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Intracavernosal injection therapy (ICI) is a well-established second-line therapy used in the treatment of erectile dysfunction (ED). Controversy exists as to whether oral phosphodiesterase type 5 inhibitors (PDE5i) or injection therapy lead to higher satisfaction.This study addressed ICI satisfaction in a modern cohort of patients in the PDE5i era.Patients on ICI for at least 6 months were included in our study. Patients were administered the International Index of Erectile Function (IIEF) at the initial visit. On subsequent visits, patients were administered the IIEF and the Erection Hardness Scale (EHS).Study end points were change in baseline scores in the satisfaction domains (SD) of the IIEF, type of injection medication used, and predictors of satisfaction. Multiple logistic regressions were performed for predictors of satisfaction.One hundred twenty-two patients met inclusion criterion. Mean time to follow-up was 25±12 months (range 6-106 months). Sixty-five percent of patients continued injections at the time of follow-up. When SD scores were examined, intercourse SD scores increased from 4.8±1.7 at baseline to 12.3±3.1 (P0.01); overall SD scores increased from 4.1±1.8 to 7.2±2.0 (P0.05). On multivariate analysis, predictors of satisfaction included older age (odds ratio [OR]=2.1), younger partner age (OR=2.5), clinically significant increase in the erectile function domain score (OR=3.1), and attainment of a "fully rigid" erection (EHS 4) (OR=6.8).We have evaluated satisfaction in a modern cohort of ICI patients. While dropout rates are significant, for those patients who continue to inject, we have found high levels of satisfaction using the IIEF, the gold standard for evaluation of erectile function. On multivariate analysis, we found that older age, younger partner age, and fully rigid erections were predictors of increased satisfaction. ICI remains a robust second-line therapy in the treatment of ED even in the era of PDE5i.

Neurogenic erectile dysfunction (ED) is one of major causes of ED and is often difficult to treat. In this review, we report significant improvements of ED caused by diabetes mellitus (DM) or cavernous nerve injury by using a gene therapy approach in rat models of ED. Herpes simplex virus (HSV) vectors were used to deliver neurotrophic factors, such as neurotrophin 3 (NT3), glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN), into cavernous nerves. The retrograde transport of HSV vector-mediated neurotrophic factors to pelvic ganglion neurons occurred after the administration of the vector around the cavernous nerves. HSV vector administration around the cavernous nerves can improve DM-induced ED and promote the recovery of erectile function after cavernous nerve injury. The HSV vector-mediated delivery of neurotrophic factors could be applicable for the treatment of neurogenic ED. NT3, GDNF, and NTN would be the possible factors that could be used for this gene therapy application.

The immunophilin-ligand FK506 has been shown to ameliorate erectile function and preserve cavernous nerve (CN) architecture in short-term-studies using rat models of CN injury.The aim of this series was to ascertain the optimal dose and timing of FK506 administration in this animal model.Rats underwent bilateral CN crush and were treated with FK506 at different time points. There were control (C) and sham groups for each time point. Based on preliminary experiments, the CN-crush rats had no treatment (C) or either FK506 1 mg/kg (BL) or 3.2 mg/kg (BH) for 3 days prior to and the day of CN crush (PRE), on the day of and for 3 days following CN crush (POST) and for 3 days pre-, on the day of, and 3 days post-CN crush (PP).All animals had measurement of intracavernosal pressure/mean arterial blood pressure (ICP/MAP) ratios at 28 days post-CN crush. Structural analysis was conducted in the POST groups. Penile tissue was assessed for apoptosis with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay and immunohistochemically for neural factors (growth associated protein 43 [GAP43], nerve growth factor [NGF], and neural nitric oxide synthase [nNOS]). The CN architecture was examined by transmission electron microscopy (TEM).Sham animals had an ICP/MAP ratio of 70%. Only the BH-POST group revealed an improved ICP/MAP ratio compared with C (50 +/- 9% vs. 32 +/- 8%, P0.01). nNOS staining was significantly restored reaching sham levels in BL-POST and BH-POST groups vs. C (P0.05). NGF and GAP43 staining displayed no significant differences between C and treatment groups (P0.05). Apoptosis was significantly reduced in BL-POST and BH-POST groups compared with C (16 +/- 4%, 21 +/- 9%, and 63 +/- 7%, P0.001). TEM exhibited preservation of CN architecture for BH-POST compared with C.These results suggest that short-term treatment with doses of FK506 higher than previously utilized preserves erectile function in the rat CN-injury model. Pretreatment appears to offer no advantage. However, FK506 administration just prior to CN injury and for a short-time post-injury achieves the best functional and structural preservation outcomes.

