Although vardenafil does not seem to produce significant clinical QT prolongation, it has been suggested that it be avoided in patients who have congenital QT prolongation abnormalities and in patients using class I antiarrhythmic drugs, such as quinidine and procainamide. It is also best to avoid the use of vardenafil with class III antiarrhythmic drugs, such as amiodarone or sotalol.
In 1983, Brindley injected the corpora of several SCI men with phentolamine (85). Two out of the three men had a sufficient erection produced. Since then multiple reports on the efficacy of intracavernosal therapy have been published using, phentolamine, papaverine, prostaglandin, vasoactive intestinal peptide (VIP), and these medications in combination (86-90). These medications have been found to be extremely effective for neurogenic ED due to their ability act locally and essentially bypassing neuronal pathways. Local therapies are usually considered second-line after PDE5i fail to elicit a desired response which can occur in about 25–30% of men with ED, in general (91). Furthermore, the locally delivered medications can be quite dangerous if not used appropriately as priapism and significant pain with injections can occur. These specific occurrences have been suggested as a reason for high discontinuation rates with intracavernosal therapy (92).
Vascular damage may result from radiation therapy to the pelvis and prostate in the treatment of prostate cancer.  Both the blood vessels and the nerves to the penis may be affected. Radiation damage to the crura of the penis, which are highly susceptible to radiation damage, can induce ED. Data indicate that 50% of men undergoing radiation therapy lose erectile function within 5 years after completing therapy; fortunately, some respond to one of the PDE5 inhibitors.
ED usually has a multifactorial etiology. Organic, physiologic, endocrine, and psychogenic factors are involved in the ability to obtain and maintain erections. In general, ED is divided into 2 broad categories, organic and psychogenic. Although most ED was once attributed to psychological factors, pure psychogenic ED is in fact uncommon; however, many men with organic etiologies may also have an associated psychogenic component.
An analysis of 14 studies involving more than 90,000 patients with ED confirmed the relation between ED and an increased risk of cardiovascular events and mortality.  Compared with patients without ED, those with ED had a 44% increased risk of cardiovascular events, a 25% increased risk of all-cause mortality, a 62% increased risk of MI, and a 39% increased risk of cerebrovascular events. Treatment of ED, either through lifestyle interventions or by pharmacologic means, may improve prognosis and reduce risk.
Over a 2-year period, a third of the men randomized to a weight loss program demonstrated resolution of erectile dysfunction.10 A Mediterranean diet and nutritional counseling reported increased erectile quality.18 Little evidence supports that increased physical activity alone improves erectile quality; however, the strong association between physical activity and lower BMI is well described, and therefore recommended for men with erectile dysfunction and without a contraindication to physical activity.
In fact, one common reason many younger men visit their doctor is to get erectile dysfunction medication. Often, men with erectile dysfunction suffer with diabetes or heart disease, or may be sedentary or obese, but they don’t realize the impact of these health conditions on sexual function. Along with erectile dysfunction treatment, the doctor may recommend managing the illness, being more physically active, or losing weight.
Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
Inside the cell, NOS catalyzes the oxidation of L-arginine to NO and L-citrulline. Endogenous blockers of this pathway have been identified. The gaseous NO that is produced acts as a neurotransmitter or paracrine messenger. Its biologic half-life is only 5 seconds. NO may act within the cell or diffuse and interact with nearby target cells. In the corpora cavernosa, NO activates guanylate cyclase, which in turn increases cyclic guanosine monophosphate (cGMP). Relaxation of vascular smooth muscles by cGMP leads to vasodilation and increased blood flow.
The role of the endothelium in ED has been noted for a number of years and the overlapping of ED and other conditions, especially coronary heart disease, CVD, affecting endothelial function/dysfunction, is clearly present. The endothelial cell is now known to affect vascular tone and impact the process of atherosclerosis, and impacting ED, CVD and peripheral vascular disease.16
Your doctor will ask you questions about your symptoms and health history. They may do tests to determine if your symptoms are caused by an underlying condition. You should expect a physical exam where your doctor will listen to your heart and lungs, check your blood pressure, and examine your testicles and penis. They may also recommend a rectal exam to check your prostate. Additionally, you may need blood or urine tests to rule out other conditions.
Examples of common neurologic conditions that can lead to ED include cerebral vascular accident, multiple sclerosis, Parkinson’s disease, and spinal cord injury. Microvascular disease associated with diabetes is thought to compound the endothelial and neural injuries associated with this disease. Pelvic surgery may disrupt both neural and vascular pathways, resulting in ED.
