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.
Surgery to repair arteries (penile arterial reconstructive surgery) can reduce impotence caused by obstructions that block the flow of blood to the penis. The best candidates for such surgery are young men with discrete blockage of an artery because of a physical injury to the pubic area or a fracture of the pelvis. The procedure is less successful in older men with widespread blockage of arteries.

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.


Adverse effects related to PDE5i use with mild-moderate and transient (58). Furthermore, side effects usually attenuate if use is not discontinued. Autonomic dysreflexia, a life-threatening phenomenon characterized by bradycardia, hypertension, facial flushing and headaches associated with SCI lesions above T6, has not been reported with use. However, hypotension leading to dizziness in individuals treated with sildenafil has been noted with high thoracic and cervical levels of injury (72). No adverse events were noted within the study; however, the dizziness was reported by use of sildenafil 50 mg in the cervical LOI and 100 mg in the thoracic LOI patients. Headache is the most reported side effect of all PDE5i, followed by dyspepsia and flushing. Priapism, and death have not been reported after use of PDE5i by SCI patients.

A duplex ultrasound is a diagnostic technique that uses painless, high frequency sound waves to visualize structures beneath the skin's surface. The principle is similar to the sonar used on submarines. Sound waves are reflected back when they contact relatively dense structures such as fibrous tissue or blood vessel walls. These reflected sound waves can be converted into pictures of the internal structures being studied.
Factors that mediate contraction in the penis include noradrenaline, endothelin-1, neuropeptide Y, prostanoids, angiotensin II, and others not yet identified. Factors that mediate relaxation include acetylcholine, nitric oxide (NO), vasoactive intestinal polypeptide, pituitary adenylyl cyclase–activating peptide, calcitonin gene–related peptide, adrenomedullin, adenosine triphosphate, and adenosine prostanoids.
PDE5i for ED in patients with MS can be considered as reasonably effective and safe. Fowler et al. performed a randomized, multicenter, double-blind, flexible dose trial with open label extensions comparing sildenafil to placebo (75). A nearly 4-fold increase in effective erections was noted in the treatment arm, 96% vs. 24%. Sexual satisfaction and overall satisfaction were also improved in the treatment group based on IIEF scores, and quality of life assessments. Lombardi et al. evaluated tadalafil use in men with MS (71). Seventy eight percent of the men responded with improved erections, better quality of life with regards to sexual function, partner relationship and family life. Just less than half the men who responded to the tadalafil did so at the lower dosage of 10 mg. Subjects in either studies did not have any significant adverse side effects beyond flushing, and headache with PDE5i use.
"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.
The first step in treating the patient with ED is to take a thorough sexual, medical, and psychosocial history. Questionnaires are available to assist clinicians in obtaining important patient data. (See Presentation.) Successful treatment of sexual dysfunction has been demonstrated to improve sexual intimacy and satisfaction, improve sexual aspects of quality of life, improve overall quality of life, and relieve symptoms of depression. (See Treatment.)

In patients with low testosterone, testosterone treatment can improve libido and erectile dysfunction, but many men still may need additional oral medications such as sildenafil, vardenafil, or tadalafil. Some studies suggest that men with ED and low testosterone may respond better to PDE5 inhibitors when given testosterone therapy; however, this is controversial.


2 inability of the adult male to achieve or sustain a penile erection or, less commonly, to ejaculate after achieving an erection. Several forms are recognized. Functional impotence has a psychological basis. Organic impotence includes vasculogenic, neurogenic, endocrinic, and anatomical factors. Anatomical impotence results from physically defective genitalia. Atonic impotence involves disturbed neuromuscular function. Poor health, old or advancing age, drugs, smoking, trauma, and fatigue can induce impotence. Also called erectile dysfunction, impotency. impotent, adj.

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.

Positron emission tomorgraphy (PET), and functional magnetic resonance imaging (fMRI) have led to a greater understanding to which center are activated during arousal. These imaging studies measure increases in cerebral blood flow or changes in cerebral activity on a real-time basis. Studies are performed when male subject are aroused by visual cues (usually sexual explicit photos or videos) and compared to images obtained during exposure to sexually neutral cues differences can be measured. Several studies have identified that the inferior frontal lobes, inferior temporal lobes and insular gyrus, and occipital lobes are involved with processing arousal cues, although each are likely to process different stimuli (20-23).

