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The treatment of male hypogonadism is complicated by the multitude of treatments available, the lack of a clear understanding of the differences between treatment modalities, barriers to treatment, and patient misperceptions, unrealistic expectations, and anxieties. This article is intended to help the practitioner better understand the challenges of testosterone replacement options in order to better counsel and treat their patients with hypogonadism., Competing Interests: Disclosure No conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Acute otitis media (AOM) is associated with high antibiotic prescribing rates. Antibiotics are somewhat effective in improving pain and middle ear effusion (MEE); however, they have unfavourable effects. Alternative treatments, such as corticosteroids as anti-inflammatory agents, are needed. Evidence for the efficacy of these remains inconclusive. We conducted a pilot study to test feasibility of a proposed large-scale randomised controlled trial (RCT) to assess the efficacy of corticosteroids for AOM., Methods: We conducted a pilot, pragmatic, parallel, open-label RCT of oral corticosteroids for paediatric AOM in primary and secondary/tertiary care centres in Indonesia. Children aged 6 months-12 years with AOM were randomised to either prednisolone or control (1:1). Physicians were blinded to allocation. Our objectives were to test the feasibility of our full RCT procedures and design, and assess the mechanistic effect of corticosteroids, using tympanometry, in suppressing middle ear inflammation by reducing MEE., Results: We screened 512 children; 62 (38%) of 161 eligible children were randomised and 60 were analysed for the primary clinical outcome. All study procedures were completed successfully by healthcare personnel and parents/caregivers, despite time constraints and high workload. All eligible, consenting children were appropriately randomised. One child did not take the medication and four received additional oral corticosteroids. Our revised sample size calculation verified 444 children are needed for the full RCT. Oral corticosteroids did not have any discernible effects on MEE resolution and duration. There was no correlation between pain or other symptoms and MEE change. However, prednisolone may reduce pain intensity at day 3 (Visual Analogue Scale mean difference - 7.4 mm, 95% confidence interval (CI) - 13.4 to - 1.3, p = 0.018), but cause drowsiness (relative risk (RR) 1.8, 95% CI 1.1 to 2.8, p = 0.016). Tympanometry curves at day 7 may be improved (RR 1.8, 95% CI 1.0 to 2.9). We cannot yet confirm these as effects of corticosteroids due to insufficient sample size in this pilot study., Conclusions: It is feasible to conduct a large, pragmatic RCT of corticosteroids for paediatric AOM in Indonesia. Although oral corticosteroids may reduce pain and improve tympanometry curves, it requires an adequately powered clinical trial to confirm this., Trial Registration: Study registry number: ACTRN12618000049279. Name of registry: the Australian New Zealand Clinical Trials Registry (ANZCTR). Date of registration: 16 January 2018., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Aims: Two phase 1 trials were performed in healthy women with the overactive bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity (DO), with the aim to demonstrate the safety and potential efficacy of URO-902, which comprises a gene therapy plasmid vector expressing the human big potassium channel α subunit., Methods: ION-02 (intravesical instillation) and ION-03 (direct injection) were double-blind, placebo-controlled, multicenter studies without overlap in enrollment between studies. Active doses were administered and evaluated sequentially (lowest dose first) for safety. ION-02 participants received either 5000 µg or 10 000 µg URO-902, or placebo. ION-03 participants received either 16 000 or 24 000 µg URO-902, or placebo, injected directly into the bladder wall using cystoscopy. Primary outcome variables were safety parameters occurring subsequent to URO-902 administration; secondary efficacy variables also were evaluated., Results: Among the safety outcomes, there were no dose-limiting toxicities or significant adverse events (AEs) preventing dose escalation during either trial, and no participants withdrew due to AEs. For efficacy, in ION-02 (N = 21), involuntary detrusor contractions on urodynamics at 24 weeks in patients receiving URO-902 (P < .0508 vs placebo) and mean urgency incontinence episodes in the 5000 µg group (P = .0812 vs placebo) each showed a downward trend. In ION-03 (N = 13), significant reduction versus placebo in urgency episodes (16 000 µg, P = .036; 24 000 µg, P = .046) and number of voids (16 000 µg, -2.16, P = .044; 24 000 µg, -2.73, P = .047) were observed 1 week after injection., Conclusion: Promising safety and efficacy results in these preliminary phase 1 studies suggest gene transfer may be a promising therapy for OAB/DO, warranting further investigation., (© 2020 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.)

