Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

ED occurs in up to 70% of men with MS, and MS is one of the most prevalent neurological disorders that affect the younger adult population worldwide (33-35). The mean time for SD and ED to develop is about 9 years and is rarely a presenting symptom of MS (36). Men with MS and ED may continue to have nocturnal erections, and psychogenic erections; however, this does not mean they have psychogenic ED but could be an indicator that MS involves the spinal cord (37).
The recommended starting dose of vardenafil is 10 mg taken orally approximately one hour before sexual activity. A doctor may adjust the dose higher or lower depending on efficacy and side effects. The maximum recommended dose is 20 mg, and the maximum recommended dosing frequency is no more than once per day. Patients can take vardenafil with or without food. As with sildenafil, for vardenafil to be effective, sexual stimulation must occur.

PDE5i medications are absolutely not to be taken by men with heart conditions who are taking nitrates such as nitroglycerine or isosorbide (Isordil, Ismo, Imdur). Those with serious heart disease, exertional angina (chest pain), and those taking multiple drugs for high blood pressure are advised to seek the advice of a heart specialist before beginning therapy with sildenafil.


Apomorphine is a non-selective D1/D2 receptor agonist with moderate efficacy and good tolerability in the treatment of mild ED (80). Apomorphine can be administered via subcutaneous injection or sublingually. However, studies have shows a lower efficacy for apomorphine compared to oral sildenafil (81,82). Apomorphine has a set role in the management of PD for non-motor symptoms, and has been reported to cause spontaneous erections and possible hypersexuality in PD men (83,84). Its role in the management of ED has been postulated for men with PD but should be considered as an alternative to sildenafil.
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.
Oral ED medication is considered highly effective and studies show it works on the majority of men. But no medication works for everyone and ED medication is no exception. Everyone’s reaction to a medication is unique and anything potent enough to help is strong enough to have side effects. If the medication isn’t working, it is important to tell your doctor. Sometimes it is a matter of needing a higher dose. Also, it has been shown that it takes 6 to 8 tries using the medication to experience the best result.
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.
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.
If PDE-5 inhibitors are not suitable or don’t work, other therapies include injections into the base of the penis, which cause flow of blood into the penis and a fairly immediate erection that lasts around an hour. The drugs injected are alprostadil (Caverject and Erectile dysfunctionex) and Invicorp (VIP and phentolamine). Alprostadil may also be inserted as a gel into the opening of the penis. This is not suitable if your partner is pregnant.
Whenever I am prescribing a medication to a patient, I’m always asking myself, what can the patient do before requiring the medication? What changes do they have to make in order to reduce the amount of medication or preclude their even needing it? So a good candidate is somebody who has an understanding of a healthy lifestyle, about physical activity, about sleep, about nutrition, alcohol, smoking. So patients, individuals, have to do their share before they’re a candidate for anything. All right?
Conditions that may be associated with ED include diabetes, [25, 26, 27] hypertension, [28] , and CAD, as well as neurologic disorders, endocrinopathies, benign prostatic hyperplasia, [29] , sleep apnea [30] , COPD, [31] and depression (see Table 1 below). [32, 33, 34, 35] In fact, almost any disease may affect erectile function by altering the nervous, vascular, or hormonal systems. Various diseases may produce changes in the smooth muscle tissue of the corpora cavernosa or influence the patient’s psychological mood and behavior.
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.

Other factors leading to erectile dysfunction are diabetes mellitus, which is a well-known cause of neuropathy).[2] ED is also related to generally poor physical health, poor dietary habits, obesity, and most specifically cardiovascular disease, such as coronary artery disease and peripheral vascular disease.[2] Screening for cardiovascular risk factors, such as smoking, dyslipidemia, hypertension, and alcoholism is helpful.[2]
The dorsal artery provides for engorgement of the glans during erection, whereas the bulbourethral artery supplies the bulb and the corpus spongiosum. The cavernous artery effects tumescence of the corpus cavernosum and thus is principally responsible for erection. The cavernous artery gives off many helicine arteries, which supply the trabecular erectile tissue and the sinusoids. These helicine arteries are contracted and tortuous in the flaccid state and become dilated and straight during erection. [9]
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.
MalaCards based summary : Impotence, also known as erectile dysfunction, is related to vasculogenic impotence and hyperprolactinemia, and has symptoms including angina pectoris, pelvic pain and tremor. An important gene associated with Impotence is NOS1 (Nitric Oxide Synthase 1), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Platelet homeostasis. The drugs Methyltestosterone and Testosterone have been mentioned in the context of this disorder. Affiliated tissues include prostate, spinal cord and endothelial, and related phenotypes are normal and reproductive system

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.