Objectives To define the impact of intralesional verapamil injection therapy on penile deformity in men with Peyronie’s disease. Methods Patients underwent a total of 6 intralesional injections of verapamil. Penile deformity was assessed at baseline and 3 months after the last intralesional injection of verapamil during penile erection after the administration of intracavernosal medication. Measurement was recorded using a goniometer at maximum penile rigidity. Endpoints included change in magnitude of curvature, stretched penile length, penetration ability, and resolution of pain. Results Ninety-four consecutive patients met all inclusion criteria. Mean (± standard deviation) patient age and duration of Peyronie’s disease at time of baseline deformity assessment were 44 ± 18 years and 5.2 ± 2.7 months, respectively. At baseline 86% had dorsal and 14% lateral curvature. The mean curvature and stretched flaccid length were 50° ± 28° and 12.6 ± 3.1 cm, respectively. At the follow-up evaluation, patients were 5.2 ± 1.8 months after their last ILV injection and were 11.7 ± 4.2 months after the onset of Peyronie’s disease. Eighteen percent of patients had improvement of curvature, 60% were unchanged, and 22% worsened. Pain resolved in 100% of patients. Conclusions In response to intralesional verapamil, a minority of men experienced improvement in penile deformity; however, the majority of patients had stabilization of their deformity. This information may permit clinicians to give realistic expectations to patients considering intralesional verapamil therapy.

Peyronie’s disease (PD) is a progressive wound-healing disorder highlighted by an inelastic fibrous scar in the tunica albuginea. Its etiology has been linked to a history of penile trauma and subsequent microvascular insults followed by extravascular activation of the fibrotic cascade. The most common clinical manifestation is a dorsal curvature and an associated palpable plaque. Subjective symptoms include painful erections, sexual dysfunction, and significant psychosocial burden. Options for non-surgical management of PD include penile stretching programs and devices, oral medications, and injectable agents (interferon-alpha 2B, verapamil). No single agent or modality has been shown to reliably alter fibrotic disease process resulting in modest and inconsistent benefits in a minority of men. Collagenase clostridium histolyticum (CCh) intralesional injection is Food and Drug Administration approved for adult men with PD with a palpable plaque and non-ventral curvature of at least 30 degrees at the start of therapy. CCh is a bacterially derived collagenase that cleaves the collagen triple-helix within the Peyronie’s plaque potentially leading to change in plaque and penile morphology. Each CCh injection cycle consists of two Peyronie’s plaque injections followed by an in-office penile modeling session. The patient may require up to four cycles of CCh to achieve maximal penile straightening. CCh is packaged in two vials. The first vial contains 0.9 mg of lyophilized CCh that requires reconstitution. The second vial is the diluent; a calcium dihydrate-containing solution that is required for activation of the CCh enzyme. Both vials should be removed from the refrigerator and allowed to rest at room temperature for 15 minutes prior to mixing. To reconstitute, 0.39 mL of diluent is injected into the vial containing lyophilized powder. This reconstituted solution of CCH can be kept for 1 hour at room temperature or refrigerated at 2–8°C for up to 4 hours.

Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder afferent neurons. In adult female rats, NGF (2.5 μg/μl) was infused continuously into the intrathecal space at the L6–S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 μl/h). Bladder afferent neurons were labeled with axonal transport of Fast Blue injected into the bladder wall. After intrathecal injection of NGF, cystometrograms under an awake condition showed bladder overactivity revealed by time-dependent reductions in intercontraction intervals and voided volume. ELISA analyses showed significant increases in NGF levels in L6–S1 dorsal root ganglia of NGF-treated rats. In patch-clamp recordings, dissociated bladder afferent neurons exhibiting tetrodotoxin (TTX)-resistant action potentials from NGF-treated animals were larger in diameter and had significantly lower thresholds for spike activation compared with sham rats. In addition, the number of TTX-resistant action potentials during 600 ms depolarizing pulses was significantly increased time dependently after 1 or 2 weeks of NGF application. The density of slowly inactivating A-type K+currents was decreased by 52% in bladder afferent neurons with TTX-resistant spikes after 2 week NGF treatment. These results indicate that increased NGF levels in bladder afferent pathways and NGF-induced reduction in A-type K+current density could contribute to the emergence of bladder overactivity as well as somal hypertrophy and hyperexcitability of bladder afferent neurons.

