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Erectile Dysfunction

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. Nerve trauma from prostatectomy surgery can cause chronic erectile dysfunction.

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 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.

Current Research

For current research articles click - here

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 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 level of the hormone testosterone).
  • Arterial Disorders (peripheral vascular disease, hypertension; reduced blood flow to the penis).
  • Cavernosal Disorders (Peyronie's disease.)
  • Nonphysical 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.)
  • Aging.
  • 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.

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). 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:

Oral Treatment

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.

Alprostadil

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

BEFAR

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 an onset action of 10-15 minutes and can continue on past 4-hours, and is favorably comparable to the efficacy of the injectable alprostadil.

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.

Vacuum Pumps

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

Hormone Treatment

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.

Surgery

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.

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 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. This is especially useful if blindfolded, as it helps to clear the mind of anxiety issues.

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.

Other Treatment Methods

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

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 Zakarīya Rāzi, 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.


(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Erectile_dysfunction)





Findings From Current Research

A Prospective Study of Lower Urinary Tract Symptoms and Erectile Dysfunction

Authors: Mondul AM, Rimm EB, Giovannucci E, Glasser DB, Platz EA.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health (AMM, EAP).

PURPOSE: Several studies have shown that men with lower urinary tract symptoms are more likely to experience erectile dysfunction. All except 1 of these studies were cross-sectional, limiting inferences about whether lower urinary tract symptoms precipitate erectile dysfunction. MATERIALS AND METHODS: The association between lower urinary tract symptoms and incident erectile dysfunction was examined prospectively in the Health Professionals Follow-Up Study. Lower urinary tract symptoms were assessed biennially by the American Urological Association symptom index, which captures symptoms of frequency, urgency and force of urinary stream. Severe lower urinary tract symptoms was defined as a symptom score of 20 points or greater and no lower urinary tract symptoms was defined as a score of 7 points or less in men not treated for lower urinary tract symptoms. In 2000 the men were asked to rate erectile function for several periods. Erectile dysfunction was defined as poor or very poor function, or erectile dysfunction medication use, while no erectile dysfunction was defined as very good or good function and no erectile dysfunction medication use. We estimated the RR using Poisson regression, adjusting for age and other potentially confounding factors. RESULTS: We observed 3,953 incident erectile dysfunction cases among 17,086 men. Men with severe lower urinary tract symptoms in 1994 or earlier had a statistically significant 40% higher risk of erectile dysfunction subsequently than men without lower urinary tract symptoms. The risk of erectile dysfunction increased with increasing lower urinary tract symptom severity (p trend <0.0001). The positive association between lower urinary tract symptoms and erectile dysfunction was stronger in younger than in older men (p interaction = 0.03). CONCLUSIONS: This study provides evidence that men with lower urinary tract symptoms are more likely to have erectile dysfunction subsequently.

Journal: J Urol. 2008 Apr 17
Adapted from PubMed; click here to access full journal article.




Socioeconomic Status, Not Race/Ethnicity, Contributes to Variation in the Prevalence of Erectile Dysfunction: Results from the Boston Area Community Health (BACH) Survey

Authors: Kupelian V, Link CL, Rosen RC, McKinlay JB.

New England Research Institutes, Watertown, MA, USA.

Introduction. Few population-based studies have assessed variations in the burden of erectile dysfunction (ED) by race/ethnicity. Aim. To estimate prevalence rates of ED by race/ethnicity and determine the contribution of behavioral risk factors, chronic illnesses, and socioeconomic factors to potential race/ethnic differences in ED. Methods. The Boston Area Community Health (BACH) Survey is a study of urologic symptoms in a racially and ethnically diverse population. BACH used a multistage stratified random sample to recruit 2,301 men aged 30-79 years from the city of Boston. Self-reported race/ethnicity was defined as Black, Hispanic, and White. Socioeconomic status (SES) was defined as a combination of education and household income. Main Outcome Measures. ED assessed using the 5-item International Index of Erectile Function (IIEF-5). IIEF-5 scores were used both as a continuous variable and dichotomized as </=16 vs. >/=17. Results. Overall prevalence of ED (defined as an IIEF-5 score </=16) was 20.7% with higher prevalence observed among both Black men (24.9%) and Hispanic men (25.3%) compared to White men (18.1%). Increased odds of ED were observed for both Black and Hispanic men after adjusting for age, comorbid conditions (cardiovascular disease, diabetes, depression), and behavioral risk factors (smoking, physical activity, alcohol use). After controlling for the effect of SES, the association between race/ethnicity and ED disappeared. In contrast, men in the low SES category had an over two-fold increase in risk of ED (adjusted odds ratio of 2.26, 95% confidence interval 1.39, 3.66). Conclusions. The increased risk of ED in Black and Hispanic men is associated with differences in SES rather than differences in known risk factors of ED.

