Diabetes mellitus: Erectile dysfunction tends to develop 10 to 15 years earlier in diabetic men than among nondiabetic men. The increased risk of erectile dysfunction among men with diabetes mellitus may be due to the earlier onset and greater severity of atherosclerosis (hardening of the arteries) that narrows the arteries and thereby reduces the delivery of blood to the penis. Atherosclerosis can affect the arteries in the penis, as well as the arteries in the pelvis that supply the penile arteries. Diabetes mellitus also causes erectile dysfunction by damaging nerves that go to the penis, much like the effect of diabetes on nerves in other areas of the body (diabetic neuropathy). Diabetes can also affect the muscles in the penis, leading to troubles with erections. Smoking cigarettes, obesity, poor control of blood glucose levels, and having diabetes mellitus for a long time further increase the risk of erectile dysfunction in people with diabetes.

Erectile dysfunction is defined as the persistent inability to achieve or maintain penile erection sufficient for satisfactory sexual performance. The Massachusetts Male Aging Study surveyed 1,709 men aged 40–70 years between 1987 and 1989 and found there was a total prevalence of erectile dysfunction of 52 percent. It was estimated that, in 1995, over 152 million men worldwide experienced ED. For 2025, the prevalence of ED is predicted to be approximately 322 million worldwide.

The pathogenesis of organic ED is related to dysfunction of the endothelium. Endothelial cells can become injured through a variety of mechanisms, most of which cause oxidative stress on the tissues. Many of these causes of oxidative stress are related to lifestyle issues which lead to hypertension, diabetes and dyslipidaemia (figure 1). Endothelial cell dysfunction results in reduction of endothelium-dependent vasorelaxation as well as increased adhesion of leukocytes to the endothelium. Endothelial cell injury then leads to a variety of sequelae, including ED, other types of vasoconstriction, atherosclerosis and thrombus formation.18
Physicians make a diagnosis of erectile dysfunction in men who complain of troubles having a hard enough erection or a hard erection that does not last long enough. It is important as you talk with your doctor that you be candid in terms of when your troubles started, how bothersome your erectile dysfunction is, how severe it is, and discuss all your medical conditions along with all prescribed and nonprescribed medications that you are taking. Your doctor will ask several questions to determine if your symptoms are suggestive of erectile dysfunction and to assess its severity and possible causes. Your doctor will try to get information to answer the following questions:

Alprostadil, a drug also discussed in Penile Injection Therapy, has been formulated into a small suppository. This applicator is inserted into the urethra (the canal through which urine and semen are excreted), and with compression of the applicator, the small suppository is released into the urethra. With massage/rubbing of the penis, the suppository dissolves in the urethra and the medication is absorbed into the penis where it acts to increase blood flow into the penis. One cannot use any form of lubricant (for example, K-Y jelly, Vaseline, etc) to help with the insertion of the suppository. Urinating prior to inserting the applicator will help moisten/lubricate the urethra.
Sexual dysfunction is highly prevalent in men and women. In the MMAS, 52% of the respondents reported some degree of erectile difficulty. Complete ED, defined as (1) the total inability to obtain or maintain an erection during sexual stimulation and (2) the absence of nocturnal erections, occurred in 10% of the respondents. Mild and moderate ED occurred in 17% and 25% of responders, respectively. [15]
Medications such as sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) may help improve sexual function in men by increasing blood flow to the penis. Men who are on medicines that contain nitrates such as nitroglycerine should not take oral ED medications. The combination of nitrates and these specific medications can cause low blood pressure (hypotension).

"The good news is, our study also found that a large proportion of men were naturally overcoming erectile dysfunction issues. The remission rate of those with erectile dysfunction was 29%, which is very high. This shows that many of these factors affecting men are modifiable, offering them an opportunity to do something about their condition," Professor Wittert says.

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.

Finally, gene therapy and stem cell research has widened the frontier of ED treatment proposed as possibility to even reverse ED. Specifically, gene therapy pertains to repairing the cause of ED by restoring defective gene function and/or altering the expression of the mutant gene (32). Most of the available data on gene therapy are in the animal model. However, a phase I clinical trial in men with ED undergoing intracavernous injection with a DNA plasmid carrying the alpha-subunit of the corporal smooth muscle Maxi-K channel showed promise in increased erectile function based on IIEF assessment sustained throughout the 3-month study period (122).

