Neurologic Aspects of Sexual Function

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Chapter 16 Neurologic Aspects of Sexual Function

Whatever its underlying psychology, sexual function depends on two complex and delicate neurologic pathways: (1) a connection between the brain and the genitals; and (2) a reflex loop between the genitals and spinal cord. Both involve the central nervous system (CNS), peripheral nervous system (PNS), and autonomic nervous system (ANS).

In the first pathway, the brain converts various stimuli, including sleep-related events, into neurologic impulses that are usually excitatory, although occasionally inhibitory. These impulses travel down the spinal cord. Some impulses descend all the way down to the cord’s sacral region where they exit to travel through the pudendal nerve. At this juncture, they leave the CNS to join the PNS (Fig. 16-1). Meanwhile, as if diverted to a parallel route, some impulses leave the spinal cord at its low thoracic and upper lumbar regions (T11–L2) to travel through the sympathetic division of the ANS. Still others leave the spinal cord’s lower sacral segments (S2–4) to travel through the parasympathetic division of the ANS.

FIGURE 16-1 The sacral spinal cord segments (S2–4) give rise to the pudendal nerves, which supply the genital muscles and skin. Those segments also supply the vaginal canal. They convey sensations for pleasure during sex and pain during vaginal delivery. The sympathetic and parasympathetic components of the autonomic nervous system also innervate the genitals, and the reproductive organs, bladder, sweat glands, and arterial wall muscles.

Excitatory descending stimuli increase parasympathetic ANS activity, which reduces (relaxes) tone in the wall muscles of genital arteries. As the relaxed arteries dilate, they allow increased blood flow. In men, increased blood flow inflates the penis and produces an erection. In women, it produces clitoral engorgement.

With continued excitatory stimulation, a complex series of predominantly sympathetic ANS-mediated events produce an orgasm. Afterward, a return to normal, relatively constricted arterial wall muscle tone reduces blood flow. The resultant reduced vascular engorgement results in detumescence.

Although the sympathetic and parasympathetic components of the ANS are complementary, they depend on different neurotransmitters – acetylcholine in the parasympathetic and monoamines in the sympathetic. Moreover, the ANS components have different roles. An admittedly crude mnemonic describes the parasympathetic and sympathetic ANS roles in sexual response: “point and shoot.” (The mnemonic also reflects that current knowledge of sexual function rests primarily on male physiology, evaluation, and treatment.)

The second pathway – the genital–spinal cord reflex – is shorter and simpler. In it, erotic impulses from genital stimulation pass through the pudendal nerve to the spinal cord. Most impulses synapse in the sacral region of the spinal cord and return, via the ANS, to the genitals.

Neurologic Impairment

Without accepting a complete distinction between neurologic and psychologic sexual impairment, certain elements of the patient’s history (Box 16-1) and neurologic examination (Box 16-2) reliably indicate a neurologic origin. For example, either spinal cord or peripheral nerve injury might lead to a pattern of weakness and sensory loss below the waist or only around the genitals, anus, and buttocks – the “saddle area” (Fig. 16-2). Plantar and deep tendon reflex (DTR) testing will indicate which system is responsible: spinal cord injury causes hyperactive DTRs and Babinski signs, whereas peripheral nerve injury causes hypoactive DTRs and no Babinski signs. Both CNS and PNS impairment lead to loss of the relevant “superficial reflexes”: scrotal, cremasteric, and anal (Fig. 16-3).

FIGURE 16-2 The sacral dermatomes (S2–5) innervate the skin overlying the genitals and anus, but the lumbar dermatomes innervate the legs.

FIGURE 16-3 A, The scrotal reflex: When the examiner applies a cold surface to the scrotum, the ipsilateral skin contracts and testicle retracts. B, The cremasteric reflex: Stroking the inner thigh elicits the same response. C, The anal reflex: When the examiner scratches the skin surrounding the anus, it tightens.

Signs of ANS impairment, although often subtle, carry great weight. For example, orthostatic hypotension, usually defined as a fall of 10 mmHg in blood pressure upon standing, reliably indicates ANS impairment, as might result from diabetes, medications, or idiopathic systemic conditions. Similarly, anhidrosis, lack of sweating, indicates ANS impairment. In this condition, urinary incontinence and hairless and sallow skin usually accompany dry axillae, groins, and legs. Finally, if microscopic examination of urine obtained after orgasm reveals sperm, the man probably has retrograde ejaculation, which usually reflects a disorder of the finely tuned, ANS-based mechanism.