Journal: J Sex Med. 2008 Apr 10
Adapted from PubMed; click here to access full journal article.




Randomized, Double-Blind, Crossover Trial of Sildenafil in Men with Mild to Moderate Erectile Dysfunction: Efficacy at 8 and 12 Hours Postdose

Authors: McCullough AR, Steidle CP, Klee B, Tseng LJ.

New York University School of Medicine, New York, New York 10016, USA. andy.mccullough@nyumc.org

OBJECTIVES: To clarify the period of responsiveness to sildenafil. METHODS: Under a double-blind protocol, men with mild to moderate erectile dysfunction (International Index of Erectile Function [IIEF] Erectile Function domain score, 11 to 25) were randomized to sildenafil (100 mg) or placebo and attempted intercourse 8 hours (range, 7 to 9 hours) postdose (first 4-week phase) and 12 hours (11 to 13 hours) postdose (second 4-week phase after treatment crossover). The primary outcome was the per-patient proportion (PPP; least squares means [95% confidence interval]) of affirmative responses to the Sexual Encounter Profile question 3 (SEP3: "Did your erection last long enough for you to have successful intercourse?"). RESULTS: For sildenafil (n = 174) versus placebo (n = 177), baseline values were similar but the PPP of successful intercourse attempts increased to 76% (69% to 82%) versus 50% (43% to 57%) in phase 1 (odds ratio [OR] = 3.2) and 79% (72% to 85%) versus 52% (44% to 60%) in phase 2 (OR = 3.5), and the PPP of Erection Hardness Score 4 erections (completely hard and fully rigid) was 41% (34% to 48%) versus 10% (7% to 15%) in phase 1 (OR = 6.2) and 44% (37% to 51%) versus 17% (12% to 23%) in phase 2 (OR = 4.0). Thus, at 12 hours, the odds of successful intercourse tripled and of a completely hard erection quadrupled. The sildenafil group achieved greater (P <0.001) PPP of successful penetration (SEP2), satisfaction with erection hardness (SEP4), and satisfaction with the sexual experience (SEP5); improvement in IIEF domain scores; and treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction. CONCLUSIONS: In men with mild to moderate ED, responsiveness to sildenafil may persist much longer than 4 hours.

Journal: Urology. 2008 Apr;71(4):686-92.
Adapted from PubMed; click here to access full journal article.




Molecular Yin and Yang of Erectile Function and Dysfunction

Authors: Lin CS, Xin ZC, Wang Z, Lin G, Lue TF.

Knuppe Molecular Urology Laboratory, University of California, San Francisco, CA 94143, USA. clin@urology.ucsf.edu.

In regard to erectile function, Yin is flaccidity and Yang erection. In the past decade, research has mostly focused on the Yang aspect of erectile function. However, in recent years, the Yin side is attracting increasingly greater attention. This is due to the realization that penile flaccidity is no less important than penile erection and is actively maintained by mechanisms that play critical roles in certain types of erectile dysfunction (ED); for example, in diabetic patients. In addition, there is evidence that the Yin and Yang signaling pathways interact with each other during the transition from flaccidity to erection, and vice versa. As such, it is important that we view erectile function from not only the Yang but also the Yin side. The purpose of this article is to review recent advances in the understanding of the molecular mechanisms that regulate the Yin and Yang of the penis. Emphasis is given to the Rho kinase signaling pathway that regulates the Yin, and to the cyclic nucleotide signaling pathway that regulates the Yang. Discussion is organized in such a way so as to follow the signaling cascade, that is, beginning with the extracellular signaling molecules (e.g., norepinephrin and nitric oxide) and their receptors, converging onto the intracellular effectors (e.g., Rho kinase and protein kinase G), branching into secondary effectors, and finishing with contractile molecules and phosphodiesterases. Interactions between the Yin and Yang signaling pathways are discussed as well. 2008, Asian Journal of Andrology, SIMM and SJTU. All rights reserved.

Journal: Asian J Androl. 2008 May;10(3):433-40.
Adapted from PubMed; click here to access full journal article.




An Assessment of Patient-Reported Outcomes for Men with Erectile Dysfunction: Pfizer's Perspective

Authors: Cappelleri JC, Stecher VJ.

Pfizer Inc, Global Research and Development, New London, CT, USA.