The occurrence of breast cancer in men is rare in comparison to women. Public knowledge that men can get breast cancer and of male breast self-examination are lacking. Research in the course and treatment of breast cancer in men is needed. Men generally present in more advanced stages of breast cancer than women, and have a poorer prognosis. In this article, the epidemiology, common symptoms, diagnostic methods, and current treatment of breast cancer in men are described. Gender differences in presentation and course of illness are discussed. Additionally, the psychological implications of breast cancer for male gender roles and masculine identity are explored. Directions for further investigation are given. Treatment providers are encouraged to educate themselves and their male patients on breast cancer in men and male breast examination techniques so that this disease may be identified earlier in its course and survival rates improved.

Introduction Intracavernosal injection (ICI) therapy is a well‐recognized treatment strategy with high success rates for men with erectile dysfunction. Despite this, injection anxiety and pain related to injection are significant barriers to its use. Aims This study aims to examine injection anxiety and injection pain in patients using ICI. Methods Men starting ICI therapy post radical pelvic surgery completed questionnaires at initial visit, at each of the two ICI training sessions and at a 4‐month follow‐up visit. Main Outcome Measures Injection Anxiety Scale, Injection Pain Scale, Injection Reaction Inventory, and the Erectile Function Domain of the International Index of Erectile Function. Results Average age of the 68 men was 60 ± 8 years. At 4 months, the self‐reported frequency of ICI use was: 29% P P = 0.003) at 4 months. Anxiety at first injection was negatively related to ICI frequency at 4 months ( r = −0.23, P = 0.08). Mean injection pain score at first injection was low (2.2 ± 1.8, range 0–10) and 59% rated injection pain ≤2. Injection pain remained consistent across time periods. At first injection, injection anxiety (assessed prior to injection) was related to injection pain ( r = 0.21, P = 0.04) and subjects (n = 21) who reported high injection anxiety (≥5) across time points, reported an increase in injection pain scores from first injection to 4 months (2.7 vs. 3.7, P = 0.05). Conclusions Although injection anxiety decreased with ICI use, mean injection anxiety remained at a moderate level (4.4) and 42% of men continued to report “high” injection anxiety at 4 months. While injection pain was low, injection anxiety and pain were related. These data suggest the need for a psychological intervention to help lower injection anxiety related to ICI. Nelson CJ, Hsiao W, Balk E, Narus J, Tal R, Bennett NE, and Mulhall JP. Injection anxiety and pain in men using intracavernosal injection therapy after radical pelvic surgery. J Sex Med 2013;10:2559–2565.

Anatomy of reproductive function The reproductive functional axis of the male can be divided into three major subdivisions: (1) the hypothalamus, (2) the pituitary gland, and (3) the testis. Each level elaborates a signal, or transmitter molecule, that stimulates or inhibits the subsequent level of the axis. The end result is the production and expulsion of semen that contains spermatozoa. This chapter examines the hypothalamic–pituitary–gonadal (HPG) axis, and reviews the functional anatomy of the testis, epididymis, vas deferens, seminal vesicles, prostate, and penis.

Circumcision is one of the most common surgical procedures performed on males in the United States. Ethical considerations of the procedure have been considered for many years and, recently, research on the topic has shed more light on the debate. The purpose of this study was to review the history and emergence, current demographics, and practices of male circumcision, specifically, nonreligious, nonmedically indicated routine neonatal circumcision. A review of the current literature was conducted using PubMed and current practices from guidelines of major professional societies. Physicians should consider the various ethical concerns and provide the patient's guardians with unbiased counsel. There is a lack of evidence both in favor of and against recommending routine neonatal circumcisions in the United States. The question remains whether we should continue unwarranted male circumcisions, especially when the major tenet of medical ethics is "do no harm."

An updated method for obtaining purified]glucosylgalactosyl hydroxylysine (Glc-Gal-Hyl) is presented. Marine sponge is subjected to alkaline hydrolysis followed by ion-exchange chromatography and gel filtration. Identification is confirmed by consecutive mild acid hydrolysis of the extract to produce galactosyl hydroxylysine (Gal-Hyl) and hydroxylysine (Hyl). High-performance liquid chromatography (HPLC) with a sodium acetate-acetonitrile-buffer and dabsyl chloride as the derivatizing agent demonstrated the purity of the extract and its hydrolyzates. Glc-Gal-Hyl is not commercially available but this easy and efficient method can provide large amounts of it for collagen metabolism studies.

