However, in contrast, a recent systematic review of published studies, the authors concluded that overall, the addition of testosterone to PDE-5 inhibitors might benefit patients with ED associated with testosterone levels of less than 300 ng/dL (10.4 nmol/L) who failed monotherapy. [20] A limitation of existing studies are their heterogeneous nature and methodological drawbacks.
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.
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.

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:
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
Infection is a concern after placement of a penile prosthesis and is reported as a complication in up to 20% of men undergoing placement of a penile prosthesis. If the device becomes infected more commonly, it needs to be removed. Another prosthesis can be placed after the infection is treated and the penile tissues have healed, but it is a difficult surgery. Erosion of the prosthesis, whereby it compresses through the corporal tissue, into the urethra may occur. Symptoms include pain, blood in the urine, discharge, abnormal stream, and malfunction of the prosthesis. If the prosthesis erodes, it will need to be removed. A catheter is placed to allow the urethra to heal.
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 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.

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. 


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
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.
The other 5 percent of prostheses are either pump devices in which the saline is permanently in the prosthesis, not in a separate reservoir (urologists may recommend this for men who have had multiple surgeries); or a pair of semi-rigid, malleable rods implanted in the penis, which render it hard at all times. The patient manually shifts the penis into an erect position for sex.

With drug therapy, there’s a risk of side effects such as headaches, back pain or an upset stomach. Before taking any medication for erectile dysfunction it is important to ensure your doctor is ok with that decision. Medication may not work for all men, for instance, if you have diabetes or have previously had prostate surgery. ED medication might also have serious risks if you’re currently taking nitrates (commonly prescribed for chest pain), have heart disease or have low blood pressure.22

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.

This is one of many types of constricting devices placed at the base of the penis to diminish venous outflow and improve the quality and duration of the erection. This is particularly useful in men who have a venous leak and are only able to obtain partial erections that they are unable to maintain. These constricting devices may be used in conjunction with oral agents, injection therapy, and vacuum devices.

These devices are generally safe, but bruising can occur. Other unwanted effects include pain, lower penile temperature, numbness, no or painful ejaculation, blood in the ejaculate or urine, and pulling of scrotal tissue into the cylinder. Partners may complain about the bluish discoloration and coolness of the penis. Many of these problems can be helped by proper selection of the tension rings and cylinder, use of adequate lubrication, and proper technique.


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.
3. Testosterone replacement. Before oral medications like Viagra, testosterone was routinely used to treat erectile dysfunction as it is central in the male sexual response, including the desire for sex and the process of getting an erection. Testosterone can be administered in a number of ways, for example orally, by means of an injection, skin patch, or subcutaneous (under the skin) pellet. 
Traditionally, erectile impotence (the classical definition of impotence) is the failure to achieve penile erection during intercourse. It may have either physical or psychological causes. Alcoholism, endocrine disease, and neurological disorders are typical physical causes. Psychological causes include anxiety over performance, hostility or other negative feelings toward the sexual partner, and stress, anxiety, depression, or other emotional conflicts outside of the relationship. Erectile impotence occasionally occurs with age and, although attributed by the individual to the aging process itself, it is usually secondary to disorders of aging, such as faulty blood circulation or prostate disease. In cases of impotence caused by blood vessel dysfunction, an insufficient supply of blood flows into the penis, or the blood diffuses out into adjacent tissues.
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.

Additionally, the physiologic processes involving erections begin at the genetic level. Certain genes become activated at critical times to produce proteins vital to sustaining this pathway. Some researchers have focused on identifying particular genes that place men at risk for ED. At present, these studies are limited to animal models, and little success has been reported to date. [4] Nevertheless, this research has given rise to many new treatment targets and a better understanding of the entire process.

These medications don’t work for everyone but they are easy to use and work for around 60% of people who try them. They work by making it easier to get an erection by reducing the effect of (inhibiting) the chemical PDE-5. This chemical is used in the body to make sure there isn’t too much blood in the penis during an erection, but if you have erectile dysfunction then this chemical ends up over-compensating.
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.

