All NOS subtypes produce NO, but each may play a different biologic role in various tissues. nNOS and eNOS are considered constitutive forms because they share biochemical features: They are calcium-dependent, they require calmodulin and reduced nicotinamide adenine dinucleotide phosphate for catalytic activity, and they are competitively inhibited by arginine derivatives. nNOS is involved in the regulation of neurotransmission, and eNOS is involved in the regulation of blood flow.
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.
Other medical therapies under evaluation include ROCK inhibitors and soluble guanyl cyclase activators. Melanocortin receptor agonists are a new set of medications being developed in the field of erectile dysfunction. Their action is on the nervous system rather than the vascular system. PT-141 is a nasal preparation that appears to be effective alone or in combination with PDE5 inhibitors. The main side effects include flushing and nausea. These drugs are currently not approved for commercial use.

Psychosocial problems are important and may cause erectile dysfunction by themselves or together with other causes of erectile dysfunction, such as diabetes and heart disease. Relationships are complicated and many factors cause tensions, which can affect sexual relations. For some men, these problems can become ongoing and it can help to talk through the issue with a skilled counsellor. It is important to know that the longer erectile dysfunction is left untreated, the greater the effect on relationships. This is another reason why early treatment of erectile dysfunction is important.
In addition, when research has shown a nutrient such as zinc or niacin to improve sexual function, it's usually in people who are deficient in it. So, before you stock up on over-the-counter nutritional supplements for ED, speak with your doctor. He can test you for deficiencies and steer you toward the most effective and safest way to treat your erectile dysfunction. 
Some men should not take PDE5 inhibitors. They can cause hypotension (abnormally low blood pressure that can lead to fainting and even shock) when given to patients who are taking nitrates (medications taken for heart disease). Therefore, patients taking nitrates daily should not take any of the PDE5 inhibitors. Nitrates relieve angina (chest pain due to insufficient blood supply to the heart muscle because of narrowing of the coronary arteries); these include nitroglycerine tablets, patches, ointments, sprays, and pastes, as well as isosorbide dinitrate and isosorbide mononitrate. Other nitrates such as amyl nitrate and butyl nitrate also are in some recreational drugs called "poppers."
"For men who are unwilling or unable to self-inject alprostadil, the FDA has approved this dissolvable pellet that can be inserted directly into the urethra, the opening of the penis," says Dr. Feloney. MUSE, with an inspiring name that actually stands for medicated urethral system for erection, will trigger an erection in about 10 minutes that may last as long as an hour. Using MUSE to treat ED can result in somewhat unpleasant side effects, however — including an aching sensation, burning, redness, and minor bleeding.
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).
According to whom? What's the source of your statistic? Because it sounds astonishingly high, for me to get erections and then lose them. If what you are talking about is men not being able to get erections, why don't you be honest and say that normally this is completely associated with age (say, over-60, and especially over 75), and that the Viagra-class of medications is the simplest and easiest response.
ED may occur with or without other sexual dysfunction, including decreased libido (decreased interest in sexual activity), orgasmic dysfunction (troubles achieving an orgasm/climax), and ejaculatory dysfunction (problems with the fluid released during sex, including lack of ejaculation [anejaculation], small volume ejaculate, ejaculation that occurs too quickly [premature ejaculation], ejaculate that goes backward into the bladder [retrograde ejaculation] and pain with ejaculation).
Radical prostatectomy for the treatment of prostate cancer poses a significant risk of ED. A number of factors are associated with the chance of preserving erectile function. If both nerves that course on the lateral edges of the prostate can be saved, the chance of maintaining erectile function is reasonable. The odds depend on the age of the patient. Men younger than 60 years have a 75-80% chance of preserving potency, but men older than 70 years have only a 10-15% chance.
Among the phenomena in the ageing man are a decrease in erectile function and testosterone levels. Add to these, increased risk for CVD, muscle wasting, decrease in bone density and libido, with all of these factors having an interplay with testosterone metabolism.33 Androgens play a key role in maintaining erectile function through four main mechanisms. Androgen deprivation has been shown to result in impairment of NO synthase release, altered PDE5 expression and activity, impaired cavernosal nerve function, and contribution to veno-occlusive disease in the penis.34 The role of testosterone replacement therapy (TRT) as a potential to improve erectile function in the man with ED remains an issue for patient and physicians who are comfortable treating androgen deficiency which include primary care physicians and specialists. Androgens are known to have a significant impact on the function of the smooth musculature within the corpus spongiosum.35
You may find that using a vacuum device requires some practice or adjustment. Using the device may make your penis feel cold or numb and have a purple color. You also may have bruising on your penis. However, the bruises are most often painless and disappear in a few days. Vacuum devices may weaken ejaculation but, in most cases, the devices do not affect the pleasure of climax, or orgasm.
Neurogenic erectile dysfunction (NED) is a traditional classification of erectile dysfunction (ED) encompassing disorders impairing erections via neurologic compromise or dysfunction. The disorders compromising erections may act centrally, peripherally or both. The prevalence of neurogenic ED has been suspected to be between 10% and 19% of all causes of ED (1,2). However, several classically defined neurogenic processes may affect several components of the normal pathway to achieve erection e.g., multiple sclerosis (MS), diabetes mellitus, iatrogenic surgical and spinal cord injury. Each disease state has its own unique characteristics that require acknowledgement to fully understand their effect on ED.