The association between low testosterone and ED is not entirely clear. Although these 2 processes certainly overlap in some instances, they are distinct entities. Some 2-21% of men have both hypogonadism and ED; however, it is unclear to what degree treating the former will improve erectile function. [17] About 35-40% of men with low testosterone see an improvement in their erections with testosterone replacement; however, almost 65% of these men see no improvement. [15]


Another tip is to make sure you communicate with your partner what you like during the process of sex.  Many men are not communicative about what really turns them on.  If you are not aroused by what is going on, then you might experience ED.  Make sure you tell your partner what turns you on.  Communicating about intimacy should also lead to feeling more connected with your partner aiding in relaxing when you are sexual together.
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:
Cavernosography measurement of the vascular pressure in the corpus cavernosum. Saline is infused under pressure into the corpus cavernosum with a butterfly needle, and the flow rate needed to maintain an erection indicates the degree of venous leakage. The leaking veins responsible may be visualized by infusing a mixture of saline and x-ray contrast medium and performing a cavernosogram.[21] In Digital Subtraction Angiography (DSA), the images are acquired digitally.
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.
There are so many potential reasons a man might develop erectile dysfunction (ED), it's nearly impossible to generalize the best ways to treat it. What works for one man may not work for another simply because they are having problems for different reasons. That said, it may encouraging to hear that there are a variety of options that may be considered, from psychological counseling to lifestyle changes, medications to treatments and devices.
Certain types of blood pressure medications, antiulcer drugs, antihistamines, tranquilizers (especially before intercourse), antifungals (hetoconazole), antipsychotics, antianxiety drugs, and antidepressants, known as selective serotonin reuptake inhibitors (SSRIs, including Prozac and Paxil), can interfere with erectile function. Smoking, excessive alcohol consumption, and illicit drug use may also contribute. In rare cases, low levels of the male hormone testosterone may contribute to erectile failure. Finally, psychological factors, such as stress, guilt, or anxiety, may also play a role, even when the impotence is primarily due to organic causes.
When sexually stimulated there is a release of a chemical, nitric oxide (NO) in the blood vessels of the corpus cavernosum. The NO stimulates the production of a compound called cGMP, which causes relaxation of the smooth muscle in the blood vessels supplying the corpus cavernosum. PDE 5 is an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP by PDE5, these medications allow cGMP to build up in the penis. cGMP causes muscles in the corpora cavernosa of the penis to relax. When the muscle is relaxed, more blood can flow into the penis and fill the spaces in the penis. As the penis fills with blood, the veins in the penis are compressed, and this results a hard erection. When the effect on PDE5 decreases, the cGMP levels go down and the muscle in the penis contracts, causing less blood to flow into the penis and allowing the veins to open up and drain blood out of the penis.
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.
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.
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.
Erosion of the prosthesis, whereby it presses through the corporal tissue into the urethra, may occur. Symptoms and signs may include pain, blood in the urine, discharge, abnormal urine stream, and malfunction. If the prosthesis erodes into the urethra, a physician must remove it. If the other cylinder remains intact, it can be left in place. A physician leaves a catheter in place to allow the urethra to heal.
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.
The most common inflatable prosthesis is the three-piece penile prosthesis. It is composed of a pair of cylinders that are surgically placed into the corpora cavernosa, a reservoir containing sterile fluid that is placed in the abdomen and a pump that is placed in the scrotum. Tubing connects the cylinders, reservoir, and the cylinders. By pressing the pump several times, fluid is transferred from the reservoir into the cylinders. As the cylinders fill with fluid, they increase in width and this causes the erection. When one is finished with sexual activity, pressing the release valve on the pump allows the fluid to drain out of the cylinders back into the reservoir. Given the mechanical nature of the three-piece prosthesis, it has a greater risk of mechanical malfunction; however, modifications have been made such as lock out valves to prevent the prosthesis from automatically inflating as well as improving the tubing to prevent tubing leaks.

