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.
As is true in so many medical conditions, lifestyle modifications, considered first-line therapy, can have a salutary effect in ED management, and men should be encouraged to make the necessary changes to the benefit of their sexual function and to their overall health as well. Despite the benefits of behaviour modification, men presenting with ED want the physician to help with measures that can have an immediate impact.
Monitoring erections that occur during sleep (nocturnal penile tumescence) can help you and your doctor to understand if the erectile dysfunction is due to psychological or physical causes. The nocturnal penile tumescence test is a study to evaluate erections at night. Normally men have three to five erections per eight hours of sleep. The test can be performed at home or in a sleep lab. The most accurate way to perform the test involves a special device that is connected to two rings. The rings are placed around the penis, one at the tip of the penis and the other at the bottom (base) of the penis. The device records how many erections occur, how long they last, and how rigid they are. The test is limited in that it does not assess the ability to penetrate.
Taking one of these tablets will not automatically produce an erection. Sexual stimulation is needed first to cause the release of nitric oxide from your penile nerves. These medications amplify that signal, allowing some men to function normally. Oral erectile dysfunction medications are not aphrodisiacs, will not cause excitement and are not needed in men who get normal erections.

Because the burning side effect is triggered by alprostadil, the formulations with the least alprostadil — tri-mix and certain versions of bi-mix — could work for men who experience burning with the single-drug formula. But some men might choose alprostadil alone because the multi-drug cocktails can cost more and must be dispensed by a compounding pharmacy — one that is authorized to mix medications on site — which could mean the added hassle of a long drive to pick up the drug.
As with most other organ system in the human body, changes and loss of function is normal consequence of the ageing process. This is also true of the endocrine system, specifically the levels of testosterone production from the Leydig cells of the testicle. Accompanying the decrease in testosterone is a decrease in erections which also has a component in decrease in the blood supply to the penis making erection not as frequent and not as rigid compared with a young man’s erectile function. Although these changes are in itself not life threatening, they can impact a man’s relationship with his partner, and also ED may be a harbinger of other undiagnosed conditions such as coronary artery disease (CAD), hypercholesterolaemia or diabetes mellitus.6
The phrase “use it before you lose it” can be applied when it comes to helping men with ED regain normal erectile function. Pelvic exercises, more commonly known as kegel exercises, are used to promote urinary continence and sexual health. They help to strengthen the bulbocavernosus muscle, which does three things: allows the penis to engorge with blood during erection, it pumps during ejaculation, and it helps empty the urethra after urination, according to Healthline.
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.
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.
Surgery: If neither drugs nor the vacuum pump works, your doctor may suggest surgery. With surgery, the doctor can place a device in your penis that will cause enough hardness for intercourse. In a few cases, infections may develop after the operation, and the doctor may have to remove the device. Another operation that may help you is rebuilding the blood vessels in the penis to increase blood flow into the penis or decrease blood flow out of the penis. These procedures can help you to get and maintain an erection.

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.
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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.
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).

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.
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
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]
Diabetes is an example of an endocrine disease that can cause a person to experience impotence. Diabetes affects the body’s ability to utilize the hormone insulin. One of the side effects associated with chronic diabetes is nerve damage. This affects penis sensations. Other complications associated with diabetes are impaired blood flow and hormone levels. Both of these factors can contribute to impotence.
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. 
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.
A number of treatments are available to treat erectile dysfunction. The typical treatment strategy starts with simple to use, noninvasive therapies and progresses to more invasive surgical therapies as needed. In all men, the first step is determining if there are any modifiable risks factors that can either improve or prevent progression of erectile dysfunction. Since the risk of developing ED is increased in the presence of diabetes, heart disease, and hypertension, it is thought that better control/prevention of these conditions may have a benefit in ED. Similarly, it is thought that lifestyle modifications to improve vascular function such as avoiding smoking, maintaining ideal body weight, and engaging in regular exercise might either prevent or reverse ED. Sexual counseling may also be useful in addressing relationship stressors as you work on improving your erectile function.

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
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. 

Normal erectile function depends on the release of NO and endothelial-dependent vasodilation of the penile arteries. The ‘artery size’ hypothesis, first described by Dr Montorsi, offers an explanation why men are more likely to develop ED before a myocardial infacrtion. It is believed that atherosclerosis affects all vascular beds equally but smaller arteries are more likely to become occluded than larger arteries.31 32 The penile arteries are 1–2 mm while the coronary arteries are 3–4 mm. Thus, the same degree of endothelial dysfunction and atherosclerosis is more likely to occlude blood flow in the penile arteries compared with the coronary arteries. The penile arteries therefore serve as a sensitive indicator for subsequent CVD. This theory is supported by the fact that ED occurs approximately 3 years prior to cardiac symptoms in virtually all patients with chronic coronary syndrome whereas patients with acute coronary syndrome have a much lower prevalence of sexual dysfunction.32
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.
Certain street drugs such as "poppers" also can cause serious problems if taken with PDE5i medications. These poppers are often types of nitrates and can cause severe drops in blood pressure. Ecstasy is another street drug that may increase sexual desire but interferes with performance. This has prompted some men to combine ecstasy with PDE5i medications. This mixture (a combination sometimes called "sextasy") can improve erection ability but also causes severe headache and priapism. (Priapism is an abnormally prolonged erection that becomes extremely painful and may result in permanent damage to the erection mechanism.) There are also potentially dangerous effects to your heart from mixing PDE5i medications with various other street drugs.
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.
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. 
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

In order to establish whether normal erections are occurring overnight (nocturnal erections), the doctor may organise nocturnal penile tumescence (NPT) testing. This involves wearing a monitor overnight in your own home. The data from this monitor is then assessed to analyse how often erections occurred, how long they lasted, and how rigid and large the penis was during the erections. If NPT testing is normal, the cause of erectile dysfunction is usually psychological. If not, further testing of the blood flow in the genital area may be required to see if there is blockage or leakage. The doctor may also organise a blood test of levels of hormones such as testosterone, prolactin and thyroid stimulating hormone to see if these are contributing to the erectile dysfunction.
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A physical examination is necessary. The doctor will pay particular attention to the genitals and nervous, vascular, and urinary systems. Your blood pressure will be checked because several studies have demonstrated a connection between high blood pressure and erectile dysfunction. The physical examination will confirm information you gave the doctor in your medical history and may help reveal unsuspected disorders such as diabetes, vascular disease, penile plaques (scar tissue or firm lumps under the skin of the penis), testicular problems, low male hormone production, injury, or disease to the nerves of the penis and various prostate disorders.
Instead of injecting a medicine, some men insert a suppository of alprostadil into the urethra. A suppository is a solid piece of medicine that you insert into your body where it dissolves. A health care professional will prescribe a prefilled applicator for you to insert the pellet about an inch into your urethra. An erection will begin within 8 to 10 minutes and may last 30 to 60 minutes.
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.

Because the burning side effect is triggered by alprostadil, the formulations with the least alprostadil — tri-mix and certain versions of bi-mix — could work for men who experience burning with the single-drug formula. But some men might choose alprostadil alone because the multi-drug cocktails can cost more and must be dispensed by a compounding pharmacy — one that is authorized to mix medications on site — which could mean the added hassle of a long drive to pick up the drug.
A physical exam checks your total health. Examination focusing on your genitals (penis and testicles) is often done to check for ED. Based on your age and risk factors, the exam may also focus on your heart and blood system: heart, peripheral pulses and blood pressure. Based on your age and family history your doctor may do a rectal exam to check the prostate. These tests are not painful. Most patients do not need a lot of testing before starting treatment.
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