Male Sexual Dysfunction

From The Merck Manual of Diagnosis and Therapy, Edition 18, pp. 1947-1950, and pp. 2099-2104, edited by Mark H. Beers. Copyright 2006 by Merck & Co., Inc., Whitehouse Station, NJ. Available at: http://www.merck.com/mmpe/index.html.

 

Erection: Erection occurs as the result of a complex neuropsychologic process. Higher cortical input and a sacrally mediated parasympathetic reflex arc combine to stimulate erection. Nerve output travels through the pudendal nerves, which traverse the posterolateral aspect of the prostate. Terminating in the penis, these nonadrenergic/noncholinergic nerves activate nitric oxide synthase, producing nitric oxide, which relaxes smooth muscle lining the sinusoidal spaces that connect the arterioles and venules within the corpus cavernosa. The blood flow within the sinusoids increases markedly, distending them and compressing the venules, causing veno-occlusion. The increased inflow and veno-occlusion together produce penile rigidity. Many factors affect the ability to have an erection (see below).

Ejaculation and orgasm: Ejaculation is controlled by the sympathetic nervous system. ?-Adrenergic stimulation produces contractions of the epididymis, vas deferens, prostate, and muscles of the pelvic floor. In addition, the neck of the bladder closes, preventing retrograde ejaculation of semen into the bladder. SSRIs may delay or inhibit ejaculation.

Orgasm is the highly pleasurable sensation that occurs in the brain generally simultaneously with ejaculation. Anorgasmia may be a physical phenomenon due to decreased penile sensation (eg, from neuropathy).

Ejaculatory insufficiency is reduced or absent semen volume that may result from retrograde ejaculation or interruption of sympathetic stimulation. Retrograde ejaculation (prostatic fluid flowing backward into the bladder) is common in diabetics and can also be caused by surgery on the neck of the bladder or transurethral resection of the prostate. Sympathetic interruption, either from surgery or with drugs (eg, guanethidine, phentolamine, phenoxybenzamine, thioridazine), diminishes ejaculatory volume.

Premature ejaculation is ejaculation occurring sooner than desired by the man or his partner. It is usually caused by sexual inexperience, anxiety, and other psychologic factors instead of disease. It can be treated successfully with sex therapy and SSRIs.

ERECTILE DYSFUNCTION (ED) (Impotence)

Erectile dysfunction is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, and hormonal disorders; drug use and sometimes psychologic disorders are also causes. Evaluation typically includes screening for underlying diseases and measuring testosterone levels. Treatment options include oral phosphodiesterase inhibitors or apomorphine, intraurethral or intracavernosal prostaglandins, mechanical pump devices, and surgical implants.

The term impotence has been replaced by the term erectile dysfunction (ED). In the US, at least 10 to 20 million men > 18 are affected. The prevalence is about 50% in men 40 to 70 and increases with aging. However, many men can be successfully treated.

Etiology

Primary ED (ie, the man has never been able to attain or sustain erections) is rare and is almost always due to psychologic factors (guilt, fear of intimacy, depression, severe anxiety) or clinically obvious anatomic abnormalities. Most often, ED is secondary (ie, a man who previously could attain and sustain erections no longer can). Over 80% of secondary ED cases have an organic etiology. However, in many men with organic disease, ED leads to secondary psychologic difficulties that compound the problem. Psychologic factors must be considered in every case.

Psychologic causes may relate to performance anxiety, stress, or mood disorder (particularly depression). ED may be situational, involving a particular place, time, or partner.

The major organic causes of ED are vascular and neurologic disorders, often stemming from atherosclerosis and diabetes. Complications of surgery, usually prostate surgery, are another common cause. Other causes include hormonal disorders, drugs, and structural disorders of the penis (eg, Peyronie’s disease).

The most common vascular cause is atherosclerosis of penile arteries, often secondary to diabetes. Atherosclerosis and aging decrease the capacity for dilation of arterial blood vessels and smooth muscle relaxation, limiting the amount of blood that can enter the penis. Inadequate impedance of venous outflow (venous leaks) may cause ED or, more commonly, failure to maintain tumescence as long as desired. Venous leaks make it difficult for blood to remain in the penis during erection, so erections occur but cannot be sustained. Priapism, particularly as in sickle cell disease, may damage penile vasculature and lead to ED.

Stroke, partial complex seizures, multiple sclerosis, peripheral and autonomic neuropathies, and spinal cord injuries are among the neurologic causes. Diabetic neuropathy and surgical injury are particularly common causes.

Any endocrinopathy associated with testosterone deficiency (hypogonadism) may decrease libido and cause ED. However, erectile function only rarely improves with normalization of serum testosterone levels.

Numerous drug causes are possible. Alcohol can cause temporary ED.

Commonly Used Drugs That Can Cause Erectile Dysfunction

Antihypertensives: Clonidine, thiazides, probably loop diuretics, spironolactone, ?-blockers

CNS drugs: Monoamine oxidase inhibitors, SSRIs, tricyclics, anxiolytics, alcohol, opioids, cocaine

Other: Anticholinergics, estrogens, cimetidine, antimetabolites, anticancer drugs, amphetamines

Of men who have undergone transurethral resection of the prostate, 15 to 40% experience problems with erections because of disruption of the pudendal nerve. ED is more common after more extensive prostatic resection. Prolonged perineal pressure (as occurs during bicycle riding) can cause temporary ED.

