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Erectile dysfunction (ED) or impotence is estimated to affect around 20-30 million men in the United States (Rhoden et al, 2002). Vascular etiology is purported to be the most prevalent cause of ED in the elderly population, with venogenic ED being the most common subtype (Shafik et al, 2007; Rebonato et al, 2014). A patient, who developed severe venogenic ED, was referred to interventional radiology after ineffective pharmaceutical treatments. Selective embolization of bilateral external and internal pudendal veins was performed through accessing the deep dorsal vein of penis. Subsequent venogram verified successful embolization with stasis within the outflow of the deep dorsal vein of penis. Close to 6 weeks after the procedure, the patient purports to be able to achieve approximately 65% of full penile erection and complete penile erection with penile stimulation and 0.25 mL injection of alprostadil after 25 minutes.

Plication procedures for the correction of Peyronie’s disease (PD) curvature are management options for PD patients. There are basically three types of procedures: excisional corporoplasty, incisional corporoplasty, and plication-only. This review is a compilation of English literature, peer-reviewed, published articles addressing these types of operations for Peyronie’s curvature correction, not congenital curvature. According to the urology literature, this surgical type was initially used for correction of curvature associated with hypospadias repair or congenital penile curvature. The procedures also, for the most part, historically became an alternative for plaque excision and graft repair, because of the difficulty with such repairs and the often-resultant erectile dysfunction (ED). A brief section traces some of the origins of these various repairs, followed by a brief section on the selection criteria for these types of surgery for the patient with PD penile curvature. We also review the significant articles in which the three types were presented with modifications. Finally, several articles that compare the various surgical repairs are summarized in the order that they appear in the literature. These types of surgery have become a mainstay for the surgical correction of penile curvature due to PD.

BACKGROUND Approximately 70% of all suicides in patients aged >60 years are attributed to physical illness, with higher rates noted in patients with cancer. The purpose of the current study was to characterize suicide rates among patients with genitourinary cancers and identify factors associated with suicide in this specific cohort. METHODS Patients with prostate, bladder, kidney, testis, and penile cancer were identified in the Surveillance, Epidemiology, and End Results database (1988-2010). Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated for each anatomic site. Multivariable logistic regression models generated odds ratios (ORs) for the identification of factors associated with suicide for each malignancy. RESULTS There were 2268 suicides identified among 1,239,522 individuals with genitourinary malignancies observed for 7,307,377 person-years. The SMRs for patients with cancer were 1.37 for prostate cancer (95% CI, 0.99-1.86), 2.71 for bladder cancer (95% CI, 2.02-3.62), 1.86 for kidney cancer (95% CI, 1.32-2.62), 1.23 for testis cancer (95% CI, 0.88-1.73), and 0.95 for penile cancer (95% CI, 0.65-1.35). On multivariable analysis, male sex was found to be associated with odds of suicide among patients with bladder cancer (OR, 6.63) and kidney cancer (OR, 4.98). Increasing age was associated with suicide for patients with prostate, bladder, and testis cancer (OR range, 1.03-1.06). Distant disease was associated with suicide in patients with prostate, bladder, and kidney cancer (OR range, 2.82-5.43). Among patients with prostate, bladder, and kidney cancer, African American patients were less likely to commit suicide compared with white individuals (OR range, 0.26-0.46). CONCLUSIONS Suicide in patients with genitourinary malignancies poses a public health dilemma, especially among men, the elderly, and those with aggressive disease. Clinicians should be aware of risk factors for suicide in these patients. Cancer 2015;121:1864–1872. © 2015 American Cancer Society.

The history of sexual medicine as a science is relatively new. This is no attempt to go back into ancient history to examine early practices for treating sexual disorders but starts with the modern era with the work of Masters and Johnson and Kinsey. It would be encyclopedic to include the details from all the contributors who have made this field now science but I have attempted to divide the topic in areas that have made this modern science and to include citations that have comprehensive reference sections that include major contributors. Each of the areas that I have divided this chapter could be a volume in itself. I know that by even doing this that I inadvertently have overlooked a few important contributors. There is a concentration on erectile dysfunction (ED) because from the days of vascular surgery there has been a tremendous explosion of anatomical, physiological, and molecular studies to examine the function of erection, both centrally and in the end organ and to define the pathophysiology of ED. But other sexual disorders in the male have been defined by science within the last 40 years. The focus on sexual disorders in women is relatively new, but it is truly become more scientific as well and I have tried to include references to some key papers that reflect that science. Since the mid-1970s the history has been intense and has led to logarithmic advances which, at best, are only partially discussed in this chapter. This chapter includes brief sections on psychotherapy history, vascular revascularization, penile prostheses, venous surgery, vacuum devices, epidemiology, diagnostic tools, intracavernosal injection therapy, oral therapy of ED, basic science, Peyronie’s disease, priapism, ejaculation problems, hormonal treatment and evaluation, and women’s disorders. I have tried to keep these in some order of when key studies evolved and show how the interaction of one area led to more scientific studies in the other area.

