The role of the endothelium in erectile function became clearer with the observation that the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil, enhanced erectile function. Erection occurs with the release of nitric oxide (NO) from the vascular endothelial cells.17 The reduction in endothelial cell production of NO results in the negative impact on the smooth muscles in the corporal bodies and results in less relaxation of the smooth muscle cells with decrease in blood supply and resulting ED. A similar phenomenon is well known to impact the coronary arterial system resulting in CVD.
"Medications that create blood flow to the penis can't help when an erection is blocked by the fear or anxiety of the fight-or-flight response,” says Feloney. “This type of erectile dysfunction probably has a lot to do with evolution — men didn't need an erection when a dinosaur was chasing them." The best way to treat erectile dysfunction caused by performance anxiety, depression, a poor relationship, or stress may be with a combination of ED drug treatment and sex therapy, individual therapy, or couples therapy from sexual health professionals.
In most healthy men, some of the drug will remain in the body for more than two days after a single dose of tadalafil. Metabolism (clearing of the drug from the body) of tadalafil can be slowed by liver disease, kidney disease, and concurrent use of certain medications (such as erythromycin, ketoconazole, and protease inhibitors). Slowed breakdown allows tadalafil to stay in the body longer and potentially increase the risk for side effects. Therefore, doctors have to lower the dose and frequency of tadalafil in the following examples:
Additionally, the physiologic processes involving erections begin at the genetic level. Certain genes become activated at critical times to produce proteins vital to sustaining this pathway. Some researchers have focused on identifying particular genes that place men at risk for ED. At present, these studies are limited to animal models, and little success has been reported to date. [4] Nevertheless, this research has given rise to many new treatment targets and a better understanding of the entire process.

Alprostadil injections, which produce an erection in five to 20 minutes that lasts for about an hour. Patients use a fine needle to inject alprostadil (commonly known by the brand names Caverject Impulse and Edex) into the base or side of the penis. Side effects can include bleeding or fibrous tissue formation at the injection site as well as prolonged erection, according to the Mayo Clinic.
Experiencing ED can also be a reason to try not penetrative sex.  Try planning a sex session with your partner hat isn't focused on your erection at all.  Things like kissing, licking, sucking, foreplay and teasing all are super stimulating and don't focus on penetration.  Feel free to bring each other to orgasm using these ideas and see if you are able to relax and enjoy the experience.  Many men feel like failures when their erections become unreliable.  Having a few successful sexual sessions that lead to orgasm without penetration can put the fun back into having sex.  Many couples find success using this technique and begin to reengage sexually instead of avoiding being sexual for fear of failure.

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).

If PDE5 drugs don't work or cannot be used because of potential side effects, your doctor can recommend other therapies. The drug alprostadil (Caverject, Edex, Muse) allows blood to flow more freely in the penis, leading to an erection. The drug can be injected with a tiny needle into your penis. Or, a small pellet (suppository) can be inserted into the opening of the penis. Suppositories and injections are effective in the majority of men.
Erectile dysfunction (ED) affects 50% of men older than 40 years, [4] exerting substantial effects on quality of life. [5] This common problem is complex and involves multiple pathways. Penile erections are produced by an integration of physiologic processes involving the central nervous, peripheral nervous, hormonal, and vascular systems. Any abnormality in these systems, whether from medication or disease, has a significant impact on the ability to develop and sustain an erection, ejaculate, and experience orgasm.
No nitrate-based drugs should be given to men with suspected heart attacks if they have taken PDE5i medications within 24 hours. Combining PDE5i with nitrate-based medications can cause a severe and dramatic drop in blood pressure with potentially very dangerous consequences. This is also why someone should absolutely never share PDE5i medications with anyone else. If they happen to be taking one of the drugs that interacts dangerously with PDE5i medications, the results could be very serious. If there is any question about possible drug interactions, always check with a doctor or pharmacist.
On the horizon is gene therapy that would deliver genes that produce products or proteins that may not be functioning properly in the penile tissue of men with ED. Replacement of these proteins may result in improvement in erectile function. Experimental animal models have demonstrated improvement in erectile function with gene therapy. Human studies may also demonstrate success with this therapy. Gene therapy may take a long time for regulatory approval and public acceptance.
Surgery to repair arteries (penile arterial reconstructive surgery) can reduce impotence caused by obstructions that block the flow of blood to the penis. The best candidates for such surgery are young men with discrete blockage of an artery because of a physical injury to the pubic area or a fracture of the pelvis. The procedure is less successful in older men with widespread blockage of arteries.