Oral therapies via the PDE5i sildenafil, vardenafil, and tadalafil have been proven to be generally safe and effective in select NED populations. The majority of the treatment effectiveness data has been generated in the SCI population. Data regarding the use of PDE5i outside of the SCI population is lacking (58). Furthermore, the ED that exists in the population with neurologic disorders is often multifactorial and may be caused by psychogenic, psychosocial, hormonal, medication-related and disability-related factors. A careful evaluation of each patient must be performed to isolate these factors prior to initiating vasoactive 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.
PDE5i use in PD has not been well studied; however its benefits have been shown. Raffaele performed an open label, prospective study evaluating the efficacy of sildenafil 50 mg on demand and depressive symptoms experienced by the PD patient (73). Erections were improved in approximately 85% of men and 75% noted improvements in their depressive symptoms as well. Sildenafil was well tolerated without significant side effects. Zesiewicz et al., performed a shorter study showing improvements in erectile function but no change in depression and parkinsonisms after ED treatment (74).
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.
L-arginine, an amino acid that is naturally present in the body and helps make nitric oxide, supports a successful erection. Nitric oxide is responsible for making the blood vessels relax, which helps sustain an erection for men. A 1999 study, observed the effects of six weeks of high-dose (5 grams/day) orally administered nitric oxide (NO) donor L-arginine on men with organic ED. Thirty-one percent of those who took 5 grams/day of L-arginine experienced significant improvements in sexual function. Burns told Medical Daily, “l-arginine and deer antler velvet” have been the most popular go-to natural treatments for men.
If you’re experiencing psychological ED, you may benefit from talk therapy. Therapy can help you manage your mental health. You’ll likely work with your therapist over several sessions, and your therapist will address things like major stress or anxiety factors, feelings around sex, or subconscious conflicts that could be affecting your sexual well-being.

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.


This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings through its clearinghouses and education programs to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.
The prostaglandin E1 is contained in a small suppository located at the tip of an applicator. You should urinate first as this lubricates the urethra and makes it easier to insert the applicator into the tip of the urethra (urethral meatus, the opening at the tip of the penis that urine passes through). A patient can release the suppository into urethra by gently wiggling the applicator and pressing the button at the end. Rubbing the penis allows the suppository to dissolve, and the prostaglandin is absorbed through the tissue of the urethra into the penis. It takes 15 to 30 minutes for this occur. Once into the penis, the prostaglandin causes increased blood flow into the penis. The prostaglandin can be present in the ejaculate, and thus doctors recommend that men use a condom when having intercourse with a pregnant partner. Men may need to use a condom if vaginal irritation occurs in female partner.
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.
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.

Clinical experience in switching medications to improve ED has been disappointing in that improvement does not often occur. Nonetheless, it is important to try to discontinue possible offending medications before proceeding to more invasive ED treatment options. Oral ED medications have changed the way clinicians discontinue medications in patients with ED and has improved the approach. For example, a patient may develop ED on a thiazide diuretic. The diuretic may be withdrawn, but a trial of oral ED therapy can be initiated during the observation period while the patient is waiting to see if any spontaneous improvement in ED occurs after drug withdrawal. Alternatively, if diuretic therapy is effective, well tolerated, and controlling blood pressure, oral ED therapy can be used on an ongoing basis to treat the side effect of ED.
There are hundreds of medications that have the side effect of ED and/or decreased libido. Examples of drugs implicated as a cause of ED include hydrochlorothiazides and beta-blocking agents. Medications used to treat depression, particularly the SSRIs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Prozac Weekly, Sarafem), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR, Pexeva) and sertraline (Zoloft), may also contribute to ED.9 Bupropion (Wellbutrin) which has a predominant effect on blocking the reuptake of dopamine is an antidepressant with lower incidence of ED.10 The side effects of 5ARIs occurring in fewer than 5% of patients can include gynaecomastia, ED, loss of libido and ejaculatory dysfunction.11
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