Erectile dysfunction may be an unpleasant condition that no one really wants to talk about, failing to acknowledge it won’t make the problem go away. Your best defense against health problems like this is to learn everything you can about it so you can tackle the problem at the root. If you’re ready to stop living in embarrassment about your sexual function, become an advocate for yourself and your own health and talk to your doctor.
Trauma to the pelvic blood vessels or nerves can also lead result in ED. Bicycle riding for long periods has been implicated as an etiologic factor; direct compression of the perineum by the bicycle seat may cause vascular and nerve injury.  On the other hand, bicycling for less than 3 hours per week may be somewhat protective against ED.  Some of the newer bicycle seats have been designed to diminish pressure on the perineum. [37, 38]
Finally, gene therapy and stem cell research has widened the frontier of ED treatment proposed as possibility to even reverse ED. Specifically, gene therapy pertains to repairing the cause of ED by restoring defective gene function and/or altering the expression of the mutant gene (32). Most of the available data on gene therapy are in the animal model. However, a phase I clinical trial in men with ED undergoing intracavernous injection with a DNA plasmid carrying the alpha-subunit of the corporal smooth muscle Maxi-K channel showed promise in increased erectile function based on IIEF assessment sustained throughout the 3-month study period (122).
Finally, there are NO-releasing polymers that are capable of delivering NO in a pharmacologically useful way. Such compounds include compounds that release NO upon being metabolised and compounds that release NO spontaneously in aqueous solution. Initial animal studies suggest that cavernosal injections of NO polymers can significantly improve erectile function.48
Erections are initiated and maintained via integration of afferent inputs in the supra sacral regions of the central nervous system. Regions of the brain cited to have key roles in the integration of signals include the medial amygdala, MPOA, periaqueductal gray matter, paraventricular nucleus (PVN), and ventral tegmentum among others (16). Studies in animal models, particularly in rats, have been paramount in identifying these key areas of signal integration and control. Electrostimulation of the MPOA, PVN and hippocampus lead to erection and lesions in these areas may prevent erection (17). Marson et al. injected labeled pseudorabies virus into rat corpora cavernosa and traced them to neurons in the spinal cord, brain stem and hypothalamus (18). Stimulation of the rat dorsal nerve led to increased firing in the MPOA not found elsewhere (19). Axonal tracing in animals have shows direct projections from the hypothalamus to the lumbosacral autonomic erection centers. Oxytocin and vasopressin have been identified as central neurotransmitters within the hypothalamic nuclei and may have a role in penile erection (17). These signaling studies identifying key areas of erectile response integration may explain how ED is associated with cerebrovascular accident (CVA), Parkinson’s, epilepsy and MS.
Oral PDE5i remains the first line treatment for NED from SCI. Three of the four PDE5i currently available in the U.S., avanafil excluded, have been investigated in the SCI, and all of the more recent studies have shown improvements in erectile function based on IIEF score compared to placebo when included (59-63). Other studies have also shown significant improvements in the IIEF score when compared to baseline (64-69). Furthermore, treatment efficacy when compared to placebo occurs despite LOI or American Spinal Injury Association (ASIA) score characterizing impairment related to the injury (59,61).
Impotence, also known as erectile dysfunction or ED, is a condition in which a man is unable to get or hold an erection long enough to have a satisfactory sex life. Impotence is a common problem, affecting up to half of Australian men between the ages of 40 and 70 years. The risk of developing erectile dysfunction increases as you get older.In the past, doctors considered impotence to be a mainly psychological problem, caused by performance anxiety or stress. Now, doctors know that many cases of impotence have a physical cause, which usually can be treated. Often, a combination of physical and psychological factors contributes to erectile dysfunction.Physical causes of impotencePhysical causes of impotence can include:problems with blood to flow into and out of the penis;damage to the nerves that send signals from the body’s central nervous system to the penis; and, more rarely,a deficiency in testosterone or other hormones.Some medicines can contribute to impotence, as can some types of surgery and radiotherapy treatments.Blocked blood vessels to the penisA very common cause of impotence is when blood flow into the penis is reduced. This can be due to atherosclerosis, also known as hardening of the arteries. In atherosclerosis, the arteries are clogged and narrowed, resulting in reduced blood flow.Risk factors for atherosclerosis include:high cholesterol;high blood pressure;obesity;sleep apnoea;diabetes; andsmoking.If your erection problems are caused by atherosclerosis, there is a chance that the arteries in other parts of your body (e.g. the coronary arteries that supply your heart) are also affected by atherosclerosis. In fact, erection problems may be the first sign that you are at risk of coronary heart disease.Because the arteries to the penis are narrower than those to the heart, you may develop symptoms of erectile