INTRODUCTION AND OBJECTIVES: The effect of venereal disease (VD) during World War I (WWI) was an underappreciated morbidity afflicting American soldiers. Along with mental illness and tuberculosis, VD was one of the most common non-combat related causes for soldier disability. The objective of this study is to review the impact of VD on the American military during WWI and to highlight the role of Hugh Hampton Young in assisting commanding officers in combating VD amongst their ranks. METHODS: A review of medical journals and historical textbooks was performed in order to give a comprehensive dissertation of the impact of VD on the American military during WWI. RESULTS: Prior to American involvement in WWI, prevalence of VD (primarily gonorrhea) among Allied forces was estimated to be 11-25%. Soldiers with gonorrhea were unable to fight and were problematic for commanding officers. VD was mainly the result of unsanctioned brothels in Europe, as soldiers frequented these establishments in an attempt to escape the rigors of war. With the arrival of American soldiers in France and their unregulated use of French prostitutes, General John Pershing became aware of this public health dilemma and immediately notified Secretary of War Newton Baker. Baker, with knowledge of President Wilson’s Presbyterian background and American civilian conservatism, subsequently instituted a policy that commanding officers were responsible for the general health of their soldiers. To aid the commanding officers, General Pershing enlisted the assistance of Urologist Dr. Hugh Hampton Young to Europe in May 1917 as Director of the Division of Urology in the American Expeditionary Force. American soldiers were ordered to be chaste and prohibited from encountering French women. Soldiers found to have VD were subject to irrigation of the bladder and penis with potassium permanganate and threatened with ‘court martial’. Commanders failing to keep VD to a minimum among their soldiers were at risk of losing rank. As a result of these combined efforts the prevalence of VD in the American military decreased after the institution of the policy, and was considerably lower than Allied forces from other countries. CONCLUSIONS: VD was an important public health dilemma for soldiers during WWI resulting in significant morbidity and affecting a soldier’s ability to perform in combat. With the assistance of Hugh Hampton Young, American military leaders were able to institute policies to counter the effects of VD and concomitantly maintain American conservative morals overseas. For his efforts, Dr. Young was promoted to Colonel in 1918 and received the Distinguished Service Medal in 1919.

Introduction The incidence and prevalence of various sexual dysfunctions in women and men are important to understand to designate priorities for epidemiologic and clinical research. Aim This manuscript was designed to conduct a review of the literature to determine the incidence and prevalence of sexual dysfunction in women and men. Methods Members of Committee 1 of the Fourth International Consultation on Sexual Medicine (2015) searched and reviewed epidemiologic literature on the incidence and prevalence of sexual dysfunctions. Key older studies and most studies published after 2009 were included in the text of this article. Main outcome measures The outcome measures were the reports in the various studies of the incidence and prevalence of sexual dysfunction among women and men. Results There are more studies on incidence and prevalence for men than for women and many more studies on prevalence than incidence for women and men. The data indicate that the most frequent sexual dysfunctions for women are desire and arousal dysfunctions. In addition, there is a large proportion of women who experience multiple sexual dysfunctions. For men, premature ejaculation and erectile dysfunction are the most common sexual dysfunctions, with less comorbidity across sexual dysfunctions for men compared with women. Conclusion These data need to be treated with caution, because there is a high level of variability across studies caused by methodologic differences in the instruments used to assess presence of sexual dysfunction, ages of samples, nature of samples, methodology used to gather the data, and cultural differences. Future research needs to use well-validated tools to gather data and ensure that the data collection strategy is clearly described.

Introduction This article presents a review of previous research concerning risk factors for sexual dysfunction in women and men. Aim The aim is to evaluate past research studies to determine the contribution of all risk factors to the development and maintenance of sexual dysfunction among women and men. Methods Studies were organized under a biopsychosocial framework, with the bulk of studies of women and men having investigated the role of biological factors. Main Outcome Measures The outcome measures were the data on factors for sexual dysfunction. Results Many more studies investigated risk factors for sexual dysfunction in men than in women. For women and men, diabetes, heart disease, urinary tract disorders, and chronic illness were significant risk factors for sexual dysfunction. Depression and anxiety and the medications used to treat these disorders also were risk factors for sexual dysfunction in women and men. In addition, substance abuse was associated with sexual dysfunction. Many other social and cultural factors were related to sexual dysfunction in women and men. Conclusion Psychosocial factors are clearly risk factors for sexual dysfunction. Women and men with sexual dysfunction should be offered psychosocial evaluation and treatment, if available, in addition to medical evaluation and treatment. The impact of social and cultural factors on sexual function requires substantially more research. The evidence that erectile dysfunction is a harbinger of other forms of cardiovascular disease is strong enough to recommend that clinical evaluation for occult cardiovascular disease should be undertaken in men who do not have known cardiovascular disease but who develop organic erectile dysfunction, especially in men younger than 70 years.

What's known on the subject? and What does the study add? Phosphoesterase type 5 inhibitors (PDE5is) are considered standard-of-care for the treatment of men with erectile dysfunction. Recommended administration of currently used PDE5is are between 60- to 120-minutes before sexual activity. RigiScan® monitoring has been validated in previous clinical studies of PDE5 inhibitors. Using a highly objective measure of sexual function (RigiScan monitoring), data show that the onset of action of avanafil was rapid. Response to treatment with avanafil was associated most frequently with the earliest time interval tested (20–40 minutes after dosing), compared with sildenafil 50 mg (100 to 120 minutes after dosing). However, avanafil treatments showed some degree of efficacy across all time intervals tested (including 60–80 minutes and 100–120 minutes post-dosing). These results were consistent with data from phase 3 trials which showed a rapid onset of action with avanafil (as early as 15 minutes) and a long duration of effect (up to 6 hours in some patients). Safety results were consistent with those reported in phase 3 trials, and showed that avanafil was well tolerated and adverse events were generally low and mild in severity. Objective To evaluate the safety, efficacy and time course of three doses of avanafil (50 mg, 100 mg and 200 mg) compared with sildenafil 50 mg or placebo, given in conjunction with visual sexual stimulation (VSS) videos in men with mild to moderate erectile dysfunction (ED). Patients and Methods Male patients, 35–70 years of age, with mild to moderate ED of ≥6 months duration, were included in the study. During the course of the study, each patient received placebo, active control (sildenafil 50 mg), and one dose of avanafil (50 mg, 100 mg or 200 mg), all administered in random order at least 72 h apart. RigiScan® (Dacomed Corp., Minneapolis, MN, USA) monitoring was used in conjunction with 20-min VSS videos (20, 60, and 100 min after dosing) to determine the duration of and time to ≥60% penile rigidity, maximum rigidity, tumescent activity units (TAUs), rigidity activity units (RAUs), and responses to the five-point Erection Assessment Scale. Safety assessments included adverse events (AEs), vital sign changes in response to dosing, laboratory results (complete blood counts, chemistry panel, prostate-specific antigen, serum testosterone, prothrombin time and urine analysis) and physical examination findings. Results Eighty-three patients were randomized and received at least one dose of study medication; 82 patients completed the study. Peak response to avanafil occurred in the early interval (20–40 min after dosing), while peak response to sildenafil occurred either in the middle (60–80 min) or late (100–120 min) intervals after dosing. Results were qualitatively similar for all other efficacy endpoints. During the 20–40-min interval, the majority of values for TAUs and RAUs with the avanafil 50-mg, 100-mg and 200-mg treatments were significantly superior to placebo (P < 0.05). Avanafil treatment was generally well tolerated; facial flushing (7–15%) was the most commonly observed AE, and no visual disturbances were reported. Conclusion A favourable safety profile and improvement in sexual function, coupled with rapid onset of action and durability of effect, make avanafil an attractive option for males with ED, especially in the setting of on-demand treatment.