The recommended starting dose of tadalafil for use as needed for most patients is 10 mg taken orally approximately one hour before sexual activity. A doctor may adjust the dose higher to 20 mg or lower to 5 mg depending on efficacy and side effects. Doctors recommended that patients take tadalafil no more frequently than once per day. Some patients can take tadalafil less frequently since the improvement in erectile function may last 36 hours. Patients may take tadalafil with or without food. Tadalafil is currently the only PDE5 inhibitor that is FDA-approved for daily use for erectile dysfunction and is available in 2.5 mg or 5 mg dosages for daily use.
Psychotherapy, marital counseling, or sex therapy may be helpful in treating cases of impotence that have psychological or emotional causes. A range of other treatments exists for cases of impotence that arise from purely physiological causes. These treatments include vacuum devices, penile injections, and penile implants. These mechanical or physically invasive approaches have largely been superseded, however, by the drug sildenafil citrate (trade name Viagra), which is taken in pill form. This drug works by enhancing the effects of nitric oxide, a chemical that, upon sexual stimulation, is normally released to widen the blood vessels supplying the penis. The increased flow of blood through those vessels into certain tissues in the penis causes an erection. See also sexual dysfunction.

NO is produced by the enzyme NO synthase (NOS). [13] NOS plays many roles, ranging from homeostasis to immune system regulation. To date, 3 subtypes have been identified: nNOS, iNOS, and eNOS, which are produced by the genes NOS1, NOS2, and NOS3, respectively. This nomenclature is derived from the sources of the original isolates: neuronal tissue (nNOS), immunoactivated macrophage cell lines (iNOS), and vascular endothelium (eNOS). The subtypes are not, however, limited to the tissues from which they were first isolated.

Other form of sexual dysfunction, such as premature ejaculation and loss of libido (decreased sexual desire), are also very common. The NHSLS found that 28.5% of men 18-59 years of age reported premature ejaculation, and 15.8% lacked interest during the past year. An additional 17% reported anxiety about sexual performance, and 8.1% indicated a lack of pleasure from sexual activity.
A number of herbs have been promoted for treating impotence. The most widely touted herbs for this purpose are Coryanthe yohimbe (available by prescription as yohimbine, with the trade name Yocon) and gingko (Gingko biloba), although neither has been conclusively shown to help the condition in controlled studies. In addition, gingko carries some risk of abnormal blood clotting and should be avoided by men taking blood thinners such as coumadin. Other herbs promoted for treating impotence include true unicorn root (Aletrius farinosa), saw palmetto (Serenoa repens), ginseng (Panax ginseng), and Siberian ginseng (Eleuthrococcus senticosus). Strychnos Nux vomica has been recommended, especially when impotence is caused by excessive alcohol, cigarettes, or dietary indiscretions, but it can be very toxic if taken improperly, so it should be used only under the strict supervision of a physician trained in its use.

Penile prostheses are very effective, and most patients who have a prosthesis placed are satisfied with the prosthesis. However, placement of a prosthesis causes scarring of the tissue within the corpora cavernosa, and if the prosthesis requires removal, other forms of therapy, except for the vacuum device, are often not effective. Thus, most physicians reserve placement of a prosthesis for men who have tried and failed or have contraindications to other therapies.


Erections are more complicated than you think. Your brain, nerves, heart, blood vessels, and a whole lot of hormones have to work together perfectly or nothing happens. It’s a lot to ask, and sometimes things break down. And while ED happens to most guys at some point in their lives, erectile dysfunction isn’t something you can just ignore and hope it goes away.

