It appears that testosterone has NOS-independent pathways as well. In one study, castrated rats were implanted with testosterone pellets and then divided into a group that received an NOS inhibitor (L-nitro-L-arginine methyl ester [L-NAME]) and a control group that received no enzyme. [24] The castrated rats that were given testosterone pellets and L-NAME still had partial erections, a result suggesting the presence of a pathway independent of NOS activity.
Can’t or don’t want to take ED drugs? The vacuum pump method is the next most common choice among men with erectile dysfunction who pass on pills, says Dr. Bennett. To create an erection, you place a plastic cylinder over the penis and pump the air out of the cylinder to force blood to flow into the penis. An elastic ring that you slide onto the base of your penis holds the erection. This ED treatment device is effective for about 75 percent of men. Side effects include numbness, bruising, and weak ejaculation — and the ring must be removed after 30 minutes.
ED exists in approximately 75% of men with SB and is dependent upon the level of the neurologic lesion (54). The level of the neurologic lesions usually corresponds to sensation and penile sensation indicates pudendal nerve signaling. With absent sacral reflexes ED is variable. Furthermore, Diamond et al. reported that 64% of men with lesions below T10 obtained erections versus 14% with a lesion above T10 (55). It has also been suggested that ED may be underreported due to lack of sexual education even in men without associated cognitive impairment (56).
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]
Erectile dysfunction in older men. Because erections primarily involve the blood vessels, it is not surprising that the most common causes in older men are conditions that block blood flow to the penis, such as atherosclerosis or diabetes. Another vascular cause may be a faulty vein, which lets blood drain too quickly from the penis. Other physical disorders, as well as hormonal imbalances and certain operations, may also result in erectile dysfunction.
Normal erectile function depends on the release of NO and endothelial-dependent vasodilation of the penile arteries. The ‘artery size’ hypothesis, first described by Dr Montorsi, offers an explanation why men are more likely to develop ED before a myocardial infacrtion. It is believed that atherosclerosis affects all vascular beds equally but smaller arteries are more likely to become occluded than larger arteries.31 32 The penile arteries are 1–2 mm while the coronary arteries are 3–4 mm. Thus, the same degree of endothelial dysfunction and atherosclerosis is more likely to occlude blood flow in the penile arteries compared with the coronary arteries. The penile arteries therefore serve as a sensitive indicator for subsequent CVD. This theory is supported by the fact that ED occurs approximately 3 years prior to cardiac symptoms in virtually all patients with chronic coronary syndrome whereas patients with acute coronary syndrome have a much lower prevalence of sexual dysfunction.32

The availability of phosphodiesterase-5 (PDE5) inhibitors—sildenafil, vardenafil, tadalafil, and avanafil—has fundamentally altered the medical management of ED. In addition, direct-to-consumer marketing of these agents over the last 15 years has increased the general public’s awareness of ED as a medical condition with underlying causes and effective treatments.
If you can't take one of these oral medications, your physician may have you try Caverject (alprostadil for injection), a hormone that you inject into your penis using a fine needle, or Muse (alprostadil urogenital), a tiny suppository that you insert into the tip of the penis. Both of these will bring on an erection within five to 15 minutes without sexual stimulation.
Instead of the hesitation with which he had accosted the cardinal a quarter of an hour before, there might be read in the eyes of the young king that will against which a struggle might be maintained, and which might be crushed by its own impotence, but which, at least, would preserve, like a wound in the depth of the heart, the remembrance of its defeat.
Stress is your body responding to your environment. And it’s a good thing—in limited doses. When you get stressed out your body makes chemicals like adrenaline that make you stronger, faster, fitter, and even able to think more clearly. Most people call this reaction the “fight-or-flight” response, and it’s a life-saver in dangerous situations. In a very real sense, adrenaline makes you a part-time superhero. The problems happen when your body deals with constant stress.
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.
All studies demonstrate a strong association with age, even when data are adjusted for the confounding effects of other risk factors. The independent association with aging suggests that vascular changes in the arteries and sinusoids of the corpora cavernosa, similar to those found elsewhere in the body, are contributing factors. Other risk factors associated with aging include depression, sleep apnea, and low HDL levels.
Erections occur in response to tactile, olfactory, and visual stimuli. The ability to achieve and maintain a full erection depends not only on the penile portion of the process but also on the status of the peripheral nerves, the integrity of the vascular supply, and biochemical events within the corpora. The autonomic nervous system is involved in erection, orgasm, and tumescence. The parasympathetic nervous system is primarily involved in sustaining and maintaining an erection, which is derived from S2-S4 nerve roots.
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]
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.