There have been a limited number of epidemiological studies published on sexual disorders in persons from Asia. This paper aims to assess the reports of sexual dysfunction epidemiological studies published in the English language that involved Asian countries. Key points are summarized in this paper from nine epidemiological papers on sexual dysfunction from Asia that were published in the English language. Seven met the criteria for evidence-based studies reaching a Prins score of at least 10 or more. Papers included in this report came from national and regional representative studies in peer review journals. These results for sexual dysfunction in the nine papers are summarized for various sexual dysfunctions in men and women in Asian countries. In three of these, worldwide data were presented in the same paper allowing comparisons with Asian data on prevalence rates. Detailed descriptions from each of these studies are presented in paragraph form. More detailed data on erectile dysfunction (ED) is presented in a tabular form. Collectively, there seems to be a need for country- and population-specific further descriptive and analytical epidemiological studies in all of the sexual disorders from Asia. This critical review paper should help guide these studies for reaching evidence-based literature standards.

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 men's and women's 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; Peyronie's disease; and priapism. Conclusions. Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective. Montorsi F, Adaikan G, Becher E, Giuliano F, Khoury S, Lue TF, Sharlip I, Althof SE, Andersson K-E, Brock G, Broderick G, Burnett A, Buvat J, Dean J, Donatucci C, Eardley I, Fugl-Meyer KS, Goldstein I, Hackett G, Hatzichristou D, Hellstrom W, Incrocci L, Jackson G, Kadioglu A, Levine L, Lewis RW, Maggi M, McCabe M, McMahon CG, Montague D, Montorsi P, Mulhall J, Pfaus J, Porst H, Ralph D, Rosen R, Rowland D, Sadeghi-Nejad H, Shabsigh R, Stief C, Vardi Y, Wallen K, and Wasserman M. Summary of the recommendations on sexual dysfunctions in men. J Sex Med 2010;7:3572-3588.

Objectives Men with previously negative prostate biopsies but continued suspicion for carcinoma present a diagnostic dilemma often managed by saturation prostate biopsy (SPB). We sought to determine the patient characteristics for which repeat biopsy by SPB provides the greatest utility for prostate cancer detection. Methods The records of the men at the state hospital and affiliated Veterans Affairs Medical Center with previously negative prostate biopsy findings who had then undergone SPB were reviewed. The predictors of cancer were analyzed, and those that were significant were included in a multivariate logistic regression model. Results A total of 82 men underwent SPB from November 2001 to March 2006. Their mean age was 61 years (range 43 to 76), and 44 (54%) were white, 37 (45%) were African American, and 1 (1%) was Asian. The mean prostate-specific antigen level at SPB was 9.1 ng/mL (range 1.0 to 34). The number of prior biopsies was one in 43 patients (52%) and two or more in 39 patients (47%). The prostate volume averaged 53 cm 3 (range 12 to 200). SPB included a median of 24 cores (range 24 to 40). Of the 82 patients, 16 (19.5%) were diagnosed with cancer, of whom 10 (63%) elected to undergo radical prostatectomy. The only significant predictors of prostate cancer were the prostate-specific antigen level ( P = 0.009) and prostate volume. The cancer detection rate was 57% for patients with a prostate volume less than 37 cm 3 and 7% for those with larger glands, and the difference was significant on multivariate analysis (odds ratio 31, 95% confidence interval 6 to 158, P Conclusions The results of our study have shown that SPB is an effective diagnostic tool with a high yield for men with persistent suspicion for prostate cancer, prior negative biopsy findings, and a prostate volume less than 37 cm 3 .

Introduction Intracavernosal injection (ICI) of a vasoactive agent has been an important part of the diagnosis, evaluation, and treatment of erectile dysfunction (ED) since its initial description by Virag in 1982. Aim To review the literature and summarize the use of ICI and its role in the diagnosis, evaluation, and treatment of ED. Methods Literature review. Main Outcome Measure To define the role of ICI's utility in the diagnosis, evaluation, and treatment of ED. Results When used in conjunction with color penile Doppler ultrasound for ED evaluation and diagnosis, ICI helps to detect penile vascular abnormalities and allows for differentiation between the multiple vasculogenic causes of impotence, thus helping clinicians to select the optimal treatment modality for each patient. Patients utilizing ICI continue to report high efficacy and satisfaction rates relative to other treatment options despite ICI's designation as a second‐line therapy since the introduction of oral phosphodiesterase type 5 inhibitors in 1998. In recent years, ICI has also become an important part of penile rehabilitation programs following radical prostatectomy, as regular use of ICI is thought to increase the rate at which patients experience return of spontaneous erection through preservation of penile tissue integrity and prevention of corporeal smooth muscle atrophy. Conclusions ICI of vasoactive agents remains an important tool in treating and diagnosing ED, with high patient satisfaction and efficacy rates. However, the dropout rate for ICI therapy remains relatively high, and it may be associated with priapism, ecchymoses, hematoma formation, and penile fibrosis. Patients should be educated on the benefits and limitations of ICI therapy prior to beginning treatment in order to minimize dropout rates. Additional studies are necessary to better understand the possible long‐term benefits of ICI therapy and how to most effectively structure the penile rehabilitation program after radical prostatectomy. Belew D, Klaassen Z, and Lewis RW. Intracavernosal injection for the diagnosis, evaluation, and treatment of erectile dysfunction: A review. Sex Med Rev 2015;3:11–23.

