PDE5i for ED in patients with MS can be considered as reasonably effective and safe. Fowler et al. performed a randomized, multicenter, double-blind, flexible dose trial with open label extensions comparing sildenafil to placebo (75). A nearly 4-fold increase in effective erections was noted in the treatment arm, 96% vs. 24%. Sexual satisfaction and overall satisfaction were also improved in the treatment group based on IIEF scores, and quality of life assessments. Lombardi et al. evaluated tadalafil use in men with MS (71). Seventy eight percent of the men responded with improved erections, better quality of life with regards to sexual function, partner relationship and family life. Just less than half the men who responded to the tadalafil did so at the lower dosage of 10 mg. Subjects in either studies did not have any significant adverse side effects beyond flushing, and headache with PDE5i use.
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.
Penile erection is managed by two mechanisms: the reflex erection, which is achieved by directly touching the penile shaft, and the psychogenic erection, which is achieved by erotic or emotional stimuli. The former uses the peripheral nerves and the lower parts of the spinal cord, whereas the latter uses the limbic system of the brain. In both cases, an intact neural system is required for a successful and complete erection. Stimulation of the penile shaft by the nervous system leads to the secretion of nitric oxide (NO), which causes the relaxation of smooth muscles of corpora cavernosa (the main erectile tissue of penis), and subsequently penile erection. Additionally, adequate levels of testosterone (produced by the testes) and an intact pituitary gland are required for the development of a healthy erectile system. As can be understood from the mechanisms of a normal erection, impotence may develop due to hormonal deficiency, disorders of the neural system, lack of adequate penile blood supply or psychological problems.[18] Spinal cord injury causes sexual dysfunction including ED. Restriction of blood flow can arise from impaired endothelial function due to the usual causes associated with coronary artery disease, but can also be caused by prolonged exposure to bright light.

Alprostadil, a synthetic PGE1, is the most commonly used single drug for injections into the penis as a treatment for ED. It works well in the majority of men who try it. In one study of 683 men with ED, 94% reported having erections suitable for penetration after PGE1 injections. When PGE1 is used in combination with papaverine and Regitine, the mixture is called Trimix, which has roughly twice the effectiveness of alprostadil alone. However, Trimix is quite expensive and is usually not covered by insurance, while PGE1 is often a covered benefit in most insurance medication plans. The main side effects are pain from the medication (not from the injection), priapism (persistent or abnormally prolonged erection), and scarring at the site of the injection. It is recommended that one alternate the side of the penis being injected to help decrease the risk of penile scarring. Many men are uncomfortable with penile injection therapy even though the injection itself is painless. The injection cannot be done more often than every other day. Men on anticoagulant medications (blood thinners) must be careful with injection therapy.

Since sexual arousal is a complex process involving hormones, emotions, nerves, muscles, blood vessels and the brain, a malfunction in any of these can lead to ED. Stress, exhaustion and psychological issues can also contribute, and anxiety over maintaining an erection can actually make it harder to attain. In short, any condition that inhibits blood flow to the penis can lead to ED.

Alprostadil, a synthetic PGE1, is the most commonly used single drug for injections into the penis as a treatment for ED. It works well in the majority of men who try it. In one study of 683 men with ED, 94% reported having erections suitable for penetration after PGE1 injections. When PGE1 is used in combination with papaverine and Regitine, the mixture is called Trimix, which has roughly twice the effectiveness of alprostadil alone. However, Trimix is quite expensive and is usually not covered by insurance, while PGE1 is often a covered benefit in most insurance medication plans. The main side effects are pain from the medication (not from the injection), priapism (persistent or abnormally prolonged erection), and scarring at the site of the injection. It is recommended that one alternate the side of the penis being injected to help decrease the risk of penile scarring. Many men are uncomfortable with penile injection therapy even though the injection itself is painless. The injection cannot be done more often than every other day. Men on anticoagulant medications (blood thinners) must be careful with injection therapy.
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.

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.

There have been some studies to suggest that a placebo effect that improves ED may work for some men. One study found that men taking an oral placebo pill showed as much improvement in ED symptoms as men who took actual medication to improve ED. Conversely, men who were given therapeutic suggestions to improve ED did not see signs of symptom improvement.


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.
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.

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).

