Gregory A. Broderick

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.

International Society for Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation.

INTRODUCTION Over the past 20 years our knowledge of premature ejaculation (PE) has significantly advanced. Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the disorder, assessing the psychosocial impact on patients and partners, designing validated diagnostic and outcome measures, proposing new pharmacologic strategies and examining the efficacy, safety and satisfaction of these new and established therapies. Given the abundance of high level research it seemed like an opportune time for the International Society for Sexual Medicine (ISSM) to promulgate an evidenced-based, comprehensive and practical set of clinical guidelines for the diagnosis and treatment of PE. AIM Develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. Method.  Review of the literature. RESULTS This article contains the report of the ISSM PE Guidelines Committee. It affirms the ISSM definition of PE and suggests that the prevalence is considerably lower than previously thought. Evidence-based data regarding biological and psychological etiology of PE are presented, as is population-based statistics on normal ejaculatory latency. Brief assessment procedures are delineated and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. Therefore, it is strongly recommended that these guidelines be re-evaluated and updated by the ISSM every 4 years.

Priapism: pathogenesis, epidemiology, and management.

INTRODUCTION Priapism describes a persistent erection arising from dysfunction of mechanisms regulating penile tumescence, rigidity, and flaccidity. A correct diagnosis of priapism is a matter of urgency requiring identification of underlying hemodynamics. AIMS To define the types of priapism, address its pathogenesis and epidemiology, and develop an evidence-based guideline for effective management. METHODS Six experts from four countries developed a consensus document on priapism; this document was presented for peer review and debate in a public forum and revisions were made based on recommendations of chairpersons to the International Consultation on Sexual Medicine. This report focuses on guidelines written over the past decade and reviews the priapism literature from 2003 to 2009. Although the literature is predominantly case series, recent reports have more detailed methodology including duration of priapism, etiology of priapism, and erectile function outcomes. MAIN OUTCOME MEASURES Consensus recommendations were based on evidence-based literature, best medical practices, and bench research. RESULTS Basic science supporting current concepts in the pathophysiology of priapism, and clinical research supporting the most effective treatment strategies are summarized in this review. CONCLUSIONS Prompt diagnosis and appropriate management of priapism are necessary to spare patients ineffective interventions and maximize erectile function outcomes. Future research is needed to understand corporal smooth muscle pathology associated with genetic and acquired conditions resulting in ischemic priapism. Better understanding of molecular mechanisms involved in the pathogenesis of stuttering ischemic priapism will offer new avenues for medical intervention. Documenting erectile function outcomes based on duration of ischemic priapism, time to interventions, and types of interventions is needed to establish evidence-based guidance. In contrast, pathogenesis of nonischemic priapism is understood, and largely attributable to trauma. Better documentation of onset of high-flow priapism in relation to time of injury, and response to conservative management vs. angiogroaphic or surgical interventions is needed to establish evidence-based guidance.

An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation

To develop a contemporary, evidence‐based definition of premature ejaculation (PE).

Endoluminal magnetic resonance imaging in the evaluation of urethral diverticula in women

OBJECTIVES Accurate determination of the size and extent of urethral diverticula can be important in planning operative reconstruction and repair. Voiding cystourethrography (VCUG) is currently the most commonly used study in the preoperative evaluation of urethral diverticula. We reviewed our experience with the use of endoluminal (endorectal or endovaginal) magnetic resonance imaging (eMRI) in these patients as an adjunctive study to VCUG to evaluate whether the MRI provided anatomically important information that was not apparent on VCUG. METHODS A retrospective analysis of all patients with a clinical diagnosis of urethral diverticula undergoing MRI at a single institution was performed. Patients were evaluated with history, physical examination, cystoscopy, VCUG, and eMRI. Endoluminal MRI was retrospectively compared to VCUG with respect to size, extent, and location found at operative exploration. RESULTS Twenty-seven consecutive patients underwent endorectal or endovaginal coil MRI in the evaluation of suspected urethral diverticula. Twenty patients subsequently had attempted transvaginal operative repair of the diverticulum. In 2 patients, eMRI demonstrated a urethral diverticulum, whereas VCUG did not. Operative exploration in these patients revealed a urethral diverticulum. In 14 of 27 patients, the VCUG underestimated the size and complexity of the urethral diverticulum as compared to eMRI and operative exploration. In 13 of 27 patients, the size, location, and extent of the urethral diverticulum on VCUG correlated well with the eMRI and/or operative findings. CONCLUSIONS We have found endorectal and endovaginal coil MRI to be extremely accurate in determining the size and extent of urethral diverticula as compared to VCUG. This information can be critical when planning the approach, dissection, and reconstruction of these sometimes complex cases.

Systematic transperineal ultrasound guided template biopsy of the prostate in patients at high risk.