In many conditions, such as spinal cord injury or severe ANS damage, urinary and fecal incontinence accompany neurologic-induced sexual impairment because the bladder, bowel, and genitals share many elements of innervation. The anus, like the bladder, has two sphincters (see Fig. 15-5). Its internal sphincter, more powerful than the external one, constricts in response to increased sympathetic activity and relaxes to parasympathetic activity. The external sphincter of the anus is under voluntary control through the pudendal nerves and other branches of the S3 and S4 peripheral nerve roots. Thus, to produce a bowel movement, individuals must deliberately relax their external sphincter while the internal sphincter, under involuntary parasympathetic control, simultaneously relaxes.

As could be anticipated, excess sympathetic ANS activity, as in the “fight or flight” response, inhibits both urinating and defecating by constricting the sphincter. Moreover, excess ANS activity, typically caused by anxiety, often impairs sexual arousal, inhibits an erection, and precipitates premature ejaculation.

Laboratory Tests

Sleep-Related Studies

From infancy to old age, normal men have erections and other signs of ANS activity during their rapid eye movement (REM) periods of sleep. The erections develop during dreams, regardless of their overt content. Thus, normal men have three to five erections per night, each lasting about 20 minutes. In a nocturnal penile tumescence (NPT) study, a device monitors a man’s erections and correlates them with REM periods over one to three nights.

Because NPT studies take place in a secluded setting, the testing frees men with erectile dysfunction from most social and psychologic influences. During NPT studies, some men casually diagnosed as having erectile dysfunction actually develop erections. Those who develop no erections usually have a physiologic disturbance; however, some of them suffer from depression, a sleep disorder, or a test-induced artifact.

Other Tests

Depending on the circumstances – peripheral vascular disease, atherosclerosis, diabetes, or pelvic injuries – physicians may assess men with erectile dysfunction and other sexual impairments by measuring the blood pressure and blood flow in the dorsal artery of the penis using a small blood pressure cuff, Doppler ultrasound apparatus, and other devices. Barring vascular disease, an injection of a vasodilator into the penis (i.e., an intracorporeal vasodilator injection) produces an erection. In fact, such injections provide a treatment option.

If physicians suspect polyneuropathy, pudendal nerve damage, or spinal cord injury, neurologists may perform electrophysiologic studies, such as peripheral nerve conduction velocity, penile nerve conduction velocity, and somatosensory-evoked potentials for women as well as men. These tests help in the diagnosis of patients with diabetic neuropathy, prostate cancer, pelvic or spine trauma, or multiple sclerosis (MS) (see later).

Individuals with an endocrinologic basis of their sexual dysfunction usually have other signs of hormone imbalance. Relevant screening tests usually measure blood glucose, prolactin, testosterone, estrogen, and gonadotropic hormone concentrations. Other tests may reveal hypogonadism, hypothyroidism, diabetes, or a disruption of the hypothalamic–pituitary–gonadal axis. In performing an endocrinologic evaluation, physicians should note that, although an elevated prolactin concentration usually indicates a pituitary adenoma, antipsychotic and other medicines might elevate it.

Medical Treatment of Erectile Dysfunction

Several medications can produce erections adequate for sexual intercourse despite neurologic injury or vascular insufficiency. They can also restore erections in men experiencing psychogenic erectile dysfunction and in those taking psychotropic medication.

Many physicians prescribe yohimbine, a centrally acting α₂-adrenergic antagonist (see Chapter 21). This medicine may slightly increase sympathetic vasomotor activity, provide mild psychologic stimulation, and create an aphrodisiac sensation. Although yohimbine may alleviate psychogenic erectile dysfunction, it does not help in cases of sexual function due to medical or neurologic illness. Moreover, it often causes anxiety.

Testosterone injections are popular mostly because they may increase muscle mass, especially in body builders, and provide psychologic stimulation. However, except in cases of hypogonadism, testosterone injections have no effect on sexual function and, in high doses for long periods, they may induce prostate cancer.