Alteration of NO levels is the focus of several approaches to the treatment of ED. Inhibitors of phosphodiesterase, which primarily hydrolyze cGMP type 5, provided the basis for the development of the PDE5 inhibitors. Chen et al administered oral L-arginine and reported subjective improvement in 50 men with ED. [14] These supplements are readily available commercially. Reported adverse effects include nausea, diarrhea, headache, flushing, numbness, and hypotension.
Patients should continue testosterone therapy only if there is improvement in the symptoms of hypogonadism and should be monitored regularly. You will need periodic blood tests for testosterone levels and blood tests to monitor your blood count and PSA. Testosterone therapy has health risks, and thus doctors should closely monitor its use. Testosterone therapy can worsen sleep apnea and congestive heart failure.
If laboratory tests are performed, they would normally start with an evaluation of your hormone status (testosterone or male hormone), particularly if one of your symptoms is low sexual desire (low libido). Blood tests for testosterone should ideally be taken early in the morning because that's when levels are usually at their highest. It is recommended that if the first testosterone level is low to repeat it as testosterone levels can vary. If the testosterone level is low, other blood tests, such a luteinizing hormone and prolactin, can help determine if there is a problem with the pituitary gland.
"Medications that create blood flow to the penis can't help when an erection is blocked by the fear or anxiety of the fight-or-flight response,” says Feloney. “This type of erectile dysfunction probably has a lot to do with evolution — men didn't need an erection when a dinosaur was chasing them." The best way to treat erectile dysfunction caused by performance anxiety, depression, a poor relationship, or stress may be with a combination of ED drug treatment and sex therapy, individual therapy, or couples therapy from sexual health professionals.
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]

There are many different body parts that play an important role for a man to get and maintain an erection during sexual intercourse. Beyond the physical causes that can lead to ED, it has been reported that 20% of ED is related to psychological causes.2 With so many possibilities leading to erectile dysfunction, it becomes particularly important to find a specialist who can correctly diagnosis the direct cause of your ED and find a treatment option that is right for you.
Nocturnal penile tumescence testing (NPT) may be useful in distinguishing mental from physical impotence. This test involves the placement of a band around the penis that you would wear during two or three successive nights. If an erection occurs, which is expected during rapid eye movement (REM) sleep, the force and duration are measured on a graph. Inadequate or no erections during sleep suggests an organic or physical problem, while a normal result may indicate a high likelihood of emotional, psychological, or mental causes.
When lifestyle changes alone don’t work, drug therapy (Viagra®, Cialis®, Levitra®, etc.) is normally the next step. Most of these medications work similarly to enhance a natural chemical in your body that relaxes the muscles in your penis. The goal of this medication is to increase your response to sexual stimulation by increasing the blood flow in your penis allowing you to get an erection.22
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).
Proper informed consent with your physician should be performed to understand all risks and benefits of hormonal replacement therapy. Follow-up testosterone (hormone) levels and periodic blood counts as testosterone therapy is associated with a risk of an abnormally high red blood cell count, and prostate checks are necessary for all men on long-term testosterone replacement therapy as there are concerns regarding the risk of testosterone therapy in men with an underlying prostate cancer. The use of testosterone therapy does not cause the development of prostate cancer. Testosterone therapy may increase the size of the prostate and cause urinary troubles.
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.
Sexual functioning involves a complex interaction among biologic, sociocultural, and psychological factors, and the complexity of this interaction makes it difficult to ascertain the clinical etiology of sexual dysfunction. Before any diagnosis of sexual dysfunction is made, problems that are explained by a nonsexual mental disorder or other stressors must first be addressed. Thus, in addition to the criteria for erectile disorder, the following must be considered:
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.

The severity of ED has been correlated with the extent of CVD. Banks et al reported that the risk of future CV events increased progressively according to ED severity.28 This was shown in both men with and without known CVD at baseline and after controlling for confounders. Solomon and colleagues found an inverse correlation between international index of erectile function (IIEF) scores and plaque burden seen on coronary angiography.29 In addition, Yaman et al demonstrated a significant correlation between ED severity on IIEF questionnaires and coronary artery calcification.30


If you have a neurological disorder or spinal cord injury and other erectile dysfunction treatments aren’t effective, two types of surgical implants could offer solutions to your ED. “An implantable pump can be used to manually create an erection by pumping fluid into cylinders placed inside the penis,” explains Feloney. “The other option is a malleable prosthesis that works like a gooseneck lamp to direct the penis into position for intercourse." Risks for these ED treatments include infection and mechanical breakdown.
In most healthy men, some of the drug will remain in the body for more than two days after a single dose of tadalafil. Metabolism (clearing of the drug from the body) of tadalafil can be slowed by liver disease, kidney disease, and concurrent use of certain medications (such as erythromycin, ketoconazole, and protease inhibitors). Slowed breakdown allows tadalafil to stay in the body longer and potentially increase the risk for side effects. Therefore, doctors have to lower the dose and frequency of tadalafil in the following examples:
With the pumps, erections last until the user hits the deflate button, which Kohler says “doesn’t happen” accidentally. He adds that pump prostheses “are locker-room proof: Nobody can see that you have one.” (Obviously, this is not the case with the always-on malleable rod option.) Implanted pumps are reliable, experts say, with more than 90 percent of the devices working for 12 to 15 years. 
"Erectile dysfunction can be a very serious issue because it's a marker of underlying cardiovascular disease, and it often occurs before heart conditions become apparent. Therefore, men should consider improving their weight and overall nutrition, exercise more, drink less alcohol and have a better night's sleep, as well as address risk factors such as diabetes, high blood pressure and cholesterol.
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.
In patients who either fail to respond to first or second-line therapy, or are not interested in the conservative therapies, penile prosthesis implantation is available. Malleable and rigid implants were available for many years, but in 1973 the world of penile prosthetics took a giant leap forward with the advent of the inflatable penile implant. Most implants done nowadays are of the inflatable variety. Adverse events including malfunction and infection are rare, and patient satisfaction is very high.45

