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.

ED is defined as the inability to achieve a full erection or the inability to maintain an erection adequate for sexual intimacy. Other types of sexual dysfunction such as premature ejaculation and low libido may occur; however, the most common and disruptive problem in men is ED. Although most men will experience periodic episodes of ED, these episodes tend to become more frequent with advancing age.

Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
You’ve probably heard of Viagra, but it’s not the only pill for ED. This class of drugs also includes Cialis, Levitra,  Staxyn, and Stendra. All work by improving blood flow to the penis during arousal. They're generally taken 30-60 minutes before sexual activity and should not be used more than once a day. Cialis can be taken up to 36 hours before sexual activity and also comes in a lower, daily dose. Staxyn dissolves in the mouth. All require an OK from your doctor first for safety.
For obvious reasons, ED can be a sensitive subject, one that until relatively recently men were more likely to try to hide than to deal with. Fortunately, a deeper understanding of the variety of causes of erectile dysfunction has led to medications, therapies, and other treatments that can be more individualized and more likely to be effective—and more open discussion about addressing the concern.
If the structure of the penis is healthy (not fibrosed or scarred), the use of injectable drugs is almost always effective. If one chooses this therapy, a doctor or nurse will teach the individual how to perform the injections, and the urologist (specialist) must determine the appropriate dose. The dosage is adjusted to achieve an erection with adequate rigidity for no more than 90 minutes.
Conditions associated with reduced nerve and endothelium function (eg, aging, hypertension, smoking, hypercholesterolemia, and diabetes) alter the balance between contraction and relaxation factors (see Pathophysiology). These conditions cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defective smooth muscle relaxation. In some patients, sexual dysfunction may be the presenting symptom of these disorders.
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.

The art of acupuncture has become the new treatment for everything from back pain, depression, and even ED. Impotence could be more of a state of mind, and acupuncture may help. Through this alternative therapy, fine needles are placed in various parts of the body to relieve pain or stress. Although there are many mixed studies for acupuncture and ED, many tend to confirm positive results. A 1999 study found acupuncture improved the quality of erection and even restored sexual activity in 39 percent of participants.


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 dorsal artery provides for engorgement of the glans during erection, whereas the bulbourethral artery supplies the bulb and the corpus spongiosum. The cavernous artery effects tumescence of the corpus cavernosum and thus is principally responsible for erection. The cavernous artery gives off many helicine arteries, which supply the trabecular erectile tissue and the sinusoids. These helicine arteries are contracted and tortuous in the flaccid state and become dilated and straight during erection. [9]


Uses and risks of viagra Viagra treats erectile dysfunction and pulmonary arterial hypertension. For sexual purposes, it helps someone with erectile dysfunction achieve and maintain an erection. However, Viagra can have unpleasant side effects, and an overdose can be serious. We cover everything you need to know about Viagra in this article. Read now
Several medications can interfere with the chemical processing of PDE5i medications by the liver. These can include ketoconazole (an antifungal medication known by the brand name Nizoral), erythromycin (an antibiotic), and cimetidine (also known as Tagamet, for reducing stomach acid). A lower dose of PDE5i medications should be used if one is taking any of these medications.
A physical cause can be identified in about 80% of cases.[2] These include cardiovascular disease, diabetes mellitus, neurological problems such as following prostatectomy, hypogonadism, and drug side effects. Psychological impotence is where erection or penetration fails due to thoughts or feelings; this is somewhat less frequent, in the order of about 10% of cases.[2] In psychological impotence, there is a strong response to placebo treatment.

