| Pathophysiology
Penile erection is managed by two different mechanisms. The first one is the reflex erection, which is achieved by directly touching the penile shaft. The second is the psychogenic erection, which is achieved by erotic or emotional stimuli. The former uses the peripheral nerves and the lower parts of the spinal cord, whereas the latter uses the limbic system of the brain. In both conditions, an intact neural system is required for a successful and complete erection. Stimulation of penile shaft by the nervous system leads to the secretion of nitric oxide (NO), which causes the relaxation of smooth muscles of corpora cavernosa (the main erectile tissue of penis), and subsequently penile erection. Additionally, adequate levels of testosterone (produced by the testes) and an intact pituitary gland are required for the development of a healthy erectile system. As can be understood from the mechanisms of a normal erection, impotence may develop due to hormonal deficiency, disorders of the neural system, lack of adequate penile blood supply or psychological problems. Restriction of blood flow can arise from impaired endothelial function due to the usual causes associated with coronary artery disease, but can also be caused by prolonged exposure to bright light.
Causes
* Neurogenic Disorders (spinal cord and brain injuries, nerve disorders such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and stroke.)
* Hormonal Disorders (pituitary gland tumor; low or abnormally high levels of the hormone testosterone).
* Arterial Disorders (peripheral vascular disease, hypertension; reduced blood flow to the penis).
* Cavernosal Disorders (Peyronie's disease.)
* Psychological causes: Mental disorders (clinical depression, schizophrenia, substance abuse, panic disorder, generalized anxiety disorder, personality disorders or traits.), psychological problems, negative feelings.
* Surgery (radiation therapy, surgery of the colon, prostate, bladder, or rectum may damage the nerves and blood vessels involved in erection. Prostate and bladder cancer surgery often require removing tissue and nerves surrounding a tumor, which increases the risk for impotence.)
* Ageing.
* Lifestyle: alcohol and drugs, obesity, cigarette smoking (Incidence of impotence is approximately 85 percent higher in male smokers compared to non-smokers., Smoking is a key cause of erectile dysfunction. Smoking causes impotence because it promotes arterial narrowing. See also Tobacco and health. )
* Other disorders.
A few causes of impotence may be iatrogenic (medically caused). Various antihypertensives (medications intended to control high blood pressure) and some drugs that modify central nervous system response may inhibit erection by denying blood supply or by altering nerve activity.
Surgical intervention for a number of different conditions may remove anatomical structures necessary to erection, damage nerves, or impair blood supply. Complete removal of the prostate gland or external beam radiotherapy of the gland are common causes of impotence; both are treatments for prostate cancer. Some studies have shown that male circumcision may result in an increased risk of impotence, while others have found no such effect, and another found the opposite.
Excessive alcohol use has long been recognised as one cause of impotence, leading to the euphemism "brewer's droop," or "whiskey dick;" Shakespeare made light of this phenomenon in Macbeth.
A study in 2002 found that ED can also be associated with bicycling. The number of hours on a bike and/or the pressure on the penis from the saddle of an upright bicycle is directly related to erectile dysfunction.
Some evidence suggests that smaller penis size is associated with erectile dysfunction.
Diagnosis
Medical diagnosis
There are no formal tests to diagnose erectile dysfunction. Some blood tests are generally done to exclude underlying disease, such as diabetes, hypogonadism and prolactinoma. Impotence is also related to generally poor physical health, poor dietary habits, obesity, and most specifically cardiovascular disease such as coronary artery disease and peripheral vascular disease.
A useful and simple way to distinguish between physiological and psychological impotence is to determine whether the patient ever has an erection. If never, the problem is likely to be physiological; if sometimes (however rarely), it could be physiological or psychological. The current diagnostic and statistical manual of mental diseases (DSM-IV) has included a listing for impotence.
Clinical Tests Used to Diagnose ED
Duplex ultrasound
Duplex ultrasound is used to evaluate blood flow, venous leak, signs of atherosclerosis, and scarring or calcification of erectile tissue. Injecting prostaglandin, a hormone-like stimulator produced in the body, induces erection. Ultrasound is then used to see vascular dilation and measure penile blood pressure. Measurements are compared to those taken when the penis is flaccid.
Penile nerves function
Tests such as the bulbocavernosus reflex test are used to determine if there is sufficient nerve sensation in the penis. The physician squeezes the glans (head) of the penis, which immediately causes the anus to contract if nerve function is normal. A physician measures the latency between squeeze and contraction by observing the anal sphincter or by feeling it with a gloved finger inserted past the anus. Specific nerve tests are used in patients with suspected nerve damage as a result of diabetes or nerve disease.
Nocturnal penile tumescence (NPT)
It is normal for a man to have five to six erections during sleep, especially during rapid eye movement (REM). The absence or reduction of nocturnal erections 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. (It should be noted that a significant proportion of men who have no sexual dysfunction nonetheless do not have regular nocturnal erections. Thus presence of NPT tends to signify physically functional systems, but absence of NPT may be ambiguous and not rule out either cause.)
