Erectile Dysfunction: A Merck Manual of Patient Symptoms podcast

Erectile dysfunction (ED) is the inability to attain or sustain an erection satisfactory for sexual intercourse. Most erectile dysfunction is related to vascular, neurologic, psychologic, and hormonal disorders; drug use can also be a cause. Evaluation typically includes screening for underlying disorders and measuring testosterone levels. Treatment options include oral phosphodiesterase inhibitors, intraurethral or intracavernosal prostaglandins, vacuum erection devices, and surgical implants.

Erectile dysfunction (formerly called impotence) affects up to 20 million men in the US. The prevalence of partial or complete ED is > 50% in men aged 40 to 70, and prevalence increases with aging. Most affected 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 (acquired later in life by a man who previously was able to attain erection). Over 90% 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 depression. Psychogenic ED may be situational, involving a particular place, time, or partner.

The major organic causes of ED are.

• Vascular disorders
• Neurologic disorders

These disorders often stem from atherosclerosis or diabetes.

The most common vascular cause is atherosclerosis of cavernous arteries of the penis, often caused by smoking and 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 compression of venous outflow (veno-occlusive dysfunction) results in failure to maintain erectile rigidity until orgasm. Priapism (see Symptoms of Genitourinary Disorders: Priapism), usually associated with trazodoneSome Trade Names
DESYREL
Click for Drug Monograph
use, cocaine abuse, and 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.

Complications of pelvic surgery (eg, radical prostatectomy [with or without cystectomy, and even with nerve-sparing techniques], cystectomy, transurethral resection of the prostate, rectal cancer surgery) are other common causes. Other causes include hormonal disorders, drugs, pelvic radiation, and structural disorders of the penis (eg, Peyronie disease). Prolonged perineal pressure (as occurs during bicycle riding) or perineal trauma can cause ED.

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 because most affected men also have neurovascular causes of ED.

Numerous drug causes are possible (see Table 1: Male Sexual Dysfunction: Commonly Used Drugs That Can Cause Erectile Dysfunction). Alcohol can cause temporary ED.

Table 1
PrintOpen table in new window
Commonly Used Drugs That Can Cause Erectile Dysfunction Class Drugs Antihypertensives β-Blockers, clonidineSome Trade Names CATAPRES Click for Drug Monograph , loop diuretics (probably), spironolactoneSome Trade Names ALDACTONE Click for Drug Monograph , thiazide diuretics CNS drugs Alcohol, anxiolytics, cocaine, monoamine oxidase inhibitors, opioids, SSRIs, tricyclic antidepressants Others Amphetamines, 5α-reductase inhibitors, antiandrogens, cancer chemotherapy drugs, anticholinergics, cimetidineSome Trade Names TAGAMET Click for Drug Monograph , estrogensSome Trade Names PREMARIN Click for Drug Monograph , luteinizing hormone‒releasing hormone agonists and antagonists

Diagnosis

• Clinical evaluation
• Screening for depression
• Testosterone level

Evaluation should include history of drug (including prescription drugs and herbal products) and alcohol use, pelvic surgery and trauma, smoking, diabetes, hypertension, and atherosclerosis and 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, in older men, the Yesavage Geriatric Depression Scale (see Table 7: Approach to the Geriatric Patient: Geriatric Depression Scale (Short Form)) is easy to administer and may be useful. Satisfaction with sexual relationships should also be explored. Partner sexual dysfunction (eg, atrophic vaginitis, dyspareunia, 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 disease). Poor rectal tone, decreased 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 include measurement of testosterone level; if the level is low or low-normal, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) should be measured (see Male Reproductive Endocrinology and Related Disorders: Diagnosis of primary and secondary hypogonadism). Evaluation for occult diabetes, dyslipidemias, hyperprolactinemia, thyroid disease, and Cushing syndrome should be done based on clinical suspicion.

Historically, the penile pressure–brachial pressure index (systolic BP in the penis divided by systolic BP in the arm) was recorded, with values < 0.6 indicating impaired blood flow to the penis. This test is now seldom done. Currently, duplex ultrasonography after intracavernous injection of a vasoactive drug such as prostaglandin E₁ is most often used to evaluate penile vasculature. Rarely, in selected patients for whom penile revascularization surgery is being considered after pelvic trauma, dynamic infusion cavernosography and cavernosometry may be done.

Treatment

• Treatment of underlying causes
• Oral phosphodiesterase inhibitor (1st-line treatment)
• Vacuum erection device or intracavernosal or intraurethral prostaglandin E₁ (2nd-line treatment)
• If other treatments fail, surgical implantation of penile prosthesis

Underlying organic disorders (eg, diabetes, hypogonadism, Peyronie disease) 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, an oral phosphodiesterase inhibitor is tried first. If necessary, another noninvasive method, such as a vacuum erection device or intracavernosal or intraurethral prostaglandin E₁ is tried next. Invasive treatments are used only when noninvasive methods fail. All drugs and devices should be tried ≥ 5 times before being considered ineffective.

Drugs: First-line treatment of ED is usually an oral phosphodiesterase inhibitor. Other drugs used include intracavernosal or intraurethral prostaglandin E₁. However, because almost all patients prefer oral drug therapy, oral drugs are used unless they are contraindicated or not tolerated.