Patient-reported outcomes (PROs) for men with erectile dysfunction (ED) have blossomed in the published literature and at professional conferences. These outcomes have been central to study the science of ED itself and to evaluate efficacy of treatment for men with ED. In this review article we highlight and distinguish among seven key PROs: the International Index of Erectile Function, for sexual function including erectile function; the Sexual Health Inventory for Men (SHIM), for diagnosis of ED; the Quality of Erection Questionnaire, for satisfaction with quality of erections; the Erectile Dysfunction Inventory of Treatment Satisfaction, for personal evaluation of treatment received; the Self-Esteem And Relationship questionnaire, for emotional well-being; the Erection Hardness Score (EHS), for targeting erection hardness and the Sexual Experience Questionnaire, for erection (both function and quality), individual satisfaction and couples satisfaction. Depending on the purpose of the investigation, all seven PROs have merit for use in clinical trials and at least deserve consideration in clinical practice. The SHIM and the EHS, given their aims and brevity, deserve special consideration in clinical practice. As a unit these seven PROs complement and supplement each other. Which ones to choose in a particular undertaking depends on the objective or purpose of a given study. These PROs acknowledge that sexual dysfunction and its treatment have multiple dimensions. Each of these instruments represents a significant contribution to sexual medicine research and, when used judiciously and appropriately, can help to provide optimal patient care and management. International Journal of Impotence Research advance online publication, 27 March 2008; doi:10.1038/ijir.2008.8.

Journal: Int J Impot Res. 2008 Mar 27
Adapted from PubMed; click here to access full journal article.




Erectile Dysfunction and Dyslipidemia: Relevance and Role of Phosphodiesterase Type-5 Inhibitors and Statins

Authors: Miner M, Billups KL.

Men's Health Center, The Miriam Hospital, Warren Alpert School of Medicine, Brown University, Swansea, MA, USA.

Introduction. There is a close link between hyperlipidemia/dyslipidemia and erectile dysfunction (ED), with endothelial dysfunction as a common mechanism. Both ED and hyperlipidemia/dyslipidemia are rising in prevalence with mounting evidence that these conditions are harbingers of cardiovascular disease. Aim. This review was conducted to provide an update on the epidemiology and oral therapy of both dyslipidemia and ED, the connection between these two conditions, and clinical outcomes relating to the use of statins and phosphodiesterase type-5 (PDE5) inhibitors in men with ED who have associated dyslipidemia. Methods. A systematic search was performed of MEDLINE and EMBASE research databases to obtain articles pertaining to the epidemiology, mechanism, and clinical outcomes of statins and PDE5 inhibitors in men with ED and associated dyslipidemia. Main Outcome Measures. The clinical and preclinical studies related to ED and dyslipidemia are analyzed and their findings are assessed and summarized. Results. Hyperlipidemia/Dyslipidemia constitute a vascular risk factor having a considerable impact on erectile function. Furthermore, the role of endothelial dysfunction in the pathophysiology of both ED and dyslipidemia is paramount suggesting the importance of comanaging these conditions. Therefore, hyperlipidemia/dyslipidemia when present in patients with ED should prompt management with diet/exercise as well as appropriate pharmacotherapy. With ED being often associated with comorbidities, the use of concomitant pharmacotherapies enhances opportunities for managing the overall global cardiometabolic risk. Newer studies assessing the effect of PDE5 inhibitors in men with dyslipidemia will shed more light on the clinical profile of these agents when used in this patient population. Conclusions. While dyslipidemia and ED are important concerns for clinicians, there exists a gap that needs to be closed between the number of individuals who have either or both conditions and those who are receiving appropriate therapy based on evidence and patient-driven goals regarding clinical outcomes.

Journal: J Sex Med. 2008 Mar 5
Adapted from PubMed; click here to access full journal article.




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Generalized Anxiety Disorder - New York NY
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Are You Ready to Quit Smoking? - Menlo Park CA
in Menlo Park, CA


Psoriasis - Baltimore MD
in Baltimore, MD


Migraine- Virginia Beach VA
in Virginia Beach, VA


ADHD in Children and Adolescents - Chapel Hill NC
in Chapel Hill, NC


Eczema (Atopic Dermatitis) - NATIONWIDE
in NATIONWIDE,


Osteoarthritis - Virginia Beach VA
in Virginia Beach, VA


Genital Warts - NATIONWIDE
in NATIONWIDE,


Diabetic Neuropathy - DeLand FL
in DeLand, FL


Osteoarthritis of the Knee - NATIONWIDE
in NATIONWIDE,


Healthy Volunteers (Sleep Disorders) - DeLand FL
in DeLand, FL


ADHD in Children and Adolescents - NATIONWIDE
in NATIONWIDE,


 


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