A physical cause can be identified in about 80% of cases.[2] These include cardiovascular disease, diabetes mellitus, neurological problems such as following prostatectomy, hypogonadism, and drug side effects. Psychological impotence is where erection or penetration fails due to thoughts or feelings; this is somewhat less frequent, in the order of about 10% of cases.[2] In psychological impotence, there is a strong response to placebo treatment.
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.
Conditions that may be associated with ED include diabetes, [25, 26, 27] hypertension, [28] , and CAD, as well as neurologic disorders, endocrinopathies, benign prostatic hyperplasia, [29] , sleep apnea [30] , COPD, [31] and depression (see Table 1 below). [32, 33, 34, 35] In fact, almost any disease may affect erectile function by altering the nervous, vascular, or hormonal systems. Various diseases may produce changes in the smooth muscle tissue of the corpora cavernosa or influence the patient’s psychological mood and behavior.
PD is a chronic neurodegenerative disease characterized by “motor” and “non-motor” symptoms that lead to progressive disability. Erectile and SD are “non-motor” symptoms and can occur in 50–69% of males with PD (39-42). Ejaculatory and orgasmic function are also impaired. PD affects the dopaminergic pathways leading to erection and arousal. Dopaminergic therapy for PD can improve ED, and sometimes therapy may lead to hypersexuality (43,44). A comparison of married men with PD to age matched controls with non-neurologic chronic disease such as arthritis did not show any discrepancy in ED rates (45). This suggests that ED in certain groups with PD may occur from disease related factors common in chronic illness, in general.
I think that a very powerful argument to young men who want to perform at the highest level is to point out the destructive nature of what they’re doing. If they’re having 18 drinks per week, if they’re having three, four, five drinks at any one time, they’re going to guarantee that their erections are not going to be at the highest level. I can’t tell you the number of men who come in saying, they went out, they had a date, they had a big dinner– which, by the way, is also not a great thing for erections, because all the blood is now going to your gut instead of to the genital area. And how important lifestyle changes are to improving your performance, as well, if not better, than the medications. So make certain that you exercise modestly, not excessively. Make certain that you have a smaller meal on an evening or a day that you want to have a sexual encounter, because you want the blood to go, once again, to the penile area and not to your gut. And really, the whole idea of stress– if you’re stressed out, if you’re worried about a lot of things, if you’re distracted, you can’t initiate that psychic stimulus to your spinal cord and then ultimately to your penis. So stress management is incredibly important.

Alprostadil may also be administered into the urethral opening of the penis. In MUSE (medical urethral system for erection), the man inserts a thin tube the width of a vermicelli noodle into his urethral opening and presses down on a plunger to deliver a tiny pellet containing alprostadil into his penis. The drug takes about 10 minutes to work and the erection lasts about an hour. The main side effect is a sensation of pain and burning in the urethra, which can last about five to 15 minutes.
There are many effective treatments for impotence. The most popular is a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors. These include sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis) and avanafil (STENDRA). These drugs are taken in pill form. They work in most men. But they are less effective in men with neurological causes of impotence.
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.
Alprostadil is a potent vasodilator and smooth muscle relaxant identical to the naturally occurring PGE1. PGE1 binds with specific receptors on smooth muscle cells and activates intracellular adenylate cyclase to produce cAMP, which in turn induces tissue relaxation through a second messenger system (96). PGE1 is the only FDA approved form of intracavernosal therapy and is available commercailly as EDEX, or Caverject. Its efficacy was demonstrated in several clinical trials where the rate of responders ranged from 40% to 80% (97,98). The most common adverse event is penile pain, which is not related to the injection of the medication itself. In men with prolonged use the pain is usually self-limited (99).
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.
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
Tadalafil shares the common side effects of the PDE5 inhibitors, however, due to its effect on PDE11, another phosphodiesterase located in muscle, tadalafil has been associated with muscle aches. Back pain and muscle aches occur in less than 7% of men taking tadalafil and in most patients will go away without treatment within 48 hours. When treatment was necessary, acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil) or naproxen (Aleve) were effective. Rarely do the muscle aches and back pain cause men to stop using tadalafil.
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).
It is normal for a man to have five to six erections during sleep, especially during rapid eye movement (REM). Their absence may indicate a problem with nerve function or blood supply in the penis. There are two methods for measuring changes in penile rigidity and circumference during nocturnal erection: snap gauge and strain gauge. A significant proportion of men who have no sexual dysfunction nonetheless do not have regular nocturnal erections.
Erectile dysfunction (ED), or impotence, is the inability to obtain or maintain an erection suitable for intimate activity. While most frequently seen in 50-65% of males aged 65 and older and nearly all men over the age of 70, erectile dysfunction affects up to 39% of 40-year-old men, too; more than 35 million men total in the United States. Left untreated, the physical frustrations of living with erectile dysfunction can quickly turn emotionally stressful as well, with men often reporting relationship and related issues. And that’s why NuMale Medical Center offers the most advanced and effective therapies to treat erectile dysfunction, so you and your partner can experience sex and intimacy both joyfully and confidently.

