No nitrate-based drugs should be given to men with suspected heart attacks if they have taken PDE5i medications within 24 hours. Combining PDE5i with nitrate-based medications can cause a severe and dramatic drop in blood pressure with potentially very dangerous consequences. This is also why someone should absolutely never share PDE5i medications with anyone else. If they happen to be taking one of the drugs that interacts dangerously with PDE5i medications, the results could be very serious. If there is any question about possible drug interactions, always check with a doctor or pharmacist.
Another potential new treatment consists of penile low-intensity shock wave lithotripsy. This consists of 1500 shocks twice a week for 3–6 weeks. The purpose is to stimulate neovascularisation to the corporal bodies with improvement in penile blood flow and endothelial function. The use of low-intensity shock wave lithotripsy may convert PDE5 inhibitor non-responders to responders.47
The 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]
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.
The American Urological Association Guideline on the Management of ED states oral PDE5i are considered first line therapy for the treatment of ED, unless contraindicated (57). Sildenafil, the first oral PDE5i, was introduced in 1998 and has revolutionized ED therapy due to its broad applicability, effectiveness and safety profile. PDE5i work by preventing hydrolysis of cGMP by the PDE5 enzyme in the smooth muscle of the corpora cavernosa. cGMP degradation typically leads to smooth muscle contraction and detumescence prevented by PDE5i administration. Two other PDE5i, vardenafil and tadalafil are other PDE5i with different pharmacokinetics, PDE receptor selectivity and side effect profiles.
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.
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.
Since endothelial dysfunction, CVD and ED are closely associated in epidemiological studies, the question for clinicians is whether to recommend the man presenting with ED undergo a cardiovascular (CV) evaluation. Clearly, based on numerous studies, ED can be considered at least a ‘marker’ for possible further vascular disease or CVD.15 In their report, Vlachopoulos and coworkers make the point that the man presenting with ED, the clinician, is offered an opportunity to attempt to improve the health of the man by addressing lifestyle modification, and consider further vascular evaluation owing to the clear relationship between endothelial dysfunction, ED and CVD.19
What you need to know about delayed ejaculation Delayed ejaculation is a sexual disorder that can be distressing for a man and his partner and may disrupt a relationship. There are many reasons why delayed ejaculation occurs, including tissue damage, age, drugs, and the side effects of medication. They may be physiological or psychological. Find out how to get help. Read now
When other treatments haven’t helped, a penile implant may be the right solution. A penile implant is a medical device that is surgically placed into a penis to mimic the look and performance of a natural erection9. Implants are custom-fitted to your anatomy. Sensitivity and the ability to ejaculate aren’t typically affected either, so you’ll be able to have an orgasm normally (unless you have a medical condition that prevents this)7.
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]

Vacuum devices for ED, also called pumps, offer an alternative to medication. The penis is placed inside a cylinder. A pump draws air out of the cylinder, creating a partial vacuum around the penis. This causes it to fill with blood, leading to an erection. An elastic band worn around the base of the penis maintains the erection during intercourse.
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.
Another approach is vacuum therapy. The man inserts his penis into a clear plastic cylinder and uses a pump to force air out of the cylinder. This forms a partial vacuum around the penis, which helps to draw blood into the corpora cavernosa. The man then places a special ring over the base of the penis to trap the blood inside it. The only side effect with this type of treatment is occasional bruising if the vacuum is left on too long.
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]
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.
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.
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.
Qaseem, A., Snow, V., Denberg, T. D., Casey, D. E., Forciea, M. A., Owens, D. K., & Shekelle, P. (2009). Hormonal testing and pharmacologic treatment of erectile dysfunction: A clinical practice guideline from the American College of Physicians. Annals of internal medicine, 151(9), 639-649. Retrieved from http://annals.org/aim/article/745155/hormonal-testing-pharmacologic-treatment-erectile-dysfunction-clinical-practice-guideline-from

Moemen et al. compared the effectiveness and satisfaction associated with use of several ED therapies including sildenafil alone, intracavernosal injections (ICI) followed by sildenafil after ICI discontinuation and vacuum erections devices (VED) followed by sildenafil therapy after VED discontinuation (60). Seventy percent of men receiving vasoactive medications preferred sildenafil to ICI, even though rigidity was superior in the ICI group. All men using VEDs were dissatisfied with that form of therapy.


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.

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.


