VIP is a neurotransmitter with regulatory actions on blood flow, secretion and muscle tone with intracorporal adenylate cyclase activation and smooth muscle relaxation. VIP has been shown to elevate cAMP intracellular concentrations without affecting cGMP levels. However, when VIP is given alone it may not induce erection and requires combination with phentolamine or papaverine for it to be effective (88). Common associated adverse effects were facial flushing and headache. VIP in combination with phentolamine is currently being used in the UK and Europe and is seeking regulatory approval for use in the United States.
The penis contains three cylinders, the two corpora cavernosa, which are on the top of the penis (see figure 1 below). These two cylinders are involved in erections. The third cylinder contains the urethra, the tube that the urine and ejaculate passes through, runs along the underside of the penis. The corpus spongiosum surrounds the urethra. Spongy tissue that has muscles, fibrous tissues, veins, and arteries within it makes up the corpora cavernosa. The inside of the corpora cavernosa is like a sponge, with potential spaces that can fill with blood and distend (known as sinusoids). A layer of tissue that is like Saran Wrap, called the tunica albuginea, surrounds the corpora. Veins located just under the tunica albuginea drain blood out of the penis.
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).

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.


Erectile dysfunction can occur as a side effect of medication taken for another health condition. Common culprits are high blood pressure meds, antidepressants, some diuretics, beta-blockers, heart medication, cholesterol meds, antipsychotic drugs, hormone drugs, corticosteroids, chemotherapy, and medication for male pattern baldness, among others.
There are hundreds of medications that have the side effect of ED and/or decreased libido. Examples of drugs implicated as a cause of ED include hydrochlorothiazides and beta-blocking agents. Medications used to treat depression, particularly the SSRIs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Prozac Weekly, Sarafem), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR, Pexeva) and sertraline (Zoloft), may also contribute to ED.9 Bupropion (Wellbutrin) which has a predominant effect on blocking the reuptake of dopamine is an antidepressant with lower incidence of ED.10 The side effects of 5ARIs occurring in fewer than 5% of patients can include gynaecomastia, ED, loss of libido and ejaculatory dysfunction.11
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.
Recently, several advances in the uses of stem cells have bet met with great anticipation. Stem cells have the ability to differentiate into different cell lines based on the cellular signaling they receive. Bone marrow mononuclear cells in particular have been used for the treatment of ED in animal models. Yiou et al. recently delivered bone marrow-mononuclear cells (BM-MNC) into the intracavernous smooth muscle of post radical prostatectomy men (123). The open label, dose escalation phase I/II trial showed improvements in IIEF-15 assessment as well as increased vascularization of the corpora based on penile Doppler arterial velocity measurements. Although promising, further investigation in humans is required to substantiate BM-MNCs impact on erections, and erectile function recovery going forward.
Alprostadil should not be used in men at higher risk for priapism (erection lasting longer than six hours) including men with sickle cell anemia, thrombocytopenia (low platelet count), polycythemia (increased red blood cell count), multiple myeloma (a cancer of the white blood cells), and is contraindicated in men prone to venous thrombosis (blood clots in the veins) or hyperviscosity syndrome who are at increased risk for priapism.
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.

Causes of impotence are many and include heart disease, high cholesterol, high blood pressure, obesity, metabolic syndrome, Parkinson's disease, Peyronie's disease, substance abuse, sleep disorders, BPH treatments, relationship problems, blood vessel diseases (such as peripheral vascular disease and others), systemic disease, hormonal imbalance, and medications (such as blood pressure and heart medications).
Treatments include psychotherapy, adopting a healthy lifestyle, oral phosphodiesterase type V (PDE5) inhibitors (Viagra, Levitra, Cialis, Stendra, and Staxyn), intraurethral prostaglandin E1 (MUSE), intracavernosal injections (prostaglandin E1 [Caverject, Edex], Bimix and Trimix), vacuum devices, penile prosthesis and vascular surgery, and (in some cases) changes in medications when appropriate.

The physical side effects of chemotherapy are usually temporary and resolve within one to two weeks after stopping the chemotherapy. However, chemotherapy agents, such as Ciplatin or Vincristine, may interfere with the nerves that control erection leading to possible impotence. Make sure you discuss potential side effects of cancer chemotherapy with your doctor or healthcare provider.
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.