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).

Picture of penile tumescence monitor. This penile tumescence monitor is placed at the base and near the corona of the penis. It is connected to a monitor that records a continuous graph depicting the force and duration of erections that occur during sleep. The monitor is strapped to the leg. The nocturnal penile tumescence (NPT) test is conducted on several nights to obtain an accurate indication of erections that normally occur during the alpha phase of sleep.
Oral PDE5i remains the first line treatment for NED from SCI. Three of the four PDE5i currently available in the U.S., avanafil excluded, have been investigated in the SCI, and all of the more recent studies have shown improvements in erectile function based on IIEF score compared to placebo when included (59-63). Other studies have also shown significant improvements in the IIEF score when compared to baseline (64-69). Furthermore, treatment efficacy when compared to placebo occurs despite LOI or American Spinal Injury Association (ASIA) score characterizing impairment related to the injury (59,61).

Aging: There are two reasons why older men are more likely to experience erectile dysfunction than younger men. First, older men are more likely to develop diseases (such as heart attacks, angina, cardiovascular disease, strokes, diabetes mellitus, and high blood pressure) that are associated with erectile dysfunction. Second, the aging process alone can cause erectile dysfunction in some men by causing changes in the muscle and tissue within the penis.
Alprostadil is an FDA-approved erectile dysfunction drug that can be injected directly into the penis to trigger an automatic erection. "Penile injection is the most effective type of ED treatment for men who can't take oral treatment," says Nelson Bennett, MD, a urologist at the Lahey Clinic in Burlington, Mass. In fact, it has an 85 percent success rate. Possible side effects include a burning sensation and priapism, an erection that lasts more than four hours and requires medical treatment.
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.
The role of the endothelium in ED has been noted for a number of years and the overlapping of ED and other conditions, especially coronary heart disease, CVD, affecting endothelial function/dysfunction, is clearly present. The endothelial cell is now known to affect vascular tone and impact the process of atherosclerosis, and impacting ED, CVD and peripheral vascular disease.16

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.
Malleable implants usually consist of paired rods, inserted surgically into each of the corpora cavernosa. The rods are stiff, and to have an erection, one bends them up and then when finished with intercourse one bends them down. They do not change in length or width. The malleable implants are the least mechanical and thus have the lowest risk of malfunction. However, also have the least "normal appearance."
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The laboratory results should be discussed with the patient and, if possible, with his sexual partner. This educational process allows a review of the basic aspects of the anatomy and physiology of the sexual response and an explanation of the possible etiology and associated risk factors (eg, smoking and the use of various medications). Treatment options and their benefits and risks should be discussed. This type of dialogue allows the patient and physician to cooperate in developing an optimal management strategy.
In the short term, alcohol relaxes muscles in the penis, letting blood to flow in (which is a good thing). However, alcohol also prevents other blood vessels from closing and trapping all the extra blood. Erections depend on trapping increased blood flow in the erectile tissue of the penis. If you don’t trap that extra blood, you don’t get an erection. In the long run, excessive alcohol consumption can cause liver scarring, high blood pressure, and can damage your blood vessels resulting in erectile dysfunction.
There are, as you listen to all of the advertisements, if your erection lasts for more than four hours, there are very, very unusual cases where that can happen. There are very rare cases of visual problems. There are even rarer cases of hearing problems. But with every medication, there always a potential downside. But the absolute contraindication is an unstable medical condition, an unstable cardiovascular condition, being on nitrates.

Tadalafil (Cialis) is the third oral medicine approved by the U.S. FDA for the treatment of erectile dysfunction. Like sildenafil (Viagra) and vardenafil (Levitra), tadalafil inhibits PDE5 (as described earlier). Unlike the other PDE 5 inhibitors, patients should take tadalafil once daily and is approved for the treatment of BPH (benign enlargement of the prostate).

