NO is produced by the enzyme NO synthase (NOS).  NOS plays many roles, ranging from homeostasis to immune system regulation. To date, 3 subtypes have been identified: nNOS, iNOS, and eNOS, which are produced by the genes NOS1, NOS2, and NOS3, respectively. This nomenclature is derived from the sources of the original isolates: neuronal tissue (nNOS), immunoactivated macrophage cell lines (iNOS), and vascular endothelium (eNOS). The subtypes are not, however, limited to the tissues from which they were first isolated.
The dose of PDE5 inhibitor that you start with may vary with underlying medical conditions and medications that you are taking. Thus, it is important to review all medications (even over the counter medications) with your physician. Typically, one starts with a lower dose and increases as needed. Some medical conditions prevent going up to higher doses. You can review the drug prescribing information or consult with your doctor regarding the dose(s) that are appropriate for you.
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Alprostadil is a potent vasodilator and smooth muscle relaxant identical to the naturally occurring PGE1. PGE1 binds with specific receptors on smooth muscle cells and activates intracellular adenylate cyclase to produce cAMP, which in turn induces tissue relaxation through a second messenger system (96). PGE1 is the only FDA approved form of intracavernosal therapy and is available commercailly as EDEX, or Caverject. Its efficacy was demonstrated in several clinical trials where the rate of responders ranged from 40% to 80% (97,98). The most common adverse event is penile pain, which is not related to the injection of the medication itself. In men with prolonged use the pain is usually self-limited (99).
Recently, the US Food and Drug Administration (FDA) has issued a safety announcement regarding TRT. In part it reads ‘The benefit and safety of these medications have not been established. We are also requiring these manufacturers to add information to the labeling about a possible increased risk of heart attacks and strokes in patients taking testosterone.’37
The main surgical treatment of ED involves insertion of a penile implant (also called penile prostheses). Because penile vascular surgery is not recommended for aging males who have failed oral PDE5 inhibitors, ICI or IU therapies, implants are the next step for these patients. Although placement of a penile implant is a surgery which carries risks, they have the highest rates of success and satisfaction among ED treatment options.
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.
For obvious reasons, ED can be a sensitive subject, one that until relatively recently men were more likely to try to hide than to deal with. Fortunately, a deeper understanding of the variety of causes of erectile dysfunction has led to medications, therapies, and other treatments that can be more individualized and more likely to be effective—and more open discussion about addressing the concern.
A vacuum erection device helps draw blood into the penis by applying negative pressure. This type of device is sometimes referred to as penis pump and may be used just prior to sexual intercourse. Several types of FDA approved vacuum therapy devices are available under prescription. When pharmacological methods fail, a purpose-designed external vacuum pump can be used to attain erection, with a separate compression ring fitted to the base of the penis to maintain it. These pumps should be distinguished from other penis pumps (supplied without compression rings) which, rather than being used for temporary treatment of impotence, are claimed to increase penis length if used frequently, or vibrate as an aid to masturbation. More drastically, inflatable or rigid penile implants may be fitted surgically.
Penis pumps produce erections by drawing blood, via air suction, into the penis. The devices consist of a cylindrical tube, 12 to 18 inches long, connected by a small air hose to a hand pump (on many models this resembles the squeeze mechanism on a blood pressure monitor). Users place the tube over the penis then pump to produce an erection. They must then place an elastic band around the base of the penis to keep the blood there and maintain the erection.
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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If you have symptoms of ED, it’s important to check with your doctor before trying any treatments on your own. This is because ED can be a sign of other health problems. For instance, heart disease or high cholesterol could cause ED symptoms. With a diagnosis, your doctor could recommend a number of steps that would likely improve both your heart health and your ED. These steps include lowering your cholesterol, reducing your weight, or taking medications to unclog your blood vessels.
There have been rare reports of priapism (prolonged and painful erections lasting more than six hours) with the use of PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil. Patients with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penis and lead to permanent impotence. Therefore, if your erection lasts four hours, you should seek emergency medical care.
The Massachusetts Male Aging Study (MMAS) documented an inverse correlation between ED risk and high-density lipoprotein (HDL) cholesterol levels but did not identify any effect from elevated total cholesterol levels.  Another study involving male subjects aged 45-54 years found a correlation with abnormal HDL cholesterol levels but also found a correlation with elevated total cholesterol levels. The MMAS included a preponderance of older men.
2 inability of the adult male to achieve or sustain a penile erection or, less commonly, to ejaculate after achieving an erection. Several forms are recognized. Functional impotence has a psychological basis. Organic impotence includes vasculogenic, neurogenic, endocrinic, and anatomical factors. Anatomical impotence results from physically defective genitalia. Atonic impotence involves disturbed neuromuscular function. Poor health, old or advancing age, drugs, smoking, trauma, and fatigue can induce impotence. Also called erectile dysfunction, impotency. impotent, adj.
