Qaseem, A., Snow, V., Denberg, T. D., Casey, D. E., Forciea, M. A., Owens, D. K., & Shekelle, P. (2009). Hormonal testing and pharmacologic treatment of erectile dysfunction: A clinical practice guideline from the American College of Physicians. Annals of internal medicine, 151(9), 639-649. Retrieved from http://annals.org/aim/article/745155/hormonal-testing-pharmacologic-treatment-erectile-dysfunction-clinical-practice-guideline-from
Examples of common neurologic conditions that can lead to ED include cerebral vascular accident, multiple sclerosis, Parkinson’s disease, and spinal cord injury. Microvascular disease associated with diabetes is thought to compound the endothelial and neural injuries associated with this disease. Pelvic surgery may disrupt both neural and vascular pathways, resulting in ED.
If you are taking medications (alpha-blockers) for problems with an enlarged prostate, you should discuss your prostate medications with your doctor. Alpha-blockers also can cause lowering of the blood pressure. Thus your doctor will need to carefully watch your blood pressure when you start the PDE5 inhibitor. Common alpha-blockers include doxazosin (Cardura), terazosin (Hytrin), and tamsulosin (Flomax).

Soler et al. compared sildenafil to vardenafil and tadalafil (69). Sildenafil was effective in 85% of SCI patients, 74% of the patients on vardenafil and 72% of the patients on tadalafil. Sildenafil was associated with more rigid and longer lasting erections. Additionally, 50 mg of sildenafil was effective in 55% of patients compared to more than 70% of the patients on vardenafil and tadalafil requiring 20 mg for a similar response. Men who used tadalafil were able to achieve erections 24 hours after administration, improving overall satisfaction related to the possible spontaneity of sexual encounters. Del Popolo also evaluated the time/duration effectiveness of PDE5i sildenafil 50 mg versus tadalafil 10 mg (64). Tadalafil 10 mg significantly increased the percentage of successful intercourse attempts at 12–24 hours compared with sildenafil. One can suspect that vardenafil, which has a longer half-life than sildenafil, could offer a similar benefit but a study investigating this occurrence has yet to be performed.


Robbins, C. L., Schick, V., Reece. M., Herbenick, D., Sanders, S. A. Dodge, B., & Fortenberry J. D., (2011, December 1). Prevalence, frequency, and associations of masturbation with partnered sexual behaviors among US adolescents. JAMA Pediatrics, 165(12), 1087–1093. Retrieved from https://jamanetwork.com/journals/jamapediatrics/fullarticle/1107656
Many experts believe that atrophy, a partial or complete wasting away of tissue, and fibrosis, the growth of excess tissue, of the smooth muscle tissue in the body of the penis (cavernous smooth muscle) triggers problems with being able to maintain a firm erection. Poor ability to maintain an erection is often an early symptom of erectile dysfunction. Although the condition is called venous leak, the real problem is not with the veins but malfunction of the smooth muscle that surrounds the veins. The end result is difficulty with maintain a firm erection (losing an erection too quickly) that is now believe to be an early manifestation of atherosclerosis and vascular disease.
Much of the emphasis on erectile pathophysiology has been placed on penile smooth muscle function and cavernosal hemodynamics. The neuroanatomy and neurophysiology of erection can be characterized but its full extent is poorly understood. Neurologic disease does not always reproducibly affect erections in a uniform manner compared to other types of sexual dysfunction (SD). This offers many obstacles to understanding the role the nervous systems plays in SD and consequently obscures what treatment options readily optimize erections specific to the neurologic insult.
Sexual stimulation causes the release of neurotransmitters from cavernosal nerve endings and relaxation factors from endothelial cells lining the sinusoids. NOS produces NO from L-arginine, and this, in turn, produces other muscle-relaxing chemicals, such as cGMP and cyclic adenosine monophosphate (cAMP), which work via calcium channel and protein kinase mechanisms (see the image below). This results in the relaxation of smooth muscle in the arteries and arterioles that supply the erectile tissue, producing a dramatic increase in penile blood flow.
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.
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.
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.
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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.

Prior to the introduction of PDE5i in 1998, intracavernosal vasoactive medications and penile implant surgery were the mainstays of treatment. Penile implant surgery involves placement of inflatable or malleable rods within the corpora cavernosa to provide rigidity for intercourse. Choice of which implant to place usually depends upon manual dexterity and function of the patient, patient anatomy, physician preference and surgical approach.


Erectile problems can happen to men of any age.  There are many factors that contribute to ED including poor health, untreated medical problems, medications and pornography use.  Many men struggle with understanding when they are experiencing situational sexual dysfunction verses when is your erectile issue an ongoing problem that requires medical help.


