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Mulhall J.P.,Sloan Kettering Cancer Center | Bivalacqua T.J.,The James Buchanan Brady Urological Institute | Becher E.F.,University of Buenos Aires
Journal of Sexual Medicine

Introduction. Prostate cancer is common, and, thus, more men are being treated surgically. Long-term functional outcomes are of significant importance to the patient and their partners. Erectile function (EF) preservation (rehabilitation) has gained significant traction worldwide, despite the absence of definitive evidence supporting its use. Aim. To review the effectiveness of specific pharmacological therapies and other erectogenic aids in the treatment of post-radical prostatectomy (RP) erectile dysfunction. Methods. A systematic literature review of original peer-reviewed manuscripts and clinical trials reported in Medline. Main Outcome Measure. This review focused on the evaluation of interventions that aimed to improve EF recovery following RP. Results. Although well documented in animal models, studies supporting the rehabilitation with phosphodiesterase type 5 inhibitors in humans are scarce. Daily sildenafil has been used in trials (only one randomized placebo-controlled trial) with a significant improvement in erection recovery when compared to placebo or no rehabilitation but with a low return to baseline rates (27% vs. 4% placebo). Nightly vardenafil vs. on demand vs. placebo has been studied in the Recovery of Erections: INtervention with Vardenafil Early Nightly Therapy trial with no difference in erection recovery following RP. Intracavernosal injections, although widely used and attractive from a rehabilitation standpoint, does not yet have definitive supporting its role in rehabilitation. Vacuum erection devices use following RP has been reported, but there are no data to support its role as monotherapy. Intraurethral alprostadil was also studied vs. sildenafil in a multicenter, randomized, open-label trial, and no superiority was found. Conclusions. At this time, we are unable to define what represents the optimal rehabilitation program in regard to strategies utilized, timing of intervention, or duration of treatment. © 2012 International Society for Sexual Medicine. Source

Rubio-Aurioles E.,Clinical Research | Bivalacqua T.J.,The James Buchanan Brady Urological Institute
Journal of Sexual Medicine

Introduction. Low sexual desire in men is a condition that has received little attention; nevertheless it occurs with high frequency. Clinicians are in need of clear guidelines to address this problem. Aim. To develop standardized operational procedures to be implemented with men presenting low sexual desire/interest (LSD/I). Methods. Review of relevant evidence-based literature and published guidelines, integrated with expert opinion. Main Outcome. Operational procedures for LSD/I that are recommended for clinical practice with various degrees of support from published evidence. Results. A new classification scheme is proposed; LSD/I is proposed as an umbrella term for which hypoactive sexual desire disorder (HSDD) is only a subtype. The following standard operational procedures are described: (i) Detection of LSD/I: screening for LSD/I, screening for LSD/I in patients with other sexual dysfunctions; (ii) Diagnosis and assessment of etiology: diagnostic criteria for LSD/I, assessment of depression status, assessment of relationship status, assessment of endocrinologic status, diagnostic criteria for HSDD in men; (iii) Treatment: treatment of LSD/I secondary to low testosterone, treatment of LSD/I secondary to elevated prolactin, treatment of LSD/I secondary to other endocrinologic disorders, treatment of LSD/I secondary to depressive illness and or anxiety disorders, treatment of LSD/I secondary to relationship conflict and treatment of HSDD. A diagnostic and treatment algorithm is presented. Conclusions. LSD/I is a common condition that should be identified in patients; it is recommended that this condition be actively investigated by the clinician. Once the diagnosis of LSD/I in men is confirmed, a thorough search for possible causes needs to include both biological and psychological causes. Treatment should be etiologically oriented. © 2012 International Society for Sexual Medicine. Source

Bivalacqua T.J.,The James Buchanan Brady Urological Institute | Musicki B.,The James Buchanan Brady Urological Institute | Hsu L.L.,U.S. National Institutes of Health | Hsu L.L.,University of Illinois at Chicago | And 3 more authors.

Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders. © 2013 Bivalacqua et al. Source

Lu C.,The James Buchanan Brady Urological Institute | Luo J.,The James Buchanan Brady Urological Institute
Translational Andrology and Urology

In the past five years, multiple structurally and functionally distinct androgen receptor (AR) splice variants have been decoded and characterized. The mature transcripts for the majority of the fully decoded AR splice variants contain a transcribed "intronic" sequence, capable of encoding a short variant-specific peptide to replace the AR ligand-binding domain (LBD). Functionally, AR splice variants represent a diverse group of molecules often demonstrating cell context-specific genomic functions that may or may not be coupled with the functions of the canonical full-length AR (AR-FL). However, the full spectrum of their functional diversity and the underlying mechanistic basis remains very poorly characterized. In clinical specimens derived from men treated with a variety of hormone therapy regimens, AR splice variants are almost always expressed at detectable, yet lower levels when compared to that of AR-FL. In spite of the collective in vitro data supporting the putative role of AR splice variants in therapeutic resistance to hormone therapies, the extent to which AR splice variants mediate resistance to each individual regimen is not known and awaits thorough investigations in a clinically relevant setting using specimens from men undergoing treatments. Among the AR splice variants, AR-V7 is more abundantly and frequently expressed in castration-resistant prostate cancer (CRPC) and remains the most important variant identified so far. The relative importance of different AR molecules, including AR-FL, should be functionally dissected in the setting of castration-resistant prostate cancer, particularly in tumors resistant to more potent inhibitors of AR-FL recently approved by the FDA. In this review, we will focus on the discovery and characterization of AR splice variants, their putative functions and roles in mediating constitutively active AR signaling, and key areas of investigation that are necessary to establish their clinical relevance. © AME Publishing Company. Source

Meldrum D.R.,University of California at Los Angeles | Burnett A.L.,The James Buchanan Brady Urological Institute | Dorey G.,University of the West of England | Esposito K.,The Second University of Naples | Ignarro L.J.,University of California at Los Angeles
Journal of Sexual Medicine

Introduction: Penile rigidity depends on maximizing inflow while minimizing outflow. Aim: The aim of this review is to describe the principal factors and mechanisms involved. Main Outcome Measure: Erectile quality is the main outcome measure. Methods: Data from the pertinent literature were examined to inform our conclusions. Results: Nitric oxide (NO) is the principal factor increasing blood flow into the penis. Penile engorgement and the pelvic floor muscles maintain an adequate erection by impeding outflow of blood by exerting pressure on the penile veins from within and from outside of the penile tunica. Extrinsic pressure by the pelvic floor muscles further raises intracavernosal pressure above maximum inflow pressure to achieve full penile rigidity. Aging and poor lifestyle choices are associated with metabolic impediments to NO production. Aging is also associated with fewer smooth muscle cells and increased fibrosis within the corpora cavernosa, preventing adequate penile engorgement and pressure on the penile veins. Those same penile structural changes occur rapidly following the penile nerve injury that accompanies even "nerve-sparing" radical prostatectomy and are largely prevented in animal models by early chronic use of a phosphodiesterase type 5 (PDE5) inhibitor. Pelvic floor muscles may also decrease in tone and bulk with age, and pelvic floor muscle exercises have been shown to improve erectile function to a similar degree compared with a PDE5 inhibitor in men with erectile dysfunction (ED). Conclusions: Because NO is critical for vascular health and ED is strongly associated with cardiovascular disease, maximal attention should be focused on measures known to increase vascular NO production, including the use of PDE5 inhibitors. Attention should also be paid to early, regular use of PDE5 inhibition to reduce the incidence of ED following penile nerve injury and to assuring normal function of the pelvic floor muscles. These approaches to maximizing erectile function are complementary rather than competitive, as they operate on entirely different aspects of erectile hydraulics. © 2014 International Society for Sexual Medicine. Source

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