dysfunction before you experience any symptoms of heart disease, such as angina. So seeing your doctor about erection problems may be important for your overall physical health.Impotence can also be caused by a blood clot that prevents enough blood from flowing into the penis to cause an erection.Venous leakageIn some men, blood can flow in to the penis easily, but the problem is that it leaks out again, so an erection cannot be sustained. This is called venous leakage. Doctors aren’t certain of the cause of venous leakage, but they can perform surgery to help repair it.Medicines that can cause impotenceMany medicines can cause erection problems as a side effect, including:diuretics (sometimes known as ‘water tablets’ - often used for high blood pressure);high blood pressure medications;cholesterol-lowering medicines (including statins);some types of antipsychotics;antidepressants;cancer treatments;some medicines used to treat heartburn and stomach ulcers;antihistamines;some pain medicines; andcertain epilepsy medications.If you experience impotence after starting a new medication, tell your doctor, who may be able to prescribe a different medicine for you. Don’t stop taking a medicine without first consulting your doctor. You should also tell your doctor about any over-the-counter medicines or complementary remedies you may be taking.The following table contains a list of specific medicines that may cause or contribute to erectile dysfunction. This list may not cover all types of medicines that can cause erectile dysfunction, so always ask your doctor if you are in doubt. Also, for some of these medicines ED is a very rare side effect. Most men taking these medicines do not experience erectile dysfunction.Medicines that may cause erectile dysfunctionType of medicineExamplesACE inhibitorscaptopril (Capoten), enalapril (Renitec), perindopril (Perindo), ramipril (Tritace), and othersAntidepressantsamitriptyline (Endep), clomipramine (Anafranil), desvenlafaxine (Pristiq), fluoxetine (Prozac), paroxetine (Aropax), sertraline (Zoloft), venlafaxine (Altven, Efexor), and othersAnti-epilepticsclonazepam (Rivotril), pregabalin (Lyrica)Antifungalsitraconazole (Sporanox)Anti-ulcer drugscimetidine (Magicul), nizatidine (Tazac), ranitidine (Zantac), and othersBeta-blockerspropranolol (Inderal), metoprolol (Betaloc, Lopresor), and othersOther blood pressure-lowering medicinesclonidine (Catapres), lercanidipine/enalapril (Zan-Extra), losartan (Cozaar), perindopril/amlodipine (Coveram), olmesartan/amlodipine (Sevikar), telmisartan/amlodipine (Twynsta), valsartan/hydrochlorothiazide (Co-Diovan)Calcium-channel blockersdiltiazem (Cardizem), felodipine (Plendil), nifedipine (Adalat)Cholesterol-lowering drugsatorvastatin (Lipitor), ezetimibe/simvastatin (Vytorin), fluvastatin (Lescol, Vastin), gemfibrozil (Ausgem), pravastatin (Pravachol), simvastatin (APO-simvastatin, Lipex, Zocor), and othersDiuretics ('water tablets')bumetanide (Burinex), chlorthalidone (Hygroton), spironolactone (Aldactone), and othersSchizophrenia drugsamisulpride (Solian, Sulprix), haloperidol (Haldol, Serenace), olanzapine (Lanzek, Ozin, Zypine, Zyprexa), paliperidone (Invega), risperidone (Rispa, Risperdal), ziprasidone (Zeldox)Combination cholesterol-lowering and anti-hypertensiveamlodipine/atorvastatin (Caduet, Cadatin)Pain medicinesfentanyl (Denpax, Durogesic), hydromorphone (Jurnista), morphine (Momex SR, MS Contin), oxycodone (OxyContin, OxyNorm, Targin), tramadolMiscellaneousoestrogens, antiandrogens, anticancer drugs and some chemotherapy treatments, baclofen (Clofen, Lioresal); cyproterone (Androcur, Cyprohexal, Cyprostat), degarelix (Firmagon), etoricoxib (Arcoxia), finasteride (Proscar and Propecia), flutamide (Flutamin), rotigotine (Neupro), triptorelin (Diphereline)*The names in brackets are just some examples of the trade names each specific medicine is marketed under in Australia. The medicine may also be known by other trade names.Diabetes and erectile dysfunctionMen who have diabetes have a higher risk of developing impotence than other men. Diabetes contributes to impotence because it can damage blood vessels and cause a type of nerve damage known as peripheral neuropathy.Hormones and impotenceLow levels of the male hormone, testosterone, are more commonly linked to a lowered sex drive, rather than impotence itself. Only a small percentage of cases of impotence are caused by hormone deficiency.Low testosterone levels may be the result of a condition called hypogonadism, in which the testicles don’t produce enough testosterone. More rarely, low testosterone can be caused by the pituitary (a small gland at the base of the brain) not secreting sufficient hormones to stimulate the testes to produce testosterone. The pituitary is also sometimes affected by small benign (non-cancerous) tumours that secrete prolactin, another hormone that can cause impotence.Mildly decreased levels of testosterone are often not due to specific testicular or pituitary problems, but rather stress or depression. In this situation, testosterone replacement is rarely of any benefit.Other hormone problems, including thyroid disease, can also cause impotence.Prostate cancer and erectile dysfunctionThe advanced stages of prostate cancer can affect the nerves and arteries that are vital for an erection.Radiation treatment for prostate cancer can harm the erectile tissues of the penis, and prostate cancer surgery can cause nerve or artery damage to the penis.Treatment for advanced prostate cancer often includes medicines that counteract testosterone, and commonly cause erectile dysfunction as well as loss of sexual interest.Peyronie’s