A more descriptive term for impotence is erectile dysfunction (ED). Classically, ED has been defined as the inability to attain and maintain an erection of sufficient rigidity for sexual intercourse in at least 50% of attempts. This definition is important to consider because any normal man can have occasional ED, and treating men with only occasional symptoms is not without risk.

Most men with ED are able to ejaculate. Premature ejaculation may precede the development of impotence and is sometimes associated with drug therapy. Sexual desire (libido) is also usually preserved; loss of libido is suggestive of hypogonadism or severe systemic or psychiatric illness.

At least 10 million American men and perhaps as many as 20 million are impotent. Another 10 million may suffer from partial ED. The prevalence of impotence increases with age; about 2% of 40-year-old, 20% of 55-year-old, and 50% to 75% of 80-year-old men are impotent. There is a libido-potency gap in that many elderly men continue to have active libidos, but only 15% of them engage in sexual activity.

Erection is primarily a vascular event that results from the complex interplay of the hormonal, vascular, and peripheral and central nervous systems. There is considerable psychiatric interplay in that underlying psychiatric conditions or medications can cause decreased erectile function. Conversely, undesired sexual symptoms can also adversely affect mood and self-perception.

Erection is usually initiated by various psychological and/or physiologic stimuli in the cerebral cortex. The stimuli are modulated in the limbic system and other areas of the brain, integrated in the hypothalamus, transmitted down the spinal cord, and carried to the penis via both autonomic and sacral spinal nerves. (For the few remaining Latin scholars, these are the nervi erigentes derived from the verb erigo, erigere, erexi, erectus.) Sensory nerves from the glans of the penis enhance the message and help to maintain erection during sexual activity via a reflex arc.

Nervous system stimuli release neurotransmitters that reverse the tonic smooth muscle constriction maintained by norepinephrine, endothelin, and other vasoconstrictive factors. The most important of these are the potent vasodilators nitric oxide (NO) and prostaglandin E₁ (PGE₁). In addition to neural sources, NO is derived from endothelial cells, and this may explain why endothelial integrity may be necessary for maintenance of an erection. NO works by increasing cyclic guanosine monophosphate (cGMP) and causing a decrease in intracellular calcium. This results in relaxation of vascular smooth muscle cells secondary to dissociation of actin-myosin. The role of testosterone in erectile function remains complex and controversial. Testosterone has a critical role in stabilizing intracavernosal NO synthase, and for fully satisfactory sexual function, a “normal” quotient of testosterone must be present. Testosterone is also the main hormonal mediator of male libido; this means that deficiency can have a psychologic impact on erectile function. Regardless, some men with testosterone levels below the reference limit still have normal erections. Testosterone replacement is therefore not guaranteed to cure ED in hypogonadal men, nor is it indicated in men with normal testosterone levels but impaired sexual function.

Within the two spongy corpora cavernosa of the penis are millions of tiny spaces called lacunae, each lined by a wall of trabecular smooth muscle. As neurotransmitters dilate cavernosal and helicine arteries to the penis and relax the trabecular smooth muscle, the lacunar spaces in the penis become engorged with blood. This results in entrapment of outflow vessels between the expanding trabecular walls and the rigid tunica albuginea that surrounds the corpora cavernosa, thereby greatly reducing venous outflow from the penis. This venoocclusive mechanism accounts for both rigidity and tumescence. Failure of venous occlusion (venous leak) is one of the intractable causes of impotence.

At least three neuroeffector systems play a role in penile erection. Adrenergic nerves generally inhibit erection; cholinergic nerves and nonadrenergic, noncholinergic (NANC) substances enhance erection as follows:

Phosphodiesterase 5 (PD5), by causing a decrease in cGMP, allows for reversal of the process (i.e., detumescence), thus making PD5 inhibitors, such as sildenafil, vardenafil, and tadalafil, important therapeutic agents for the treatment of impotence (see the following).

The frequency of the various causes of impotence is difficult to assess because of the large number of patients who do not report the problem, confusion regarding the diagnosis, and variability in the sophistication of the initial evaluation. Primary causes of impotence in men presenting to a medical outpatient clinic are approximated as follows:

 Low levels of physical activity

 Overeating and obesity

 Smoking

 Excessive television viewing

 Alcohol consumption

 Primary (hypergonadotropic) hypogonadism (increased luteinizing hormone [LH] and decreased testosterone)

 Secondary (hypogonadotropic) hypogonadism (“inappropriately” normal or actually decreased LH combined with decreased testosterone)

 Hyperprolactinemia

Less common causes include hyperthyroidism, hypothyroidism, adrenal insufficiency, and Cushing’s syndrome.

Nonprescription drugs, such as alcohol (as the porter says to Macduff in Act II, Scene 3 of Macbeth, “It provokes the desire but takes away the performance”), and illicit drugs, such as cocaine, methadone, and heroin, can cause impotence. The prescription drugs most commonly associated with impotence include the following:

Virtually every blood pressure medication has been associated with impotence. Although there is little overall difference in the rate of erectile problems among the commonly prescribed antihypertensive agents, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers are the agents least likely to affect erectile ability. When beta-blockade is required, selective beta-antagonists, such as atenolol or acebutolol, are preferred because they have minimal impact on sexual function.

Impotence alternating with periods of entirely normal sexual function is termed stuttering impotence. Multiple sclerosis (MS) is the most significant organic cause of stuttering impotence. It may be the initial manifestation of MS and may be present in up to 50% of men with the disease.

True psychogenic impotence is uncommon and should be a diagnosis of exclusion. Questions that may help to separate psychogenic from organic impotence are listed in Table 45-1. A detailed history assessing for contributing physical and psychiatric conditions can also help with this distinction. These include obesity, hypertension, hyperlipidemia, atherosclerosis, diabetes mellitus or other endocrinopathy, neurologic disease, prior pelvic surgery or irradiation, trauma, Peyronie’s disease, substance abuse, depression, or the aforementioned medications. A detailed social history is also important and includes assessment of stressors and the patient’s coping mechanisms, concomitant psychosexual problems such as premature ejaculation, and relationship dynamics with partners.