Since sexual arousal is a complex process involving hormones, emotions, nerves, muscles, blood vessels and the brain, a malfunction in any of these can lead to ED. Stress, exhaustion and psychological issues can also contribute, and anxiety over maintaining an erection can actually make it harder to attain. In short, any condition that inhibits blood flow to the penis can lead to ED.
Of particularly concern are antihypertensive medications for CVD (eg, digoxin, disopyramide [Norpace], gemfibrozil [Lopid]), anxiety, depression (eg, lithium, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants), or psychosis (eg, chlorpromazine, haloperidol, pimozide [Orap], thioridazine, thiothixene). Antihypertensive drugs, such as diuretics (eg, spironolactone, thiazides) and beta blockers, may be associated with ED. Discontinuation or switching to alternative drugs, such as angiotensin-converting enzyme inhibitors or calcium channel blockers (eg, diltiazem, nifedipine, amlodipine), may reduce ED. The newer angiotensin II receptor antagonists may be less problematic with respect to ED, but long-term data is needed to evaluate this.
ED usually has something physical behind it, particularly in older men. But psychological factors can be a factor in many cases of ED. Experts say stress, depression, poor self-esteem, and performance anxiety can short-circuit the process that leads to an erection. These factors can also make the problem worse in men whose ED stems from something physical.
Alprostadil is an FDA-approved erectile dysfunction drug that can be injected directly into the penis to trigger an automatic erection. "Penile injection is the most effective type of ED treatment for men who can't take oral treatment," says Nelson Bennett, MD, a urologist at the Lahey Clinic in Burlington, Mass. In fact, it has an 85 percent success rate. Possible side effects include a burning sensation and priapism, an erection that lasts more than four hours and requires medical treatment.
Another approach is vacuum therapy. The man inserts his penis into a clear plastic cylinder and uses a pump to force air out of the cylinder. This forms a partial vacuum around the penis, which helps to draw blood into the corpora cavernosa. The man then places a special ring over the base of the penis to trap the blood inside it. The only side effect with this type of treatment is occasional bruising if the vacuum is left on too long.
Injection therapy involves injecting a substance into the penis to enhance blood flow and cause an erection. The Food and Drug Administration (FDA) approved a drug called alprostadil (Caverject) for this purpose in July of 1995. Alprostadil relaxes smooth muscle tissue to enhance blood flow into the penis. It must be injected shortly before intercourse. Another, similar drug that is sometimes used is papaverine—not yet been approved by the FDA for this use. Either drug may sometimes cause painful erections or priapism (uncomfortable, prolonged erections) that must be treated with a shot of epinephrine.

Induction of erection occurs after stimulation of the cavernous and pelvic nerve plexus. Conversely, stimulation of the sympathetic trunk leads to detumescence. The reflex erectile response requires that the sacral reflex arc remain intact. Tactile and sensory signals are received by the somatic sensory pathways and integrate with parasympathetic nuclei within the sacral spinal cord (S2-4) leading to induction of erection via cholinergic signaling. These reflexogenic erections remain intact with upper motor neuron injuries. Psychogenic erections do not require that the sacral reflex arc remain intact. In a cat models, spinal cord removal below L4/L5 led to absence of a reflexogenic erection but stimulation of the medial preoptic area (MPOA) or placement near a female cat in heat led to erection (5,6). Psychogenic erections occur via induction of central pathways traveling from the brain through the sympathetic chain. Non-penile sensory pathways induced by sight, sound, touch and smell travel through the MPOA to the erection centers within the cord T11-L2, and S2-S4 to induce erections (7). When a sacral lower motor neuron injury is present in men, below T12 these types of erections are more likely to occur (8). Spinal cord lesions above T9 are not associated with psychogenic erections (9). Rigidity of erections is less with psychogenic erections because the thoracolumbar sympathetic outflow may contain a decreased concentration of neurons compared to the parasympathetic outflow from the sacral spinal cord.
You may find that using a vacuum device requires some practice or adjustment. Using the device may make your penis feel cold or numb and have a purple color. You also may have bruising on your penis. However, the bruises are most often painless and disappear in a few days. Vacuum devices may weaken ejaculation but, in most cases, the devices do not affect the pleasure of climax, or orgasm.
Choosing the treatment that is best for you comes down to preference and efficacy. Montague cites a study that surveyed three groups of men, all of whom were successfully using an ED treatment. One group was on oral medications, one was using injections and a third had surgically implanted pumps. The most satisfied users were those with the implanted prostheses.
When you become aroused, your brain sends chemical messages to the blood vessels in the penis, causing them to dilate or open, allowing blood to flow into the penis. As the pressure builds, the blood becomes trapped in the corpora cavernosa, keeping the penis erect. If blood flow to the penis is insufficient or if it fails to stay inside the penis, it can lead to erectile dysfunction.

The Prostate Cancer Prevention Trial was a landmark study by Thompson et al that prospectively assessed the time to developing CVD after the diagnosis of ED. There were 4247 men with no ED at study entry; 2420 developed incident ED (defined as the first report of ED of any grade) over 5 years. Those men that developed ED had a 1.45-fold higher probability of experiencing a CV event compared with men who did not develop ED.27
Sexual stimulation causes the release of neurotransmitters from cavernosal nerve endings and relaxation factors from endothelial cells lining the sinusoids. NOS produces NO from L-arginine, and this, in turn, produces other muscle-relaxing chemicals, such as cGMP and cyclic adenosine monophosphate (cAMP), which work via calcium channel and protein kinase mechanisms (see the image below). This results in the relaxation of smooth muscle in the arteries and arterioles that supply the erectile tissue, producing a dramatic increase in penile blood flow.
There are two kinds of surgery for ED: one involves implantation of a penile prosthesis; the other attempts vascular reconstruction. Expert opinion about surgical implants has changed during recent years; today, surgery is no longer so widely recommended. There are many less-invasive and less-expensive options, and surgery should be considered only as a last resort.
Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties. Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization (118). It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine (32,119).

ICI Alprostadil may be used as a mixture with two other drugs to treat ED. This combination therapy called "bimix or trimix" is stronger than alprostadil alone and has become standard treatment for ED. Only the Alprostadil ingredient is FDA approved for ED. The amount of each drug used can be changed based on the severity of your ED, by an experienced health professional. You will be trained by your health professional on how to inject, how much to inject and how to safely raise the drug's dosage if necessary.
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