diseasePeyronie’s disease is an uncommon condition that affects a man’s sex life because his penis curves abnormally and causes pain when he has an erection. He might also be unable to have a hard erection. The curvature of the penis is caused by a scar, called a plaque, that forms in the penis.Other physical causes of impotenceSeveral other factors and conditions can contribute to erectile dysfunction, including the following.Depression. Many men find that when they’re suffering from depression, they lose interest in sex and can’t get or keep an erection. Asking your doctor for treatments for depression may help alleviate your erection problems as well.Smoking contributes to vascular disease (disease of the blood vessels), so it can contribute to erectile dysfunction by affecting blood flow to the penis. Giving up smoking often has a beneficial effect on erectile function.Excessive alcohol use. Alcoholism can cause permanent nerve damage, resulting in impotence. This nerve damage is called peripheral neuropathy. Long-term alcohol use can impair the liver’s ability to function, resulting in a hormone imbalance in which a man has too much of the female sex hormone, oestrogen. On a day-to-day level, alcohol dulls the central nervous system, adversely affecting sexual response.Illicit drug use. Illicit drugs such as marijuana, cocaine, heroin, barbiturates, and amphetamines act on the central nervous system, impairing the body’s ability to respond sexually.Certain exercises. Nerve and artery damage can be caused by prolonged cycling, rodeo riding, or use of a rowing machine, resulting in the inability to get an erection. Often, minimising the use of hard bicycle seats and exercise machine seats, as well as correct positioning of the seat, will help restore sexual function.Surgery to organs near the nerve pathways of the penis, such as the bladder, rectum and prostate, can cause nerve or artery damage to the penis, resulting in the inability to have an erection.Injuries. Impotence can be caused by spinal cord injury; injury to your sex organs; or a pelvic fracture, which can cause damage to the nerves of the penis, or damage the blood vessels, resulting in reduced blood flow to the penis.Conditions affecting the nervous system. Multiple sclerosis (MS) and other degenerative diseases of the nervous system, such as Parkinson’s disease, can damage the nerves involved in erections.Psychological causes of impotenceMost cases of impotence have physical causes, but, in some men, psychological factors are the main contributors to impotence.Impotence that’s triggered by psychological factors is more common in men who are sexually inexperienced. Psychological erectile dysfunction may only occur when you’re with just one particular person. You’re also more likely to have morning erections, and be able to have an erection when you masturbate, than men whose impotence has a physical cause.Here are some psychological factors that can have an impact on your erections.Stress and anxietyWhen you’re stressed and focusing on other issues apart from sex, you might find that you don’t want to have sex as often and there might be a drop in your ability to perform when you do try. You might find that tackling the source of your stress can have benefits in the bedroom as well.Fear of failureAnxiety about your sexual prowess (commonly called performance anxiety) can, in itself, contribute to failure. By putting pressure on yourself, you become too anxious to get an adequate erection.Most men experience isolated episodes of erectile failure. Even when the transient physical cause has passed, anxiety that it may recur is sufficient to prevent erection. Anxiety, whether about something specifically sexual or part of a wider anxiety syndrome, is never helpful to good sexual function.Problems with your relationship and impotenceImpotence may be a manifestation of a poor relationship, or a problematic time in a relationship. Sexual boredom, tension or anger among partners, and lack of intimacy and communication are all possible triggers of erectile dysfunction. In these cases, seeing a counsellor may help.It’s worth remembering that impotence is a complex medical condition, which may have more than one cause. For example, if impotence is the result of a side effect of medicine or an underlying disease, the anxiety caused by lack of performance may perpetuate the erectile dysfunction even after the physical cause has been dealt with.Almost any chronic (ongoing) physical or mental health disorder, including those with no direct effect on penile nerves or blood supply, can have a powerful effect on sexuality, sexual self-image and erectile function.If you’re worried about your sexual response or the quality of your erections, don’t be afraid to talk to your doctor, who has access to treatments that can help. Last Reviewed: 16 December 2016
Nerves originating in the spinal cord and peripheral ganglia innervate the penis. There are autonomic (parasympathetic and sympathetic), and somatic separate and integrated pathways. The autonomic pathways neurons originate in the spinal cord and peripheral ganglia from the sympathetic and parasympathetic systems, respectively. They merge to form the cavernous nerves that travel alongside the prostate, enter the corpora cavernosa and corpus spongiosum to affect the neurovascular events required for tumescence and detumescence. The somatic nerves send sensory information from the penile skin, glans, and urethra via the dorsal penile nerve and pudendal nerve to the spinal cord. The somatic nerves also initiate contraction of the ischio- and bulbocavernosus muscles.