Lubricity is a key property of hydrophilic-coated urinary catheter surfaces. In vitro tests are commonly employed for evaluation of surface properties in the development of novel catheter coating technologies; however, their value in predicting the more subjective feeling of lubricity requires validation. We herein perform a range of in vitro assessments and human organoleptic studies to characterise surface properties of developmental hydrophilic coating formulations, including water wettability, coefficient of friction, dry-out kinetics and lubricity. Significant reductions of up to 40% in the contact angles and coefficient of friction values of the novel coating formulations in comparison with the control poly(vinylpyrrolidone)-coated surfaces were demonstrated during quantitative laboratory assessments. In contrast, no significant differences in the more subjective feeling of lubricity between the novel formulations and the control-coated surfaces were observed when formulations were haptically assessed by the techniques described herein. This study, importantly, highlights the need for optimisation of in vitro and human haptic assessments to more reliably predict patient preferences.

Background: Acute otitis media (AOM) is an acute inflammation of the middle ear commonly found in children, for which antibiotics are frequently prescribed. However, antibiotics are beneficial for only one third of AOM cases, and then, with only modest benefit. Since antibiotic use leads to risk of side effects and resistance, effective alternative treatments are required. Corticosteroids are a candidate because of their anti-inflammatory effects, although evidence of their efficacy and harms is insufficient. Accordingly, we plan a large, rigorous clinical trial to test this. Initially, we will test pre-specified methods and procedures (including the overall process, resources, management, and scientific components) in a pilot study of corticosteroids for AOM, which will inform a future, definitive trial., Methods: This is a pilot pragmatic, randomised, open-label, single-blind, controlled study of corticosteroids as either monotherapy or an addition to antibiotics in 60 children aged 6 months to 12 years with AOM in two cities (Jakarta and Bekasi) in Indonesia. We will randomise eligible children to prednisolone or control. We will also stratify by disease severity and randomise those with mild AOM to expectant observation plus prednisolone or observation alone and those with severe AOM to prednisolone plus antibiotic or antibiotic alone. Our outcomes are to determine (1) recruitment rates, (2) the success of the study procedures, (3) the ability to measure planned outcomes of the proposed main study, (4) the compliance to study visits and study medication, and (5) verification of the sample size calculation for the main study. We will also assess middle ear effusion using tympanometry as part of a mechanistic sub-study., Discussion: This study will test all procedures in preparation for the main study, including several potential obstacles and challenges from the perspective of participating physicians, nurses, pharmacists, and the parents of eligible children. This information will be useful for developing strategies to overcome practical and procedural issues. This study may also provide information about the effects of corticosteroids on middle ear effusion in AOM., Trial Registration: Study registry number: ACTRN12618000049279. Name of registry: the Australian New Zealand Clinical Trials Registry (ANZCTR). Date of registration: 16 January 2018., Competing Interests: This study protocol was reviewed and approved by the Ethics Committee FMUI Indonesia (No. 852/UN2.F1/ETIK/2017 and Amendment No. 1088/UN2.F1/ETIK/X/2017) and the BUHREC Australia (No. 16151 and Amendment No. 16208). We received approval for conducting clinical research from the One Stop Integrated Service Agency Province of DKI Jakarta (No. 0204/AF.1/31/-1.862.9/2017). We will also seek clinical study permits from the Training and Research division at each participating hospital. We will provide the patient information sheet, including the whole study process and procedures and potential risks from the study, and obtain consent from the parent(s) or legal guardian of patients, before conducting the recruitment and randomisation process. However, for children aged 12 years, they have also to provide their consent to participate in the study (Additional file 2. Case report forms—Pilot OPAL Study: CRF01. Information sheet and consent form). The person who delivers the consent also will provide their signatures on the consent form, stating that they have provided information and opportunity for potential participants to understand and raise relevant questions to the study. We will ensure that the consent process is free of coercion. As the participation into the study is voluntary, we will emphasise their rights to withdraw from the study at any time without any consequences, particularly on the quality of their healthcare services.