Since the advent of PDE5i, many other selective and non-selective peripheral acting compounds have been developed or are in development. Avanafil has shown promising results in treating ED in post-prostatectomy patients with suspected cavernous nerve injury (111). Other PDE5i marked in Asia such as udenafil, and mirodenafil also effective at treating ED may minimize side effects due to shorter half-lives (112-114). Soluable guanylate-cyclase inhibitors and potassium channel activators are compounds that have induced erections in animal models but remain experimental requiring further investigation (115-117).
Recognized risk factors for ED include cardiovascular disease (CVD) (hypertension, atherosclerosis, and hyperlipidemia), diabetes, depression, alcohol use, smoking, pelvic/perineal surgery or trauma, neurologic disease, obesity, pelvic radiation, and Peyronie’s disease. One study suggested that the relationship between arterial disease and ED is very strong, with 49% (147 of 300) of patients with coronary artery disease noted on cardiac catheterization reporting significant erectile dysfunction.6 Endothelial dysfunction has been indicated as the pathophysiologic mechanism responsible for both CVD and ED.7 The Boston Area Community Health survey demonstrated a dose-response between smoking and incidence of erectile dysfunction.8 Animal studies have demonstrated both smooth-muscle disruption and decreased production of neural nitric oxide synthase in cigarette-exposed animals.9

Adverse effects related to PDE5i use with mild-moderate and transient (58). Furthermore, side effects usually attenuate if use is not discontinued. Autonomic dysreflexia, a life-threatening phenomenon characterized by bradycardia, hypertension, facial flushing and headaches associated with SCI lesions above T6, has not been reported with use. However, hypotension leading to dizziness in individuals treated with sildenafil has been noted with high thoracic and cervical levels of injury (72). No adverse events were noted within the study; however, the dizziness was reported by use of sildenafil 50 mg in the cervical LOI and 100 mg in the thoracic LOI patients. Headache is the most reported side effect of all PDE5i, followed by dyspepsia and flushing. Priapism, and death have not been reported after use of PDE5i by SCI patients.
Physical causes may include the narrowing of the blood vessels caused by hypertension (high blood pressure), nutritional deficiencies, certain prescription treatments and medications for enlarged prostate or prostate cancer, excess drinking, obesity, heavy smoking, kidney issues, thyroid problems, hormonal changes due to aging, injury, or surgery, diabetes, and high cholesterol levels.
Medical conditions, such as hypertension, diabetes mellitus, and cardiovascular disease (CVD), and psychological conditions, such as depression and anxiety, also contribute to sexual dysfunction in middle-aged or elderly men. CVD and hypertension cause a narrowing and hardening of the arteries, leading to reduced blood flow to the corporal bodies, which is essential for achieving an erection. Diabetes is a common aetiology of sexual dysfunction, because it can affect both the blood vessels and the nerves that supply the penis. Men with diabetes are four times more likely to experience ED, and on average, experience ED 15 years earlier than men without diabetes.7 Obesity is also correlated to the development of several types of dysfunction, including a decrease in sex drive and an increase in episodes of ED.8
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.
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.
The success of treatment for sexual dysfunction depends on the underlying cause of the problem. The outlook is good for dysfunction that is related to a condition that can be treated or reversed. Mild dysfunction that is related to stress, fear, or anxiety often can be successfully treated with counseling, education, and improved communication between partners.
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.
When lifestyle changes alone don’t work, drug therapy (Viagra®, Cialis®, Levitra®, etc.) is normally the next step. Most of these medications work similarly to enhance a natural chemical in your body that relaxes the muscles in your penis. The goal of this medication is to increase your response to sexual stimulation by increasing the blood flow in your penis allowing you to get an erection.22
When other treatments haven’t helped, a penile implant may be the right solution. A penile implant is a medical device that is surgically placed into a penis to mimic the look and performance of a natural erection9. Implants are custom-fitted to your anatomy. Sensitivity and the ability to ejaculate aren’t typically affected either, so you’ll be able to have an orgasm normally (unless you have a medical condition that prevents this)7.
Clearly, PDE5i have revolutionized the treatment of ED in general and the neurogenic ED population is no exception. They remain safe and effective in most men with neurogenic ED; however, care must be taken in prescribing PDE5i to men high spinal cord lesions, MSA or possibly PD. VEDs are minimally-invasive and can be as effective as other modalities at leading to erection. However, high discontinuation rates are associated with VED use related to pain, difficulty using the device or cold penis. Intracavernosal therapy has been a mainstay of treatment for neurogenic ED and remains extremely successful in the SCI population. Trial of intracavernosal therapy for other causes of neurogenic ED can be considered second-line therapy, but there is a relative paucity of data for clinical outcomes related to its use outside of SCI men. Surgical therapy via penile implantation remains another second line approach and may also be utilized to assist men with bladder management. Higher complication rates of infections, and perforation have been reported compared to neurologically intact men. Many other compounds are currently being evaluated for the treatment of neurogenic ED as well as gene and stem cell therapy, but still should be considered investigational until substantiated by randomized controlled trials.
When you become aroused, your brain sends chemical messages to the blood vessels in the penis, causing them to dilate or open, allowing blood to flow into the penis. As the pressure builds, the blood becomes trapped in the corpora cavernosa, keeping the penis erect. If blood flow to the penis is insufficient or if it fails to stay inside the penis, it can lead to erectile dysfunction.
Recognized risk factors for ED include cardiovascular disease (CVD) (hypertension, atherosclerosis, and hyperlipidemia), diabetes, depression, alcohol use, smoking, pelvic/perineal surgery or trauma, neurologic disease, obesity, pelvic radiation, and Peyronie’s disease. One study suggested that the relationship between arterial disease and ED is very strong, with 49% (147 of 300) of patients with coronary artery disease noted on cardiac catheterization reporting significant erectile dysfunction.6 Endothelial dysfunction has been indicated as the pathophysiologic mechanism responsible for both CVD and ED.7 The Boston Area Community Health survey demonstrated a dose-response between smoking and incidence of erectile dysfunction.8 Animal studies have demonstrated both smooth-muscle disruption and decreased production of neural nitric oxide synthase in cigarette-exposed animals.9
It is important to understand that ED is frequently, if not usually, directly related to endothelial dysfunction, and that the release of NO by the vasculature of the penile arteries is directly related to the function of intact, healthy endothelium. In the face of endothelial dysfunction, the process of erection fails to occur in a normal fashion.16
Communication is key: don’t try to hide your erectile dysfunction from your partner, or to avoid discussing it out of embarrassment or shame. Sometimes just admitting that you are concerned can reduce the stress and anxiety you’re feeling. Remember, your partner may be just as confused and upset by this as you are, so try initiating a frank and open discussion on the issue.

