Erectile dysfunction

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Editor-in-Chief: Joel Gelman, M.D. [mailto:jgelman@uci.edu], Director of the Center for Reconstructive Urology and Associate Clinical Professor in the Department of Urology at the University of  California, Irvine

Synonyms and keywords: ED, impotence

Overview
Erectile dysfunction (ED or (male) impotence) is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis. There are various underlying causes, such as cardiovascular leakage and diabetes, many of which are medically treatable.

The causes of erectile dysfunction may be physiological or psychological. Physiologically, erection is a hydraulic mechanism based upon blood entering and being retained in the penis, and there are various ways in which this can be impeded, most of which are amenable to treatment. Psychological impotence is where erection or penetration fails due to thoughts or feelings (psychological reasons) rather than physical impossibility; this can often be helped. Notably in psychological impotence there is a very strong placebo effect.

Erectile dysfunction, tied closely as it is to cultural notions of potency, success and masculinity, can have devastating psychological consequences including feelings of shame, loss or inadequacy; often unnecessary since in most cases the matter can be helped. There is a strong conspiracy of silence (expression)|culture of silence and inability to discuss the matter. In fact around 1 in 10 men will experience recurring impotence problems at some point in their lives.

Folk remedies have long been advocated, with some being advertised widely since the 1930s. The introduction of the first pharmacologically approved remedy for impotence, sildenafil (trade name Viagra), in the 1990s caused a wave of public attention, propelled in part by heavy advertising.

The Latin term impotentia coeundi describes simple inability to insert the penis into the vagina. It is now mostly replaced by more precise terms. The study of erectile dysfunction within medicine is covered by andrology, a sub-field within urology.

Overview and symptoms
Erectile dysfunction is characterized by the regular or repeated inability to obtain or maintain an erection. There are several ways that erectile dysfunction is analyzed:


 * Obtaining full erections at some times, such as when asleep (when the mind and psychological issues if any are less present), tends to suggest the physical structures are functionally working. However the opposite case, a lack of nocturnal erections, does not imply the opposite, since a significant proportion of sexually functional men do not routinely get nocturnal erections or wet dreams.


 * Obtaining erections which are either not rigid or full (lazy erection), or are lost more rapidly than would be expected (often before or during penetration), can be a sign of a failure of the mechanism which keeps blood held in the penis, and may signify an underlying clinical condition, often cardiovascular in origin.


 * Other factors leading to erectile dysfunction are diabetes mellitus (causing neuropathy) or hypogonadism (decreased testosterone levels due to disease affecting the testicles or the pituitary gland).

Erection problems are very common. The Sexual Dysfunction Association estimates that 1 in 10 men in the UK have recurring problems with their erections at some point in their life.

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 male 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 include causation by prolonged exposure to bright light or chronic exposure to high noise levels.

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 advanced 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.

Differential Diagnosis

 * Acromegaly
 * Addison's Disease
 * Adiposogenital dystrophy
 * Advanced age
 * After sexual abuse
 * After testicle injury or infection
 * Aging
 * Angitis obliterans
 * Apoplexy
 * Arteriosclerosis
 * Autoantibodies against sperm
 * Azoospermia
 * Balanitis
 * Cachexia
 * Castration
 * Chemotherapy
 * Chronic hepatopathy
 * Chronic Renal Failure
 * Circulatory disorders
 * Cirrhosis
 * Conus Medullaris Syndrome
 * Cryptorchidism
 * Depression
 * Diabetes Mellitus
 * Drugs, toxins
 * Epididymitis
 * Epispadia
 * Exhaustion
 * Exogenous testosterone substitution
 * Gonadal agenesis
 * Heart failure
 * Hormone secreting adrenocortical tumors
 * Hydrocele
 * Hyperadrenocorticalism
 * Hyperprolactinemia
 * Hypertension
 * Hyperthyroidism
 * Hypogonadism
 * Hypopituitarism
 * Hypospadia
 * Hypothyroidism
 * Idiopathic
 * Incomplete descent of one or both testes
 * Insecurity
 * Klinefelter's Syndrome
 * Leriche's Syndrome
 * Lipid metabolism disorders
 * Lymphoma
 * Male menopause
 * Male pseudohermaphroditism
 * Multiple Sclerosis
 * Mumps
 * Necrospermia
 * Noonan's Syndrome
 * Oligospermia
 * Orchitis
 * Paraplegia
 * Pelvic ring fracture
 * Phimosis
 * Pituitary adenoma
 * Polyneuropathy
 * Priapism
 * Prolapsed disk
 * Prostatitis
 * Pyelitis
 * Radiation therapy
 * Reifenstein's Syndrome
 * Relationship conflict
 * Renal anomaly
 * Repressed homoeroticism
 * Schizophrenia
 * Sertoli-cell-only syndrome
 * Severe systemic diseases
 * Spermatocytosis
 * Stress
 * Surgery
 * Tabes Dorsalis
 * Testicular hypoplasia
 * Testicular torsion
 * Testicular trauma
 * Testosterone deficiency
 * Tuberculosis
 * Tuberous Sclerosis
 * Tumor of the genital organs
 * Urethritis
 * Varicocele