Although not proven, it is likely that erectile dysfunction can be prevented by good general health, paying particular attention to body weight, exercise, and cigarette smoking. For example, heart disease and diabetes are problems that can cause erectile dysfunction, and both are preventable through lifestyle changes such as sensible eating and regular exercise. Furthermore, early diagnosis and treatment of associated conditions like diabetes, hypertension and high cholesterol may prevent or delay erectile dysfunction, or stop the erectile dysfunction from getting more serious.
Sexual functioning involves a complex interaction among biologic, sociocultural, and psychological factors, and the complexity of this interaction makes it difficult to ascertain the clinical etiology of sexual dysfunction. Before any diagnosis of sexual dysfunction is made, problems that are explained by a nonsexual mental disorder or other stressors must first be addressed. Thus, in addition to the criteria for erectile disorder, the following must be considered:
It is estimated that up to 20 million American men frequently suffer from impotence and that it strikes up to half of all men between the ages of 40 and 70. Doctors used to think that most cases of impotence were psychological in origin, but they now recognize that, at least in older men, physical causes may play a primary role in 60% or more of all cases. In men over the age of 60, the leading cause is atherosclerosis, or narrowing of the arteries, which can restrict the flow of blood to the penis. Injury or disease of the connective tissue, such as Peyronie's disease, may prevent the corpora cavernosa from completely expanding. Damage to the nerves of the penis, from certain types of surgery or neurological conditions, such as Parkinson's disease or multiple sclerosis, may also cause impotence. Men with diabetes are especially at risk for impotence because of their high risk of both atherosclerosis and a nerve disease called diabetic neuropathy.
The association between low testosterone and ED is not entirely clear. Although these 2 processes certainly overlap in some instances, they are distinct entities. Some 2-21% of men have both hypogonadism and ED; however, it is unclear to what degree treating the former will improve erectile function. [17] About 35-40% of men with low testosterone see an improvement in their erections with testosterone replacement; however, almost 65% of these men see no improvement. [15]
Injection therapy: The modern age of such drug therapies began in 1993 when the injection of papaverine (Pavabid), an alpha-blocker that produces vasodilatation (widening of the blood vessels), was shown to produce erections when injected directly into the penis. Soon afterward, other vasodilators, such as prostaglandin E1 (PGE 1) monotherapy (Caverject, Edex), PGE1 and phentolamine (Regitine), and Trimix (papaverine, phentolamine and prostaglandin E1), were demonstrated to be effective. The benefit of combination therapy is the decreased dosing of each with less side effects. Most important is the reduction of the prostaglandin PGE1 dosing, which is associated to the localized pain.
The physical examination can reveal clues for physical causes of erectile dysfunction. A doctor will perform an assessment of BMI and waist circumference to evaluate for abdominal obesity. A genital examination is part of the evaluation of erectile dysfunction. The examination will focus on the penis and testes. The doctor will ask you about penile curvature and will examine the penis to see if there are any plaques (hard areas) palpable. The doctor will examine the testes to make sure they are in the proper location in the scrotum and are normal in size. Small testicles, lack of facial hair, and enlarged breasts (gynecomastia) can point to hormonal problems such as hypogonadism with low testosterone levels. A health care provider may check pulses in your groin and feet to determine if there is a suggestion of hardening of the arteries that could also affect the arteries to the penis.
Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties. Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization (118). It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine (32,119).
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).

Trauma to the pelvic blood vessels and nerves is another potential factor in the development of ED. Bicycle riding for long periods has been implicated, so some of the newer bicycle seats have been designed to soften pressure on the perineum (the soft area between the anus and the scrotum). Certainly, history of pelvic bone fracture, as well as previous pelvic surgery (orthopedic, vascular, colon-rectum, and prostate) may result in injury to the arteries or nerves that go to the penis.
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.
There have been rare reports of priapism (prolonged and painful erections lasting more than six hours) with the use of PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil. Patients with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penis and lead to permanent impotence. Therefore, if your erection lasts four hours, you should seek emergency medical care.
Knowing about your history of ED will help your health provider learn if your problems are because of your desire for sex, erection function, ejaculation, or orgasm (climax). Some of these questions may seem private or even embarrassing. However, be assured that your doctor is a professional and your honest answers will help find the cause and best treatment for you.
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