If you have unstable heart disease of any kind, heart failure or unstable, what we call angina, contraindication to using the medications. All right? So if you’re in an unstable medical state, these medications are not a good idea. Now, there are relative issues. If you may be taking a blood pressure medicine or a medicine for your prostate which dilates your blood vessel a little bit– you know, the typical ones are what we call the alpha blockers– you may have an additive effect from the medication. But for the most part, the medicines are incredibly safe.
Acupuncture may help treat psychological ED, though studies are limited and inconclusive. You’ll likely need several appointments before you begin to notice any improvements. When choosing an acupuncturist, look for a certified practitioner who uses disposable needles and follows U.S. Food and Drug Administration guidelines for needle disposal and sterilization.
Fortunately, impotence is usually treatable. A thorough evaluation starting with a history and physical exam is needed to help diagnose the underlying cause. Once the cause of impotence is determined, treatment can be tailored to target that cause and any other contributing factors. Treatments used for impotence may include medications, vacuum devices, surgery, and psychotherapy.
Ejaculatory incompetence, erectile difficulty, erectile dysfunction, erectile failure, frigidity–female Medtalk The inability to achieve or maintain a penile erection adequate for the successful completion of intercourse, terminating in ejaculation; penile erection is mediated by nitric oxide Epidemiology Prevalence of minimal, moderate, and complete impotence in the Massachusetts Male Aging Study was 52%; age is the most important factor; complete impotence ↑ from 5%–age 40 to 15%–age 70; for an erection to achieve a successful outcome, it requires

When we say it’s a barometer of men’s health, it’s a signal. It’s an indicator that things may be right or not. And so when a man develops an erectile problem– and we’re talking about something that is occurring over time. It’s not something that just occurred overnight. When it occurs overnight, it’s more often than not a psychogenic, an anxiety reaction.


Erectile problems can happen to men of any age.  There are many factors that contribute to ED including poor health, untreated medical problems, medications and pornography use.  Many men struggle with understanding when they are experiencing situational sexual dysfunction verses when is your erectile issue an ongoing problem that requires medical help.

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Nerve or spinal cord damage: Damage to the spinal cord and nerves in the pelvis can cause erectile dysfunction. Nerve damage can be due to disease, trauma, or surgical procedures. Examples include injury to the spinal cord from automobile accidents, injury to the pelvic nerves from prostate surgery for cancer (prostatectomy), and some surgeries for colorectal cancer, radiation to the prostate, surgery for benign prostatic enlargement, multiple sclerosis (a neurological disease with the potential to cause widespread damage to nerves), and long-term diabetes mellitus.
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.
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.
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.
Melanocortin receptor agonists were found to induce erections serendipitously. A study investigating the dermatologic use of Melanotan-II (MT-II) was found to generate erections unexpectedly leading to the development of MTII derivatives for ED treatment (120). MT-II was initially used to induce pigment changes in the skin for artificial tanning but has been suspected to induce melanoma, however (121).
The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) study, designed to determine whether an individual man’s sexual outcomes after most common treatments for early-stage prostate cancer could be accurately predicted on the basis of baseline characteristics and treatment plans, found that 2 years after treatment, 177 (35%) of 511 men who underwent prostatectomy reported the ability to attain functional erections suitable for intercourse. [45]
Chancellor et al. (109) compared VEDs with papaverine injections in 18 males with SCI. The injections and pumps were equally effective in inducing erections and no adverse effects from the treatments were reported. Treatment arms were crossed over, subsequently seven men chose the VED and seven men chose the papavarine highlighting equal efficacy in this population. In another treatment arm topical minoxidil was applied without any effective erections achieved by the study subjects.
The downside to these prostheses includes the standard risks of surgery, the very low risk of infection — less than 2 percent in most patients, slightly higher in diabetics — and a slight drop in penis length versus a natural erection or other ED treatments. Also, unlike with other methods, any hope for a natural erection is abolished once a pump is implanted. The cost for surgical options varies, and insurance coverage is typically good.
Since sexual arousal is a complex process involving hormones, emotions, nerves, muscles, blood vessels and the brain, a malfunction in any of these can lead to ED. Stress, exhaustion and psychological issues can also contribute, and anxiety over maintaining an erection can actually make it harder to attain. In short, any condition that inhibits blood flow to the penis can lead to ED.
In this study, ED proceeded CVD in almost 70% of cases. Similarly, many men with ED have been found to have pre-existing CVD. A study by Vlachopoulos et al evaluated the incidence of asymptomatic CVD in 50 men with ED.22 These authors found that 19% of men with ED had asymptomatic CVD. Similarly, Mulhall and colleagues found that 20% of men presenting with ED and vascular insufficiency on penile duplex had asymptomatic CVD.23