Taking one of these tablets will not automatically produce an erection. Sexual stimulation is needed first to cause the release of nitric oxide from your penile nerves. These medications amplify that signal, allowing some men to function normally. Oral erectile dysfunction medications are not aphrodisiacs, will not cause excitement and are not needed in men who get normal erections.
What happens is that the blood vessels of the penis are rather small, and a small amount of plaque in the penile arteries is going to result in erectile dysfunction. You need more plaque before the person’s actually symptomatic from a heart problem, but they’re linked. And so when anybody, any man has an erectile issue, it’s incumbent upon the physician to make certain that their cardiac status is healthy.

Cavernosography measurement of the vascular pressure in the corpus cavernosum. Saline is infused under pressure into the corpus cavernosum with a butterfly needle, and the flow rate needed to maintain an erection indicates the degree of venous leakage. The leaking veins responsible may be visualized by infusing a mixture of saline and x-ray contrast medium and performing a cavernosogram.[21] In Digital Subtraction Angiography (DSA), the images are acquired digitally.


Erectile dysfunction (ED) related to compromise of the nervous system is an increasingly common occurrence. This may be due to the multifactorial nature of ED, the myriad of disorders affecting the neurotransmission of erectogenic signals, and improved awareness and diagnosis of ED. Nevertheless, neurogenic ED remains poorly understood and characterized. Disease related factors such as depression, decreased physical and mental function, the burden of chronic illness, and loss of independence may preclude sexual intimacy and lead to ED as well. The amount of data regarding treatment options in subpopulations of differing neurologic disorders remains scarce except for men with spinal cord injury. The treatment options including phosphodiesterase inhibitors, intracavernosal or intraurethral vasoactive agents, vacuum erection devices (VED) and penile prosthetic implantation remain constant. This review discusses the options in specific neurologic conditions, and briefly provides insight into new and future developments that may reshape the management of neurogenic ED.
When sexually stimulated/aroused, the nerves supplying the penis release a chemical, nitric oxide (NO). Nitric oxide is important because it stimulates the production of a chemical called cyclic guanosine monophosphate (cGMP). cGMP causes the muscle in arteries of the penis to relax and increase blood flow into the penis. NO is broken down in the body by phosphodiesterase enzymes. PDE5 inhibitors thus prevent the breakdown of NO and thus promote increased blood flow into the penis.
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.
So here’s something that’s really fascinating. Healthy eating is a way to reduce anxiety and stress. Now how, you may be asking, right? Well, think about it. We live in a world where there are so many variables and where we don’t have control over our lives. But now, with healthy eating, we have control over what goes into our body. And now having that control empowers us to be even healthier, to be more directive in what we do. And certainly, that begins then to reduce the anxiety and the stress. So all in one, you have a healthier body, but certainly a healthier mind.
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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. [37] On the other hand, bicycling for less than 3 hours per week may be somewhat protective against ED. [37] Some of the newer bicycle seats have been designed to diminish pressure on the perineum. [37, 38]

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.
This procedure is usually performed before and after injection of a smooth-muscle-relaxing medication into the penis, which normally should significantly increase the diameter of the penile arteries. The procedure itself is painless. Duplex ultrasonography is most useful in evaluating possible penile arterial disorders, but in those individuals considering surgery for problems with the arteries to the penis, a more invasive study, angiogram, is needed to identify the location of the damaged artery.
In a randomized double-blind, parallel, placebo-controlled trial, sildenafil plus testosterone was not superior to sildenafil plus placebo in improving erectile function in men with ED and low testosterone levels. [19] The objective of the study was to determine whether the addition of testosterone to sildenafil therapy improves erectile response in men with ED and low testosterone levels.

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.