Between 10 and 88% of patients diagnosed with cancer experience sexual problems following diagnosis and treatment. The prevalence varies according to the location and type of cancer, and the treatment modalities used. Sexuality may be affected by chemotherapy, alterations in body image due to weight change, hair loss or surgical disfigurement, hormonal changes, and cancer treatments that directly affect the pelvic region.
"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.
The PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken orally.[22]:20–21 Additionally, a cream combining alprostadil with the permeation enhancer DDAIP has been approved in Canada as a first line treatment for erectile dysfunction.[25] Penile injections, on the other hand, can involve one of the following medications: papaverine, phentolamine, and prostaglandin E1, also known as alprostadil.[22]:25

Alprostadil may be delivered via the urethra in the form of a pellet (MUSE) (107). This form of therapy has been trialed in SCI men with intermediate success (108). Bodner trialed MUSE dose escalation in SCI men and found 1,000 μg to be the most effective dose. Several men had hypotension when a constriction ring was not used in conjunction with the MUSE therapy.

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.

The nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles. Although the membrane receptors play an important role, downstream signaling pathways are also important. The RhoA–Rho kinase pathway is involved in the regulation of cavernosal smooth muscle contraction. [12]
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).
Vacuum therapy devices have a few disadvantages. One must interrupt foreplay to use them. You must use the correct-size tension ring and remove it, to prevent penile bruising, after sustaining the erection for 30 minutes. Initial use may produce some soreness. Such devices may be unsuitable for men with certain bleeding disorders. In general, vacuum constriction devices are successful in management of long-term ED.
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.
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 obvious risks are the same that accompany any surgery: infection, pain, bleeding, and scarring. If for some reason the prosthesis or parts become damaged or dislocated, surgical removal may be necessary. With a general success rate of about 90 percent, any of the devices will restore erections, but they will not affect sexual desire, ejaculation, or orgasm.
The physical side effects of chemotherapy are usually temporary and resolve within one to two weeks after stopping the chemotherapy. However, chemotherapy agents, such as Ciplatin or Vincristine, may interfere with the nerves that control erection leading to possible impotence. Make sure you discuss potential side effects of cancer chemotherapy with your doctor or healthcare provider.
Is your erectile dysfunction due to psychological (stress, relationship problems, etc.) or physical factors? Your doctor may ask if you note erections at night or in the early morning. Men have involuntary erections in the early morning and during REM sleep (a stage in the sleep cycle with rapid eye movements). Men with psychogenic erectile dysfunction (erectile dysfunction due to psychological factors such as stress and anxiety rather than physical factors) usually maintain these involuntary erections. Men with physical causes of erectile dysfunction (for example, atherosclerosis, smoking, and diabetes) usually do not have these involuntary erections. Men with psychogenic erectile dysfunction may relate the onset of problems to a "stressor," such as failed relationship. Your doctor may suggest a test to determine if you have erections during sleep, which may suggest that there may be a psychological cause of the erectile dysfunction.
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).
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.
Parasympathetic pathways originate from the intermediolateral cell columns of the 2nd, 3rd and 4th sacral spinal cord segments. Preganglionic fibers pass through the pelvic plexus where they coalesce with sympathetic fibers from the superior hypogastric plexus. The cavernous nerves that innervate the penis arise from the portion of the pelvic plexus. The pelvic plexus also contains nerves that innervate the rectum, bladder and urinary sphincter and the nerve projections can be damaged during radical excision of the bladder, prostate and rectum, leading to iatrogenic ED (4).
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).
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.
Inflatable prostheses are complex mechanical devices that imitate the natural process of erection. Parts are inserted surgically into the penis and scrotum, and activated by squeezing. When erection is no longer desired, a valve on the pump is pressed, and the penis becomes flaccid. Self-contained single-unit prostheses are similar to the inflatable types, but more compact. The entire device is implanted into the penis. When erection is desired, the unit is activated by either squeezing or bending, depending on which of the two types of self-contained prostheses is used.
Martha K Terris, MD, FACS is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Institute of Ultrasound in Medicine, American Society of Clinical Oncology, American Urological Association, Association of Women Surgeons, New York Academy of Sciences, Society of Government Service Urologists, Society of University Urologists, Society of Urology Chairpersons and Program Directors, and Society of Women in Urology
A study published in May 2014 in The Journal of Sexual Medicine found that some men can reverse erectile dysfunction with healthy lifestyle changes, such as exercise, weight loss, a varied diet, and good sleep. The Australian researchers also showed that even if erectile dysfunction medication is required, it's likely to be more effective if you implement these healthy lifestyle changes.

The Food and Drug Administration (FDA) does not recommend alternative therapies to treat sexual dysfunction.[27] Many products are advertised as "herbal viagra" or "natural" sexual enhancement products, but no clinical trials or scientific studies support the effectiveness of these products for the treatment of ED, and synthetic chemical compounds similar to sildenafil have been found as adulterants in many of these products.[28][29][30][31][32] The FDA has warned consumers that any sexual enhancement product that claims to work as well as prescription products is likely to contain such a contaminant.[33]
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.
Since endothelial dysfunction, CVD and ED are closely associated in epidemiological studies, the question for clinicians is whether to recommend the man presenting with ED undergo a cardiovascular (CV) evaluation. Clearly, based on numerous studies, ED can be considered at least a ‘marker’ for possible further vascular disease or CVD.15 In their report, Vlachopoulos and coworkers make the point that the man presenting with ED, the clinician, is offered an opportunity to attempt to improve the health of the man by addressing lifestyle modification, and consider further vascular evaluation owing to the clear relationship between endothelial dysfunction, ED and CVD.19

When stimulated by the nerves, the spongy tissue arranges itself in such a way that more blood can be stored in the penis. The veins running through the outer sheath of the penis then compress which stops the blood from leaving the penis. As the blood is stopped from flowing out, the penis fills with blood and stretches within the outer casing, giving an erection.

