Alteration of NO levels is the focus of several approaches to the treatment of ED. Inhibitors of phosphodiesterase, which primarily hydrolyze cGMP type 5, provided the basis for the development of the PDE5 inhibitors. Chen et al administered oral L-arginine and reported subjective improvement in 50 men with ED. [14] These supplements are readily available commercially. Reported adverse effects include nausea, diarrhea, headache, flushing, numbness, and hypotension.
If it is determined that ED is a problem, the patient evaluation should include a detailed sexual and medical history and a physical exam. In particular, it is important to evaluate the ED within the context of ejaculatory problems. There is a strong interplay between premature ejaculation (PE) and ED, with about a third of ED patients reporting PE. The relationship between the PE and ED is bidirectional and successful treatment of one often requires treatment of the other.14
The venous constriction device is a device designed to compress the veins that drain blood flow out of the penis to keep blood in the penis. These devices may help individuals who have a "venous leak." In these individuals, although blood flow is coming into the penis, it is draining out at the same time and this persistent drainage prevents a fully rigid erection. These devices may be used with other forms of medical therapy, such as medications, injection therapy, or the vacuum device.

A meta-analysis of 36 744 men with ED in 12 prospective cohort studies found that the presence of ED significantly increased the risk of CVD, CAD, stroke and all-cause mortality, and the presence of ED was an independent risk factor for CVD. Ponholzer et al found that men with moderate to severe ED had a 65% increased relative risk for developing symptomatic CAD compared with men who did not have ED.26


Erections are neurovascular events, meaning that nerves and blood vessels (arteries and veins) are involved in the process of an erection and all must work properly to develop a hard erection that lasts long enough. Erection begins with sexual stimulation. Sexual stimulation can be tactile (for example, by a partner touching the penis or by masturbation) or mental (for example, by having sexual fantasies, viewing porn). Sexual stimulation or sexual arousal causes the nerves going to the penis to release a chemical, nitric oxide. Nitric oxide increases the production of another chemical, cyclic GMP (cGMP), in the muscle of the corpora cavernosa. The cGMP causes the muscles of the corpora cavernosa to relax, and this allows more blood to flow into the penis. The incoming blood fills the corpora cavernosa, making the penis expand.


Stanley A Brosman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for the Advancement of Science, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Urological Association, Society for Basic Urologic Research, Society of Surgical Oncology, Society of Urologic Oncology, Western Section of the American Urological Association, Association of Clinical Research Professionals, American Society of Clinical Oncology, International Society of Urology, International Society of Urological Pathology
All NOS subtypes produce NO, but each may play a different biologic role in various tissues. nNOS and eNOS are considered constitutive forms because they share biochemical features: They are calcium-dependent, they require calmodulin and reduced nicotinamide adenine dinucleotide phosphate for catalytic activity, and they are competitively inhibited by arginine derivatives. nNOS is involved in the regulation of neurotransmission, and eNOS is involved in the regulation of blood flow.
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Erectile dysfunction - (ED) or impotence is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual activity. A penile erection is the hydraulic effect of blood entering and being retained in sponge-like bodies within the penis. The process is most often initiated as a result of sexual arousal, when signals are transmitted from the brain to nerves in the penis.
The first stem cell study for the treatment of ED was published in 2004. This study used embryonic stem cells to treat ED. At this time, there is a total of 36 published basic studies assessing stem cell therapy for ED, with two clinical trials. The mechanism of action of stem cells is to generate angiogenesis with subsequent increase in cavernosal smooth muscle cells within the corporal bodies.46

Sexual dysfunction is highly prevalent in men and women. In the MMAS, 52% of the respondents reported some degree of erectile difficulty. Complete ED, defined as (1) the total inability to obtain or maintain an erection during sexual stimulation and (2) the absence of nocturnal erections, occurred in 10% of the respondents. Mild and moderate ED occurred in 17% and 25% of responders, respectively. [15]

Chronic stress dumps adrenaline in your system multiple times a day. And that can lead to high blood pressure, heart disease, obesity, and diabetes. Chronic stress is like red-lining your car all day long. When you drive 100 mph all the time, something is going to break down. A high-stress environment can actually change the way your brain sends messages to your body. Dumping too much adrenaline into your bloodstream can affect blood flow and severely limit your ability to achieve and maintain an erection.


