Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erectile dysfunction is a condition that is estimated to affect more than 30 million men in the United States alone. The prevalence of erectile dysfunction is increased with age and is often secondary to diseases such as depression, hypertension and diabetes. Causes of erectile dysfunction include physical injury to the cavernosum and abnormal cerebral and peripheral nervous system functioning. However, many cases of erectile dysfunction are the result of dysfunctional signaling in the cavernosal vasculature. This article will detail the important role of a vasoconstrictor mechanism mediated by the small G-protein RhoA and a downstream serine/threonine kinase, Rho-kinase, in the maintenance of penile flaccidity. Recent evidence demonstrates that inhibition of endogenous Rho-kinase initiates an erectile response in an in vivo rat model. These initial findings introduce a novel potential therapeutic approach for the treatment of erectile dysfunction.
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PMID:Rho-kinase as a potential target for the treatment of erectile dysfunction. 1280 26

The Food & Drug Administration has recently approved, or is in the process of approving newer drugs such as the phosphodiesterase inhibitors and apomorphine to treat men's health issues including erectile dysfunction. Increasing age results in a gradual hypogonadal state in men, for which different novel delivery systems of androgens are currently offered for the symptomatic patient. As such, many men are presenting to healthcare practitioners for the first time. The age of presentation for erectile dysfunction and andropause often overlaps, typically in the fifties and beyond, therefore, it makes sense to screen for erectile dysfunction in andropause patients and vice versa. Erectile dysfunction is usually a harbinger for other illnesses, such as coronary heart disease and depression. The hypogonadal state, likewise, could be a harbinger for other ill health states in men, including obesity, depression, osteoporosis and possibly memory loss. While the newer treatments for erectile dysfunction and andropause are distinctly different and targeted at symptom relief, the presentation of the patient with erectile dysfunction or andropause offers an excellent opportunity for screening for other health states and health education strategies.
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PMID:Novel treatment options for overlapping yet distinct erectile dysfunction and andropause syndromes. 1280 83

The prevalence and correlates of erectile dysfunction (ED) in developing countries are largely unknown. Our objectives were to determine the prevalence and associated factors of ED in three countries (Pakistan, Egypt, Nigeria) that represent very different cultures. Men 35-70y of age seeking primary medical care answered a structured questionnaire adapted to reflect local cultures. Degree of ED was categorized as 'none,' 'mild,' 'moderate,' or 'complete.' The age-adjusted prevalence rates of ED among men attending primary care clinics was 57.4% in Nigeria, 63.6% in Egypt, and 80.8% in Pakistan. Older age, diabetes, peptic ulcers, prostate disease, depression-related symptoms, and caffeine consumption were independently associated with increased prevalence of ED, whereas being moderately active to very active at work (hard physical labor) and during leisure time (strenuous exercise) was associated with half the prevalence of moderate-to-complete ED. Our multicultural study demonstrates that in every country studied, high proportions of men older than age 35 have some degree of ED (57-81%). Both severity and prevalence increase consistently with age. Factors associated with ED are similar, but their distribution differs across countries.
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PMID:Prevalence of erectile dysfunction and its correlates among men attending primary care clinics in three countries: Pakistan, Egypt, and Nigeria. 1282 3

Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erection which is adequate for satisfactory sexual intercourse. It is a significant male health problem affecting approximately 150 million men worldwide. This value is expected to more than double by the year 2025. The incidence of ED increases sharply with age since it is a common cross-cultural denominator, affecting 19 to 64% of men aged 40 to 80 years, both in developing and industrialized countries. Epidemiological studies may underestimate the true dimensions of the problem because of the embarrassment or stigma that is associated with ED. Men with ED may experience diminished self-image and self-esteem, anxiety and fears of rejection, and even depression as psychogenic factors. Pathologic conditions which are commonly encountered in the ageing male (diabetes, hypertension, atherosclerosis, cardiovascular disease, etc) as well as chronic diseases (arthritis, renal and hepatic failure, pulmonary disease) represent a frequent cause of organic ED and are often treated with medications that can interfere with sexual function at central and/or peripheral level. In addition, incorrect lifestyle--i.e. obesity, cigarette smoking, alcohol or drug abuse--may all contribute to the onset of ED. Finally, trauma or surgery affecting either the nervous system or interfering with the blood supply to the penis are associated with increased incidence of ED.
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PMID:Pathology of erection. 1283 29

Sildenafil citrate (Viagra) is a potent orally active cGMP-specific phosphodiesterase type 5 (PDE5) inhibitor that is effective as a peripheral conditioner in the treatment of male erectile dysfunction (ED) of organic, psychogenic or mixed aetiology. Sildenafil is the first effective oral agent in the management of ED that has had a revolutionary impact on management of ED. The present review has been subdivided into five major sections. Based on the most recent peer-reviewed publications, the first section is aimed at critically evaluating PDE5 selectivity as well as the pharmacokinetics and pharmacodynamics of the drug, mainly to assess the best doses for each group of patients (i.e. adult and elderly men). Effectiveness in a broad spectrum ED population is the subject of the second section of the review, principally reporting post-marketing company-independent results. Safety and tolerability are the key concerns of the third section, with a broad consideration of the most commonly reported adverse events. Special attention has been paid to the cardiovascular safety of the drug, chiefly outlining the positive and potentially protective cardiac effects of sildenafil. Moreover, the impact of sildenafil in special patient populations is considered, namely in men complaining of diabetes mellitus, depression, neurological disorders, renal failure and those who have undergone a radical prostatectomy. Sildenafil and the ageing male has been especially underlined. Finally, the review covers a few new potential applications of sildenafil in ED patients with regard to high-dose treatment and combination therapy. The review ends with several considerations regarding the direct and/or indirect impact of sildenafil over quality of life and quality of partnership.
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PMID:Sildenafil in erectile dysfunction: a critical review. 1284 17