Surgical intervention for a number of conditions may remove anatomical structures necessary to erection, damage nerves, or impair blood supply.[8] Erectile dysfunction is a common complication of treatments for prostate cancer, including prostatectomy and destruction of the prostate by external beam radiation, although the prostate gland itself is not necessary to achieve an erection. As far as inguinal hernia surgery is concerned, in most cases, and in the absence of postoperative complications, the operative repair can lead to a recovery of the sexual life of people with preoperative sexual dysfunction, while, in most cases, it does not affect people with a preoperative normal sexual life.[13]

Research is mixed on the effectiveness of acupuncture as an erectile dysfunction cure, but one study published in November 2013 in the Journal of Alternative and Complementary Medicine found that acupuncture can be beneficial for men experiencing erectile dysfunction as a side effect of antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs).
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.
Erectile dysfunction is common, increases with age, and is associated with multiple common medical problems. A variety of successful therapies exist for men with erectile dysfunction. The success of the therapies can vary with the cause of the erectile dysfunction. A stepwise approach to the treatment of ED allows one to identify the therapy that is effective and the least invasive for the individual. Oral therapy remains the first line medical therapy for ED, however, is effective overall in 40%-80% of individuals. For those individuals who cannot take PDE5 inhibitors or fail from an efficacy or side effect standpoint, a number of alternatives exist. Intracavernous injection therapy is the most effective therapy for ED, however, the invasive nature can affect compliance. Penile prosthesis is a highly effective surgical procedure, but men undergoing placement of a penile prosthesis should be aware of the benefits and risks associated with placement of a penile prosthesis. Other surgical therapies, such as arterial surgery, are rarely needed.
Diabetes is a well-recognized risk factor for ED. A systematic review and meta-analysis found that the prevalence of ED was 37.5% in type 1 diabetes, 66.3% in type 2 diabetes, and 52.5% in diabetes overall—a rate approximately 3.5 times higher than that in controls. [39]  The etiology of ED in diabetic men probably involves both vascular and neurogenic mechanisms. Evidence indicates that establishing good glycemic control can minimize this risk.
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).
Yes, the vacuum device is effective. In fact, with use of the vacuum device, 88% of men will have an erection that is satisfactory for completion of sexual activity. The vacuum device may be the only therapy that is effective after the removal of a penile prosthesis. Patients also use vacuum devices as part of penile rehabilitation after radical prostatectomy to help preserve the tissue of the penis and prevent scarring within the penis and loss of penile length. Its use, however, is limited by the mechanical nature of it and the time taken to pump the device and apply the band. Sex partners may complain of the penis being cool to touch.
A CVA can occur anywhere through the brain, midbrain, brainstem and spinal cord leading to varying degrees of SD depending on location. A decline in libido, erection and ejaculation are frequent in men who have had a CVA, with a reported prevalence of ED that varies from 17% to 48% (28,29). Right hemispheric infarcts seem to affect erections more so than left-sided ones. The exact effects of CVA on sexual function are complex and multifactorial, as disability, psychological and emotional status can affect sexual function aside from the location of the CVA.
In patients who either fail to respond to first or second-line therapy, or are not interested in the conservative therapies, penile prosthesis implantation is available. Malleable and rigid implants were available for many years, but in 1973 the world of penile prosthetics took a giant leap forward with the advent of the inflatable penile implant. Most implants done nowadays are of the inflatable variety. Adverse events including malfunction and infection are rare, and patient satisfaction is very high.45
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.
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.
With sex therapy, your counselor looks at the sexual problems you and your partner are having. Sex therapy works with problems such as performance anxiety, which means that you worry so much about whether you will be able to have sex that you are not able to. It also helps when you have erection problems that are not due to physical or drug problems, or premature ejaculation (you come too quickly). It may help you to reach orgasm or to learn to relax enough to avoid pain during sex. Counseling can help you to adjust to the treatment you and your doctor choose.

A variety of lifestyle choices can affect the ability to achieve and maintain an erection, so preventing ED is possible in some cases. Men are encouraged to manage chronic health problems with their doctors and to exercise regularly. They also should avoid smoking and excess alcohol and get help for anxiety or depression, according to the Mayo Clinic.
Erections are more complicated than you think. Your brain, nerves, heart, blood vessels, and a whole lot of hormones have to work together perfectly or nothing happens. It’s a lot to ask, and sometimes things break down. And while ED happens to most guys at some point in their lives, erectile dysfunction isn’t something you can just ignore and hope it goes away.
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