Penile biothesiometry
This test uses electromagnetic vibration to evaluate sensitivity and nerve function in the glans and shaft of the penis. A decreased perception of vibration may indicate nerve damage in the pelvic area, which can lead to impotence.
Penile Angiogram
Invasive test - allows visualization of the circulation in the penis and is used during the repair of a priapism.
Dynamic Infusion Cavernosometry
(Abbreviated DICC) technique in which fluid is pumped into the penis at a known rate and pressure. It gives a measurement of the vascular pressure in the corpus cavernosum during an erection. To do this test, a vasodilator like prostaglandin E-1 is injected to measure the rate of infusion required to get a rigid erection and to help find how severe the venous leak is.
Corpus Cavernosometry
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 visualised by infusing a mixture of saline and x ray contrast medium and performing a cavernosogram.
Digital Subtraction Angiography
In DSA, the images are acquired digitally. The computer creates a mask from lower-contrast x-rays of the same area and digitally isolates the blood vessels (this is done manually through darkroom masking with traditional angiography).
Magnetic resonance angiography (MRA)
This is similar to magnetic resonance imaging. Magnetic resonance angiography uses magnetic fields and radio waves to provide detailed images of the blood vessels. Doctors may inject a "contrast agent" into the patient's bloodstream that causes vascular tissues to stand out against other tissues. The contrast agent provides for enhanced information regarding blood supply and vascular anomalies. Aside from the IV used to introduce the contrast material into the bloodstream, magnetic resonance angiography is noninvasive and painless.
Treatment
Treatment depends on the cause. Testosterone supplements may be used for cases due to hormonal deficiency. However, the cause is more usually lack of adequate penile blood supply as a result of damage to inner walls of blood vessels. This damage is more frequent in older men, and often associated with disease, in particular diabetes.
Treatments (with the exception of testosterone supplementation, where effective) work on a temporary basis: they enable an erection to be attained and maintained long enough for intercourse, but do not permanently improve the underlying condition.
ED can in many cases be treated by drugs taken orally, injected, or as penile suppositories. These drugs increase the efficacy of NO, which dilates the blood vessels of corpora cavernosa. When oral drugs or suppositories fail, injections into the erectile tissue of the penile shaft are extremely effective but occasionally cause priapism.
Exercise, particularly aerobic exercise is an effective cheap treatment for erectile dysfunction.
When pharmacological methods fail, a purpose-designed external vacuum pump can be used to attain erection, with a separate compression ring fitted to the penis to maintain it. These pumps should be distinguished from other penis pumps (supplied without compression rings) which, rather than being used for temporary treatment of impotence, are claimed to increase penis length if used frequently, or vibrate as an aid to masturbation. More drastically, inflatable or rigid penile implants may be fitted surgically. Implants are irreversible and costly.
All these mechanical methods are based on simple principles of hydraulics and mechanics and are quite reliable, but have their disadvantages. In a few cases there is a vascular problem which can be treated surgically.
Oral treatment
The cyclic nucleotide phosphodiesterases constitute a group of enzymes that catalyse the hydrolysis of the cyclic nucleotides cyclic AMP and cyclic GMP. They exist in different molecular forms and are unevenly distributed throughout the body.
One of the forms of phophodiesterase is termed PDE5. The prescription PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken orally. They work by blocking the action of PDE5, which causes cGMP to degrade. CGMP specific phosphodiesterase type 5 causes the smooth muscle of the arteries in the penis to relax, allowing the corpus cavernosum to fill with blood.
These medications work when there is sexual stimulation. Depending on the treatment, it will need to be taken 20 minutes to 1 hour before sex and the period of time over which it works can vary between 3 hours and up to 36 hours.
Alprostadil
Alprostadil can be injected into the penis or inserted using a special applicator - usually just before sexual intercourse.
Alprostadil has also become available in some countries as a topical cream (under the brand name Befar), and preliminary studies have shown a clinical efficacy of up to 83%. It has an onset of action of 10–15 minutes and its effects can last over 4 hours.[citation needed]
Vacuum Therapy
Main article: penis pump
These work by placing the penis in a vacuum cylinder device. The device helps draw blood into the penis by applying negative pressure. A tension ring is applied at the base of the penis to help maintain the erection. This type of device is sometimes referred to as penis pump and may be used just prior to sexual intercourse. Several types of FDA approved vacuum therapy devices are available with a doctor's prescription.
Surgery
Main article: Penile prosthesis
Often, as a last resort if other treatments have failed, the most common procedure is prosthetic implants which involves the insertion of artificial rods into the penis.
Counselling
Counselling is often a consideration, both where a psychological cause is suspected or must be ruled out, or to assist in management of any distress.
Controversial and unapproved treatments
ED treatment drugs have a high placebo response: if a good result is expected, any highly praised, and often expensive, treatment can be effective. Reputable drugs can also benefit from the same effect.
Naltrexone
Drug used for treating drug addicts can have some success in patients with inhibited sexual desire.
