Arthur L. Burnett

Summary of the recommendations on sexual dysfunctions in men

INTRODUCTION Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being. AIM To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men. METHODS An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures.  New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations. RESULTS Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to mens and womens individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronies disease; and priapism. CONCLUSIONS Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.

Patient-reported urinary continence and sexual function after anatomic radical prostatectomy

OBJECTIVES After radical prostatectomy, the rates for recovery of urinary continence and sexual function reported by experienced surgeons are much higher than the patient-reported outcomes from other centers. It is uncertain whether this represents differences in surgical technique or in the collection of data. This study was performed to determine patient-reported rates of continence and potency after radical prostatectomy performed by an experienced surgeon at a high-volume referral center for the treatment of localized prostate cancer. METHODS Sixty-four men with localized prostate cancer who were potent preoperatively and who had sexual partners underwent anatomic radical prostatectomy between March 1997 and January 1998. A validated disease-targeted quality-of-life survey that assesses function and bother in two organ systems (urinary and sexual) was administered preoperatively and at 3, 6, 12, and 18 months postoperatively. RESULTS Urinary continence, which was defined as wearing no pads, gradually improved during the first 12 months after surgery, and at 1 2 and 18 months, 93% of the patients were dry. Throughout the study, 93% to 98% of the patients characterized their urinary bother as none or small. Potency, defined as the ability to have unassisted intercourse with or without the use of sildenafil, improved gradually, and by 18 months, 86% of patients were potent and 84% considered sexual bother as none or small. Although one third of patients at 18 months were using sildenafil intermittently, only 2 patients were not able to have intercourse without its use. CONCLUSIONS Patient-reported rates of continence and potency after radical prostatectomy performed by an experienced surgeon are high.

Nitric Oxide in the Penis: Physiology and Pathology

PURPOSE The significance of nitric oxide in the physiology of the penis was evaluated, including its role in pathophysiological mechanisms and pathological consequences involving this organ. MATERIALS AND METHODS Animal and human studies pertaining to nitric oxide in the penis were reviewed and analyzed in the context of current descriptions of the molecular biology and physiological effects of this chemical. RESULTS Potential sources of nitric oxide in the penis include neurons, sinusoidal endothelium and corporeal smooth muscle cells. Nitric oxide is perceived to exert a host of functional roles by binding with specific molecular targets. Its synthesis and action in the penis are influenced by many different regulatory factors. CONCLUSIONS Nitric oxide exerts a significant role in the physiology of the penis, operating chiefly as the principal mediator of erectile function. Alterations in the biology of nitric oxide likely account for various forms of erectile dysfunction. The diverse physiological roles of nitric oxide suggest that it may also directly contribute to or cause pathological consequences involving the penis.

Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection.

In the penis, nitric oxide (NO) can be formed by both neuronal NO synthase and endothelial NOS (eNOS). eNOS is activated by viscous drag/shear stress in blood vessels to produce NO continuously, a process mediated by the phosphatidylinositol 3-kinase (PI3kinase)/Akt pathway. Here we show that PI3-kinase/Akt physiologically mediates erection. Both electrical stimulation of the cavernous nerve and direct intracavernosal injection of the vasorelaxant drug papaverine cause rapid increases in phosphorylated (activated) Akt and eNOS. Phosphorylation is diminished by wortmannin and LY294002, inhibitors of PI3-kinase, the upstream activator of Akt. The two drugs also reduce erection. Penile erection elicited by papaverine is reduced profoundly in mice with targeted deletion of eNOS. Our findings support a model in which rapid, brief activation of neuronal NOS initiates the erectile process, whereas PI3-kinase/Akt-dependent phosphorylation and activation of eNOS leads to sustained NO production and maximal erection.

A Critical Analysis of the Current Knowledge of Surgical Anatomy Related to Optimization of Cancer Control and Preservation of Continence and Erection in Candidates for Radical Prostatectomy

CONTEXT Detailed knowledge of the anatomy of the prostate and adjacent tissues is mandatory during radical prostatectomy to ensure reliable oncologic and functional outcomes. OBJECTIVE To review critically and to summarize the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control, erectile function, and urinary continence. EVIDENCE ACQUISITION A search of the PubMed database was performed using the keywords radical prostatectomy, anatomy, neurovascular bundle, fascia, pelvis, and sphincter. Relevant articles and textbook chapters were reviewed, analyzed, and summarized. EVIDENCE SYNTHESIS Anatomy of the prostate and the adjacent tissues varies substantially. The fascia surrounding the prostate is multilayered, sometimes either fused with the prostate capsule or clearly separated from the capsule as a reflection of interindividual variations. The neurovascular bundle (NVB) is situated between the fascial layers covering the prostate. The NVB is composed of numerous nerve fibers superimposed on a scaffold of veins, arteries, and variable amounts of adipose tissue surrounding almost the entire lateral and posterior surfaces of the prostate. The NVB is also in close, cage-like contact to the seminal vesicles. The external urethral sphincter is a complex structure in close anatomic and functional relationship to the pelvic floor, and its fragile innervation is in close association to the prostate apex. Finally, the shape and size of the prostate can significantly modify the anatomy of the NVB, the urethral sphincter, the dorsal vascular complex, and the pubovesical/puboprostatic ligaments. CONCLUSIONS The surgical anatomy of the prostate and adjacent tissues involved in radical prostatectomy is complex. Precise knowledge of all relevant anatomic structures facilitates surgical orientation and dissection during radical prostatectomy and ideally translates into both superior rates of cancer control and improved functional outcomes postoperatively.

