Surgical approaches for advanced Peyronie's disease patients.

Surgical therapy for Peyronie's disease (PD) is reserved for patients with severe penile deformity that fails to improve with medical treatment and impedes sexual intercourse. The surgical treatment of PD consists of either correction of the penile deformity or insertion of a penile prosthesis in patients with concomitant erectile dysfunction (ED). Plaque incision/excision combined with grafting procedures or plication techniques are suitable in Peyronie's patients having an adequate penile vascular supply. When patients with Peyronie's disease have both penile deformity and ED, penile prosthesis implantation with or without excision or incision of the tunica is the current standard of care.

Premature ejaculation. 2. Classification and diagnosis.

A classification of premature ejaculation must distinguish between hyper-orgasmic or hypo-orgasmic, between situational or global; furthermore, it must define whether it occurs during vaginal penetration only or also in masturbation, and must study its latency periods and its relationships to the erectile dysfunction, with which it is often associated. Tests with local anesthetics, biothesiometry and penile vibrotactile stimulation, integrated with a thorough study of the general and psycho-sexual history, provide a good diagnostic classification that makes the therapeutic approach appropriate.

The effects of smoking on the reproductive health of men.

This article discusses the impact smoking can have on men's sexual and reproductive health. There is evidence to suggest that smoking can result in alterations of the male sex hormones and is a key cause of and contributor to erectile dysfunction. Smoking can therefore endanger the man's ability to have a family and enjoy sexual activity. A reduction in sperm quality and a reduced response to fertility treatments has also been linked with those men who smoke. The damaging effects of smoking are apparent throughout the lifespan of a smoker. The benefits associated with cessation of smoking are wide and varied with respect to the reproductive health of men; these benefits can include a reduction in the risk of male impotence and an improvement in sexual potency.

Cavernosal nerve mapping: current data and applications.

Although nerve-sparing prostatectomy is widely practised, the results with respect to preserving potency often do not meet expectations. The concept of intraoperative cavernosal nerve stimulation is reasonable. Data that link the response to Sildenafil Citrate ( Viagra ) after prostatectomy with bilateral nerve sparing has increased the importance of optimizing nerve sparing. The cavernosal nerves are often difficult to visualize and may have a variable course. A tumescent response to nerve stimulation can be shown consistently; the response may be subtle, and characterized by a minimal increase in penile circumference and blood flow. Immediately after prostatectomy, proximal nerve stimulation identifies whether neural continuity has been maintained, and is predictive of recovery of erectile function. The Cavermap system (Uromed Corporation, Boston, MA, USA) was developed to permit intraoperative nerve stimulation with tumescence monitoring. An initial phase 2 and subsequent phase 3 single-blinded, randomized, multicentre study that compared Cavermap-assisted prostatectomy with conventional nerve sparing showed a significant benefit in terms of the duration of nocturnal tumescence at 1 year. Other approaches are being explored, including incorporating the device into sural or genito-femoral nerve grafting, use of nerve stimulation during cystectomy or abdominal-perineal resection, and direct corpus cavernosal pressure monitoring during nerve stimulation. These approaches warrant further evaluation. erectile dysfunction Priapism--a review of the medical management.

Priapism is characterised by the presence of prolonged, often painful penile erection in the absence of a sexual stimulus. This rare condition has a range of aetiologies, but is most common following self-administration of injection therapy for impotence. Priapism may be classified into high- and low-flow states. Low-flow priapism is an emergency ischaemic condition requiring prompt recognition and treatment to avoid devastating long-term complications of erectile dysfunction. Wide-ranging medical therapies are covered in this review. Diagnostic and treatment algorithms are suggested in light of the current available literature.

Specific aspects of erectile function in urology/andrology.

The urologist/andrologist is the specialist responsible for diagnosis and treatment of health problems related to the genitourinary tract, and his or her participation in comprehensive care for a patient with erectile dysfunction (ED) is fundamental and often indispensable. The urologists/andrologists should characterize the origin of ED because of their knowledge and familiarity of all diagnostic tests and second- and third-line therapy. The origin of ED is important to determine for various reasons, such as young people suitable for etiologic treatment, medicolegal reasons, or patients' wishes for a better understanding of their condition. A review of the diagnostic tests available as well as indications for second- and third-line therapy is presented. The close relationship between ED and urological disorders, such as benign prostatic hyperplasia, prostate cancer and their treatments, and renal failure, in association with penile conditions like Peyronie's disease, priapism, and possible androgen deficiency in men older than 50 years, places the urologist at the center of integrated treatment of male ED.

Pathology of erection.

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.

Premature ejaculation. 2. Classification and diagnosis.