Diagnosis

Evaluation should include history of drug and alcohol use, smoking, diabetes, hypertension, and atherosclerosis; symptoms of vascular, hormonal, neurologic, and psychologic disorders. It is vital to screen for depression, which may not always be apparent. The Beck Depression Scale or the Yesavage Geriatric Depression Scale in older men is easy to administer and may be useful. Satisfaction with sexual relationships should also be explored. Partner sexual dysfunction (eg, atrophic vaginitis, depression) must be considered and evaluated.

Examination is focused on the genitals and extragenital signs of hormonal, neurologic, and vascular disorders. Genitals are examined for anomalies, signs of hypogonadism, and fibrous bands or plaques (Peyronie’s disease). Poor rectal tone, perineal sensation, or abnormal anal wink or bulbocavernosus reflexes may indicate neurologic dysfunction. Diminished peripheral pulses suggest vascular dysfunction.

A psychologic cause should be suspected in young healthy men with abrupt onset of ED, particularly if onset is associated with a specific emotional event or if the dysfunction occurs only in certain settings. A history of ED with spontaneous improvement also suggests psychologic origin (psychogenic ED). Men with psychogenic ED usually have normal nocturnal erections and erections upon awakening, whereas men with organic ED often do not.

Laboratory assessment should always include measurement of testosterone level; if the level is low or low-normal, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) should be measured. Evaluation for occult diabetes, dyslipidemias, hyperprolactinemia, thyroid disease, and Cushing’s syndrome should be performed based on clinical suspicion.

A penile pressure–brachial pressure index (systolic BP in the penis divided by systolic BP in the arm) < 0.6 indicates impaired blood flow to the penis, but this test is seldom performed in general clinical practice.

Treatment

Underlying organic disorders require appropriate treatment. Drugs that are temporally related to onset of ED should be stopped or switched. Depression may require treatment. For all patients, reassurance and education (including of the patient’s partner whenever possible) are important.

For further therapy, noninvasive methods (mechanical devices and drugs) are tried first. Men who can develop but not sustain an erection may use a constriction ring. As soon as erection occurs, a metal or elastic ring or a leather band with snaps (sold by prescription in pharmacies or OTC in sex paraphernalia stores as a “cock ring”) is placed around the base of the penis, preventing venous outflow. If the man cannot develop an erection, a vacuum device can draw blood into the penis, after which the band or ring is placed at the base of the penis to retain the erection. Bruising of the penis, coldness of the tip of the penis, and lack of spontaneity are some drawbacks to this modality. A constriction ring and vacuum devices might also be useful adjuncts for patients who do not respond satisfactorily to drug therapy.

Virtually all patients prefer drug therapy for ED. The primary drugs for ED are oral phosphodiesterase inhibitors, oral apomorphine (not available in the US), and intracavernosal or intraurethral prostaglandins.

Oral selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), the predominant phosphodiesterase isoform in the penis, include sildenafil, vardenafil, and tadalafil. By increasing cGMP, these drugs enhance the nitric oxide release essential for normal erection. Vardenafil and tadalafil are more selective for the penile vasculature (and therefore may have fewer adverse effects) than sildenafil. Although there are no head-to-head comparison clinical trials, all 3 drugs appear to be equally effective (60 to 75%). Sildenafil is taken 1 to 4 h before sexual intercourse. The dose is 50 mg, although most men respond best to 100 mg. Tadalafil has a significantly longer half-life than sildenafil, which might lead to more convenient dosing. The usual dosage for tadalafil and vardenafil is 10 to 20 mg 1 h before sex, not more often than daily. The maximal dosage is usually 20 mg. All PDE5 inhibitors cause direct coronary vasodilation and potentiate the hypotensive effects of other nitrates, including those used to treat cardiovascular disease as well as recreational amyl nitrate (“poppers”). Thus, all nitrates are contraindicated for 24 h after the administration of any PDE5 inhibitor. Other adverse effects of PDE5 inhibitors include flushing, visual abnormalities, and headache. Vardenafil should not be administered with ?-blockers, such as prazosin, doxazosin, and tamsulosin, because of the risk of prolonged hypotension. One study showed that sildenafil may be safely administered with doxazosin.

Apomorphine increases erectile neurogenic signals by CNS mechanisms. It appears to be only moderately effective and can cause nausea, somnolence, and hypotension.

Intraurethral insertion or intracavernosal injection of the prostaglandin alprostadil (PGE1) can produce erections with a mean duration of about 60 min. It causes priapism in approx. 1% and penile pain in about 10%. The intracavernosal dose is adjusted by the physician to minimize priapism; the patient can then self-inject at home. Priapism is less common with intraurethral therapy, but intraurethral therapy is much less effective than intracavernosal injection, the most effective pharmacotherapy for erectile dysfunction (80 to 90%). Combination therapy with a PDE5 inhibitor and alprostadil may be useful for some patients who fail to respond to oral PDE5 inhibitors alone.

For patients who do not respond to drug therapy, invasive treatment options include implantation of a penile prosthesis. Prostheses can be rigid plastic rods or hydraulically operated devices. Both involve the risks of general anesthesia, infection, and prosthetic malfunction.