In contrast, intracorporeal injections of vasoactive medicines – although briefly painful – are effective. They induce erections in men with spinal cord damage, peripheral neuropathy, or vascular disease. The most effective medicines are papaverine, a nonspecific smooth-muscle relaxant; phentolamine, an α-adrenergic antagonist; and alprostadil, a synthetic prostaglandin E₁. A man with erectile dysfunction can inject these medicines – individually or as a mixture – into the base of his corpus cavernosum (the vascular erectile tissue of the penis).

Phentolamine-induced erections illustrate an important physiologic distinction. In contrast to α-adrenergic antagonists, such as phentolamine, causing erections, adrenergic agonists, such as epinephrine (see later), soften erections – by respectively increasing or reducing blood flow into the penis.

Using an alternative treatment, men insert a short, thin alprostadil suppository into the urethra. Although initially uncomfortable, it leads to an erection by greatly promoting blood flow into the penis. This method, unlike with sildenafil (Viagra) treatment, does not require physical stimulation to achieve an erection.

Sildenafil and related medicines – tadalafil (Cialis) and vardenafil (Levitra) – have simplified the treatment of erectile dysfunction and dispensed with expensive and lengthy testing. To a greater or lesser degree they assist men with erectile dysfunction from age-related changes, diabetes, MS, spinal cord injury, and nerve damage from prostate surgery. Furthermore, they often correct erectile dysfunction associated with anxiety, decreased libido, depression, or other psychiatric disturbances. They also partially or completely reverse sexual dysfunction caused by psychotropic medications in both sexes (see later).

Sildenafil and related medicines have a well-established mechanism of action. Under normal circumstances, psychologic or tactile sexual stimulation provokes parasympathetic neurons to produce and release the neurotransmitter nitric oxide (NO) within the penis. NO, in turn, promotes the production of cyclic guanylate cyclase monophosphate (cGMP). In turn, cGMP dilates the arteries, promotes blood flow, and creates an erection. After an enzyme, cGMP-phosphodiesterase, metabolizes cGMP, the erection subsides.

As their primary mechanism of action, these medicines – phosphodiesterase inhibitors – inhibit cGMP-phosphodiesterase. The resulting increased cGMP concentration promotes blood flow in the penis (Fig. 16-4).

FIGURE 16-4 As its mechanism of action, sildenafil inhibits cyclic guanylate cyclase monophosphate-phosphodiesterase (cGMP-PDE). The resulting increase in cGMP leads to smooth-muscle relaxation, which promotes vascular congestion in the penis and thus an erection. NO, nitrous oxide; PDE, phosphodiesterase, which metabolizes cGMP but is inhibited by sildenafil.

Hardly a panacea, phosphodiesterase inhibitors help only about 60% of men with erectile dysfunction. In particular, they are often ineffective in men older than 70 years, with diabetes (especially when it is uncontrolled), undergoing cancer chemotherapy, or who smoke. In addition, they carry some risk. In addition, men taking nitroglycerin, other nitrates, doxazosin, or most α₁-adrenergic antagonists should not also take phosphodiesterase inhibitors because excess vasodilation may lead to orthostatic hypotension.

Invasive treatments are rarely satisfactory. Delicate and tedious arterial reconstructive procedures are usually disappointing, except in men with localized vascular injuries. Surgically implanted devices, such as rigid or semirigid silicone rods or a balloonlike apparatus, can mimic an erection. Unfortunately, implants are costly, unesthetic, and prone to infections and mechanical failures. In contrast, silicone penile implants have never been accused, like silicone breast implants, of causing rheumatologic or MS-like symptoms (see Chapter 15).

Underlying Conditions

Age-Related Changes

In men aged 50 years and older, although their libido generally remains intact, erections decrease in rigidity and duration. Their penis, like bodily areas, begins to lose sensitivity to touch and vibration. Also, these men’s refractory period between orgasms, which was 20 minutes when they were in their sexual prime, at age 18 years, lengthens to days to weeks. Their serum testosterone concentration decreases, but changes correlate poorly with erectile function. For example, although restoring testosterone concentrations reverses a diminished libido, it does not improve erectile dysfunction.

