The observation that TRT enhances the efficacy of PDE5 inhibitors in hypogonadal men taking these therapies with suboptimal response to the PDE5 inhibitors alone has been reported.33 In addition, investigators have demonstrated that TRT in hypogonadal men can improve erectile function even without the benefit of PDE5 inhibitors.33 In addition, guidelines for managing ED in hypogonadal men by the European Association of Urology recommend controlling the man to a eugonadal state prior to initiation of PDE5 inhibitor therapy.36 Testosterone measurement consists of a serum specimen which should be ideally obtained in the morning because of the normal diurnal variation of testosterone which is at its peak in the morning. Since TRT is relatively safe, and men can potentially see an improvement in erectile function, it seems prudent to consider this issue when presented with a patient suffering from ED.
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).
Clearly, PDE5i have revolutionized the treatment of ED in general and the neurogenic ED population is no exception. They remain safe and effective in most men with neurogenic ED; however, care must be taken in prescribing PDE5i to men high spinal cord lesions, MSA or possibly PD. VEDs are minimally-invasive and can be as effective as other modalities at leading to erection. However, high discontinuation rates are associated with VED use related to pain, difficulty using the device or cold penis. Intracavernosal therapy has been a mainstay of treatment for neurogenic ED and remains extremely successful in the SCI population. Trial of intracavernosal therapy for other causes of neurogenic ED can be considered second-line therapy, but there is a relative paucity of data for clinical outcomes related to its use outside of SCI men. Surgical therapy via penile implantation remains another second line approach and may also be utilized to assist men with bladder management. Higher complication rates of infections, and perforation have been reported compared to neurologically intact men. Many other compounds are currently being evaluated for the treatment of neurogenic ED as well as gene and stem cell therapy, but still should be considered investigational until substantiated by randomized controlled trials.
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.
Size matters, so get slim and stay slim. A trim waistline is one good defense — a man with a 42-inch waist is 50% more likely to have ED than one with a 32-inch waist. Losing weight can help fight erectile dysfunction, so getting to a healthy weight and staying there is another good strategy for avoiding or fixing ED. Obesity raises risks for vascular disease and diabetes, two major causes of ED. And excess fat interferes with several hormones that may be part of the problem as well.
Much of the emphasis on erectile pathophysiology has been placed on penile smooth muscle function and cavernosal hemodynamics. The neuroanatomy and neurophysiology of erection can be characterized but its full extent is poorly understood. Neurologic disease does not always reproducibly affect erections in a uniform manner compared to other types of sexual dysfunction (SD). This offers many obstacles to understanding the role the nervous systems plays in SD and consequently obscures what treatment options readily optimize erections specific to the neurologic insult.
Ultrasound with Doppler imaging (ultrasound plus evaluation of blood flow in the arteries and veins) can provide additional information about blood flow of the penis and may help in the evaluation of patients prior to surgical intervention. This study is typically performed after the injection of a chemical that causes the arteries to open up, a vasodilator (prostaglandin E1), into the corpora cavernosa in order to cause dilation of blood vessels and promote blood flow into the penis. The rate of blood flow into the penis can be measured along with an evaluation of problems with compression of the veins.
In a 2005 study, three months of twice-daily sets of kegel exercises combined with biofeedback and advice on lifestyle changes, such as quitting smoking, losing weight, and limiting alcohol, worked far better than just giving the participants advice. “Wearing tight pants will affect impotence along with some other medical conditions like diabetes and heart disease,” which can also affect a man’s degree of impotence, Dr. Jennifer Burns, specializing in family practice with an emphasis on gastrointestinal health at the BienEtre Center, told Medical Daily.
A common and important cause of ED is vasculogenic. Many men with ED have comorbid conditions such as hyperlipidemia, hypercholesterolemia, tobacco abuse, diabetes mellitus, or coronary artery disease (CAD).  The Princeton III Consensus recommends screening men who present with ED for cardiovascular risk factors; ED may be the earliest presentation of atherosclerosis and vascular disease. 
Soler et al. compared sildenafil to vardenafil and tadalafil (69). Sildenafil was effective in 85% of SCI patients, 74% of the patients on vardenafil and 72% of the patients on tadalafil. Sildenafil was associated with more rigid and longer lasting erections. Additionally, 50 mg of sildenafil was effective in 55% of patients compared to more than 70% of the patients on vardenafil and tadalafil requiring 20 mg for a similar response. Men who used tadalafil were able to achieve erections 24 hours after administration, improving overall satisfaction related to the possible spontaneity of sexual encounters. Del Popolo also evaluated the time/duration effectiveness of PDE5i sildenafil 50 mg versus tadalafil 10 mg (64). Tadalafil 10 mg significantly increased the percentage of successful intercourse attempts at 12–24 hours compared with sildenafil. One can suspect that vardenafil, which has a longer half-life than sildenafil, could offer a similar benefit but a study investigating this occurrence has yet to be performed.
The PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken orally.: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. Penile injections, on the other hand, can involve one of the following medications: papaverine, phentolamine, and prostaglandin E1, also known as alprostadil.:25
Recently, several advances in the uses of stem cells have bet met with great anticipation. Stem cells have the ability to differentiate into different cell lines based on the cellular signaling they receive. Bone marrow mononuclear cells in particular have been used for the treatment of ED in animal models. Yiou et al. recently delivered bone marrow-mononuclear cells (BM-MNC) into the intracavernous smooth muscle of post radical prostatectomy men (123). The open label, dose escalation phase I/II trial showed improvements in IIEF-15 assessment as well as increased vascularization of the corpora based on penile Doppler arterial velocity measurements. Although promising, further investigation in humans is required to substantiate BM-MNCs impact on erections, and erectile function recovery going forward.