Psychosexual counselling, or sex therapy, is an appropriate recommendation especially for men who are experiencing discord with their partner especially if the conflict is related to the man’s ED. Counselling usually consists of 5–20 sessions with counsellor. It is our recommendation that referral doctors treating men with ED make a referral to a psychotherapist or sex therapist who is certified by AASECT (American Association of Sexuality Educators, Counselors and Therapists) of certified sexuality educator.43

While erectile dysfunction can occur at any age, the risk of developing erectile dysfunction increases with age. According to the Massachusetts Male Aging Study, the prevalence of erectile dysfunction was 52% in men 40-70 years of age. The prevalence of complete erectile dysfunction increases from 5% at 40 years of age to 15% among men 70 years of age and older.

VED involved placing the penis in a clear plastic tube where negative pressure created by the vacuum pump leads to penile engorgement and tumescence. Usually a constriction ring can be placed on the base of penis following penile engorgement. Some men complain of bruising, a “cold” penis and pain associated with the constriction ring; however, in some men with NED sensation may not be intact mitigating the side effects of VEDs. VEDs have reported effectiveness up to 90% in certain ED populations and it remains a non-invasive means to achieve and erection.
There are many alternative impotence treatments available but many of them are neither licensed nor legitimate, Beware of sellers offering “herbal” impotence treatments - these remedies do not work and are often sold illegally. You should also be wary of online sellers who offer Viagra and other prescription drugs without asking you for a prescription. Illegal pharmacies often sell counterfeit or fake medication and buying from them could put your health at risk.
Erectile dysfunction can occur as a side effect of medication taken for another health condition. Common culprits are high blood pressure meds, antidepressants, some diuretics, beta-blockers, heart medication, cholesterol meds, antipsychotic drugs, hormone drugs, corticosteroids, chemotherapy, and medication for male pattern baldness, among others.
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).
Erectile dysfunction (ED) is the inability to get an erection or to keep one that's firm enough or that lasts long enough for a man to have a satisfying sexual experience. Occasional bouts of ED aren't unusual. In fact, as many as one in five men deal with erectile dysfunction to some degree. Symptoms, of course, are rather obvious. And while age can be a risk factor, so can medication use, health conditions, lifestyle factors (like smoking), and other concerns. Treatment is available and may involve prescriptions, habit changes, or other options.
For many men, stopping smoking is an erectile dysfunction remedy, particularly when ED is the result of vascular disease, which occurs when blood supply to the penis becomes restricted because of blockage or narrowing of the arteries. Smoking and even smokeless tobacco can also cause the narrowing of important blood vessels and have the same negative impact. 
This is one of many types of constricting devices placed at the base of the penis to diminish venous outflow and improve the quality and duration of the erection. This is particularly useful in men who have a venous leak and are only able to obtain partial erections that they are unable to maintain. These constricting devices may be used in conjunction with oral agents, injection therapy, and vacuum devices.
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.
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.
Instead of injecting a medicine, some men insert a suppository of alprostadil into the urethra. A suppository is a solid piece of medicine that you insert into your body where it dissolves. A health care professional will prescribe a prefilled applicator for you to insert the pellet about an inch into your urethra. An erection will begin within 8 to 10 minutes and may last 30 to 60 minutes.
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).
Zerman et al. performed penile implant surgery in 245 men with neurolgic impairment caused by spinal cord injury, CNS neoplasm, CNS infection, MS and SB (110). Mean follow-up time of 7.2 years was achieved in 195 patients, 50 patients were excluded for lost to follow-up or death from nonurological causes. Interestingly, 135 patients underwent penile implantation to assist with management of urinary incontinence and improve ability for condom/intermittent catheterization. Ninety-two patients patient underwent implantation for ED. Eighty two percent of patients were satisfied with implantation for ED, and 67% of partners were satisfied. Complications included infection (5%), perforation (0–18%), and technical dysfunction (7–33%). Perforation rates were high with the malleable device when it was placed through a subcoronal incision. After adopting an infrapubic approach the perforation rates dropped substantially.
Ultimately, PDE5i have had a significant impact on the treatment of ED in men with SCI. The ease of use and tolerability of the medication has also led to improved satisfaction and quality of life that had been previously affected by SD. Head to head trials evaluating specific PDE5i within the SCI population are required to further elucidate drug preference. PDE5i should be considered first line therapy, however men with high thoracic and cervical lesions should be warned about an increased chance of dizziness with sildenafil and possibly other PDE5i use.