A classification of premature ejaculation must distinguish between hyper-orgasmic or hypo-orgasmic, between situational or global; furthermore, it must define whether it occurs during vaginal penetration only or also in masturbation, and must study its latency periods and its relationships to the erectile dysfunction, with which it is often associated. Tests with local anesthetics, biothesiometry and penile vibrotactile stimulation, integrated with a thorough study of the general and psycho-sexual history, provide a good diagnostic classification that makes the therapeutic approach appropriate. erection problems Central oxytocinergic neurotransmission: a drug target for the therapy of psychogenic erectile dysfunction.

A group of oxytocinergic neurons originating in the paraventricular nucleus of the hypothalamus and projecting to extrahypothalamic brain areas (e.g. hippocampus, medulla oblongata and spinal cord) control penile erection. Activation of these neurons by dopamine and dopamine agonists, excitatory amino acids (N-methyl-D-aspartic acid) or oxytocin itself, or by electrical stimulation leads to penile erection, while their inhibition by GABA and GABA agonists or by opioid peptides and opiate-like drugs inhibits this sexual response. The activation of oxytocinergic neurons in the paraventricular nucleus by dopamine, oxytocin and excitatory amino acids is apparently secondary to the activation of nitric oxide (NO) synthase. NO in turn activates, by a mechanism that is as yet unidentified, the release of oxytocin from oxytocinergic neurons in extrahypothalamic brain areas. Several peptide analogues of hexarelin, a growth hormone releasing peptide, also induce penile erection when injected into the paraventricular nucleus and, to a lesser extent, systemically, apparently by acting on a specific receptor to activate oxytocinergic neurons as shown for the above drugs and oxytocin. Paraventricular oxytocinergic neurons and mechanisms similar to those reported above are also involved in the expression of penile erection in physiological contexts, namely when penile erection is induced in the male by the presence of an inaccessible receptive female, which is considered a model for psychogenic impotence in man, as well as during copulation. These findings show that paraventricular oxytocinergic neurons projecting to extra-hypothalamic brain areas and to the spinal cord are a likely target for the treatment of erectile dysfunction of central origin.

Epidemiology of erectile dysfunction.

Following the landmark Massachusetts Male Aging Study (MMAS) that provided the first relatively unbiased study of the epidemiology of erectile dysfunction (ED), a number of additional studies were carried out in the U.S. and around the world. The studies vary in quality because they used different definitions of ED, different assessment instruments, different and sometimes biased sources of populations, inadequate response rates to questionnaires and interviews, cultural disparities in willingness to discuss sexual issues, and differing interpretations of the results. Nevertheless, the studies demonstrated similar levels of ED by age and an exponential rise with age. They also generally confirmed the conditions that correlated with ED in the MMAS, namely, diabetes, hypertension, coronary artery disease, prostate cancer therapy, and depression. These were exacerbated by cigarette smoking.

Intranasal apomorphine. Nastech Pharmaceutical.

Nastech Pharmaceutical Co Inc is developing a nasal formulation of apomorphine for the potential treatment of erectile dysfunction and female sexual dysfunction.

Efficacy and tolerability of Tadalafil ( Cialis ) , a novel phosphodiesterase 5 inhibitor, in treatment of erectile dysfunction.

Advances in molecular biology and protein chemistry, along with increasing understanding of the mechanisms of penile erection, have spurred development of pharmacologic approaches to the treatment of erectile dysfunction (ED). The next generation of oral agents includes Tadalafil ( Cialis ) , a potent, highly selective phosphodiesterase 5 inhibitor. In vitro studies have shown that Tadalafil ( Cialis ) enhances relaxation of trabecular smooth muscle, and clinical trials have supported its efficacy and tolerability in a broad population of men with ED. The effect of Tadalafil ( Cialis ) in enhancing the erectile response to sexual stimulation is relatively rapid in onset and lasts for >or=24 hours. The ability of patients with ED treated with Tadalafil ( Cialis ) to achieve improved erectile function is demonstrated by significantly increased subjective measures of penetration ability, successful intercourse, and sexual satisfaction. Partners have expressed similar or higher levels of satisfaction with the results of treatment. Men with ED of psychogenic, organic, or mixed etiology and in a range from mild to severe have experienced significant improvment with Tadalafil ( Cialis ) treatment. Response to treatment in men with diabetes has been robust and not affected by disease severity. Tadalafil ( Cialis ) has been well tolerated. Adverse events have generally been mild or moderate and have abated with continued treatment. Headache and dyspepsia have been most frequently reported. Changes in color vision have been rare (<0.1%) with Tadalafil ( Cialis ) across all clinical trials. Tadalafil ( Cialis ) appears to be a safe and effective treatment for men with ED. erectile dysfunction Disorders of ejaculation.