Suppositories “were developed so men wouldn’t have to use needles,” Bivalacqua says. They contain the drug alprostadil (also known as prostaglandin E1) and are sold under the brand name Muse. If they are going to work, it takes about five to 10 minutes. However, Muse produces erections in only 30 to 40 percent of patients, usually those with mild ED, because some of the drug is absorbed systemically and diverted from its function of opening penile arteries to allow more blood to flow in. The out-of-pocket cost is around $20 to $30 per suppository.
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
The neurovascular events that ultimately occur result in the inhibition of adrenergic tone and the release of the nonadrenergic, noncholinergic neurotransmitter, nitric oxide. Nitric oxide is believed to be released from nonadrenergic, noncholinergic nerves and endothelial cells. It subsequently stimulates the guanylate cyclase enzyme system in penile smooth muscle. This results in increased levels of cyclic guanosine monophosphate (cGMP) and ultimately in smooth muscle relaxation, enhancement of arterial inflow, and veno-occlusion, producing adequate firmness for sexual activity.
Somatomotor penile innervation originates in Onuf’s nucleus in the S2-4 spinal segments. These nerves travel to the ischiocavernosus and bulbocavernosus muscles when activated lead to contraction necessary for the rigid-erection phase. Several animal studies show that stimulation of the somatomotor pathways may also be under sympathetic control, and adrenergic stimulation may lead to contraction of these muscles during ejaculation (13,14). Somatomotor spinal reflexes may also be initiated by genital stimulation. For instance, the well-known bulbocavernosus reflex is evidence this reflex exists; however the clinical significance of its absence in the neurological assessment of ED has not been substantiated (15).
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).

Given the high risk of priapism during escalation of therapy for intracorporeal injection, it is recommended that the drugs be administered in a supervised office visit initially and that the patient be given a well-articulated plan for treatment of priapism if it occurs. Escalation guidelines for alprostadil alone vary, but a general guideline is to start at 2.5 mcg and increase by 2.5 mcg to a dose of 5 mcg and then in increments of 5 mcg to 10 mcg until an erection sufficient for penetration, not lasting more than 1 hour, is achieved. If there is no response to the initial 2.5-mcg dose, escalation dosing can be slightly more liberal.34 A European prospective trial of PGE1 alone found 91% of the 54 patients completing the 4 years of the study reported good or better tolerability and satisfaction with therapy.35
Several pre-treatment factors have been described that may indicate success with PDE5i therapy. The presence of an upper motor neuron lesion up to T12 suggests a successful response, as well as requirement for a lower dosage of medication (62,68-71). Additionally, the presence of residual erections after injury or an incomplete SCI (ASI-A vs. ASIB-D) also improve the chance of PDE5i treatment success (59,67,68,71).

Talk with your doctor about going to a counselor if psychological or emotional issues are affecting your ED. A counselor can teach you how to lower your anxiety or stress related to sex. Your counselor may suggest that you bring your partner to counseling sessions to learn how to support you. As you work on relieving your anxiety or stress, a doctor can focus on treating the physical causes of ED.


Examples of common neurologic conditions that can lead to ED include cerebral vascular accident, multiple sclerosis, Parkinson’s disease, and spinal cord injury. Microvascular disease associated with diabetes is thought to compound the endothelial and neural injuries associated with this disease. Pelvic surgery may disrupt both neural and vascular pathways, resulting in ED.

The bad news: Men with diabetes are three times more likely to report having problems with sex than non-diabetic men. The most common sexual problem is Erectile Dysfunction, or ED, sometimes called impotence. Even worse, because ED is such a private issue, many men feel embarrassed to discuss the problem with their doctor, or even their partner, so the problem is never addressed.
Other treatment options such as penile self-injection therapy, external vacuum pumps and the medicated urethral system for erection are in rare occasions an effective long-term treatment. Only a very small percentage of men will continue with these treatments as evidenced by a very high drop out rate and a very low refill rate. These treatments require extensive planning which interferes with spontaneity. This may be the reason why the refill rate is so low and the drop out of treatment so high.  
Several studies accessed the prevalence of ED. The Massachusetts Male Aging Study reported a prevalence of 52%.2 The study demonstrated that ED is increasingly prevalent with age: approximately 40% of men are affected at age 40 and nearly 70% of men are affected at age 70. The prevalence of complete ED increased from 5% at age 40 to 15% at age 70.2 Age was the variable most strongly associated with ED.

In fact, one common reason many younger men visit their doctor is to get erectile dysfunction medication. Often, men with erectile dysfunction suffer with diabetes or heart disease, or may be sedentary or obese, but they don’t realize the impact of these health conditions on sexual function. Along with erectile dysfunction treatment, the doctor may recommend managing the illness, being more physically active, or losing weight.

