Vardenafil and tadalafil belong to the same group of chemical compounds as sildenafil, namely phos-phodiesterase type 5 (PDE-5) inhibitors. Some men cannot benefit from sildenafil or the two newer PDE-5 inhibitors because they have low levels of nitric oxide. British investigators reported in late 2002 that three different types of compounds are being studied as possible medications for men with low levels of nitric oxide. They are Rho-kinase inhibitors, soluble guanylate cyclase activators, and nitric oxide-releasing PDE-5 inhibitors.
An approach to the diagnosis and management of the impotent patient is presented in Figure 187.1. Apparent and likely causes of impotence should be considered first and, if possible, eliminated before the work-up continues. For instance, observing the patient for a few weeks off offending medication may be all that is necessary to establish the cause of impotence. When no obvious or remediable cause is present, the next step is based on the clinical impression of the likelihood of organic versus psychologic impotence. If the latter is considered more likely, it is perfectly reasonable to refer the patient directly for sexual therapy, with the option of reconsidering the diagnosis if, after appropriate therapy, there is no improvement. While an occasional patient with organic impotence will be misrouted, many more with psychogenic impotence will be spared an unnecessary and costly evaluation for organic causes. When organic impotence is likely, a serum testosterone level is the initial screening test for hypogonadism and should be obtained prior to urologic referral. Patients with low testosterone levels require further endocrine evaluations as depicted in Figure 187.1.
In comparison, 37% of men who had received external radiotherapy as their primary therapy reported the ability to attain functional erections suitable for intercourse, along with 43% of men who had received brachytherapy as primary treatment. Pretreatment sexual health-related quality of life score, age, serum prostate-specific antigen (PSA) level, race or ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. 
When stimulated by the nerves, the spongy tissue arranges itself in such a way that more blood can be stored in the penis. The veins running through the outer sheath of the penis then compress which stops the blood from leaving the penis. As the blood is stopped from flowing out, the penis fills with blood and stretches within the outer casing, giving an erection.
ED means no erections from masturbation. According to the American Urological Association, ED is “the inability to achieve or maintain an erection sufficient for satisfactory sexual performance.” Huh? That’s absurdly vague. If you define “an erection” as what you see in porn, and “satisfactory sexual performance” as porn sex—instant, hard-as-rock erections that last forever with climaxes always on cue—then just about every guy has ED. What is ED, really? For practical purposes, it means that a man who’s sober (no alcohol or other erection-impairing drugs) cannot raise even a semi-firm erection after extended masturbation.
Heart disease isn't the only risk. ED is also a predictor of stroke, because when the arteries are narrowed there is more chance of a blood clot, which can spread to the brain. It is also a common complication of diabetes. But embarrassment stops people seeking help, says Jackson. "We need to encourage men to talk to their spouses about this problem, instead of making an excuse to avoid sex.
Before delving into the causes and solutions to erectile dysfunction, it’s first important to understand how erections work. The penis is mostly comprised or fibrous tissue that fills with blood upon arousal. This is what causes an erection, and after arousal is finished, blood drains back out into the body and the penis becomes flaccid. Men can have erections for no discernible reason throughout the day, but when sexual stimulation occurs, rather through contact, visual, audible, or mental stimulation, the potential for achieving an erection increases.
Tests such as the bulbocavernosus reflex test are used to determine if there is sufficient nerve sensation in the penis. The physician squeezes the glans (head) of the penis, which immediately causes the anus to contract if nerve function is normal. A physician measures the latency between squeeze and contraction by observing the anal sphincter or by feeling it with a gloved finger inserted past the anus.
The nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles. Although the membrane receptors play an important role, downstream signaling pathways are also important. The RhoA–Rho kinase pathway is involved in the regulation of cavernosal smooth muscle contraction. 
Additionally, the physiologic processes involving erections begin at the genetic level. Certain genes become activated at critical times to produce proteins vital to sustaining this pathway. Some researchers have focused on identifying particular genes that place men at risk for ED. At present, these studies are limited to animal models, and little success has been reported to date.  Nevertheless, this research has given rise to many new treatment targets and a better understanding of the entire process.
While pills for ED are convenient, some men sustain stronger erections by injecting medication directly into the penis. Drugs approved for this purpose work by widening the blood vessels, causing the penis to become engorged with blood. Another option is inserting a medicated pellet into the urethra. The pellet can trigger an erection within 10 minutes.