The physiology of ejaculation includes emission of sperm with the accessory gland fluid into the urethra, simultaneous closure of the urethral sphincters, and forceful ejaculation of semen through the urethra. Emission and closure of the bladder neck are primarily alpha-adrenergically mediated thoracolumbar sympathetic reflex events with supraspinal modulation. Ejaculation is a sacralspinal reflex mediated by the pudendal nerve. The most common ejaculation disorder is premature ejaculation, but there is little agreement regarding the definition of this disorder or its etiology, diagnosis, and treatment options. Premature ejaculation is in fact classically considered psychogenic in nature. However, recent data have demonstrated that prostatic inflammation/infection has been found with high frequency in premature ejaculation, suggesting a role of prostatic pathologies in the pathogenesis of some cases of failure of ejaculatory control. Rarer disorders are emission and ejaculation failure and urine contamination of semen. The new use of diagnostic procedures and the availability of pharmacological aids place this topic in the mainframe of medical sexology.

Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction.

The scientific rationale of pharmacologically inhibiting phosphodiesterase type 5 (PDE5) in the treatment of erectile dysfunction (ED) is reviewed. Published literature on the nitric oxide-cyclic guanosine monophosphate (cGMP) pathway for penile erection and on PDE5 inhibition using Sildenafil Citrate ( Viagra ) as the model for pharmacologic PDE5 inhibition are assessed. The key second messenger in the mediation of penile erection is cGMP. PDE5 is the predominant PDE in the corpus cavernosum, and cGMP is its primary substrate. Therefore, in men with ED, elevation of cGMP in corpus cavernosal tissue via selective inhibition of cGMP-specific PDE5 is a means of improving erectile function at minimal risk of adverse events. This approach is validated by the clinical efficacy and safety of sildenafil, the pioneering drug for selective PDE5 inhibitor therapy for ED. Sildenafil Citrate ( Viagra ) exhibits inhibitory potency against PDE5 and a 10-fold lower dose-related inhibitory potency against rod outer segment PDE6, the predominant PDE in the phototransduction cascade in rods. Thus, its pharmacologic profile is predictable, with close correlation between pharmacodynamic and pharmacokinetic properties. Clinically, Sildenafil Citrate ( Viagra ) improves erectile function in a large percentage of men with ED. The most common adverse events are due to PDE5 inhibition in vascular and visceral smooth muscle; similar adverse events are expected during therapeutic use of all PDE5 inhibitors. As free Sildenafil Citrate ( Viagra ) plasma concentrations approach concentrations sufficient to inhibit retinal PDE6, usually at higher therapeutic doses, transient, reversible visual adverse events can occur, albeit infrequently. Selective inhibition of PDE5 is a rational therapeutic approach in ED, as proved by the clinical success of sildenafil.

Trazodone for erectile dysfunction: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of trazodone in the treatment of erectile dysfunction (ED) in a meta-analysis. METHODS: The data sources used were Medline and the Cochrane Library databases (January 1966 to May 2002), bibliographies of retrieved articles and review articles, and conference proceedings and abstracts. Trials were eligible for inclusion in the review if they included men with ED, compared trazodone with a control, were randomized, of > or = 7 days' duration and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. RESULTS: Six trials (comprising 396 men) met the inclusion criteria; they consisted of heterogeneous populations, were small, brief and in some cases methodologically weak. Three of the six trials showed an apparently clinically meaningful benefit of trazodone for ED compared with placebo, the differences being statistically significant in two. In pooled results, trazodone monotherapy appeared more likely than placebo to lead to a 'positive treatment response', although this difference was not statistically significant (37% vs 20%; relative benefit increase, 1.6; 95% confidence interval, CI, 0.8-3.3). Subgroup analyses suggested that men with psychogenic ED might be more likely to benefit from trazodone than those with mixed or physiological ED. The efficacy of trazodone also appeared greater at higher doses (150-200 vs 50 mg/day). Men randomized to trazodone were not significantly more likely than those receiving placebo to withdraw for any reason or for an adverse event, or to have specific adverse events, but wide CIs could not exclude a greater risk of these adverse outcomes with trazodone. Specific adverse events with trazodone included dry mouth (19%), sedation (16%), dizziness (16%) and fatigue (15%). CONCLUSION: Trazodone may be helpful in men with ED, possibly more so at higher doses, and in men with psychogenic ED. Future high-quality trials should compare trazodone with placebo and other therapies in men with depression and psychogenic ED.

Neurochemical aspects of the sexual response cycle.

What drives the human sexual response cycle? The human sexual response cycle is a highly complex phenomenon that encompasses many transmitters and transmitter systems centrally and peripherally. The endocrine system is also intricately involved in the brain and in the periphery organs. Integration of these systems is a function of the nervous system that ultimately produces a vast array of cognitive, emotional, physiological, and behavioral responses. Therefore, it is not surprising that a disturbance in even a single system will lead to dysfunction in one or more phases of the sexual response cycle. This article highlights the complex roles the aminergic system plays along with key hormones that are equally involved. The article also points out how rudimentary and fragmented our knowledge is in this field and how few controlled studies are available. The potential for development of specific agents that target selective sexual dysfunctions is exemplified in sildenafil, the first such agent ever to be brought to market.