For many men, stopping smoking is an erectile dysfunction remedy, particularly when ED is the result of vascular disease, which occurs when blood supply to the penis becomes restricted because of blockage or narrowing of the arteries. Smoking and even smokeless tobacco can also cause the narrowing of important blood vessels and have the same negative impact. 

Penile implants - are generally used if physical damage (like an accident) makes the anatomical parts needed for an erection not work. These are inserted by surgery and can provide a permanent treatment choice if others fail to work. The implants can be semi-rigid or inflatable. They can be pretty expensive and are not usually available on the NHS.
Research has even found possible links to frequent ejaculation and a lower risk of prostate cancer. In one study of 32,000 men published in 2016 in the journal European Urology, for example, men who ejaculated at least 21 times per month while in their 20s were less likely to be diagnosed with prostate cancer than those who ejaculated four to seven times per month. And men who ejaculated more often in their 40s were 22 percent less likely to get a prostate cancer diagnosis.
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 common medications for treating hypertension, depression, and high blood lipids (high cholesterol) can contribute to erectile dysfunction (see above). Treatment of hypertension is an example. There are many different types (classes) of medications for high blood pressure; these include beta-blockers, calcium channel blockers, diuretics (medications that increase urine volume), angiotensin converting enzyme inhibitors (ACE inhibitors), and angiotensin receptor blockers (ARBs). Patients may use these medications alone or in combination to control blood pressure. Some of these medications can cause troubles with erections. For example, Inderal (a beta-blocker) and hydrochlorothiazide (a diuretic) cause erectile dysfunction, while calcium channel blockers and ACE inhibitors do not seem to affect erectile function. On the other hand, other medications (such as angiotensin receptor blockers [ARB] including losartan [Cozaar] and valsartan [Diovan]) may actually help with erections. Therefore, if possible, you may benefit from changing your medications, but this requires approval by your prescribing health care provider.
PDE 5 inhibitors are broken down primarily by enzyme, cytochrome P450enzyme CYP3A4. Medications that decrease or increase the activity of CYP3A4 may affect levels and effectiveness of PDE 5 inhibitors. Such drugs include medications for the treatment of HIV (protease inhibitors) and the antifungal medications ketoconazole and itraconazole. Thus caution is recommended.
The vacuum device creates a vacuum to pull blood into the penis. Unlike a normal erection, the inflow of blood does not continue once the individual removes the vacuum device. The rubber band placed at the base of the penis constricts the penis to prevent the blood from leaving the penis. As there is no inflow or outflow of blood when the rubber band is in place, it is uncommon for the tip of the penis (the glans) to appear a little blue and the penis to be cooler. Once intercourse is completed, the individual removes the rubber band and the blood drains out of the penis.
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.  

Before taking any medication for erectile dysfunction, including over-the-counter supplements and herbal remedies, get your doctor's OK. Medications for erectile dysfunction do not work in all men and might be less effective in certain conditions, such as after prostate surgery or if you have diabetes. Some medications might also be dangerous if you:
Vascular damage may result from radiation therapy to the pelvis and prostate in the treatment of prostate cancer. [36] Both the blood vessels and the nerves to the penis may be affected. Radiation damage to the crura of the penis, which are highly susceptible to radiation damage, can induce ED. Data indicate that 50% of men undergoing radiation therapy lose erectile function within 5 years after completing therapy; fortunately, some respond to one of the PDE5 inhibitors.
Another potential new treatment consists of penile low-intensity shock wave lithotripsy. This consists of 1500 shocks twice a week for 3–6 weeks. The purpose is to stimulate neovascularisation to the corporal bodies with improvement in penile blood flow and endothelial function. The use of low-intensity shock wave lithotripsy may convert PDE5 inhibitor non-responders to responders.47
The use of injection therapy requires being taught how to properly inject the medication, determination of the best dose, and monitoring for side effects. It is recommended that one inject on the side of the penis at the base and to alternate sides. Injection therapy should be used no more frequently than once every 24 hours. Individuals on blood thinners must be careful with use of injection therapy.
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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]
ED usually has something physical behind it, particularly in older men. But psychological factors can be a factor in many cases of ED. Experts say stress, depression, poor self-esteem, and performance anxiety can short-circuit the process that leads to an erection. These factors can also make the problem worse in men whose ED stems from something physical.
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