Medication therapy is extremely effective in augmenting the quality of man’s erection such that he is able to have satisfactory intercourse. Indeed medications referred to as phospho-diesterase inhibitors such as Cialis, Viagra, Levitra and Stendra work in 65% of men suffering from erectile dysfunction. Cialis is currently the preferred drug since it is the only one that may be taking on a full stomach and lasts for 36 hours. This favors a more romantic and natural sexual interaction. Planning kills the mood!


One study by Palmer and colleagues evaluated sildenafil use in SB males with thoracic lesions (76). A prospective, blinded, randomized, placebo-controlled, dose-escalation, crossover study in 17 patients with SB and ED was performed. All study participates took sets of tablet in groups, two sets of placebo, one of 25 mg, and the last 50 mg. Overall response to the tablet sets was measured by IIEF response and self-report of erectile rigidity. Patients reported that taking 50 mg of sildenafil led to improved erections, duration of erections, frequency of erections and level of confidence compared to sildenafil 25 mg and more significantly compared to placebo. Of the five patients who reported side effects, two experienced mild hematological changes that reverted to baseline after study completion.
Testosterone replacement: Men with low sex drive (libido) and ED may be found to have low testosterone levels. Hormone replacement may be of benefit by itself or as a complementary therapy used with other treatments. Libido and an overall sense of well-being are likely to improve when serum testosterone levels are restored. The constitution of symptoms of low libido, fatigue, decreased muscle mass and force, and increased body fat may be related to andropause. As mentioned previously, in the patient workup section, serum total testosterone and bioavailable testosterone blood tests can be performed to evaluate for low serum levels. If determined to be below normal, replacement of testosterone may be suggested as a treatment option. The primary objective of testosterone replacement is to improve libido, energy levels, and symptoms of andropause. Only secondarily would correction of low testosterone levels potentially have impact on erectile function. Some studies suggest that in men with low or low normal testosterone levels and ED who fail PDE5 inhibitors that the use of hormone therapy may improve the success of PDE5 inhibitors.
Iatrogenic hypotension can occur in men in neurodegenerative disease using sildenafil (49). Hussain et al. placed men with PD and MSA on sildenafil and recorded blood pressure before and after. Half of the 12 MSA patients developed postural hypotension, while none of the twelve PD patients did. Since MSA can be difficult to distinguished diagnostically from PD, baseline blood pressure measurements prior to prescribing the medication and seeking medical assistance if symptomatic hypotension occurred was recommended for all patients with PD, and MSA. Of note, none of the men with MSA who developed hypotension discontinued sildenafil use due to its effectiveness at improving their erections.
The Latin term impotentia coeundi describes simple inability to insert the penis into the vagina; it is now mostly replaced by more precise terms, such as erectile dysfunction (ED). The study of ED within medicine is covered by andrology, a sub-field within urology. Research indicates that ED is common, and it is suggested that approximately 40% of males experience symptoms compatible with ED, at least occasionally.[38] The condition is also on occasion called phallic impotence.[39] Its antonym, or opposite condition, is priapism.[40][41]
Surgery to repair arteries (penile arterial reconstructive surgery) can reduce impotence caused by obstructions that block the flow of blood to the penis. The best candidates for such surgery are young men with discrete blockage of an artery because of a physical injury to the pubic area or a fracture of the pelvis. The procedure is less successful in older men with widespread blockage of arteries.
early 15c., "physical weakness," also "poverty," from Middle French impotence "weakness," from Latin impotentia "lack of control or power," from impotentem (nominative impotens); see impotent. In reference to a want of (male) sexual potency, from c.1500. The figurative senses of the word in Latin were "violence, fury, unbridled passion." Related: Impotency.
The PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken orally.[22]:20–21 Additionally, a cream combining alprostadil with the permeation enhancer DDAIP has been approved in Canada as a first line treatment for erectile dysfunction.[25] Penile injections, on the other hand, can involve one of the following medications: papaverine, phentolamine, and prostaglandin E1, also known as alprostadil.[22]:25
Under normal circumstances, when a man is sexually stimulated, his brain sends a message down the spinal cord and into the nerves of the penis. The nerve endings in the penis release chemical messengers, called neurotransmitters, that signal the corpora cavernosa (the two spongy rods of tissue that span the length of the penis) to relax and fill with blood. As they expand, the corpora cavernosa close off other veins that would normally drain blood from the penis. As the penis becomes engorged with blood, it enlarges and stiffens, causing an erection. Problems with blood vessels, nerves, or tissues of the penis can interfere with an erection.