Objectives To address in a questionnaire-based study the frequency at which fertility is a concern for men when they consider their prostate cancer treatment options. A secondary aim was to assess the rate at which men were informed of the fertility implications of prostate cancer treatment by their physician before their selection of a treatment option. Methods Two questionnaires were used. One questionnaire was distributed to men with localized prostate cancer who had undergone treatment within the past year. These questions addressed whether continence, erectile function, and fertility were discussed with them by their physician during the prostate cancer treatment selection process. The second questionnaire was distributed to men with newly diagnosed prostate cancer and queried their level of concern about the effects of prostate cancer treatment on sexual function, urinary function, and fertility. Results All patients receiving the first questionnaire stated that they were informed of the incontinence and impotence side effects of prostate cancer treatments, but only 8.7% stated that they were informed of the effect that prostate cancer treatments would have on their future fertility. Of the patients completing the second questionnaire, 53.7% responded that incontinence was the side effect of prostate cancer treatment that caused them the most concern, 42.6% stated that erectile dysfunction was the most concerning, and 3.7% listed fertility as the major concern. Conclusions Urologists should consider approaching the topic of infertility when discussing the pros and cons of various prostate cancer therapies with their younger patients.

Introduction There are few published guidelines for the management of sexual dysfunctions in men and women, despite the prevalence and lack of attention to these problems. Disorders of sexual function in men include erectile dysfunction, orgasm/ejaculation disorders, priapism, and Peyronie's disease. Aim To provide evidence-based and expert-opinion consensus guidelines for the clinical management of men's sexual dysfunctions. Methods An International Consultation in collaboration with major urological and sexual medicine societies assembled over 200 multidisciplinary experts from 60 countries into 17 consultation committees. Committee members established the scope and objectives for each chapter. Following intensive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measure New algorithms and guidelines for assessment and treatment of men's sexual dysfunction were developed. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of the medical literature, in addition to cultural and ethical considerations. Results Recommendations and guidelines for men's sexual dysfunction are presented. These guidelines were developed as evidence-based, patient-centered, and multidisciplinary in focus. For the clinical assessment and diagnosis of ED, a basic evaluation was recommended for all patients, with optional and specialized testing reserved for special cases. A new treatment algorithm is proposed. This algorithm provides a clinically relevant guideline for managing ED in the large majority of men. New treatment guidelines and algorithms are provided for men's orgasm and ejaculation disorders, including premature ejaculation, retrograde and delayed ejaculation. Finally, expert opinion-based guidelines for the clinical management of priapism and Peyronie's disease are provided. Conclusions Additional research is needed to validate and extend these guidelines. Nonetheless, this summary encompasses the recommendations concerning men's sexual dysfunctions presented at the 2nd International Consultation on Sexual Medicine in Paris, France, June 28–July 1, 2003.

Introduction Accurate estimates of prevalence/incidence are important in understanding the true burden of male and female sexual dysfunction and in identifying risk factors for prevention efforts. Aim To provide recommendations/guidelines concerning state-of-the-art knowledge for the epidemiology/risk factors of sexual dysfunctions in men and women. Methods An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. Concerning the Epidemiology/Risk Factors Committee, there were seven experts from four countries. Main Outcome Measure Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. Results Standard definitions of male and female sexual dysfunctions are needed. The incidence rate for erectile dysfunction is 25–30 cases per thousand person years and increases with age. There are no parallel data for women's sexual dysfunctions. The prevalence of sexual dysfunction increases as men and women age; about 40–45% of adult women and 20–30% of adult men have at least one manifest sexual dysfunction. Common risk factor categories associated with sexual dysfunction exist for men and women including: individual general health status, diabetes mellitus, cardiovascular disease, other genitourinary disease, psychiatric/psychological disorders, other chronic diseases, and socio-demographic conditions. Endothelial dysfunction is a condition present in many cases of erectile dysfunction and there are common etiological pathways for other vascular disease states. Increasing physical activity lowers incidence of ED in males who initiate follow-up in their middle ages. Conclusions There is a need for more epidemiologic research in male and female sexual dysfunction.

Studies from this laboratory have demonstrated that RhoA/Rho-kinase signaling mediates vasoconstriction in the penile circulation of the rat and that erection results from inhibition of this activity with Y-27632. In prior animal studies, Y-27632 was administered to the rats by intracavernous injection. To determine if topical application of the Rho-kinase inhibitor is an effective mode of delivery, Y-27632 was applied to the surface of the tunica albuginea or to the glans penis and surrounding skin in intact or castrated rats. Both sites of drug administration resulted in a marked increase in the erectile response both with and without stimulation of the autonomic innervation of the penile vasculature. Although high doses of the drug were found to reduce systemic blood pressure, topical administration of the Rho-kinase inhibitor, in appropriate doses, may have clinical value for the treatment erectile dysfunction.