The U.S. FDA (Food and Drug Administration) has a list of 29 OTC products that claim to treat erectile dysfunction. Patients should avoid these because many contain harmful ingredients. Other natural or herbal remedies such as DHEA, L-arginine, ginseng, and yohimbe are supplements that have been used but have not been proven safe and effective according to some researchers. Before using such compounds, individuals should consult their doctor. According to some experts, acupuncture does not effectively treat erectile dysfunction. Other home remedies for reducing ED symptoms include diet changes such as eating blueberries and citrus fruits and drinking red wine.
Individuals at higher risk for priapism (painful erection lasting longer than six hours), including men with sickle cell anemia, thrombocytopenia (low platelet count), polycythemia (increased red blood cell count), multiple myeloma (a cancer of the white blood cells), and history of blood clots (for example, deep venous thrombosis [DVT]) or hyperviscosity (thick blood) syndrome are at increased risk for priapism with MUSE.
Because the burning side effect is triggered by alprostadil, the formulations with the least alprostadil — tri-mix and certain versions of bi-mix — could work for men who experience burning with the single-drug formula. But some men might choose alprostadil alone because the multi-drug cocktails can cost more and must be dispensed by a compounding pharmacy — one that is authorized to mix medications on site — which could mean the added hassle of a long drive to pick up the drug.
Testosterone replacement: Men with low sex drive (libido) and ED may be found to have low testosterone levels. Hormone replacement may be of benefit by itself or as a complementary therapy used with other treatments. Libido and an overall sense of well-being are likely to improve when serum testosterone levels are restored. The constitution of symptoms of low libido, fatigue, decreased muscle mass and force, and increased body fat may be related to andropause. As mentioned previously, in the patient workup section, serum total testosterone and bioavailable testosterone blood tests can be performed to evaluate for low serum levels. If determined to be below normal, replacement of testosterone may be suggested as a treatment option. The primary objective of testosterone replacement is to improve libido, energy levels, and symptoms of andropause. Only secondarily would correction of low testosterone levels potentially have impact on erectile function. Some studies suggest that in men with low or low normal testosterone levels and ED who fail PDE5 inhibitors that the use of hormone therapy may improve the success of PDE5 inhibitors.
You have the right to help plan your care. Learn about your health condition and how it may be treated. Discuss treatment options with your healthcare providers to decide what care you want to receive. You always have the right to refuse treatment. The above information is an educational aid only. It is not intended as medical advice for individual conditions or treatments. Talk to your doctor, nurse or pharmacist before following any medical regimen to see if it is safe and effective for you.

Erectile dysfunation medications may not be suitable for you if you have been told not to have sex, not to engage in sexual activity/actions that widen your blood vessels, have low blood pressure (hypotension), have recently had a stroke, have unstable angina, have had a heart attack or have a history of non-arteritic anterior ischaemic optic neuropathy. Men with cardiovascular disease/anatomical issue with their penis/priapism/taking long-lasting alpha-blockers should use with caution and discuss with a doctor first. Do not mix with drugs/medications containing nitrates.


Associated morbidity may include various other male sexual dysfunctions, such as premature (early) ejaculation and male hypoactive sexual desire disorder. The NHSLS found that 28.5% of men aged 18-59 years reported premature ejaculation, and 15.8% lacked sexual interest during the past year. An additional 17% reported anxiety about sexual performance, and 8.1% had a lack of pleasure in sex. [51]
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.

Herbal supplements such as ginkgo biloba, saw palmetto, and yohimbe have been touted as sexual enhancers, and some men have been tempted to try them to treat erectile dysfunction. Bennett warns, however, that none has been approved by the FDA or even shown by any reliable studies to prevent, treat, or improve erectile dysfunction. Moreover, supplements are unregulated and can have many side effects or interfere with prescribed medications you’re already taking. Don’t jeopardize your health by taking a supplement to treat erectile dysfunction without first talking with your doctor.
It is important for clinicians prescribing these drugs to make the patient aware of the action of the drugs especially the fact that they do not result in an immediate erection, and that they do not cause an erection without sexual stimulation. There is frequently a great expectation when men begin using these drugs and it is wise to temper their enthusiasm and explain they do not work immediately, and may not work every time, but also let the patient know that if these drugs do not work, there are other options.
A number of herbs have been promoted for treating impotence. The most widely touted herbs for this purpose are Coryanthe yohimbe (available by prescription as yohimbine, with the trade name Yocon) and gingko (Gingko biloba), although neither has been conclusively shown to help the condition in controlled studies. In addition, gingko carries some risk of abnormal blood clotting and should be avoided by men taking blood thinners such as coumadin. Other herbs promoted for treating impotence include true unicorn root (Aletrius farinosa), saw palmetto (Serenoa repens), ginseng (Panax ginseng), and Siberian ginseng (Eleuthrococcus senticosus). Strychnos Nux vomica has been recommended, especially when impotence is caused by excessive alcohol, cigarettes, or dietary indiscretions, but it can be very toxic if taken improperly, so it should be used only under the strict supervision of a physician trained in its use.
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:

3. Are there physical causes of erectile dysfunction? Erectile dysfunction may be a symptom of underlying medical conditions, which if not detected may cause further medical problems. A prior history of cigarette smoking, heart attacks, strokes, and poor circulation in the extremities (for example, intermittent claudication or cramping in your leg[s] when you walk) suggest atherosclerosis as the cause of the erectile dysfunction. Loss of sexual desire and drive, lack of sexual fantasies, gynecomastia (enlargement of breasts), and diminished facial hair suggest low testosterone levels. A prior history of pelvic surgery or radiation and trauma to the penis/pelvis/perineum can cause problems with the nerves and blood vessels. Symptoms of intermittent claudication of the lower extremities with exercise may suggest a vascular problem as a cause of the erectile dysfunction.

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.
Your doctor will ask you questions about your symptoms and health history. They may do tests to determine if your symptoms are caused by an underlying condition. You should expect a physical exam where your doctor will listen to your heart and lungs, check your blood pressure, and examine your testicles and penis. They may also recommend a rectal exam to check your prostate. Additionally, you may need blood or urine tests to rule out other conditions.
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