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). Their absence 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. There are different treatments available:

3 different tablets are currently available from the doctor and these 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.
 * Oral treatment:

This can be injected into the penis or inserted using a special applicator - usually just before sexual intercourse.
 * Alprostadil:

Currently, only commercially available in the Far East, Befar® has shown a clinical efficacy of up to 83% in patients with varying degrees of ED. The cream itself has a onset action of 10-15 minutes and can continue on past 4-hours, and is favorably comparable to the efficacy of the injectable alprostadil.
 * BEFAR

Due to Befar’s direct application method (i.e. unlike Viagra®, Befar’s actions are limited to the area of its application), the side effects induced by the application have to date been limited to transient warm and burning sensations.

So instead of using an injectable or intra-urethral pellet, Befar® cream rapidly and effectively promotes the permeation of alprostadil into the active site of the penis. Can be purchased at:

These work by drawing blood into the penis and are also used just before sexual intercourse.
 * Vacuum pumps:

It is rare, but some men receive hormones for their erection problem. This does depend on the cause of the problem as well as other factors.
 * Hormone treatment:

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.
 * Surgery:

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.
 * Counselling:

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. 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.

Uncontroversial treatments

 * PDE5 Inhibitors: 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. These multiple forms or subtypes of phosphodiesterase were initially isolated from rat brain by Uzunov and Weiss in 1972 and were soon afterwards shown to be selectively inhibited by a variety of drugs in brain and other tissues.  The potential for selective phosphodisterase inhibitors to be used as therapeutic agents was predicted as early as 1977 by Weiss and Hait. This prediction has now come to pass in a variety of fields, one of which is in the pharmacological treatment of erectile dysfunction.

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.

(Specific devices are mentioned for information only; mention should not be taken as endorsement).


 * Dopamine Receptor Agonist


 * Inflatable implant


 * Rigid implant


 * Surgical treatment of certain cases

Controversial and unapproved treatments

 * 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:A double-blind study appears to show evidence that ginseng is better than placebo: see the ginseng article for more details.


 * 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.


 * Enzyte is a supplement that claims to increase the male libido or frequency of erections of the penis. Commercials for Enzyte are shown regularly on television. These commercials feature a man named Bob who never stops smiling, apparently because he had taken Enzyte and improved the size of his sex organs. The commercials are riddled with symbolic Phallic symbol|phallic imagery, e.g. golf clubs, remarkably tall glasses of iced tea, and a hose spraying barely a trickle of water (carried by someone who doesn't use Enzyte).


 * 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 maker Berkeley Premium Nutraceuticals, Inc., is currently under a class action lawsuit for false advertising.


 * Enzyte is said to contain: Tribulus terrestris; Yohimbe Extract; Niacin; Epimedium; Avena sativa; zinc oxide; maca; Muira Pauma; Ginkgo biloba; L-Arginine; Saw Palmetto. Other ingredients: gelatin, rice bran, oat fiber, magnesium stearate, silicon dioxide.


 * Herbal and other alternative treatments
 * These are generally ineffective when tested blind, but may be useful for their psychological (placebo) effect: 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.


 * 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.Prelox® for improvement of erectile function: A review European Bulletin of Drug Research, Volume 11, No. 3, 2003. Steven Lamm, Frank Schoenlau, Peter Rohdewald 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.

Zinc
Zinc is known to help prevent the conversion of testosterone to estradiol, and testosterone is essential for proper erectile function and the synthesis of sperm (testosterone deficiency is a primary contributor in many cases of erectile dysfunction). Moreover, zinc levels have been found to be significantly reduced in both chronic bacterial prostatitis (CBP) and non-bacterial prostatitis (NBP). Many doctors and nutritionalists recommend zinc for prostate or erectile problems.

Zinc is best taken in lozenge form, as in tablet form the zinc is difficult to absorb, and can irritate the stomach lining.

History
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.

Reference: Helgason ÁR, Adolfsson J, Dickman P, Arver S, Fredrikson M, Göthberg M, Steineck G. Sexual desire, erection, orgasm and ejaculatory functions and their importance to elderly Swedish men: A population-based study. Age and Ageing. 1996:25:285-291.