The involvement of antihypertensive therapy in the pathology of hypertension associated male erectile dysfunction is unclear. Stroke prone spontaneously hypertensive rats (SHRSP) were treated chronically with the angiotensin converting enzyme (ACE) inhibitor captopril or placebo, normotensive rats served as controls. Mean arterial and intracavernosal pressure were measured during the induction of erection by autonomic ganglion stimulation. SHRSP-placebo treated rats were hypertensive and had a blunted erectile response. Captopril treatment returned both the blood pressure and erectile response to control levels. Therefore, ACE inhibitor therapy may not be responsible for the erectile dysfunction observed in treated hypertensive subjects.

METHODS: A retrospective review of 176 patients who underwent surgical intervention for Peyronie’s Diesase between 2005 and 2013 was performed. Thirty-seven patients who underwent simultaneous IPP with Gore-Tex graft were identified; these patients had progressive failure of medical therapy for ED & history of penile curvature, or significant penile curvature found at time of IPP placement. Patient demographics, plaque characteristics, perioperative data and post-operative results are included at a median follow-up of 5.5 months. RESULTS: Mean age was 61 years (47-81) and 97.3% of patients were Caucasian; a majority (67.6%) were non-hispanic. Surgical history revealed prior radical prostatectomy in 6 and cystoprostatectomy in 1 patient. Two patients (5.4%) had prior plaque incision and grafting procedures (temporalis fascia, n1⁄41; cadaveric pericardium, n1⁄41). Median duration of symptoms of 24 months (6-216). Plaque severity was >60 in 29 patients (78.4%), and >90 in 4 patients (10.4%). Corporal waisting was found in 8 patients. Dorsal deviation was managed via infrapubic approach in 33 patients; ventral deviation was managed penoscrotally in 4 (10.8%). Biplanar plaques were found in 15 patients (40.5%). Median OR time was 159 minutes. AMS 700 systems were used in all patients, including CX (n1⁄43) and Ultrex/LGX cylinders (n-34). (American Medical Systems, MN). Median length of stay was 1 day (1-2). Median duration to prosthesis use was 4 weeks (3-8). All patients had functionally straight erections permitting intercourse. Three patients (8.1%) experienced post-operative paresthesia, resolving between 3-12 months. No patient experienced mechanical failure, cylinder aneurysm, or infection of the prosthesis or graft. CONCLUSIONS: AMS CX and LGX cylinders demonstrated durability and no infectious complications when used in conjunction with other synthetic material. For patients with ED and penile curvature, IPP placement with concomitant plaque incision and Gore-Tex grafting represents a highly efficacious surgical option with minimal morbidity.

To assess the efficacy and safety of Viagra (sildenafil citrate) in male outpatients with erectile dysfunction and patient and partner satisfaction with treatment using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS).A total of 247 patients with erectile dysfunction of broad-spectrum etiology were treated in a randomized, double-blind, parallel-group, multicenter study conducted at outpatient clinics. Patients receiving oral sildenafil (25, 50, and 100 mg) were compared with patients receiving placebo during a 12-week period. The principal efficacy measures were responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) on the International Index of Erectile Function and three global efficacy questions. Patient and partner satisfaction with treatment were assessed, for the first time, using the EDITS questionnaire.Efficacy scores for the International Index of Erectile Function questions and the global efficacy questions were significantly higher for patients receiving sildenafil than for those receiving placebo (P0.001). Both patients and partners receiving sildenafil also had significantly higher EDITS scores than those receiving placebo (P0.001). Adverse events were chiefly mild or moderate. Two patients receiving sildenafil and none receiving placebo discontinued treatment because of adverse events.Sildenafil was an effective, well-tolerated treatment for erectile dysfunction in an outpatient setting. Partner evaluations corroborated patient assessments. The results from the EDITS questionnaire indicated that after 12 weeks of receiving sildenafil both patients and partners reported higher levels of treatment satisfaction relative to placebo.

This brief review examines the history of the intraurethral (IU) pharmacotherapy for the treatment of erectile dysfunction (ED). Emphasis is placed on the design, study endpoints and results of a limited number of clinical trials undertaken with PGE(1)-MUSE to demonstrate the efficacy of this unique delivery system. Next, the theory of the iontophoretic technique of drug delivery is discussed. Clinical data collected while applying these methods are presented, but are thus far limited to treatment of patients with Peyronie's disease. Iontophoresis as a drug delivery alternative may gain popularity with ED patients who fail other types of therapy or in patients with other penile disorders. International Journal of Impotence Research (2000) 12, Suppl 4, S86-S90.

BACKGROUND Published data indicate that antiprogestins and antiestrogens could inhibit prostate cancer cell growth in vitro and in vivo. The main objective of the present studies was to explore the role of bcl2 and TGFβ1 for induction of apoptosis in LNCaP prostate cancer cells growing in culture as a treatment response to the antiprogestin, mifepristone, and the antiestrogen, 4-hydroxytamoxifen. METHODS In vitro cell viability (cytotoxicity), DNA fragmentation, and changes in the expression of bcl2 and TGFβ1 proteins were assessed using the sulforhodamine B protein dye-binding assay, specific ELISA, and competitive inhibition assays. RESULTS Both steroid antagonists induced a significant time- and dose-dependent cell growth inhibition (cytotoxicity). This inhibition of viable cells was associated with a significant increase in DNA fragmentation (apoptosis), downregulation of bcl2, and induction of TGFβ1 protein. Abrogation of the mifepristone- and 4-hydroxytamoxifen-induced cytotoxicity by TGFβ1-neutralizing antibody and by the addition of mannose-6-phosphate confirmed the correlation between induction of active TGFβ1 and subsequent prostate cancer cell death. The effect of mifepristone was not significantly reduced or prevented by occupying the progesterone or glucocorticoid receptors by their corresponding high-affinity native ligands. On the contrary, the effect of a combination of mifepristone with progesterone or hydrocortisone on the increase in DNA fragmentation, bcl2 downregulation, and induction of TGFβ1 protein was additive and significantly different (P < 0.05) from the effect of mifepristone monotherapy. CONCLUSIONS Our data suggest that mifepristone and tamoxifen are effective inducers of apoptosis and may represent nonandrogen-ablation, novel therapeutic approaches to overcome a potential intrinsic apoptosis resistance of androgen-independent prostate cancer cells. Prostate 43:31–42, 2000. © 2000 Wiley-Liss, Inc.