Melanocortin receptor agonists were found to induce erections serendipitously. A study investigating the dermatologic use of Melanotan-II (MT-II) was found to generate erections unexpectedly leading to the development of MTII derivatives for ED treatment (120). MT-II was initially used to induce pigment changes in the skin for artificial tanning but has been suspected to induce melanoma, however (121).

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).

L-arginine, an amino acid that is naturally present in the body and helps make nitric oxide, supports a successful erection. Nitric oxide is responsible for making the blood vessels relax, which helps sustain an erection for men. A 1999 study, observed the effects of six weeks of high-dose (5 grams/day) orally administered nitric oxide (NO) donor L-arginine on men with organic ED. Thirty-one percent of those who took 5 grams/day of L-arginine experienced significant improvements in sexual function. Burns told Medical Daily, “l-arginine and deer antler velvet” have been the most popular go-to natural treatments for men.


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.
Alprostadil should not be used in men with urethral stricture (scarring and narrowing of the tube that urine and the ejaculate pass through), balanitis (inflammation/infection of the glans [tip] of the penis, severe hypospadias (a condition where the opening of the urethra is not at the tip of the penis, rather on the underside of the penis), penile curvature (abnormal bend to the penis), and urethritis (inflammation/infection of the urethra).
Patients at high cardiovascular risk should not be treated for ED until their cardiac condition is stabilize. These conditions include unstable or refractory angina, myocardial infarction or cerebrovascular accident within the past 2 weeks, uncontrolled hypertension, New York Heart Association (NYHA) Functional Classification III-IV congestive heart failure, high-risk arrhythmias, hypertrophic obstructive cardiomyopathies, and moderate-to-severe valvular disease.25 This class of drugs is also contraindicated in patients who use nitroglycerin or nitrate-containing compounds.26, 27
Besides PDE5 inhibitors and among second-line therapies are VCDs which are clear plastic chambers placed over the penis, tightened against the lower abdomen with a mechanism to create a vacuum inside the chamber. This directs blood into the penis. If an adequate erection occurs inside the chamber, the patient slips a small constriction band off the end of the VCD and onto the base of the penis. An erection beyond 30 min is not recommended. These devices can be a bit cumbersome, but are very safe.40

The vacuum device creates a vacuum to pull blood into the penis. Unlike a normal erection, the inflow of blood does not continue once the individual removes the vacuum device. The rubber band placed at the base of the penis constricts the penis to prevent the blood from leaving the penis. As there is no inflow or outflow of blood when the rubber band is in place, it is uncommon for the tip of the penis (the glans) to appear a little blue and the penis to be cooler. Once intercourse is completed, the individual removes the rubber band and the blood drains out of the penis.
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.
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.
Then you have to be able to make the right diagnosis. What is the basis for their erectile dysfunction? Is it psychogenic? Is it some sort of neurological or blood vessel or hormonal issue? So you have to make a diagnosis. You have to be able to make an assessment. And then only after those things are done, then you start to think about medications.
Certain types of blood pressure medications, antiulcer drugs, antihistamines, tranquilizers (especially before intercourse), antifungals (hetoconazole), antipsychotics, antianxiety drugs, and antidepressants, known as selective serotonin reuptake inhibitors (SSRIs, including Prozac and Paxil), can interfere with erectile function. Smoking, excessive alcohol consumption, and illicit drug use may also contribute. In rare cases, low levels of the male hormone testosterone may contribute to erectile failure. Finally, psychological factors, such as stress, guilt, or anxiety, may also play a role, even when the impotence is primarily due to organic causes.
The lab testing obtained for the evaluation of erectile dysfunction may vary with the information obtained on the health history, physical examination, and recent lab testing. A testosterone level is not necessary in all men; however, a physician will order labs to determine a patient's testosterone level if other signs and symptoms of hypogonadism (low testosterone) such as decreased libido, loss of body hair, muscle loss, breast enlargement, osteoporosis, infertility, and decreased penile/testicular size are present.
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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).
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.
These are not currently approved by the FDA for ED management, but they may be offered through research studies (clinical trials). Patients who are interested should discuss the risks and benefits (informed consent) of each, as well as costs before starting any clinical trials. Most therapies not approved by the FDA are not covered by government or private insurance benefits.
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