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The next new treatments for erectile dysfunction will probably be improvements in some ED drugs already being used. "A dissolvable form of Levitra that you put under your tongue is coming that may work more quickly than the pills we have now," says Feloney. A new form of alprostadil may make it possible for you to rub it directly on the penis instead of inserting or injecting it. And newer phosphodiesterase inhibitors that last even longer and cause fewer side effects are being developed. Stay tuned!
The role of the endothelium in erectile function became clearer with the observation that the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil, enhanced erectile function. Erection occurs with the release of nitric oxide (NO) from the vascular endothelial cells.17 The reduction in endothelial cell production of NO results in the negative impact on the smooth muscles in the corporal bodies and results in less relaxation of the smooth muscle cells with decrease in blood supply and resulting ED. A similar phenomenon is well known to impact the coronary arterial system resulting in CVD.
Tadalafil should not be used with alpha-blockers (except Flomax), medicines used to treat high blood pressure, and benign prostate hypertrophy (BPH) because the combination of tadalafil and an alpha-blocker may lower the blood pressure greatly and lead to dizziness and fainting. Examples of alpha-blockers include tamsulosin (Flomax), terazosin (Hytrin), doxazosin (Cardura), alfuzosin (Uroxatral), and prazosin (Minipress). Tamsulosin (Flomax) is the only alpha-blocker that patients can use safely with tadalafil. When tadalafil (20 mg) was given to healthy men taking 0.4 mg of Flomax daily, there was no significant decrease in blood pressure and so patients on this dose of tamsulosin (Flomax) can be prescribed tadalafil. The only alpha-blocker not tested with tadalafil is alfuzosin (Uroxatral), and no recommendations can be made regarding the interaction between the two.
"For men who are unwilling or unable to self-inject alprostadil, the FDA has approved this dissolvable pellet that can be inserted directly into the urethra, the opening of the penis," says Dr. Feloney. MUSE, with an inspiring name that actually stands for medicated urethral system for erection, will trigger an erection in about 10 minutes that may last as long as an hour. Using MUSE to treat ED can result in somewhat unpleasant side effects, however — including an aching sensation, burning, redness, and minor bleeding.
In prescribing sildenafil, a doctor considers the age, general health status, and other medication(s) the patient is taking. The usual starting dose for most men is 50 mg, however, the doctor may increase or decrease the dose depending on side effects and effectiveness. The maximum recommended dose is 100 mg every 24 hours. However, many men will need 100 mg of sildenafil for optimal effectiveness, and some doctors are recommending 100 mg as the starting dose.
I think that a very powerful argument to young men who want to perform at the highest level is to point out the destructive nature of what they’re doing. If they’re having 18 drinks per week, if they’re having three, four, five drinks at any one time, they’re going to guarantee that their erections are not going to be at the highest level. I can’t tell you the number of men who come in saying, they went out, they had a date, they had a big dinner– which, by the way, is also not a great thing for erections, because all the blood is now going to your gut instead of to the genital area. And how important lifestyle changes are to improving your performance, as well, if not better, than the medications. So make certain that you exercise modestly, not excessively. Make certain that you have a smaller meal on an evening or a day that you want to have a sexual encounter, because you want the blood to go, once again, to the penile area and not to your gut. And really, the whole idea of stress– if you’re stressed out, if you’re worried about a lot of things, if you’re distracted, you can’t initiate that psychic stimulus to your spinal cord and then ultimately to your penis. So stress management is incredibly important.

Sildenafil has been previously suggested as a treatment option for ED in men with epilepsy (77,78). However, Matos et al. warned that PDE5i are potentially pro-convulsant and should be used with great caution in men with epilepsy (79). Animal studies in rat and mice overwhelmingly suggest PDE5i can reduce seizure threshold. In human trials, seizures were rare but reported. PDE5i exerted their proconvulsive effect by lower seizure threshold possibly by worsening sleep or obstructive sleep apnea, causing cardiovascular changes, or leading to EEG changes specifically with tadalafil use.


As is true in so many medical conditions, lifestyle modifications, considered first-line therapy, can have a salutary effect in ED management, and men should be encouraged to make the necessary changes to the benefit of their sexual function and to their overall health as well. Despite the benefits of behaviour modification, men presenting with ED want the physician to help with measures that can have an immediate impact.
In addition, when research has shown a nutrient such as zinc or niacin to improve sexual function, it's usually in people who are deficient in it. So, before you stock up on over-the-counter nutritional supplements for ED, speak with your doctor. He can test you for deficiencies and steer you toward the most effective and safest way to treat your erectile dysfunction. 
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

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.

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