BACKGROUND Antiprogestins are a promising new class of mammary tumor inhibitors with a unique mechanism of action. Previously published results also suggest a tumor-inhibitory effect of antiprogestins in prostate cancer models. The objective of the present studies was to determine whether androgen-sensitive and androgen-insensitive variants of the well-characterized LNCaP human prostate cancer cell line exhibit stable differences in their sensitivity to in vivo antitumor activity of the antiprogestin, mifepristone. METHODS Exponentially growing LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer cells in culture were mixed with Matrigel and injected subcutaneously (s.c.) into the flank of 6–8-week-old male nude mice. The tumors were permitted to grow until they reached a volume of 270–300 mm3. The animals were then randomly assigned to two groups. One group received mifepristone (50 mg/kg/day s.c.). Control animals were treated with vehicle. Tumor volume was determined every 4 days. After 28 days of treatment, the tumors were harvested and wet weights were determined. RESULTS The inoculated tumor cells produced progressively growing tumors in male nude mice. However, the androgen-insensitive LNCaP-C4-2 cells showed the most aggressive and most rapid growth rate and shortest time to tumor progression. The tumors derived from the LNCaP-C4 cells exhibited a higher rate of tumor growth as compared with those derived from the parental androgen-sensitive LNCaP cells. In all three models, mifepristone treatment caused a significant retardation of tumor progression: after 28 days of treatment, about 50% inhibition of tumor weight was observed in the mifepristone treatment groups (P < 0.05) compared with the corresponding control groups. CONCLUSIONS This is the first report demonstrating significant antitumor activity of mifepristone in both androgen-sensitive and androgen-insensitive variants of the LNCaP human prostate cancer model in nude mice. These results suggest a potential clinical benefit of the use of antiprogestins as a novel nonandrogen ablation therapeutic approach in the management of prostate cancer. Prostate 42:99–106, 2000. © 2000 Wiley-Liss, Inc.

Purpose: We describe a surgical modification of the Nesbit procedure to correct Peyronie's disease, and compare the results of this procedure with those of 2 other surgical techniques.Materials and Methods: In 30 patients a vertical incision in the tunica albuginea was closed in a horizontal fashion with permanent suture knots buried beneath the tunica in a running looped fashion, resulting in watertight closure with no exposed suture material. A standard Nesbit procedure and plaque excision with a polyethylene terephthalate mesh reinforced silicone sheet patch graft were done in 28 cases each.Results: Elimination of penile curvature, patient satisfaction and postoperative impotence rates were not statistically different for standard and modified Nesbit procedures. However, plaque excision and synthetic patch grafting resulted in less elimination of curvature (61%, p = 0.004), a lower rate of satisfaction (30%, p = 0.00002) and a higher incidence of impotence after surgery (18%, p = 0.04). The mod...

Erectile dysfunction can result from blunt or penetrating pelvic or perineal trauma. Rupture of the corpora cavernosa leading to loss of the veno-occlusive mechanism and penile artery occlusion have been found in these patients. We present a case of immediate loss of erectile function after penetrating perineal trauma resulting in corpus cavernosum rupture and traumatic occlusion of multiple arteries in the hypogastric-cavernous bed. Conservative management of the corpus injury resulted in post-traumatic aneurysmal dilation at the site of injury with venous leakage from aberrant veins. Penile arterial revascularization and aneurysm repair with deep penile venous ligation resulted in near-complete return of normal erectile function.