PURPOSE A negative biopsy result does not necessarily equate with cancer in specific high risk groups. We describe an alternative systematic biopsy technique for evaluating this subgroup of patients. MATERIALS AND METHODS From March 1997 to May 1999 a total of 88 men underwent systematic ultrasound guided biopsy using the transperineal template technique. All patients had undergone at least 1 and 75 (85%) had undergone 2 or more previous sets of biopsies. In addition, study inclusion required high risk parameters, including prostate specific antigen (PSA) velocity greater than 0.75 ng./ml., PSA greater than 10 ng./ml. or previous prostatic intraepithelial neoplasia on biopsy, and/or atypical small cell acinar proliferation. RESULTS Cancer was identified in 38 of the 88 men (43%) in this high risk subgroup undergoing repeat biopsy. A mean of 15.1 previous biopsy cores had been obtained. The most common biopsy grade was 6 (range 4 to 9). Adenocarcinoma was identified in the transition zone area in 29 of 38 cases (76%), including 15 (39%) in which disease was detected in the transition zone only. Persistent PSA acceleration greater than 0.75 ng./ml. was the major indicator for transperineal template biopsy in 83 of the 88 patients (94%). The only significant independent variable predictive of positive biopsy was prostate volume. Mean prostate volume in the positive and negative biopsy groups was 48 and 73 gm., respectively (p <0.001). Complications were rare and self-limiting, consisting primarily of hematuria and urinary retention requiring overnight catheterization in 2 patients. CONCLUSIONS Systematic transperineal template biopsy of the prostate is a safe and precise repeat biopsy technique in patients who remain at high risk for adenocarcinoma.

Anoxia and Corporal Smooth Muscle Dysfunction: A Model for Ischemic Priapism

The hemodynamics of penile flaccidity, erection and detumescence requires corporal smooth muscle to function across a wide variation in pO2. The present study describes the effect of anoxia on corporal smooth muscle response to field stimulation and pharmacologic agonists and antagonists of erection. The response of isolated strips of rabbit corpus cavernosal tissue to field stimulation, phenylephrine, bethanechol, ATP and KCL was determined under oxygenated and anoxic conditions. The results can be summarized as follows: 1) Anoxia eliminated spontaneous contractile activity and reduced basal tissue tension to a minimum. 2) Neither field stimulation nor pharmacological agents (ATP, bethanechol, isoproterenol) could relax basal tension below that induced by anoxia alone. 3) Under anoxic conditions alpha-adrenergic agonists produced poorly sustained phasic contractile responses; anoxia eliminated tonic contractile responses to phenylephrine. 4) In normoxic conditions field stimulation of smooth muscle precontracted with phenylephrine produced frequency-dependent graded relaxations; under anoxic conditions field stimulation yielded contractile responses at all frequencies. Our data suggest that corporal smooth muscle tone, spontaneous contractile activity, the contractile response to alpha-agonists and field stimulated relaxation depend on the state of corporal oxygenation. The inability of alpha-stimulation to induce a tonic contraction of corporal smooth muscle under anoxia in vitro parallels the failure of penile injection of alpha-adrenergic agonists to relax ischemic priapism.

Collagen injection therapy for post-radical retropubic prostatectomy incontinence : Role of valsalva leak point pressure

PURPOSE We retrospectively evaluated the role of Valsalva leak point pressure as a predictor of successful management of post-radical retropubic prostatectomy incontinence with collagen injection. MATERIALS AND METHODS Urodynamic studies and Valsalva leak point pressures of 31 men who received retrograde collagen injection for post-radical retropubic prostatectomy incontinence were reviewed. Patients were interviewed before and after treatment to assess pad use and the American Urological Association quality of life index (scale 0 to 6). Parameters for success were postoperative quality of life score 3 or less or 50% or greater decrease in pad use and that the patient would recommend collagen therapy to someone else. RESULTS Of 31 patients 11 (35%) met the criteria for success, 2 (6%) were completely dry and 9 (29%) were improved. Successfully treated patients had a mean Valsalva leak point pressure of 64.0 cm. water compared to 42.2 cm. water in the failure group (p <0.01). Of patients with Valsalva leak point pressure of 60 cm. water or greater, 70% responded favorably to collagen injection (positive predictive value), while 81% with Valsalva leak point pressure less than 60 cm. water had treatment failure (negative predictive value) (p <0.02). There were no other statistically significant differences between those successfully treated with collagen injection and those in whom treatment failed, including mean age (62.7 to 68.1 years), mean volume of collagen (26.1 to 28.9 ml.), mean number of treatment sessions (2.45 to 2.65), mean followup (14.9 to 15.1 months), preoperative quality of life score (5.1 to 4.9), and preoperative pads per day (4.0 to 3.37). CONCLUSIONS Our data suggest that collagen injection improves 35% but cures a minority of patients (less than 10%) with post-radical retropubic prostatectomy incontinence. A pretreatment Valsalva leak point pressure of 60 cm. water or greater has high predictive value for a beneficial outcome after collagen injection. We propose a role for Valsalva leak point pressure to select men cost-effectively with post-radical retropubic prostatectomy incontinence for therapy with collagen injection.