Treatments include psychotherapy, adopting a healthy lifestyle, oral phosphodiesterase type V (PDE5) inhibitors (Viagra, Levitra, Cialis, Stendra, and Staxyn), intraurethral prostaglandin E1 (MUSE), intracavernosal injections (prostaglandin E1 [Caverject, Edex], Bimix and Trimix), vacuum devices, penile prosthesis and vascular surgery, and (in some cases) changes in medications when appropriate.
Specially designed vacuum devices to produce erections have been used successfully for many years. Vacuum devices are safe, relatively inexpensive, and reliable. Vacuum devices do not require surgery. Vacuum devices are available over the counter or by prescription. It is important to make sure that the vacuum device have a mechanism to prevent too high of a vacuum (negative pressure).
Sildenafil (Viagra) was the first oral phosphodiesterase type 5 (PDE5) inhibitor approved by the FDA in the United States for the treatment of erectile dysfunction (it is not approved for women). Sildenafil inhibits PDE5, which is an enzyme that destroys cGMP. By inhibiting the destruction of cGMP by PDE5, sildenafil allows cGMP to accumulate. The cGMP in turn prolongs relaxation of the smooth muscle of the corpora cavernosa. Relaxation of the corpora cavernosa smooth muscle allows blood to flow into the penis resulting in increased engorgement of the penis. In short, sildenafil increases blood flow into the penis and decreases blood flow out of the penis.
Depression and anxiety: Psychological factors may be responsible for erectile dysfunction. These factors include stress, anxiety, guilt, depression, widower syndrome, low self-esteem, posttraumatic stress disorder, and fear of sexual failure (performance anxiety). It is also worth noting that many medications used for treatment of depression and other psychiatric disorders may cause erectile dysfunction or ejaculatory problems.

What you need to know about delayed ejaculation Delayed ejaculation is a sexual disorder that can be distressing for a man and his partner and may disrupt a relationship. There are many reasons why delayed ejaculation occurs, including tissue damage, age, drugs, and the side effects of medication. They may be physiological or psychological. Find out how to get help. Read now
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.
What you need to know about delayed ejaculation Delayed ejaculation is a sexual disorder that can be distressing for a man and his partner and may disrupt a relationship. There are many reasons why delayed ejaculation occurs, including tissue damage, age, drugs, and the side effects of medication. They may be physiological or psychological. Find out how to get help. Read now
Cialis is available in three strengths: 5mg, 10 mg, and 20 mg. Cialis can work in 30 minutes, but peak results usually take longer. Cialis has the advantage of a much longer period (24-36 hours) during which sexual ability is increased. The newest formulation of Cialis is the 5 mg dosage for daily use. The major advantage of daily dosing is that it allows for spontaneous sexual activity.
Approximately 95% of penile implant surgeries are successful in producing erections that enable men to have sexual intercourse. Moreover, patient satisfaction questionnaires show that up to 90% of men who have undergone penile implants say they would choose the surgery again, and overall satisfaction ratings are higher than those reported by men using oral medication or penile injection therapy.

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Diabetes. Erectile Dysfunction is common in people with diabetes. An estimated 10.9 million adult men in the U.S. have diabetes, and 35 to 50 percent of these men are impotent. The process involves premature and unusually severe hardening of the arteries. Peripheral neuropathy, with involvement of the nerves controlling erections, is commonly seen in people with diabetes.
The use of injection therapy requires being taught how to properly inject the medication, determination of the best dose, and monitoring for side effects. It is recommended that one inject on the side of the penis at the base and to alternate sides. Injection therapy should be used no more frequently than once every 24 hours. Individuals on blood thinners must be careful with use of injection therapy.
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According to a review of all randomized controlled trials evaluating sildenafil by the American Urological Association (AUA) Consensus Panel on Erectile Dysfunction, 36% to 76% of patients receiving the drug were "able to achieve intercourse" during treatment. For tadalafil, four randomized controlled trials revealed that 11% to 47% of patients were "able to achieve intercourse." Similar efficacy has been observed with vardenafil, although studies are fewer.19 A meta-analysis published in 2013 clearly demonstrated increased efficacy over placebo for all PDE5 inhibitors.24 Head-to-head comparison suggested that tadalafil outperforms sildenafil on validated measures of erectile dysfunction, including the international index of erectile function and sexual encounter profile-2 and -3.
In a 2005 study, three months of twice-daily sets of kegel exercises combined with biofeedback and advice on lifestyle changes, such as quitting smoking, losing weight, and limiting alcohol, worked far better than just giving the participants advice. “Wearing tight pants will affect impotence along with some other medical conditions like diabetes and heart disease,” which can also affect a man’s degree of impotence, Dr. Jennifer Burns, specializing in family practice with an emphasis on gastrointestinal health at the BienEtre Center, told Medical Daily.
Sexual dysfunction and ED become more common as men age. The percentage of complete ED increases from 5% to 15% as age increases from 40 to 70 years. But this does not mean growing older is the end of your sex life. ED can be treated at any age. Also, ED may be more common in Hispanic men and in those with a history of diabetes, obesity, smoking, and hypertension. Research shows that African-American men sought medical care for ED twice the rate of other racial groups.
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