In general, PDE5i works successfully in about 65%-70% of all men with erectile dysfunction (impotence). The greater the degree of damage to the normal erection mechanism and severity of the ED, the lower the overall success rate. Men with diabetes and those with spinal cord injury reported between 50%-60% responding successfully to treatment with oral PDE5i medications. The lowest success rate has been in men who developed ED (impotence) after prostate cancer surgery (radical prostatectomy) for more advanced prostate cancer that required removal of both sets of nerves around the prostate. In men who did not have the nerves removed/damage, there is a better chance of response to PDE5 inhibitors.
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.
Erectile dysfunction (ED) is one of the most common conditions affecting middle-aged and older men. Nearly every primary care physician, internist and geriatrician will be called upon to manage this condition or to make referrals to urologists, endocrinologists and cardiologists who will assist in the treatment of ED. This article will briefly discuss the diagnosis and management of ED. In addition, emerging concepts in ED management will be discussed, such as the use of testosterone to treat ED, the role of the endothelium in men with ED and treating the partner of the man with ED. Finally, future potential therapies for ED will be discussed.
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:

Injections are most likely to restore testosterone levels, but this therapy requires periodic injections, usually every two to four weeks, to sustain an effective level. As such, it is less ideal for patients to depend on frequent medical visits for long-duration therapy. Coupled with injection-related pain, hematoma formation, and inconvenience, the serum blood levels of testosterone are also variable. Injection therapy should not be used in men who wish to father children due to the abnormally high levels of testosterone that occur initially after the injection.
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 pathogenesis of organic ED is related to dysfunction of the endothelium. Endothelial cells can become injured through a variety of mechanisms, most of which cause oxidative stress on the tissues. Many of these causes of oxidative stress are related to lifestyle issues which lead to hypertension, diabetes and dyslipidaemia (figure 1). Endothelial cell dysfunction results in reduction of endothelium-dependent vasorelaxation as well as increased adhesion of leukocytes to the endothelium. Endothelial cell injury then leads to a variety of sequelae, including ED, other types of vasoconstriction, atherosclerosis and thrombus formation.18
Alprostadil may be delivered via the urethra in the form of a pellet (MUSE) (107). This form of therapy has been trialed in SCI men with intermediate success (108). Bodner trialed MUSE dose escalation in SCI men and found 1,000 μg to be the most effective dose. Several men had hypotension when a constriction ring was not used in conjunction with the MUSE therapy.

One of the first steps is to distinguish between physiological and psychological ED. Determining whether involuntary erections are present is important in eliminating the possibility of psychogenic causes for ED.[2] Obtaining full erections occasionally, such as nocturnal penile tumescence when asleep (that is, when the mind and psychological issues, if any, are less present), tends to suggest that the physical structures are functionally working.[19][20] Similarly, performance with manual stimulation, as well as any performance anxiety or acute situational ED, may indicate a psychogenic component to ED.[2]
Erections are initiated and maintained via integration of afferent inputs in the supra sacral regions of the central nervous system. Regions of the brain cited to have key roles in the integration of signals include the medial amygdala, MPOA, periaqueductal gray matter, paraventricular nucleus (PVN), and ventral tegmentum among others (16). Studies in animal models, particularly in rats, have been paramount in identifying these key areas of signal integration and control. Electrostimulation of the MPOA, PVN and hippocampus lead to erection and lesions in these areas may prevent erection (17). Marson et al. injected labeled pseudorabies virus into rat corpora cavernosa and traced them to neurons in the spinal cord, brain stem and hypothalamus (18). Stimulation of the rat dorsal nerve led to increased firing in the MPOA not found elsewhere (19). Axonal tracing in animals have shows direct projections from the hypothalamus to the lumbosacral autonomic erection centers. Oxytocin and vasopressin have been identified as central neurotransmitters within the hypothalamic nuclei and may have a role in penile erection (17). These signaling studies identifying key areas of erectile response integration may explain how ED is associated with cerebrovascular accident (CVA), Parkinson’s, epilepsy and MS.
The various PDE5 inhibitors for the treatment of ED share several common side effects, including headache, flushing, nasal congestion, nausea, dyspepsia (stomach discomfort), and diarrhea. Differences exist in side effects of the different PDE5 inhibitors, and thus it is important to be familiar with the prescribing information of the PDE5 inhibitor you are prescribed.
The penis is composed of three cylinders, two on the top and one on the underside of the penis. The top two cylinders are involved in the erectile process. The urethra, the tube that urine and semen pass through, is on the underside of the penis. The top two penile cylinders, the corpora cavernosa, are composed of tissue that is analogous to a sponge, containing spaces that can fill with blood and expand. These two cylinders are surrounding by a strong layer of tissue, like Saran wrap, the tunica albuginea. For an erection to occur, there must be properly functioning nerves, arteries, veins, and normal penile tissues.
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.

Before pursuing ED treatments, though, bear in mind that improving heart health by losing weight, eating a healthier diet, exercising more and quitting smoking typically enhances erectile performance as well as one’s overall health. In addition, sex therapy counseling sessions can often ease or eradicate ED symptoms, if the underlying cause is psychological in nature, says Drogo Montague, M.D., director of the Center for Genitourinary Reconstruction at the Cleveland Clinic. 


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.
Vacuum devices for ED, also called pumps, offer an alternative to medication. The penis is placed inside a cylinder. A pump draws air out of the cylinder, creating a partial vacuum around the penis. This causes it to fill with blood, leading to an erection. An elastic band worn around the base of the penis maintains the erection during intercourse.
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