All of these medicines work by relaxing smooth muscles and increasing blood flow in the penis during sexual stimulation. You should not take any of these medicines to treat ED if you are taking nitrates to treat a heart condition. Nitrates widen and relax your blood vessels. The combination can lead to a sudden drop in blood pressure, which may cause you to become faint or dizzy, or fall, leading to possible injuries.
PDE 5 inhibitors are broken down primarily by enzyme, cytochrome P450enzyme CYP3A4. Medications that decrease or increase the activity of CYP3A4 may affect levels and effectiveness of PDE 5 inhibitors. Such drugs include medications for the treatment of HIV (protease inhibitors) and the antifungal medications ketoconazole and itraconazole. Thus caution is recommended.
One study examined the role of testosterone supplementation in hypogonadal men with ED. These men were considered nonresponders to sildenafil, and their erections were monitored by assessing nocturnal penile tumescence (NPT). After these men were given testosterone transdermally for 6 months, the number of NPTs increased, as did the maximum rigidity with sildenafil. [18] This study suggests that a certain level of testosterone may be necessary for PDE5 inhibitors to function properly.
ED is a common occurrence after SCI, occurring in up to 80% of men, and results from disruption of the nerve pathways essential for erection (24,25). Different degrees of ED may occur depending on the spinal cord level of injury (LOI), extent of lesion and timing from injury. Reflexogenic erections can occur with lesions above L3 or L4 when the erectile spinal reflex arc remains intact. Psychogenic erections can occur with low lesions in the sacral and lumbar spinal cord but may not occur in complete lesions above T9 that can damage sympathetic outflow. Additionally, reflexogenic erections are not likely to occur in the spinal shock period that occurs after the initial cord trauma. Conversely, their occurrence may signal that the period of shock is over (26). Typically SCI affects younger men in their “sexual prime” and ED is associated with decreased quality of life (27).

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Positron emission tomorgraphy (PET), and functional magnetic resonance imaging (fMRI) have led to a greater understanding to which center are activated during arousal. These imaging studies measure increases in cerebral blood flow or changes in cerebral activity on a real-time basis. Studies are performed when male subject are aroused by visual cues (usually sexual explicit photos or videos) and compared to images obtained during exposure to sexually neutral cues differences can be measured. Several studies have identified that the inferior frontal lobes, inferior temporal lobes and insular gyrus, and occipital lobes are involved with processing arousal cues, although each are likely to process different stimuli (20-23).
The idea of using low-energy shock waves to treat erectile dysfunction comes from studies that show that these types of shocks help heart blood vessels regrow, a process called revascularization. Shock wave therapy may also work on the penis, and there have been some promising results, but it’s not currently an approved ED treatment. "It’s similar to the type of shock waves used to break up kidney stones, and it may cause revascularization,” says Bennett. “However, there are not yet any good controlled studies to recommend it to patients."
Oral ED medication is considered highly effective and studies show it works on the majority of men. But no medication works for everyone and ED medication is no exception. Everyone’s reaction to a medication is unique and anything potent enough to help is strong enough to have side effects. If the medication isn’t working, it is important to tell your doctor. Sometimes it is a matter of needing a higher dose. Also, it has been shown that it takes 6 to 8 tries using the medication to experience the best result.

The physical examination can reveal clues for physical causes of erectile dysfunction. A doctor will perform an assessment of BMI and waist circumference to evaluate for abdominal obesity. A genital examination is part of the evaluation of erectile dysfunction. The examination will focus on the penis and testes. The doctor will ask you about penile curvature and will examine the penis to see if there are any plaques (hard areas) palpable. The doctor will examine the testes to make sure they are in the proper location in the scrotum and are normal in size. Small testicles, lack of facial hair, and enlarged breasts (gynecomastia) can point to hormonal problems such as hypogonadism with low testosterone levels. A health care provider may check pulses in your groin and feet to determine if there is a suggestion of hardening of the arteries that could also affect the arteries to the penis.


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.
In one study, 9.6% reported ‘occasional’ erectile dysfunction, 8.9% reported erectile dysfunction occurring ‘often’, and 18.6% reported erectile dysfunction occurring ‘all the time’. Of these, only 11.6% had received treatment.In another study, only 14.1% of men reported that they had received treatment, despite experiencing erectile dysfunction for longer than 12 months.
The medications are extremely effective, which is very good. And the medications are, for the most part, extremely well-tolerated. But there are, like with any medications, a potential downside. The one absolute downside to the use of any of these erection what we call PDE5 medications is if a patient is using a nitroglycerin medication. And nitroglycerins are used for heart disease and for angina, for the most part, although there are some recreational uses of nitrites. And that’s important because your blood vessels will dilate and your blood pressure will drop. And that is an absolute contraindication.
Low-intensity extracorporeal shock wave therapy has been proposed as a new non-invasive treatment for erectile dysfunction caused by problems with blood vessels. Shock wave therapy machines are now available in some medical practices in Australia. Although there is some evidence that it may help a proportion of men with erectile dysfunction, more research is needed before clear recommendations on its use can be made.
Apomorphine is a non-selective D1/D2 receptor agonist with moderate efficacy and good tolerability in the treatment of mild ED (80). Apomorphine can be administered via subcutaneous injection or sublingually. However, studies have shows a lower efficacy for apomorphine compared to oral sildenafil (81,82). Apomorphine has a set role in the management of PD for non-motor symptoms, and has been reported to cause spontaneous erections and possible hypersexuality in PD men (83,84). Its role in the management of ED has been postulated for men with PD but should be considered as an alternative to sildenafil.
Cosgrove et al reported a higher rate of sexual dysfunction in veterans with posttraumatic stress disorder (PTSD) than in veterans who did not develop this problem. [42] The domains on the International Index of Erectile Function (IIEF) questionnaire that demonstrated the most change included overall sexual satisfaction and erectile function. [43, 44] Men with PTSD should be evaluated and treated if they have sexual dysfunction.

A physical cause can be identified in about 80% of cases.[2] These include cardiovascular disease, diabetes mellitus, neurological problems such as following prostatectomy, hypogonadism, and drug side effects. Psychological impotence is where erection or penetration fails due to thoughts or feelings; this is somewhat less frequent, in the order of about 10% of cases.[2] In psychological impotence, there is a strong response to placebo treatment.
There are treatments available to help you to get and maintain an erection. In addition, making healthy changes to your lifestyle could help with impotence. Switching to a healthier balanced diet, taking more exercise and cutting down on or giving up alcohol and cigarettes could help you to see an improvement in sexual function. If you think that the problem may be related to stress or anxiety, counselling can also help.
In patients with low testosterone, testosterone treatment can improve libido and erectile dysfunction, but many men still may need additional oral medications such as sildenafil, vardenafil, or tadalafil. Some studies suggest that men with ED and low testosterone may respond better to PDE5 inhibitors when given testosterone therapy; however, this is controversial.
This procedure is usually performed before and after injection of a smooth-muscle-relaxing medication into the penis, which normally should significantly increase the diameter of the penile arteries. The procedure itself is painless. Duplex ultrasonography is most useful in evaluating possible penile arterial disorders, but in those individuals considering surgery for problems with the arteries to the penis, a more invasive study, angiogram, is needed to identify the location of the damaged artery.
In some cases, ED can be a warning sign of more serious disease. One study suggests ED is a strong predictor of heart attack, stroke, and death from cardiovascular disease. The researchers say all men diagnosed with ED should be evaluated for cardiovascular disease. This does not mean every man with ED will develop heart disease, or that every man with heart disease has ED, but patients should be aware of the link.
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