There are myriad factors, both mental and physical, that may contribute to your erectile dysfunction symptoms. Some of the most common impotence causes include diabetes, hypertension, prostate problems, low testosterone and obesity, which can not only put a damper on your sexual enjoyment, but play a key role in your total male vitality, too. (Even medications that are often prescribed to control some of the aforementioned issues can be behind some of the frustrating symptoms of ED.) There are factors like depression, stress and anxiety that can leave you longing for your glory days, and the coping mechanisms like alcohol and tobacco that can make a roll in the sheets less satisfying for you and your partner. We’ll listen to you with a compassionate ear and thoughtfully consider what may be contributing to your ED symptoms, then draw up your perfect, personalized treatment.
Qaseem, A., Snow, V., Denberg, T. D., Casey, D. E., Forciea, M. A., Owens, D. K., & Shekelle, P. (2009). Hormonal testing and pharmacologic treatment of erectile dysfunction: A clinical practice guideline from the American College of Physicians. Annals of internal medicine, 151(9), 639-649. Retrieved from http://annals.org/aim/article/745155/hormonal-testing-pharmacologic-treatment-erectile-dysfunction-clinical-practice-guideline-from
In the short term, alcohol relaxes muscles in the penis, letting blood to flow in (which is a good thing). However, alcohol also prevents other blood vessels from closing and trapping all the extra blood. Erections depend on trapping increased blood flow in the erectile tissue of the penis. If you don’t trap that extra blood, you don’t get an erection. In the long run, excessive alcohol consumption can cause liver scarring, high blood pressure, and can damage your blood vessels resulting in erectile dysfunction.
The vascular processes that produce an erection are controlled by the nervous system and certain prescription medications may have the side effect of interfering with necessary nerve signals. Among the possible culprits are a variety of stimulants, sedatives, diuretics, antihistamines, and drugs to treat high blood pressure, cancer, or depression. But never stop a medication unless your doctor tells you to. In addition, alcohol, tobacco, and illegal drugs, such as marijuana, may contribute to the dysfunction.
Clinical experience in switching medications to improve ED has been disappointing in that improvement does not often occur. Nonetheless, it is important to try to discontinue possible offending medications before proceeding to more invasive ED treatment options. Oral ED medications have changed the way clinicians discontinue medications in patients with ED and has improved the approach. For example, a patient may develop ED on a thiazide diuretic. The diuretic may be withdrawn, but a trial of oral ED therapy can be initiated during the observation period while the patient is waiting to see if any spontaneous improvement in ED occurs after drug withdrawal. Alternatively, if diuretic therapy is effective, well tolerated, and controlling blood pressure, oral ED therapy can be used on an ongoing basis to treat the side effect of ED.
It is important for clinicians prescribing these drugs to make the patient aware of the action of the drugs especially the fact that they do not result in an immediate erection, and that they do not cause an erection without sexual stimulation. There is frequently a great expectation when men begin using these drugs and it is wise to temper their enthusiasm and explain they do not work immediately, and may not work every time, but also let the patient know that if these drugs do not work, there are other options.
Another study compared the response of surgically and medically castrated rabbits to vardenafil with that of control rabbits.  Castrated rabbits did not respond to vardenafil, whereas noncastrated rabbits did respond appropriately. This result suggests that a minimum amount of testosterone is necessary for PDE5 inhibitors to produce an erection.
…that relieve erectile dysfunction (impotence) in men. Two common commercially produced PDE-5 inhibitors are sildenafil (sold as Viagra) and vardenafil (Levitra). PDE-5 inhibitors work by blocking, or inhibiting, the action of phosphodiesterase-5 (PDE-5), an enzyme naturally present in the corpus cavernosum, the spongy erectile tissue of the penis. Under…