Vardenafil and tadalafil belong to the same group of chemical compounds as sildenafil, namely phos-phodiesterase type 5 (PDE-5) inhibitors. Some men cannot benefit from sildenafil or the two newer PDE-5 inhibitors because they have low levels of nitric oxide. British investigators reported in late 2002 that three different types of compounds are being studied as possible medications for men with low levels of nitric oxide. They are Rho-kinase inhibitors, soluble guanylate cyclase activators, and nitric oxide-releasing PDE-5 inhibitors.
The dose of PDE5 inhibitor that you start with may vary with underlying medical conditions and medications that you are taking. Thus, it is important to review all medications (even over the counter medications) with your physician. Typically, one starts with a lower dose and increases as needed. Some medical conditions prevent going up to higher doses. You can review the drug prescribing information or consult with your doctor regarding the dose(s) that are appropriate for you.

Impotence, also called erectile dysfunction, in general, the inability of a man to achieve or maintain penile erection and hence the inability to participate fully in sexual intercourse. In its broadest sense the term impotence refers to the inability to become sexually aroused; in this sense it can apply to women as well as to men. In common practice, however, the term has traditionally been used to describe only male sexual dysfunctions. Professional sex therapists, while they identify two distinct dysfunctions as forms of impotence, prefer not to use the term impotence per se. Thus, because of its pejorative connotation in lay usage and because of confusion about its definition, the word impotence has been eliminated from the technical vocabulary in favour of the term “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).

Impotence, or erectile dysfunction, is the inability of a male to attain and keep an erection sufficiently firm to engage in or complete sexual intercourse. Although it is more common in older men, impotence can occur at any age. Impotence is not a normal consequence of aging. About 70% of erectile dysfunction is due to diseases such as diabetes and atherosclerosis, another 10% to 20% is due to psychological factors, and the remaining percentage is related to medications, lifestyle factors, and injury (Source: NIDDK).
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The observation that TRT enhances the efficacy of PDE5 inhibitors in hypogonadal men taking these therapies with suboptimal response to the PDE5 inhibitors alone has been reported.33 In addition, investigators have demonstrated that TRT in hypogonadal men can improve erectile function even without the benefit of PDE5 inhibitors.33 In addition, guidelines for managing ED in hypogonadal men by the European Association of Urology recommend controlling the man to a eugonadal state prior to initiation of PDE5 inhibitor therapy.36 Testosterone measurement consists of a serum specimen which should be ideally obtained in the morning because of the normal diurnal variation of testosterone which is at its peak in the morning. Since TRT is relatively safe, and men can potentially see an improvement in erectile function, it seems prudent to consider this issue when presented with a patient suffering from ED.
ED is defined as the inability to achieve a full erection or the inability to maintain an erection adequate for sexual intimacy. Other types of sexual dysfunction such as premature ejaculation and low libido may occur; however, the most common and disruptive problem in men is ED. Although most men will experience periodic episodes of ED, these episodes tend to become more frequent with advancing age.

Q. I started to suffer from erectile dysfunction? Why is this happening and what can I do to treat it? I am a healthy 52 year old. I have hypertension but i take pills to treat it and my levels are around 130/80. except that I am at great shape. In the last few months I feel that a problem in my sex life. I want to have sex but i can't due to erectile dysfunction. What can be the reason for this? and more important what can I do?
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 causes of erectile dysfunction include aging, high blood pressure, diabetes mellitus, cigarette smoking, atherosclerosis (hardening of the arteries), depression, nerve or spinal cord damage, medication side effects, alcoholism or other substance (drug) abuse, pelvic surgery including radical prostatectomy, pelvic radiation, penile/perineal/pelvic trauma such as pelvic fracture, Peyronie's disease (a disorder that causes curvature of the penis and sometimes painful erections), and low testosterone levels.
The dose of PDE5 inhibitor that you start with may vary with underlying medical conditions and medications that you are taking. Thus, it is important to review all medications (even over the counter medications) with your physician. Typically, one starts with a lower dose and increases as needed. Some medical conditions prevent going up to higher doses. You can review the drug prescribing information or consult with your doctor regarding the dose(s) that are appropriate for you.

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. 
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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