Psychological Causes of ED – Between 10% and 20% of ED cases have a psychological cause. Because arousal starts in the brain, psychological issues can be a significant contributing factor to erectile dysfunction. Mental health conditions like depression or anxiety can negatively impact your libido, making it more difficult for you to become aroused.
Ginseng, specifically “red ginseng,” is known as the “herbal Viagra” that helps puts to rest men’s bedroom woes. Red ginseng is when the root has been steamed and then dried. The ginseng root is the part of the plant that is mostly used as a natural remedy when in its supplement form. However, the plant must be grown for a minimum of five years before it can be used. In a 2008 review, seven studies on red ginseng and ED, ranging in dosages from 600 to 1,000 milligrams three times a day, were found to provide evidence for the effectiveness of the herb in ED treatment.
Nerves originating in the spinal cord and peripheral ganglia innervate the penis. There are autonomic (parasympathetic and sympathetic), and somatic separate and integrated pathways. The autonomic pathways neurons originate in the spinal cord and peripheral ganglia from the sympathetic and parasympathetic systems, respectively. They merge to form the cavernous nerves that travel alongside the prostate, enter the corpora cavernosa and corpus spongiosum to affect the neurovascular events required for tumescence and detumescence. The somatic nerves send sensory information from the penile skin, glans, and urethra via the dorsal penile nerve and pudendal nerve to the spinal cord. The somatic nerves also initiate contraction of the ischio- and bulbocavernosus muscles.
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.
Multiple combinations of intracavernosal therapy exist and the effectiveness of them varies based on patient characteristics and varying dosing strength (Table 1). Combination therapy have been extremely effective in the SCI population, and have several advantages including a reduction in cost per dose and side effects base on the lowered dose of each component (101,102). Effectiveness of combination therapy in the spinal cord population is well established, but no specific dose recommendations can be made based on the data (103-106). The use of combination therapy on other forms of neurogenic ED have not been well studied, but there use can be trialed as second-line therapy, or for populations were the side effects of PDE5i may preclude use such as in MSA due to hypotension.

Communicate with your partner. Do you feel comfortable and accepted when it comes to your sexual performance? If you're worried about meeting your partner's too-high expectations or living up to some kind of standard, it will be harder to maintain an erection - it's called performance anxiety. If you think your partner's judgment might be hindering your ability to have satisfying sex, you need to communicate your needs and find ways to make your sexual environment more inviting.


Impotence is a common problem among men and is characterized by the consistent inability to sustain an erection sufficient for sexual intercourse or the inability to achieve ejaculation, or both. Erectile dysfunction can vary. It can involve a total inability to achieve an erection or ejaculation, an inconsistent ability to do so, or a tendency to sustain only very brief erections.
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.
When lifestyle changes alone don’t work, drug therapy (Viagra®, Cialis®, Levitra®, etc.) is normally the next step. Most of these medications work similarly to enhance a natural chemical in your body that relaxes the muscles in your penis. The goal of this medication is to increase your response to sexual stimulation by increasing the blood flow in your penis allowing you to get an erection.22
The somatosensory pathways for erections originate in the penile skin, glans and urethra. Glans afferent sensory free nerve endings are 10-fold more than their corpuscular receptors, and are derived from Aδ and unmyelinated C fibers. The nerve endings coalesce to form the dorsal penile nerve along with other sensory nerve fibers. Through the pudendal nerve they enter the S2-4 nerve roots to terminate on spinal neurons and interneurons. The dorsal nerve is not purely somatic, however. Nerve bundles within the dorsal nerve contain nitric oxide (NO) synthase, found typically in autonomic nerves, and stimulation of the sympathetic chain can leak to evoked potentials from the dorsal nerve and vice versa (10-12).

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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