We evaluated the efficacy and tolerability of higher dose oxybutynin chloride in patients with neurogenic bladder and multiple sclerosis, spinal cord injury or Parkinson's disease.The study design was a prospective, 12-week dose titration trial of controlled release oxybutynin (OXY-XL). A 7-day washout period was used before initiation of the starting dose of 10 mg OXY-XL. Doses of OXY-XL were increased by 5 mg at weekly intervals to a maximum dose of 30 mg per day guided by patient perception of efficacy versus side effect. Voiding diaries were completed at baseline, and weeks 6 and 12. Post-void residuals were recorded. Criteria for study admission included post-void residual less than 200 ml.Of the 39 patients enrolled in the study 22 had multiple sclerosis, 10 had spinal cord injury and 7 had Parkinson's disease. There were 29 women (74%) and 10 men (26%). Within 1 week a decrease in the number of voids per day was seen in greater than 50% of the subjects. At the end of the study statistically significant decreases in the number of voids in 24 hours, episodes of nocturia and incontinence episodes were observed. Residual urine remained unchanged from 33.9 +/- 7.6 ml at baseline to 51.3 +/- 10.4 ml after 12 weeks at the final dose (p = 0.17). No patient experienced serious adverse events and none dropped out during the course of the 12-week study. At the end of the study 20.5% of subjects remained on 30 mg, 15.4% on 25 mg, 23.1% on 20 mg, 15.4% on 15 mg and 25.6% on 10 mg OXY-XL.Aggressive dosing of OXY-XL is safe and effective in patients with neurogenic bladder. Compared with nonneurogenic overactive bladder, higher doses of OXY-XL (15 mg daily or greater) were requested by 74.4% of the patients in our study. The onset of clinical efficacy can occur within 1 week, and doses up to 30 mg are well tolerated and effective in this population.

The central functional unit of the penis is the corpora cavernosa. These dual cylindrical erectile bodies form the basis of erection. They are connected to each other for the distal two-thirds of their length. Within the corpora cavernosa are robust fenestrations resulting in significant cross-talk between the corpora. Proximally, they are connected to the undersurface of the inferior pubic rami. A thick-fibrous covering called the tunica albuginea surrounds each corpus cavernosa. As a result of cavernous nerve signals, the spongy sinusoidal spaces fill with blood and expand against the tunica albuginea compressing the subtunical venous plexuses, decreasing venous outflow. The sinusoidal spaces (lacunar spaces) are lined by vascular endothelium. The walls of these spaces are referred to as trabeculae and are composed of smooth muscle and collagen.

Sickle cell anemia is a common and disabling disorder profoundly affecting mortality as well as quality of life. Up to 35% of men with sickle cell disease are affected by painful, prolonged erections termed ischemic priapism. A priapic episode may result in fibrosis and permanent erectile dysfunction. The severity of sickle cell disease manifestations is variable dependent on a number of contributing genetic factors; however, priapism tends to cluster with other severe vascular complications including pulmonary hypertension, leg ulceration, and overall risk of death. The mechanisms underlying priapism in sickle cell disease have begun to be elucidated including hemolysis-mediated dysregulation of the nitric oxide signaling pathway and dysregulation of adenosine-mediated vasodilation. A better understanding of these mechanisms is leading toward novel preventative strategies. This paper will focus on the mechanisms underlying development of ischemic priapism in sickle cell disease, current acute and preventative treatment strategies, and future directions for improved management of this disorder.

The true pathophysiologic nature of Peyronie's disease continues to evolve. This pathology often results in a penile plaque(s), penile deformity, curvature, pain, and erectile dysfunction. Clinically, there are two distinct phases, acute and chronic. The focus of this review will center on the management of the acute phase of Peyronie's disease. While little data exists demonstrating disease resolution, disease stabilization is an important clinical goal for patients as this often allows acceptable sexual function. Thus, medical management during the acute phase of Peyronie's disease is aimed at limiting and stabilizing the degree of penile fibrosis, decreasing penile curvature, and reducing penile pain. In this manuscript we explain different therapies; oral, topical, intralesional injection and others like extracorporeal shockwave (ESWT), radiation and penile traction for acute phase of Peyronie's disease. Although no consensus exists for the treatment of acute phase Peyronie's disease, a majority of patients can achieve stabilization and in some cases regression of their disease with proper medical therapy. The goals of therapy should be discussed extensively with each patient, noting that erectile function will be likely despite some degree of curvature.