The placement of a penile prosthesis is typically an outpatient procedure and is typically performed through a single incision. All of the parts of the prosthesis are hidden under the skin. Antibiotics are given to decrease the risk of an infection. A catheter may be left in the penis in some men for a short period. After placement, there will be a time period of healing prior to the ability to use the prosthesis.
A meta-analysis of 36 744 men with ED in 12 prospective cohort studies found that the presence of ED significantly increased the risk of CVD, CAD, stroke and all-cause mortality, and the presence of ED was an independent risk factor for CVD. Ponholzer et al found that men with moderate to severe ED had a 65% increased relative risk for developing symptomatic CAD compared with men who did not have ED.26
Total testosterone levels: Health care professionals should obtain a patient's blood samples for total testosterone levels in the early morning (before 8 a.m.) because the testosterone levels go up and down throughout the day. If you have a low testosterone level, a health care professional should check it again to confirm that it is truly low. In some men, a specialized test measuring the active form of testosterone (free or bioavailable testosterone) may be recommended.
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
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.
When aroused, stimulated nerves supplying the penis release chemicals that cause the muscle that surrounds blood vessels in the penis to relax. As the blood vessels relax, there is an increase in blood coming into the penis. This blood fills the spaces in the corpora cavernosa, allowing each of the corpora to expand. As the corpora expand, the veins that drain blood out of the penis are compressed against the tunica albuginea. Compression of the veins prevents blood from leaving the penis and results in a fully rigid penis. When the stimulation/arousal subsides, there is a decrease in the chemicals from the nerves, the muscle around the arteries tightens, decreasing inflow of blood, resulting in a lack of compression of the veins and the drainage of blood out of the penis.

Recently, the US Food and Drug Administration (FDA) has issued a safety announcement regarding TRT. In part it reads ‘The benefit and safety of these medications have not been established. We are also requiring these manufacturers to add information to the labeling about a possible increased risk of heart attacks and strokes in patients taking testosterone.’37

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.
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.
Treatment depends on the underlying cause. In general, exercise, particularly of the aerobic type, is effective for preventing ED during midlife. Exercise as a treatment is under investigation.[22]:6, 18–19 For tobacco smokers, cessation often results in a significant improvement.[23] Oral pharmacotherapy and vacuum erection devices are first-line treatments,[22]:20, 24 followed by injections of drugs into the penis, as well as penile implants.[22]:25–26 Vascular reconstructive surgeries are beneficial in certain groups.[24]
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.
One study by Palmer and colleagues evaluated sildenafil use in SB males with thoracic lesions (76). A prospective, blinded, randomized, placebo-controlled, dose-escalation, crossover study in 17 patients with SB and ED was performed. All study participates took sets of tablet in groups, two sets of placebo, one of 25 mg, and the last 50 mg. Overall response to the tablet sets was measured by IIEF response and self-report of erectile rigidity. Patients reported that taking 50 mg of sildenafil led to improved erections, duration of erections, frequency of erections and level of confidence compared to sildenafil 25 mg and more significantly compared to placebo. Of the five patients who reported side effects, two experienced mild hematological changes that reverted to baseline after study completion.
Chancellor et al. (109) compared VEDs with papaverine injections in 18 males with SCI. The injections and pumps were equally effective in inducing erections and no adverse effects from the treatments were reported. Treatment arms were crossed over, subsequently seven men chose the VED and seven men chose the papavarine highlighting equal efficacy in this population. In another treatment arm topical minoxidil was applied without any effective erections achieved by the study subjects.
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.

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.
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