Oral phosphodiesterase inhibitors selectively inhibit cyclic guanosine monophosphate (cGMP)–specific phosphodiesterase type 5 (PDE5), the predominant phosphodiesterase isoform in the penis. These drugs include sildenafilSome Trade Names
VIAGRA
Click for Drug Monograph
, vardenafilSome Trade Names
LEVITRA
Click for Drug Monograph
, avanafil, and tadalafilSome Trade Names
CIALIS
Click for Drug Monograph
(see Table 2: Male Sexual Dysfunction: Oral Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction). By preventing the hydrolysis of cGMP, these drugs promote the cGMP-dependent smooth muscle relaxation that is essential for normal erection. Although vardenafilSome Trade Names
LEVITRA
Click for Drug Monograph
and tadalafilSome Trade Names
CIALIS
Click for Drug Monograph
are more selective for the penile vasculature than sildenafilSome Trade Names
VIAGRA
Click for Drug Monograph
, clinical responses and adverse effects of these drugs are similar. In comparative clinical trials, these drugs show comparable efficacy (60 to 75%).

Table 2
PrintOpen table in new window
Oral Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction Drug Dose* Onset of Action Comments Avanafil 50, 100, or 200 mg 30 min Can be taken 30 min before intercourse SildenafilSome Trade Names VIAGRA Click for Drug Monograph Initial: 50 mg Maintenance: 25‒100 mg (most men respond best to 100 mg) 60 min Duration: ≈ 4 h TadalafilSome Trade Names CIALIS Click for Drug Monograph 10‒20 mg 60 min Duration of action: 24‒48 h TadalafilSome Trade Names CIALIS Click for Drug Monograph , low-dose 2.5‒5 mg 60 min For daily use, taken at about the same time each day, without regard to timing of sexual activity VardenafilSome Trade Names LEVITRA Click for Drug Monograph 10‒20 mg 60 min Duration of action: ≈ 4 h VardenafilSome Trade Names LEVITRA Click for Drug Monograph , orally disintegrating form 10 mg 30 min Can be taken 30 min before intercourse *PDE5 inhibitors should be taken on an empty stomach at least 1 h before sexual intercourse except as noted. Maximum frequency is once/day unless otherwise noted. PDE5 = phosphodiesterase type 5.

All PDE5 inhibitors cause direct coronary vasodilation and potentiate the hypotensive effects of other nitrates, including those used to treat coronary artery disease as well as recreational amyl nitrate (“poppers”). Thus, the concomitant use of nitrates and PED5 inihibitors can be dangerous and should be avoided. Patients who only occasionally use nitrates (eg, for rare bouts of angina) should discuss the risks, selection, and proper timing of possible PDE5 inhibitor use with a cardiologist.

Adverse effects of PDE5 inhibitors include flushing, visual abnormalities, hearing loss, dyspepsia and headache. SildenafilSome Trade Names
VIAGRA
Click for Drug Monograph
and vardenafilSome Trade Names
LEVITRA
Click for Drug Monograph
may cause abnormal color perception (blue haze). TadalafilSome Trade Names
CIALIS
Click for Drug Monograph
use has been linked with myalgias. Rarely, nonarteritic ischemic optic neuropathy (NIAON) has been associated with PDE5 inhibitor use, but a causal relationship has not been established. All PDE5 inhibitors should be administered cautiously and at lower initial dosages to patients receiving α-blockers (eg, prazosinSome Trade Names
MINIPRESS
Click for Drug Monograph
, terazosinSome Trade Names
HYTRIN
Click for Drug Monograph
, doxazosinSome Trade Names
CARDURA
Click for Drug Monograph
, tamsulosinSome Trade Names
FLOMAX
Click for Drug Monograph
) because of the risk of hypotension. Patients taking an α-blocker should wait at least 4 h before using a PDE5 inhibitor. Rarely, PDE5 inhibitors cause priapism.

Alprostadil (prostaglandin E₁), self-administered via intraurethral insertion or intracavernosal injection, can produce erections with a mean duration of 30 to 60 min. Excessive dosing may cause priapism (see Symptoms of Genitourinary Disorders: Priapism) in ≤ 1% of patients and genital or pelvic pain in about 10%. Office teaching and monitoring by the physician helps achieve optimal and safe use, including minimizing the risk of prolonged erection. Intraurethral therapy is less effective at producing satisfactory erection (up to 60% of men) than intracavernosal injection (up to 90%). Combination therapy with a PDE5 inhibitor and intraurethral alprostadilSome Trade Names
CAVERJECT
EDEX
MUSE
Click for Drug Monograph
may be useful for some patients who fail to respond to oral PDE5 inhibitors alone.

Mechanical devices: Men who can develop but not sustain an erection may use a constriction ring to help maintain erection; an elastic ring is placed around the erect penis, preventing early loss of erection. Men who cannot achieve erection can first use a vacuum erection device that draws blood into the penis via suction, after which an elastic ring is placed at the base of the penis to maintain the erection. Bruising of the penis, coldness of the tip of the penis, and lack of spontaneity are some drawbacks to this modality. These devices can also be combined with drug therapy if needed.

Surgery: If drugs and vacuum devices fail, surgical implantation of a penile prosthesis can be considered. Prostheses include semirigid silicone rods and saline-filled multicomponent inflatable devices. Both models carry the risks of general anesthesia, infection, and prosthesis erosion or malfunction. With experienced surgeons, the long-term rate of infection or malfunction is well below 5% and the rate of patient and partner satisfaction is > 95%.

Key Points

• Vascular, neurologic, psychologic, and hormonal disorders and sometimes drug use can compromise achievement of satisfactory erections.
• Evaluate all men with ED for hormonal, neurologic, and vascular disorders and depression.
• Measure testosterone levels and consider other testing based on clinical findings.
• Treat underlying disorders and use an oral PDE5 inhibitor if necessary.
• If those measures are ineffective, consider intracavernosal or intraurethral prostaglandin E₁ or use of a vacuum device; surgical implantation of a penile prosthesis is the final line of treatment.

Last full review/revision February 2013 by Irvin H. Hirsch, MD

Content last modified March 2013