The mechanisms by which testosterone plays a role in erectile function are not completely understood. A study evaluating the effect of testosterone on erections in surgically castrated rabbits and control animals, in which the rabbits’ intracavernosal pressures were compared after cavernosal nerve stimulation, determined that castrated rabbits had much lower pressures after stimulation than control rabbits did. [21] Notably, the pressures increased when castrated rabbits received exogenous testosterone replacement.
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
In a prospective, multicenter, single-armed study of ED patients who exhibited a suboptimal response to PDE5 inhibitors, the investigators found that percutaneous implantation of zotarolimus-eluting stents in focal atherosclerotic lesions was both safe and feasible and was associated with clinically meaningful improvement on subjective and objective measures of erectile function. [3]

And surgery comes with its own serious risks, such as developing incontinence or impotence, while radiation can result in urinary problems. — Peter Loftus, WSJ, "Surgery Adds Three Years to Lives of Prostate-Cancer Patients, Study Finds," 12 Dec. 2018 Male-impotence pill Viagra began facing generic competition late last year, while the Lyrica pain treatment is expected to confront generics at the end of this year. — Jonathan D. Rockoff, WSJ, "Pfizer Narrows Guidance on Tougher Pricing, Generic Competition," 30 Oct. 2018 Arkham Horror Third Edition is a classic struggle of agency versus impotence, set in the uncanny world of H.P. Lovecraft’s Cthulhu mythos. — Charlie Theel, Ars Technica, "Arkham Horror Third Edition: The classic Lovecraft adventure returns," 24 Nov. 2018 There’s obviously a lot of anger and frustration here toward the US government at the moment—along with side effects like bottled rage and sometimes a creeping sense of ineptitude or impotence about our ability to do anything about it. — Corey Seymour, Vogue, "Pussy Riot's Nadya Tolokonnikova On Her New Guide To Activism, Raising The Next President Of Russia, And Her "Holy War" On Fairy Tales," 12 Oct. 2018 In exchange for political impotence, they would be mostly left alone and allowed to get rich. — Paul Mozur, New York Times, "Inside China’s Dystopian Dreams: A.I., Shame and Lots of Cameras," 8 July 2018 Their suspicion is compounded by rumors that the polio vaccine causes impotence, death and, ironically, paralysis. — Meher Ahmad, New York Times, "Pakistan Has Just One New Polio Case, but Isn’t Declaring Victory Yet," 20 May 2018 Fighting back, even as an exercise in impotence, did a lot for McCain. — Alex Horton, Washington Post, "John McCain rebelled at the Naval Academy — and as a POW — long before he was a Senate maverick," 3 May 2018 Feelings of desperation and impotence are being felt throughout Central America, where the lawlessness, endemic poverty and levels of gang violence akin to war zones that have driven so many families from their homes show little signs of abating. — Washington Post, "Violence keeps Central Americans coming to US despite Trump," 21 June 2018


The sensitivity of the skin of the penis to detect vibrations (biothesiometry) can be used as a simple office nerve function screening test. This involves the use of a small vibrating test probe placed on the right and left side of the penile shaft as well as on the head of the penis. The strength of the vibrations is increased until you can feel the probe vibrating clearly. Although this test does not directly measure the erectile nerves, it serves as a reasonable screening for possible sensory loss and is simple to perform. More formal nerve conduction studies are only performed in selected cases.
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).
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.

Traditionally, erectile impotence (the classical definition of impotence) is the failure to achieve penile erection during intercourse. It may have either physical or psychological causes. Alcoholism, endocrine disease, and neurological disorders are typical physical causes. Psychological causes include anxiety over performance, hostility or other negative feelings toward the sexual partner, and stress, anxiety, depression, or other emotional conflicts outside of the relationship. Erectile impotence occasionally occurs with age and, although attributed by the individual to the aging process itself, it is usually secondary to disorders of aging, such as faulty blood circulation or prostate disease. In cases of impotence caused by blood vessel dysfunction, an insufficient supply of blood flows into the penis, or the blood diffuses out into adjacent tissues.


Because impotence can be due to health problems that can affect the whole body, and because it can interfere with one’s quality of life, it is important to talk with your doctor if you have trouble attaining or maintaining an erection. With increasing discussion of impotence in the media, coupled with advances in treatment, men are now much more comfortable talking with their doctors about impotence. It is currently estimated that between 15 and 30 million men in the United States are affected by impotence (Source: NIDDK).
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