The objective of this study was to validate the German translation of the International Index of Erectile Function (IIEF). The IIEF was administered to 59 patients with erectile dysfunction (ED), to 38 patients with Peyronie's disease and to 33 controls. All patients were investigated by standardized German versions of international questionnaires of anxiety, depression, social desirability, quality of partnership, physical complaints and life-satisfaction. The five subscales of the English version, however, could not be replicated. Internal consistency for the complete questionnaire of 15 items was high (Cronbach's alpha=0.95). Based on the total scale and two subscales, we were able to discriminate sexual function between the ED group and the comparison groups. There was no significant correlation between the IIEF scores and anxiety, depression, somatic complaints and life-satisfaction. The German version of the IIEF has found good comprehension, and acceptance by the majority of patients. Its use is somewhat limited by its focus on sexual activity in partnership. In contrast to the English version, it mainly addresses a single factor of sexual function.
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PMID:Validation of the German version of the International Index of Erectile Function (IIEF) in patients with erectile dysfunction, Peyronie's disease and controls. 1290 5

We interviewed a population sample of 2412 men aged 40-70 y in Brazil, Italy, Japan and Malaysia about medical history, lifestyle habits and sexual behavior. Men were classified as having moderate or complete erectile dysfunction (ED) if they reported to be sometimes or never able to achieve and maintain an erection satisfactory for sexual intercourse, respectively. There were 1335 men with no diagnosis of cardiovascular or prostate diseases, diabetes, ulcer or depression, nor taking hormones. The prevalence of ED was 16.1%. ED was associated with age (the risk increased 8% per y), moderate (odds ratio (OR)=2.2) or severe (OR=4.9) lower urinary tract symptoms and smoking (OR=2.3 for >30 cigarettes/day). It was inversely associated with physical activity (OR=0.5) and higher educational levels. Between the ages of 40 and 70 y, almost one in six 'healthy' men is affected by ED. Further research should look at preclinical disease stages and genetic factors.
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PMID:Prevalence of erectile dysfunction and associated factors among men without concomitant diseases: a population study. 1293 52

Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.
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PMID:Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. 1295 49

Sexual dysfunction in general and erectile dysfunction in particular are common problems in the overall population but also frequent symptoms of both untreated and treated depression. Erectile dysfunction and associated sexual dysfunction secondary to antidepressant therapy may occur in up to 90% of men with antidepressant-emergent sexual side effects; accurate assessment of prevalence rates depends on taking a detailed history regarding erectile dysfunction and other aspects of sexual function prior to treatment. In this review, we examine the available data on prevalence of erectile dysfunction and related sexual dysfunction in untreated depression and secondary to antidepressant medications compared with healthy populations. Possible mechanisms involved in serotonin reuptake inhibitor (SRI)-associated erectile dysfunction are examined. The assessment of SRI-associated erectile dysfunction is presented to aid in the management of this important and prevalent side effect. Treatment of antidepressant-associated erectile dysfunction can greatly increase the likelihood that patients will continue the medication that effectively treats their depression.
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PMID:Prevalence of antidepressant-associated erectile dysfunction. 1297 10

The ideal antidepressant would control depression with no adverse effect on sexual function. Erectile dysfunction and other sexual dysfunction associated with antidepressant medication treatment are problems with many antidepressants and can lead to patient dissatisfaction and decreased compliance with treatment. A computerized MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sexual dysfunction. Emphasis was placed on studies with specific sexual function measurements taken before and after treatment and placebo control. Mixed mediator, nonserotonergic antidepressants that block postsynaptic serotonin type 2 receptors (nefazodone, mirtazapine) or that primarily increase dopamine or norepinephrine levels (bupropion) were thought to be good choices for avoiding antidepressant-associated sexual dysfunction or for switching patients in whom antidepressant-associated sexual dysfunction emerged. Comparisons with serotonin reuptake inhibitors (SRIs) have revealed less desire and orgasm dysfunction with nonserotonergic bupropion, less orgasm dysfunction with nefazodone, and superior overall satisfaction with sexual functioning with bupropion or nefazodone. However, most of these studies have design flaws that make evidence-based claims of efficacy difficult to substantiate. Agents proposed for antidote use in antidepressant-associated sexual dysfunction have either not been studied in men or not proved efficacious in randomized placebo-controlled trials. Switching to and augmentation with bupropion or nefazodone have also not clearly shown efficacy in controlled trials and require care and monitoring to avoid SRI discontinuation symptoms and loss of antidepressant efficacy. Few proposed treatment options, apart from avoidance, have proved effective for antidepressant-associated sexual dysfunction, which can have negative consequences on depression management.
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PMID:Antidepressant-related erectile dysfunction: management via avoidance, switching antidepressants, antidotes, and adaptation. 1297 11


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