The translocation t(11;22)(q24;q12) can be identified in its classical or variant form in approximately 90% of cases of Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET). In this tumor group in which the histopathologic diagnosis is often one of exclusion, the cytogenetic demonstration of this translocation has become an invaluable positive diagnostic marker. With the recent cloning of the breakpoint regions of the t(11;22), molecular genetic approaches to the detection of this translocation have become possible. By Southern blotting, the position of the breakpoints on chromosome 22 has been found to be tightly clustered within a 7-kilobase (kb) fragment of the genomic DNA, within a gene designated EWS. In the present study, we examined the efficacy of an EWS complementary DNA (cDNA) probe in detecting the t(11;22) in Southern blots of EcoRI- or HindIII-digested DNA extracted from cases of ES and PNET. We also compared the results of the molecular and cytogenetic analysis with the expression of the ES cell surface antigen MIC2, as demonstrated by immunoperoxidase staining with the monoclonal antibodies O13 and HBA71. Twenty-three specimens were studied, including 18 ES and five PNET. Of 16 cases with clonally abnormal karyotypes, 14 (88%) showed a typical or variant t(11;22). Rearrangements were demonstrated within the EWS gene with the EWS cDNA probe in 20 of 23 specimens (87%), including all of the 14 cases, as well as in one case that displayed clonal numerical chromosome abnormalities only. The MIC2 antigen was expressed in 19 of 20 cases (95%), including all three cases lacking EWS rearrangement.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the efficacy of tadalafil in men with erectile dysfunction (ED) by demographic and ED characteristics, in patients having various comorbid medical conditions, and in patients receiving drug treatment for other medical conditions.This is an analysis of 11 double-blind, placebo-controlled trials with 2,102 men with a broad spectrum of ED etiology and various comorbid medical conditions as participants. The variables analyzed in this report included race, age, body mass index (BMI), ED etiology, ED severity, ED duration, smoking, prior sildenafil use, presence of comorbid conditions (diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia, depression, benign prostatic hyperplasia), and treatment with antihypertensives or antidepressants. Patients were randomly assigned to receive tadalafil 10 mg (N=321), tadalafil 20 mg (N=1,143), or placebo (N=638). The primary efficacy variables included mean changes from baseline in the erectile function (EF) domain score of the International Index of Erectile Function (IIEF) questionnaire, and the mean per-patient percentage of "yes" responses to the Sexual Encounter Profile (SEP) diary question 3 (SEP3--successful intercourse). The Global Assessment Question 1 (GAQ) was evaluated, as was the percentage of men attaining a normal IIEF EF domain score at end point.Patients taking tadalafil 10 mg or 20 mg demonstrated significant improvement (P0.005) from baseline to end point on the IIEF EF domain score in all subpopulations analyzed compared with patients receiving placebo. The mean-per-patient percentage of "yes" responses to SEP3 increased significantly in all subpopulations taking tadalafil compared with placebo (P0.05). Tadalafil-treated patients had a significantly greater positive response rate on the GAQ in all subpopulations analyzed compared with placebo-treated patients (P0.03) except for the tadalafil 10 mg cardiovascular subpopulation (placebo, 46.8%; tadalafil 10 mg, 71.0%; P=0.127). The percentage of positive responses ranged from 72% to 91% for patients on tadalafil 20 mg and from 52% to 94% for tadalafil 10 mg compared with a range of 20% to 47% for placebo-treated patients.Tadalafil was effective in improving erectile function across a wide spectrum of ED patients including patients with various comorbid conditions.

Erectile dysfunction (ED) is a highly prevalent and often under-treated condition. Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents but also by visual, olfactory and imaginary stimuli. The generated nervous signals will influence the balance between contractile and relaxant factors, which control the degree of contraction of penile corporal cavernosal smooth muscles and, thus, determine the erectile state of the penis. The different steps involved in neurotransmission, impulse propagation and intracellular transduction of neural signals may be changed in different types of ED. Recent studies have revealed important roles for the small GTPase RhoA and its effector, Rho-kinase in regulating cavernosal smooth muscle tone. The RhoA/Rho-kinase pathway modulates the level of phosphorylation of the myosin light chain, mainly through inhibition of myosin phosphatase, and contributes to agonist-induced Ca(2+)-sensitization in smooth muscle contraction. Changes in this pathway may contribute to ED in various patient subgroups (e.g. hypertension, diabetes, hypogonadism). This review summarizes the importance of Rho-kinase signaling in the erectile response and introduces the evidence pointing to RGS-containing Rho-guanine nucleotide exchange factors (GEFs) as critical mediators of RhoA-GTPase activation in cavernosal smooth muscle and its possible compartmentalization in the caveolae. In addition, we suggest that the design of selective inhibitors of these GEFs might represent a novel class of pharmacological agents to treat ED.

Oral pharmacotherapy fails to provide an adequate erection in approx 30 to 35% of all patients tried on this initial therapy, and at higher rates in those patients who have diabetes mellitus and those who have had radical pelvic cancer surgery. In those patients with initial success from oral pharmacotherapy, there have been few reports of complete tachyphylaxis, although many who are started on lower doses initially feel that they obtain better results from the oral therapy by increasing to the higher dose recommended for use. Dropout rates owing to intolerable side effects are rare with all of the phosphodiesterase inhibitors. Occasionally, some users of oral therapy cannot afford to continue the use of the oral agents and prefer a more economical treatment for their erectile dysfunction (ED). Vacuum therapy provides such a solution. Certainly, penile prostheses are less economical for such patients. If there is a progression of disease—such as Peyronie’s disease of a severe nature, or more fibrosis of sinus smooth muscle, such as that associated with diabetes mellitus—then a penile prosthesis may become the next step in therapy for the patient with ED.

We describe the effects of tumor necrosis factor alpha-related apoptosis inducing ligand (TRAIL) on the induction of apoptosis in two related prostate cancer cell lines, PC3AR and PC3Neo. TRAIL is a potent drug, which induces apoptosis preferentially in cancer cells. Treatment of prostate cancer cells, reduced survival by approximately 41% in PC3AR, but only approximately 18% PC3Neo were killed. Western analysis demonstrated that increased apoptotic response of PC3AR cells may be due to differential response of death receptors DR4, DR5 and decoy receptors DcR1 and DcR2. Caspases-8, -9, -3 and Bid were highly activated in PC3AR cells compared to PC3Neo. Furthermore, lower apoptotic response of PC3Neo was probably due to higher expression of NFkappaB. Blocking the function of NFkappaB by adenoviral infection of mutated IkappaB, increased apoptotic response confirming the influence of NFkappaB. Thus, we have demonstrated the role of NFkappaB in the differential response of prostate cancer cells to TRAIL.

Epidemiologic studies are descriptive and analytical. The prevalence of erectile dysfunction in various community studies has varied from as low of 7% to as high as 52%. The prevalence of erectile dysfunction increases with age. Incidence data are scarce but a recent study of white males in the United States described an incidence of 26 cases per 1000 man-years. Risk factors for erectile dysfunction include certain medications, such as cardiovascular medications and psychotropic drugs, and chronic diseases, particularly neurologic diseases and diabetes mellitus.