Radical prostatectomy for the treatment of prostate cancer poses a significant risk of ED. A number of factors are associated with the chance of preserving erectile function. If both nerves that course on the lateral edges of the prostate can be saved, the chance of maintaining erectile function is reasonable. The odds depend on the age of the patient. Men younger than 60 years have a 75-80% chance of preserving potency, but men older than 70 years have only a 10-15% chance.
"Erectile dysfunction can be a very serious issue because it's a marker of underlying cardiovascular disease, and it often occurs before heart conditions become apparent. Therefore, men should consider improving their weight and overall nutrition, exercise more, drink less alcohol and have a better night's sleep, as well as address risk factors such as diabetes, high blood pressure and cholesterol.
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).
3. Testosterone replacement. Before oral medications like Viagra, testosterone was routinely used to treat erectile dysfunction as it is central in the male sexual response, including the desire for sex and the process of getting an erection. Testosterone can be administered in a number of ways, for example orally, by means of an injection, skin patch, or subcutaneous (under the skin) pellet.
Chancellor et al. (109) compared VEDs with papaverine injections in 18 males with SCI. The injections and pumps were equally effective in inducing erections and no adverse effects from the treatments were reported. Treatment arms were crossed over, subsequently seven men chose the VED and seven men chose the papavarine highlighting equal efficacy in this population. In another treatment arm topical minoxidil was applied without any effective erections achieved by the study subjects.
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.  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 cold slice of watermelon can do more than just satisfy thirst and hunger during the warm summer months; it can help with bedroom satisfaction. Citrulline, the amino acid found in high concentrations of watermelon, is found to improve blood flow to the penis. A 2011 study revealed men who suffered from mild to moderate ED and took L-citrulline supplementation showed an improvement with their erectile function and were very satisfied. Natural watermelon juice, or “nature’s Viagra,” can also be easier on the stomach, since taking pills like Viagra can cause nausea and diarrhea.
There are many effective treatments for impotence. The most popular is a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors. These include sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis) and avanafil (STENDRA). These drugs are taken in pill form. They work in most men. But they are less effective in men with neurological causes of impotence.
Before taking any medication for erectile dysfunction, including over-the-counter supplements and herbal remedies, get your doctor's OK. Medications for erectile dysfunction do not work in all men and might be less effective in certain conditions, such as after prostate surgery or if you have diabetes. Some medications might also be dangerous if you:
The inability to achieve or sustain a sufficiently firm penile erection (tumescence) to allow normal vaginal sexual intercourse. The great majority of cases are not caused by organic disease and most men experience occasional periods of impotence. It is often related to anxiety about performance and is usually readily corrected by simple counselling methods which prescribe sensual massage but forbid coitus. Organic impotence may be caused by DIABETES, MULTIPLE SCLEROSIS, spinal cord disorders and heart disease. Many cases can be helped by the drug SILDENAFIL (Viagra).
Although not proven, it is likely that erectile dysfunction can be prevented by good general health, paying particular attention to body weight, exercise, and cigarette smoking. For example, heart disease and diabetes are problems that can cause erectile dysfunction, and both are preventable through lifestyle changes such as sensible eating and regular exercise. Furthermore, early diagnosis and treatment of associated conditions like diabetes, hypertension and high cholesterol may prevent or delay erectile dysfunction, or stop the erectile dysfunction from getting more serious.
Effective treatment for erectile dysfunction is available, and for most men will allow the return to a fulfilling sex life. The side effects of the treatment for erectile dysfunction vary depending on the treatment that is used. Some may interrupt the spontaneity of sexual activity. For example, PDE-5 inhibitors typically need to be taken one hour before sex. Side effects may include headaches, indigestion, vasodilation, diarrhoea and blue tinge to vision. Other treatments such as penile injections may cause pain at the injection site, or an erection that will not go down. Treatment options need to be carefully discussed with your doctor to determine which one is best suited to you.
"The good news is, our study also found that a large proportion of men were naturally overcoming erectile dysfunction issues. The remission rate of those with erectile dysfunction was 29%, which is very high. This shows that many of these factors affecting men are modifiable, offering them an opportunity to do something about their condition," Professor Wittert says.
Lifestyle choices that impair blood circulation can contribute to ED. Smoking, excessive drinking, and drug abuse may damage the blood vessels and reduce blood flow to the penis. Smoking makes men with atherosclerosis particularly vulnerable to ED. Being overweight and getting too little exercise also contribute to ED. Studies indicate that men who exercise regularly have a lower risk of ED.