Bremelanotide
The experimental drug bremelanotide (formerly PT-141) does not act on the vascular system like the former compounds but allegedly increases sexual desire and drive in males as well as females. It is applied as a nasal spray. Bremelanotide allegedly works by activating melanocortin receptors in the brain. It is currently in Phase IIb trials.
Melanotan II
Like bremelanotide the experimental drug Melanotan II does not act on the vascular system either but increases libido. Melanotan II works by activating melanocortin receptors in the brain.
hMaxi-K
hMaxi-K is a form of gene therapy using a plasmid vector that expresses the hSlo gene, that encodes the alpha-subunit of the Maxi-K channel. It has undergone phase I safety trials.
Ginseng (Found in Magic Power Coffee)
A double-blind study appears to show evidence that ginseng is better than placebo.
Enzyte
Enzyte is a product that has been advertised by saturation coverage on television channels such as CourtTV. However, the Center for Science in the Public Interest (CSPI) has filed a complaint with the Federal Trade Commission (FTC) about Enzyte for deceptive advertising. It is manufactured by Berkeley Nutritionals, which is alleged to be the subject of an investigation by the Attorney General of Ohio and the defendant in class-action lawsuits for false advertising.
Enzyte is a supplement that claims to increase the male libido or frequency of erections of the penis.
The effectiveness of Enzyte is in dispute. Some medical professionals in fact advise against taking Enzyte, saying that it can lead to damage. The Center for Science in the Public Interest have urged the Federal Trade Commission to disallow further television advertising for Enzyte due to a lack of proper studies supporting claims.
Enzyte is said to contain: Tribulus terrestris; Yohimbe Extract; Niacin; Epimedium (Found in Magic Power Coffee); Avena sativa; zinc oxide; maca; Muira Pauma; Ginkgo biloba; L-Arginine; Saw Palmetto. Other ingredients: gelatin, rice bran, oat fiber, magnesium stearate, silicon dioxide.
Prelox
Prelox is a Proprietary mix/combination of naturally occurring ingredients, L-arginine aspartate and Pycnogenol. In double blind tests carried out by Dr. Steven Lamm at New York University School of Medicine, 81.1% of men overall judged Prelox to be effective in improving their ability to engage in sexual activity. Whilst the supplements should be taken daily, the manufacturers claim that it brings the spontaneity back into ones' love life; unlike other products which must be remembered to be taken a fixed time before sexual activity.
Alternative treatment methods
Numerous alternative therapies are used to improve sexual function. Some include: niacin, zinc, copper, Korean red ginseng root(Found in Magic Power Coffee), ginkgo, pine bark, Tribulus terrestris, arginine, Avena sativa, horny goat (Found in Magic Power Coffee) weed, maca root, muira puama, saw palmetto, and Swedish flower pollen. None of these however have been recognized as effective by the FDA. While zinc deficiency may be a cause of lower testosterone levels in hemodialysis patients, which may benefit from zinc supplementation, such supplements have no effect on the testosterone levels of healthy males who consume a zinc-sufficient diet.
Continuing research
The peptide Tx2-6 from the venom of the Brazilian wandering spider has recently received media attention as a potential prototype for new drugs targeting nitric oxide signaling.
History
The earliest attempts at treating erectile dysfunction date back to Muslim physicians and pharmacists in the medieval Islamic world. They were the first to prescribe medication for the treatment of this problem, and they developed several methods of therapy for this issue, including a single-drug therapy method where a drug was prescribed and a "combination method of either a drug or food." Most of these drugs were oral medication, though a few patients were also treated through topical and transurethral means. Erectile dysfunctions were being treated with tested drugs in the Islamic world since the 9th century until the 16th century by a number of Muslim physicians and pharmacists, including Muhammad ibn Zakariya Razi, Thabit bin Qurra, Ibn Al-Jazzar, Avicenna (The Canon of Medicine), Averroes, Ibn al-Baitar, and Ibn al-Nafis (The Comprehensive Book on Medicine).
Dr. John R. Brinkley initiated a boom in male impotence cures in the US in the 1920s and 1930s. His radio programs recommended expensive goat gland implants and "mercurochrome" injections as the path to restored male virility, including operations by surgeon Serge Voronoff. After the Kansas State Medical Board revoked his medical license and the Federal Radio Commission refused to renew his radio license (both in 1930), Brinkley moved his operations just over the Texas border to Mexico where he opened a medical clinic and broadcast advertisements into the US from a border blaster radio station.
Surgeons began providing patients with inflatable penile implants in the 1970s.
Modern drug therapy for ED made a significant advance in 1983 when British physiologist Giles Brindley, Ph.D. dropped his trousers and demonstrated to a shocked American Urological Association audience his phentolamine-induced erection. The drug Brindley injected into his penis was a non-specific vasodilator, an alpha-blocking agent, and the mechanism of action was clearly corporal smooth muscle relaxation. The effect that Brindley discovered established the fundamentals for the later development of specific, safe, orally-effective drug therapies. For more information Consult your doctor | 
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