateral to the seminal vesicles and prostate and immediately lateral to the membranous urethra continue on to innervate the corpora cavernosa. It is now known that branches of these NANC nerves are the principal innervation of the neuromuscular junction where corporal arterial smooth muscle controls penile blood flow.
Etiology of erectile dysfunction
*The anatomic sites now felt to be the most common cause of decreased erectile rigidity in the general population are the neuromuscular junction where the NANC nerves meet the smooth muscle and the vascular endothelium of the corporal bodies. This is where nitric oxide and cGMP play a critical role in regulating penile blood flow. The typical erectile dysfunction (ED) patient releases less than the normal amount of NO into the neuromuscular junction.
Neuromuscular junction disorders
*Nitric oxide is released from cavernosal nerves causing activation of guanylyl cyclase within the corpus cavernosum. Fig. 119.1 illustrates several steps that, if not functioning properly, could impede erectile function. The generation of nitric oxide by the cavernous nerves and the vascular endothelium appears to be a critical trigger for the erectile mechanism. In particular, NANC nerves innervating cavernosal artery neuromuscular junctions appear to trigger penile engorgement and rigidity. Loss of NANC nerve function can markedly impact the patient’s ability to achieve an erection. NO production by corpora cavernosa endothelium appears to play a critical role in the maintenance of erection.
Neurogenic erectile dysfunction
*Pure neurogenic erectile dysfunction is a frequent cause of erectile failure. Interruption of either somatic or autonomic nerves or their end units may cause erectile dysfunction. These nerves control the flow of blood into and likely out of the corpora cavernosa.
Endocrine disorders
*Testosterone plays a permissive role in erectile function. However, the amount of androgen necessary for normal erectile function is relatively low. Androgen replacement (testosterone cypionate 200 mg q 2-3 weeks or daily topical testosterone preparations) is expected to induce the return of erectile function in patients with very low (<200 ng/mL) or undetectable serum total testosterone concentration due to true primary or secondary hypogonadism. These patients are relatively uncommon, however. More commonly, the patient with decreased erectile rigidity will have normal or decreased free or total testosterone levels often diagnosed as adult-onset hypogonadism. Testosterone replacement rarely restores erectile function in those with mildly decreased serum testosterone levels (225-300 ng/mL) and should not be routinely given for that indication. Testosterone supplementation is never indicated for patients with normal circulating androgen levels.
The most common endocrine disorder affecting erectile ability is diabetes mellitus. The most important effect diabetes has on erectile ability appears to relate to the loss of function of long autonomic nerves. Erection is partially mediated by efferent parasympathetic cholinergic neural stimuli. Loss of long cholinergic neurons results in interruption of the efferent side of the erectile reflex arc. Diabetes also appears to produce dysfunction of the neuromuscular junction at the level of arterial smooth muscle in the penile corpora cavernosa. Studies have indicated markedly decreased acetylcholine and nitric oxide concentrations in the trabeculae of the corpora cavernosa in diabetics. These
findings probably represent a combination of neural loss and neuromuscular junction dysfunction.
Medical and surgical treatment
*Current medical therapy is based on the inhibition of phosphodiesterase type-5 (PDE-5). Fig. 119.1 illustrates that cGMP is broken down to inactive 50-GMP by PDE5. Sildenafil, vardenafil, avanafil, and tadalafil competitively inhibit PDE-5 breakdown of cGMP by binding to the catalytic domain of PDE-5 and thereby increasing cGMP concentration. The use of a PDE-5 inhibitor results in improved erectile rigidity even in patients with decreased nitric oxide production or cGMP synthesis. Generally, 60% of patients overall and 80% with ED due to spinal cord injury respond to PDE-5 inhibition.
*Autonomic dysfunction may progress to a point where NANC nerves produce little or no NO. At that point, PDE-5 inhibitors are no longer effective. Other therapeutic interventions may be used including pharmacologic injection of prostaglandin E-1 or other agents intothe penile corporal body, intraurethral delivery of prostaglandin E-1, vacuum erection devices, and inflatable penile implants. Patients who have good performance status should be offered urologic referral if initial medical therapy fails to achieve adequate penile rigidity.