Many factors can contribute to sexual dysfunction in older men, including physical and psychological conditions, comorbidities and the medications used to treat them. Aspects of an ageing man’s lifestyle and behaviour and androgen deficiency, most often decreasing testosterone levels, may affect sexual function as well. A study of men between the ages of 30 and 79 years showed that 24% had testosterone levels below 300 ng/dL and 5.6% had symptomatic androgen deficiency.2
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
You should talk to your doctor about possible treatments. You may want to talk to other patients who have had the treatment planned for you. You also may want to seek a second doctor's opinion about surgery before making your decision. You may find it difficult to talk to your doctor about impotence. You will want to find a doctor who treats this condition and will help you feel comfortable talking about the problem and choosing the best treatment. You can also get more information by contacting your local National Kidney Foundation affiliate.
Over a 2-year period, a third of the men randomized to a weight loss program demonstrated resolution of erectile dysfunction.10 A Mediterranean diet and nutritional counseling reported increased erectile quality.18 Little evidence supports that increased physical activity alone improves erectile quality; however, the strong association between physical activity and lower BMI is well described, and therefore recommended for men with erectile dysfunction and without a contraindication to physical activity.
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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.  Nevertheless, this research has given rise to many new treatment targets and a better understanding of the entire process.
Chronic stress dumps adrenaline in your system multiple times a day. And that can lead to high blood pressure, heart disease, obesity, and diabetes. Chronic stress is like red-lining your car all day long. When you drive 100 mph all the time, something is going to break down. A high-stress environment can actually change the way your brain sends messages to your body. Dumping too much adrenaline into your bloodstream can affect blood flow and severely limit your ability to achieve and maintain an erection.
As blood flows into the penis, the corpora cavernosa swell, and this swelling compresses the veins (blood vessels that drain the blood out of the penis) against the tunica albuginea. Compression of the veins prevents blood from leaving the penis. This creates a hard erection. When the amount of cGMP decreases by the action of a chemical called phosphodiesterase type 5 (PDE5), the muscles in the penis tighten, and the blood flow into the penis decreases. With less blood coming into the penis, the veins are not compressed, allowing blood to drain out of the penis, and the erection goes down.
Nerves originating in the spinal cord and peripheral ganglia innervate the penis. There are autonomic (parasympathetic and sympathetic), and somatic separate and integrated pathways. The autonomic pathways neurons originate in the spinal cord and peripheral ganglia from the sympathetic and parasympathetic systems, respectively. They merge to form the cavernous nerves that travel alongside the prostate, enter the corpora cavernosa and corpus spongiosum to affect the neurovascular events required for tumescence and detumescence. The somatic nerves send sensory information from the penile skin, glans, and urethra via the dorsal penile nerve and pudendal nerve to the spinal cord. The somatic nerves also initiate contraction of the ischio- and bulbocavernosus muscles.
Surgical intervention for a number of conditions may remove anatomical structures necessary to erection, damage nerves, or impair blood supply. Erectile dysfunction is a common complication of treatments for prostate cancer, including prostatectomy and destruction of the prostate by external beam radiation, although the prostate gland itself is not necessary to achieve an erection. As far as inguinal hernia surgery is concerned, in most cases, and in the absence of postoperative complications, the operative repair can lead to a recovery of the sexual life of people with preoperative sexual dysfunction, while, in most cases, it does not affect people with a preoperative normal sexual life.
Alprostadil, a drug also discussed in Penile Injection Therapy, has been formulated into a small suppository. This applicator is inserted into the urethra (the canal through which urine and semen are excreted), and with compression of the applicator, the small suppository is released into the urethra. With massage/rubbing of the penis, the suppository dissolves in the urethra and the medication is absorbed into the penis where it acts to increase blood flow into the penis. One cannot use any form of lubricant (for example, K-Y jelly, Vaseline, etc) to help with the insertion of the suppository. Urinating prior to inserting the applicator will help moisten/lubricate the urethra.
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.
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.
Once a complete sexual and medical history has been completed, appropriate laboratory studies should be conducted. In the initial evaluation of ED, sophisticated laboratory testing is rarely necessary. For example, serum testosterone (and sometimes prolactin) is typically only useful when the patient demonstrates hypogonadal features or testicular atrophy, or when clinical history is suggestive. Additional hormonal evaluation may include thyroid stimulating hormone in those with a clinical suspicion of hypothyroidism or appropriate diabetes screening in those presenting with a concern for impaired glucose metabolism. If the patient has not been evaluated with a lipid panel and hyperlipidemia is suspected, measurement and appropriate referral to internal medicine or cardiology is recommended. In most cases, a tentative diagnosis can be established with a complete sexual and medical history, physical examination, and limited or no laboratory testing.
Lifestyle choices that impair blood circulation can contribute to ED. Smoking, excessive drinking, and drug abuse may damage the blood vessels and reduce blood flow to the penis. Smoking makes men with atherosclerosis particularly vulnerable to ED. Being overweight and getting too little exercise also contribute to ED. Studies indicate that men who exercise regularly have a lower risk of ED.