The urogenital and rectal pain syndromes

&NA; Pain syndromes of the urogenital and rectal area are well described but poorly understood and underrecognized focal pain syndromes. They include vulvodynia, orchialgia, urethral syndrome, penile pain, prostatodynia, coccygodynia, perineal pain, proctodynia and proctalgia fugax. The etiology of these focal pain syndromes is not known. A specific secondary cause can be identified in a minority of patients, but most often the examination and work‐up remain unrevealing. Although these patients are often depressed, rarely are these pain syndromes the only manifestation of a psychiatric disease. This review article presents an overview of the neuroanatomy of the pelvis, which is a prerequisite to trying to understand the chronic pain syndromes in this region. We then discuss the clinical presentation, etiology and differential diagnosis of chronic pain syndromes of the urogenital and rectal area and review treatment options. The current knowledge of the psychological aspects of these pain syndromes is reviewed. Patients presenting with these pain syndromes are best assessed and treated using a multidisciplinary approach. Currently available treatment options are empirical only. Although cures are uncommon, some pain relief can be provided to almost all patients using a multidisciplinary approach including pain medications, local treatment regimens, physical therapy and psychological support, while exercising caution toward invasive and irreversible therapeutic procedures. Better knowledge of the underlying pathophysiological mechanisms of the urogenital and rectal pain syndromes is needed to allow investigators to develop treatment strategies, specifically targeted against the pathophysiological mechanism.

The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease

The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panels recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each mans cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.

Immunohistochemical Localization of Nitric Oxide Synthase in the Autonomic Innervation of the Human Penis

An improved understanding of the physiology of penile erection has resulted from recent evidence that implicates nitric oxide as the principal mediator of erectile function. Previously, the neuroanatomy of erection in man was established with descriptions of the autonomic innervation of the pelvic organs and external genitalia. The basis upon which novel physiological concepts of erection relate to earlier neuroanatomical principles remains to be determined. In the present study these relationships were explored with nitric oxide synthase immunohistochemistry and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry of select pelvic tissue specimens obtained from 4 men (3 at radical prostatectomy and 1 at autopsy). Nitric oxide synthase, the enzyme that catalyzes nitric oxide production, was identified in discrete neuronal locations, including the pelvic plexus, cavernous nerves and their terminal endings within the corporeal erectile tissue, branches of the dorsal penile nerves and nerve plexuses in the adventitia of the deep cavernous arteries. This distribution of nitric oxide synthase-containing nerves suggests that nitric oxide neuronally modulates local vascular smooth musculature of the penis. On this basis, nitric oxide is identified as a neuronal mediator of penile erection in man.

Immunohistochemical description of nitric oxide synthase isoforms in human clitoris

PURPOSE Our aim was to identify and localize nitric oxide synthase isoforms in the human clitoris in support of the hypothesis that nitric oxide mediates erectile function in this organ. MATERIALS AND METHODS Nitric oxide synthase immunohistochemistry studies specific for neuronal, inducible and endothelial isoforms of the enzyme were performed on human clitoral tissue obtained from 4 patients (3 with female pseudohermaphroditism and 1 with true hermaphroditism) at feminizing genitoplasty and from 1 phenotypically normal woman at autopsy. RESULTS Neuronal nitric oxide synthase immunoreactivity was detected in nerve bundles and fibers coursing within the glans clitoris and corpora cavernosa of the clitoris, predominating in the latter tissue. Specific inducible nitric oxide synthase immunoreactivity was not identified. Endothelial nitric oxide synthase immunoreactivity was detected in vascular and sinusoidal endothelium of these tissues with a predominance in the glans clitoris. CONCLUSIONS The presence and anatomical localizations of nitric oxide synthase isoforms in the human clitoris indicate that nitric oxide is generated in this organ. These data suggest that nitric oxide may be involved in the erectile physiology of the clitoris as a modulator of clitoral smooth muscle activity. Functional studies are required to support this hypothesis.

Effects of nitric oxide on human and canine prostates

OBJECTIVES To determine whether nitric oxide (NO) is a mediator of prostatic smooth muscle activity. METHODS Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of human and canine prostate. RESULTS EFS alone elicited frequency-dependent contractions in preparations of human and canine prostates. The greatest contractile activity was achieved at 30 Hz. In the presence of 10(-5) M guanethidine (GUA) and 2 x 10(-6) M atropine (ATR), EFS elicited relaxation of canine prostate strips relative to baseline tension. A weak biphasic response consisting of initial relaxation and subsequent contraction relative to baseline tension was observed in the human prostate strips exposed to similar conditions. The smooth muscle activity observed in the presence of GUA plus ATR was attributed to nonadrenergic, noncholinergic (NANC) nerve transmission. 10(-4) M L-NG-nitroarginine methylester (NAME) significantly increased EFS-elicited NANC smooth muscle activity both in human and canine prostates. L-arginine, 10(-2) M, reversed the effect of L-NAME in human and canine prostates. Sodium nitroprusside, 10(-4) M, a donor of NO, caused relaxation of both human and canine prostates. The mean magnitude of the relaxant response/cross-sectional area in human prostate (2.64 +/- 0.4 g/cm2) was significantly greater than in the canine prostate (1.09 +/- 0.17 g/cm2) (P < 0.005). CONCLUSIONS These results provide compelling evidence that NO plays a role in mediating contractile function of human and canine prostates.