The Massachusetts Male Aging Study, published in 1994, reported that in men between the ages of 40 and 70, the probability of complete impotence tripled, from 5 percent to 15 percent, while the chance of moderate impotence doubled, from 17 percent to 34 percent. More than half of American men over age 40 -- over 28 million individuals -- may have some degree of erectile dysfunction. Traditionally the term "impotence" has been used to describe a man's inability to attain or maintain an erection sufficient for sexual intercourse; urologists and other experts in the field, however, now prefer the term "erectile dysfunction."

In healthy men, an erection is a vascular response that is mediated by a complex series of events triggered by sexual stimulation. In the flaccid state, the muscles of the penis are contracted. When sexually stimulated, the brain sends signals carried by neurotransmitters, or chemical stimuli, that cause the muscles in the penis to relax. Blood fills two cylinders of sponge-like tissue, known as the corpora cavernosa, and the penis becomes erect.

In men with normal erectile function, the penis is composed of 42% to 53% smooth muscle. As men age, blood flow to the penis may decline causing the normal structure of the penis to change; smooth muscle may be replaced by fibrous tissue that cannot expand sufficiently to initiate and maintain an erection. Symptoms of erectile dysfunction typcially begin when smooth muscle in the penis falls below 42%.

Historically, drug therapy for the treatment of male sexual dysfunction consisted of delivering vasoactive drugs directly to the penis via injection and, more recently, via the urethra. In 1998, the U.S. Food and Drug Administration (FDA) approved Viagra (sildenafil), the first oral medication for erectile dysfunction.

In men, as smooth muscle is lost, impotence worsens. For approximately 50% of the impotent population, sufficient smooth muscle remains for oral therapies such as Vasomax or Viagra to provide clinical benefit. As the condition in men worsens, direct administration of vaso-active drugs injected into the penis are required to have benefit in restoring penile function. Roughly 30% of men with impotence require penile injections in order to achieve rigid erections. In the most severe cases, 20% of impotent men, penile implants are required.

Oral vaso-active drugs can improve sexual function by directly or indirectly addressing the blood flow to the genitalia via several different biologic pathways. Two physiological systems, the sympathetic and the parasympathetic, play a role in sexual response. Currently there are existing drugs, as well as new products in development, that can take advantage of either system. Alpha adrenergic blockers, such as Vasomax (phentolamine mesylate), may produce an effect in as little as 15 to 20 minutes. Drugs that inhibit the enzyme phosphodiesterase generally require about one hour or more to take effect. In both cases, sexual stimulation is necessary for a normal response.