Relaxation of the smooth muscle cells in the cavernosal arterioles and sinuses results in increased blood flow into the penis, raising corpus cavernosum pressure to culminate in penile erection. Nitric oxide, released from non-adrenergic/non-cholinergic nerves, is considered the principle stimulator of cavernosal smooth muscle relaxation, however, the inhibition of vasoconstrictors (that is, norepinephrine and endothelin-1, refs. 5-9) cannot be ignored as a potential regulator of penile erection. The calcium-sensitizing rho-A/Rho-kinase pathway may play a synergistic role in cavernosal vasoconstriction to maintain penile flaccidity. Rho-kinase is known to inhibit myosin light chain phosphatase, and to directly phosphorylate myosin light-chain (in solution), altogether resulting in a net increase in activated myosin and the promotion of cellular contraction. Although Rho-kinase protein and mRNA have been detected in cavernosal tissue, the role of Rho-kinase in the regulation of cavernosal tone is unknown. Using pharmacologic antagonism (Y-27632, ref. 13, 18), we examined the role of Rho-kinase in cavernosal tone, based on the hypothesis that antagonism of Rho-kinase results in increased corpus cavernosum pressure, initiating the erectile response independently of nitric oxide. Our finding, that Rho-kinase antagonism stimulates rat penile erection independently of nitric oxide, introduces a potential alternate avenue for the treatment of erectile dysfunction.

This Viewpoint article by Siddiqi and Lewis discusses the role of surgical therapy for the treatment of erectile dysfunction. The article explains why surgical therapy will likely always remain an option for specific patients, regardless of whether or not gene therapy is approved for erectile dysfunction treatment.

The history of the use of vacuum therapy for erectile dysfunction is summarized in Table 1. Although this is a simple noninvasive treatment, it did not gain popularity until recently and this was primarily through the work of the two American pioneer urologists. Initially, they were often greeted with a great deal of skepticism in their early advocacy for this therapy for the patient with erectile dysfunction.

In 1992, I composed a talk called “Fact or Fiction” regarding vascular impotence. In that presentation, I prepared slides with various points that needed to be questioned. One of the statements was “Veno-occlusive dysfunction is a major single entity cause of impotency”. I posed that statement for reflection. We were beginning to discover, at that time, that although veno-occlusion is an extremely important part of the male erectile cycle it is not truly a venous disorder responsible for veno-occlusive dysfunction. The faulty veno-occlusion is, in fact, a reflection of an underlying healthy cavernosa tissue with a structurally intact trabecular system, an intact arterial in-flow system, and an uncompromised elastic tunica albuginea.

Venous occlusion has been clearly established as a necessary phase of the erectile cycle, particularly for the establishment of full rigidity. This veno-occlusion is dependent on the expansion of the intracorporeal spaces due to increased arterial inflow and relaxation of the sinus smooth muscle.1,2 More recently, in a study of the tunica albuginea in men with penile veno-occlusive disorders, disruption of the normal elastic fiber arrangement has been reported, suggesting a causal relationship.3

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Novel role of androgens: Involvement in mitochondrial fission and apoptosis in prostate cancer cells The role of androgens on prostate cancer growth and proliferation is well known but very little is known about its pro-apoptotic roles. Here, we demonstrate a novel role of androgens in altering the shape and function of the mitochondria. Dynamin-related protein 1 (Drp1) is a key protein necessary for mitochondrial fragmentation or fission (MF). The expression of Drp1 (both protein and mRNA) correlated with the expression of androgen receptor (AR) in prostate cancer cell lines. Interestingly, Drp1 expression was very low in androgen refractory prostate metastatic tissues. Treatment of LNCaP cells with androgen agonist, R1881 increased the expression of Drp1 mRNA and protein. This increase was inhibited by androgen antagonist, bicalutamide. Androgen regulation of Drp1 was confirmed by knock out of AR (using siRNA), which resulted in decreased Drp1 expression. To measure mitochondrial fission (MF), cells were stably transfected with pAcGFP1-Mito, targeting the expression of GFP to mitochondria. Androgen treatment did not induce MF, although Drp1 was upregulated. However, treatment with [CGP37157][1] (CGP), a mitochondrial Na+/Ca2+ channel blocker induced MF. Pre-treatment with R1881 significantly increased CGP-induced MF, suggesting that androgen-induced Drp1 facilitated CGP-induced MF. Androgens increased the proliferation of LNCaP, which was reduced by CGP treatment. Interestingly, treatment with CGP induced apoptosis which was further enhanced by pre-treatment with R1881. Drp1 dominant negative experiments showed that Drp1 was required for enhanced apoptosis, suggesting that androgen-induced Drp1 was responsible for increasing the apoptotic effects of CGP. Experiments to examine the paradoxical effects of androgens showed that induction of proliferation by androgens may be due to differential phosphorylation of Drp1. However, induction of apoptosis by CGP alone or in combination with androgens is due to the reduction of the expression of Mfn1, a protein that promotes mitochondrial fusion (opposite of fission). Use of proteasomal inhibitor, lactacystin, suggested that CGP treatment resulted in proteasome mediated degradation of Mfn1. In summary, our results demonstrated: i) transcriptional regulation of Drp1 by androgens, ii) androgen-induced Drp1 facilitated mitochondrial fission and apoptosis. Significance of these results: Clinical: we suggest that it is not necessary to block the function of androgens, instead administration of drugs (such as calcium channel blockers) that affect mitochondrial function induced death of cancer cells in the presence of androgens. Research: addresses a fundamental question about mechanisms involved in proliferation and apoptosis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1215. [1]: /lookup/external-ref?link_type=GENPEPT&access_num=CGP37157&atom=%2Fcanres%2F70%2F8_Supplement%2F1215.atom

In November 1996, the American Urological Association (AUA) handed down guidelines for treating erectile dysfunction (ED), and urged all physicians to give sound and unbiased explanations of all ED treatments to their patients.1Currently, nearly all urologists and many primary care physicians routinely ask whether their patients are experiencing erectile problems. If the answer is positive, then treatment options are discussed.