Erectile function and quality of life after interstitial radiation therapy for prostate cancer

Few studies have evaluated erectile function after interstitial radiation therapy for localized prostate cancer. Using a validated quality of life questionnaire, we assessed post-treatment erectile function and its relationship to treatment satisfaction and quality of life. We retrospectively reviewed the records of 171 consecutive patients who underwent Pd-103 or I-125 brachytherapy for prostate cancer between December 1992 and June 1998. Seventy percent of patients received neoadjuvant androgen deprivation therapy. All patients were mailed a validated questionnaire assessing sexual function and overall quality of life (UCLA Prostate Cancer Index and SF-36). Sixty-seven percent of all questionnaires were available for evaluation (114/171). The mean age was 69.1 y with a mean follow-up of 23 months (range 4–72, median 24). Seventy-one percent of patients (81/114) had pre-treatment erections sufficient for sustained vaginal penetration. Of these patients, potency was maintained in 49% of men (40/81). An additional 26% had erections firm enough for foreplay but not penetration (21/81). Erectile dysfunction rates were significantly lower in younger patients (48%) vs older patients (55%). There was no difference in post-treatment potency between men who received neoadjuvant hormonal therapy and those who did not (P>0.05). In addition, there were no differences in physical function (86, scale 0–100), general health perception (78), emotional well-being (83), energy/fatigue (74), and overall satisfaction (84) between men with erectile dysfunction and those without.In summary, two years following brachytherapy 25% of patients complained of complete (20/81) or partial (26%, 21/81) erectile dysfunction, for an overall rate of 51% (41/81). Short-term neoadjuvant hormonal therapy (<3–6 months) did not increase the likelihood of post-treatment erectile dysfunction. Interestingly, overall satisfaction rates among brachytherapy patients were high (84/100) and surprisingly did not correlate with post-treatment sexual function.

Duplex Doppler ultrasonography: Noninvasive assessment of penile anatomy and function

E RECTION is a complex hemodynamic event regulated by the tone of smooth muscle composing the cavernous arterioles, venules, and sinusoids. In the flaccid penis baseline ot-adrenergic stimulation maintains the smooth muscle of the cavernous arterioles and corporal sinusoids contracted. Although vascular resistance to inflow is elevated in the flaccid state, venular outflow is unrestricted. Regulation of venous outflow from the penis appears to be a passive phenomenon; venules draining the sinusoidal spaces coallesce into a plexus below the outer fibroelastic tunica of the paired corporal bodies. Egress from the subtunical venular plexus is via emissary veins exiting perpendicularly through the tunica albuginea into the deep dorsal vein or directly via the cavernous and crural veins at the base of the corporal bodies. 1 Erection is initiated by at least three welldocumented neuropharmacologic stimulants2-5: 1. Inhibition or decrease in excitation of postsynaptic or-1 receptors on cavernous and arteriolar muscle. 2. Increasing cholinergic transmission: Acetylcholine acting on postganglionic adrenergic fibers inhibits norepinephrine release. Acetylcholine mediates the release of endothelial relaxant factor, which rapidly diffuses to the smooth muscle of arteriolar walls. 3. Direct nonadrenergic noncholinergic (NANC) transmission: Several substances have previously been considered to be the NANC erection transmitter (vasoactive intestinal peptide, substance P, prostaglandin E, adenosine triphosphate). Nitric oxide is currently believed to be the principal regulator of NANC corporal relaxation; penile smooth muscle relaxation is initiated by intracellular accumulation of cyclic guanosine monophosphate (cGMP). Tumescence follows a decrease in corporal smooth muscle tone and vascular resistance; arterial inflow increases and the corpora sinusoids distend with oxygenated blood. The expanding sinusoids compress the subtunical plexus and restrict venous outflow. Approximately 90% of systemic arterial pressure is transmitted to the corporal bodies as a result of increased arterial inflow and veno-occlusion. Observations of pudendal and cavernous arterial inflows and intracorporal pressures in the animal model reveal that erection can be divided into six phases: flaccid, latent, tumescence, full erection, rigid erection, and detumescence. 6 Figure 1 shows that cavernous nerve stimulation produces erection with intracorporal pressure reaching 100 mmHg during full erection and transiently exceeding 100 mmHg during the rigid phase. Contemporary clinical studies using intracavernous agents (papaverine, phentolamine, prostaglandin El, and vasoactive intestinal peptide) have revealed that impotence is most often organic in origin and predominantly vasculogenic in etiology 7-11 We believe that color duplex Doppler ultrasound (CDDU) following intracorporal vasoactive stimulation is the most reliable and least invasive means of screening for vasculogenic erectile failure and for selecting patients for more invasive tests of pathologic corporal inflow or outflow. The principles, techniques, and most recent criteria for duplex Doppler penile blood flow are reviewed.