Introduction The association between erectile dysfunction (ED) and radical prostatectomy (RP) is well established. It is our clinical experience that some men who have functional erections in the days to weeks after RP go on to lose erectile function (EF) after the first 3 months postsurgery. Aim To assess EF over a 12-month period in patients with functional erections at 3 months following RP. Methods As part of a large prospective quality-of-life (QOL) study of men undergoing RP at our institution, EF is measured postoperatively at regular time intervals using serial administration of the International Index of Erectile Function (IIEF) questionnaire. For study inclusion, patients had to have functional erections (a score 4 or 5 on IIEF question 3) at the third postoperative month, and have at least 12 months of follow-up. Main Outcome Measures Assessment of EF and phosphodiesterase type 5 inhibitor (PDE5i) use at 3, 6, and 12 months after RP. Results At 3 months, 76 of 482 patients (16%) had functional erections. Between 3 to 6 months postoperatively, 20% of men deteriorated in their functional status. Of these men, 91% had functional erections at 1 year. Comparing patients who did not require PDE5i to obtain a functional erection at 3 months with those who did, the EF outcomes were superior at 6 months (80% vs. 72%, P = 0.74) and 12 months (100% vs. 88%, P = 0.33). Conclusion The recovery of functional erections in the early postoperative phase, especially without the need for PDE5i, is a good prognostic indicator for EF at 12 months. However, a distinct cohort of men lose functional erections within 6 months after surgery. It is important to inform patients of this possibility, as it has an impact on their QOL and, potentially, on their compliance with post-RP therapy for ED. Katz D, Bennett NE, Stasi J, Eastham JA, Guillonneau BD, Scardino PT, and Mulhall JP. Chronology of erectile function in patients with early functional erections following radical prostatectomy.

La verdadera naturaleza fisiopatológica de la enfermedad de Peyronie sigue evolucionando. Esta patología suele traducirse en una placa (s) en el pene, deformidad, incurvación, dolor y disfunción eréctil. Clínicamente, hay dos fases definidas, aguda y crónica. Esta revisión se centrará en el manejo de la fase aguda de la enfermedad de Peyronie. Si bien existen pocos datos que manifiesten la resolución de la enfermedad, la estabilización es un objetivo clínico importante para los pacientes ya que permite a menudo una función sexual aceptable. Por lo tanto, el tratamiento médico durante la fase aguda de la enfermedad de Peyronie tiene como objetivo limitar y estabilizar el grado de fibrosis del pene, disminuyendo la curvatura del pene, y, reduciendo el dolor. Detallamos a continuación diferentes terapias para el tratamiento de la fase aguda de la enfermedad de Peyronie, tales como oral, tópica, inyección intralesional y otras como la Terapia Extracorpórea con Ondas de Choque (LEOC). Terapia de radiación y tracción del pene. Aunque no existe consenso para el tratamiento de la fase aguda de la enfermedad de Peyronie, la mayoría de los pacientes puede lograr la estabilización y en algunos casos la regresión de su enfermedad, con el tratamiento médico adecuado. Los objetivos de la terapia deben ser ampliamente discutidos con cada paciente, teniendo en cuenta que la función eréctil es probable, a pesar de cierto grado de curvatura.

Priapism is associated with sickle cell disease (SSD); however, few men receive education about this condition, which contributes to attenuated return of functional erections.To define the demographics, SSD status, and treatment outcomes of African-American men presenting with priapism.Demographics, medical history, self-report of sickle cell status, and outcome assessment using International Inventory of Erectile Function (IIEF) of men with priapism were retrospectively reviewed.A review of 39 cases of venocclusive priapism in African-American men was conducted. Charts were reviewed for demographics, medical history including SSD status by patient self-report, serum hemoglobin electrophoresis results, and priapism treatment and outcome.Mean duration of presenting priapism episode was 22 +/- 12 hours (6-70 hours). Eight percent of men had priapism for12 hours, 59% 12-24 hours, 22% 24-36 hours, and 11%36 hours. All patients with priapism events of12 hours complained of reduction in erectile rigidity. No patients with priapism36 hours duration had return of spontaneous functional erections, but 44% (24-36 hours), 78% (12-24 hours) and 100% (12 hours) were able to generate functional erections with or without the use of sildenafil. Follow-up IIEF erectile function domain scores paralleled incidence of functional erections. Penile shunt surgery was required in 28%. Only 5% of men recalled learning that priapism was a complication of SSD. Six men denied a history of SSD; however, hemoglobin electrophoresis revealed abnormal hemoglobin S and elevated hemoglobin F levels in four of these men.The association of SSD and venocclusive priapism is well known in the medical community, yet few patients ever receive education regarding the emergency nature of the condition. The majority of men presents in a delayed fashion, and a significant proportion requires shunt surgery leading to long-term erectile dysfunction. Of those who denied having SSD, two-thirds had SSD by hemoglobin electrophoresis.