Common medical conditions such as diabetes, heart disease, and high blood pressure are associated with an increased risk of developing erectile dysfunction. Thus, optimal management of these diseases may help prevent the development or progression of erectile dysfunction. Lifestyle modifications to improve vascular function, including smoking cessation, losing weight if overweight, and exercising regularly, may be helpful.
Quitting smoking, exercising regularly, losing excess weight, curtailing excessive alcohol consumption, controlling hypertension, and optimizing blood glucose levels in patients with diabetes are not only important for maintaining good health but also may improve or even prevent progression of erectile dysfunction. It is unclear if such lifestyle changes can reverse erectile dysfunction. However, lifestyle improvements may prevent progression of the erectile dysfunction. Some studies suggest that men who have made lifestyle improvements experience increased rates of success with oral medications.

If you are taking medications (alpha-blockers) for problems with an enlarged prostate, you should discuss your prostate medications with your doctor. Alpha-blockers also can cause lowering of the blood pressure. Thus your doctor will need to carefully watch your blood pressure when you start the PDE5 inhibitor. Common alpha-blockers include doxazosin (Cardura), terazosin (Hytrin), and tamsulosin (Flomax).


Pay attention to your vascular health. High blood pressure, high blood sugar, high cholesterol, and high triglycerides can all damage arteries in the heart (causing heart attack), in the brain (causing stroke), and leading to the penis (causing ED). An expanding waistline also contributes. Check with your doctor to find out whether your vascular system — and thus your heart, brain, and penis — is in good shape or needs a tune-up through lifestyle changes and, if necessary, medications.
MSA is a neurodegenerative disease of undetermined etiology, where ED is an early prominent sign occurring in 40% of men at the time of diagnosis (46,47). ED occurs in the majority of patients and the exact cause of it is unknown (48). Like PD, MSA likely affects the dopaminergic pathways within the brain essential for arousal (49). Orthostatic hypotension (OH) as a causal factor has been refuted by evidence that sildenafil can overcome reduced filling pressures, and the ED usually precedes the development of OH (46,49,50). Similar to other neurologic disorders that lead to ED, other disease related factors such as psychosocial stress, the burden of chronic illness, changed appearance, fatigue, decreased fine motor movement of fingers, immobility and diminished self-esteem due to loss of independence may contribute as well (51).

The sympathetic pathway originates from the 11th thoracic to the 2nd lumbar spinal segments and goes via the white rami to enter the sympathetic chain ganglia. Subsequently nerves travel through the lumbar splanchnic to inferior mesenteric and superior hypogastric nerves to the pelvic plexus. The T10 through T12 segments are most often the origin of sympathetic fibers, and the sympathetic chain ganglia that innervate the penis are located in the sacral and caudal ganglia (3).
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.

Other treatment options such as penile self-injection therapy, external vacuum pumps and the medicated urethral system for erection are in rare occasions an effective long-term treatment. Only a very small percentage of men will continue with these treatments as evidenced by a very high drop out rate and a very low refill rate. These treatments require extensive planning which interferes with spontaneity. This may be the reason why the refill rate is so low and the drop out of treatment so high.  
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.
Monitoring erections that occur during sleep (nocturnal penile tumescence) can help you and your doctor to understand if the erectile dysfunction is due to psychological or physical causes. The nocturnal penile tumescence test is a study to evaluate erections at night. Normally men have three to five erections per eight hours of sleep. The test can be performed at home or in a sleep lab. The most accurate way to perform the test involves a special device that is connected to two rings. The rings are placed around the penis, one at the tip of the penis and the other at the bottom (base) of the penis. The device records how many erections occur, how long they last, and how rigid they are. The test is limited in that it does not assess the ability to penetrate.
Penis pumps produce erections by drawing blood, via air suction, into the penis. The devices consist of a cylindrical tube, 12 to 18 inches long, connected by a small air hose to a hand pump (on many models this resembles the squeeze mechanism on a blood pressure monitor). Users place the tube over the penis then pump to produce an erection. They must then place an elastic band around the base of the penis to keep the blood there and maintain the erection.  
Supplements are popular and often cheaper than prescription drugs for ED. However, supplements have not been tested to see how well they work or if they are a safe treatment for ED. Patients should know that many over-the-counter drugs have been found on drug testing to have ‘bootlegged' PDE 5 Inhibitors as their main ingredient. The amounts of Viagra, Cialis, Levitra or Stendra that may be in these supplements is not under quality control and may differ from pill to pill. The FDA has issued consumer warnings and alerts.
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