One credible explanation for their erectile dysfunction implicates the normal age-related increased smooth-muscle tone throughout the body. Not only does increased arterial wall smooth-muscle tone cause or contribute to essential hypertension, it also leads to reduced blood flow into the penis.

Other factors common among middle-aged and older men that may cause or at least predispose them to erectile dysfunction include hypertension, atherosclerotic disease, smoking, alcohol abuse, and television viewing time. Whether in isolation or as a group, these factors also blunt the response to phosphodiesterase inhibitors.

Spinal Cord Injury

Spinal cord injury produces a triad of symptoms that varies according to the injury’s level and whether it partially or completely transects the spinal cord:

• Paraparesis or quadriparesis with spasticity, hyperactive reflexes, and Babinski signs

• Sensory loss up to a certain spinal level (see Fig. 16-2)

• Bladder, bowel, and sexual difficulties.

In addition, upper cervical cord injuries compromise the respiratory center. They also release the sympathetic nervous system from CNS control.

Cervical and Thoracic Spinal Cord Injury

When injuries sever the cervical spinal cord, patients develop quadriparesis. When injuries sever the thoracic portion, they develop paraparesis. In both of these situations, the injury interrupts ascending sensory impulses, and patients cannot sense genital stimulation. Nevertheless, because the genital–spinal cord loop remains intact, patients retain the capacity for reflex genital arousal. They can achieve an orgasm even though they are unable to perceive it.

In these cases, erections are usually too weak for intercourse. If orgasms occur, they may produce an excessive, almost violent ANS response, called autonomic hyperreflexia. This response often causes hypertension, bradycardia, nausea, and lightheadedness. Occasionally the hypertension is so severe that it leads to an intracerebral hemorrhage.

Most spinal cord injury patients also suffer from urinary incontinence and constipation, requiring catheters and enemas. Infections of the urinary tract and decubitus ulcers constantly threaten them. Furthermore, men lose fertility because of inadequate and abnormal sperm production. However, women continue to ovulate and menstruate. They retain their capacity to conceive and bear children.

Incomplete spinal cord damage, as typically occurs in MS and nonpenetrating trauma, causes less pronounced neurologic deficits. Still, because of the delicate nature of the sexual neurologic pathways, even incomplete injuries impair genital arousal and inhibit orgasm.

Lumbosacral Spinal Cord Injury

As with patients who sustain thoracic spinal cord transection, those with lumbosacral spinal cord transection also have paraparesis and incontinence. In addition, because this lower lesion interrupts both the genital–spinal cord reflex and ascending and descending spinal cord tracts, neither genital nor cerebral stimulation produces arousal or orgasm.

Nevertheless, the ANS, which travels in a parallel pathway, may remain undamaged and able to innervate the genitals. This innervation preserves fertility in men and women. Also in contrast to higher spinal cord injuries, sensation of the breasts and their erotic capacity is preserved – and relatively enhanced – because upper chest sensation remains unaffected.

Poliomyelitis and Other Exceptions

Several neurologic illnesses can be so devastating that the untrained physician might assume that their victims have lost their sexual capacity. However, evaluations may reveal that many patients with these illnesses have retained sexual desire and function.

For example, two relatively common motor neuron diseases, poliomyelitis (polio) and amyotrophic lateral sclerosis (ALS) (see Chapter 5), devastate the voluntary motor system. Polio often left survivors confined to wheelchairs and braces, but with stable deficits. ALS, in contrast, causes progressively greater disability that usually results in death after several years. Nevertheless, both these illnesses spare victims’ intellect, sensation, involuntary muscle strength, and ANS functions. Thus, they allow patients normal sexual desire and function, genital sensation, bladder and bowel control, and fertility.

Similarly, most extrapyramidal illnesses (see Chapter 18), despite causing difficulties with mobility, do not impair sexual desire, sexual function, or fertility. For example, adolescents with athetotic cerebral palsy and other varieties of congenital birth injury – even those with marked physical impairments – often have intact libido and sexual function. Among older patients, those with Parkinson disease have preserved sexual drive; however, it may remain unexpressed until dopaminergic medications, such as levodopa and ropinirole, allow it to re-emerge. Moreover, neurologic conditions, such as frontal lobe trauma, frontotemporal dementia, and Alzheimer disease, that cause loss of inhibition sometimes lead to sexual aggressiveness.