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: To compare the current rate of antibiotic prescribing for acute respiratory infections (ARIs) in Australian general practice with the recommendations in the most widely consulted therapeutic guidelines in Australia (Therapeutic Guidelines)., Design and Setting: Comparison of general practice activity data for April 2010 - March 2015 (derived from Bettering the Evaluation and Care of Health [BEACH] study) with estimated rates of prescribing recommended by Therapeutic Guidelines., Main Outcome Measures: Antibiotic prescribing rates and estimated guideline-recommended rates per 100 encounters and per full-time equivalent (FTE) GP per year for eight ARIs; number of prescriptions nationally per year., Results: An estimated mean 5.97 million (95% CI, 5.69-6.24 million) ARI cases per year were managed in Australian general practice with at least one antibiotic, equivalent to an estimated 230 cases per FTE GP/year (95% CI, 219-240 cases/FTE/year). Antibiotics are not recommended by the guidelines for acute bronchitis/bronchiolitis (current prescribing rate, 85%) or influenza (11%); they are always recommended for community-acquired pneumonia (current prescribing rate, 72%) and pertussis (71%); and they are recommended for 0.5-8% of cases of acute rhinosinusitis (current prescribing rate, 41%), 20-31% of cases of acute otitis media (89%), and 19-40% cases of acute pharyngitis or tonsillitis (94%). Had GPs adhered to the guidelines, they would have prescribed antibiotics for 0.65-1.36 million ARIs per year nationally, or at 11-23% of the current prescribing rate. Antibiotics were prescribed more frequently than recommended for acute rhinosinusitis, acute bronchitis/bronchiolitis, acute otitis media, and acute pharyngitis/tonsillitis., Conclusions: Antibiotics are prescribed for ARIs at rates 4-9 times as high as those recommended by Therapeutic Guidelines. Our data provide the basis for setting absolute targets for reducing antibiotic prescribing in Australian general practice.

Background: We sought to describe the theory used to design treatment adherence interventions, the content delivered, and the mode of delivery of these interventions in chronic respiratory disease., Methods: We included randomized controlled trials of adherence interventions (compared to another intervention or control) in adults with chronic respiratory disease (8 databases searched; inception until March 2015). Two reviewers screened and extracted data: post-intervention adherence (measured objectively); behavior change theory, content (grouped into psychological, education and self-management/supportive, telemonitoring, shared decision-making); and delivery. "Effective" studies were those with p < 0.05 for adherence rate between groups. We conducted a narrative synthesis and assessed risk of bias., Results: 12,488 articles screened; 46 included studies (n = 42,91% in OSA or asthma) testing 58 interventions (n = 27, 47% were effective). Nineteen (33%) interventions (15 studies) used 12 different behavior change theories. Use of theory (n = 11,41%) was more common amongst effective interventions. Interventions were mainly educational, self-management or supportive interventions (n = 27,47%). They were commonly delivered by a doctor (n = 20,23%), in face-to-face (n = 48,70%), one-to-one (n = 45,78%) outpatient settings (n = 46,79%) across 2-5 sessions (n = 26,45%) for 1-3 months (n = 26,45%). Doctors delivered a lower proportion (n = 7,18% vs n = 13,28%) and pharmacists (n = 6,15% vs n = 1,2%) a higher proportion of effective than ineffective interventions. Risk of bias was high in >1 domain (n = 43, 93%) in most studies., Conclusions: Behavior change theory was more commonly used to design effective interventions. Few adherence interventions have been developed using theory, representing a gap between intervention design recommendations and research practice., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Adherence to treatment is low in bronchiectasis and is associated with poorer health outcomes. Factors affecting adherence decisions have not been explored in patients with bronchiectasis., Objective: We aimed to explore patients' perspectives on adherence, factors affecting adherence decision making and to develop a conceptual model explaining this decision-making process in adults with bronchiectasis., Methods: Adults with bronchiectasis participated in one-to-one semi-structured interviews. Interviews were audio-recorded, transcribed verbatim and analysed independently by two researchers using thematic analysis. Data from core themes were extracted, categorized into factors affecting adherence decision making and used to develop the conceptual model., Results: Participants' beliefs about treatment, the practical aspects of managing treatment, their trust in health-care professionals and acceptance of disease and treatment were important aspects of treatment adherence. The conceptual model demonstrated that adherence decisions were influenced by participants' individual balance of barriers and motivating factors (treatment-related, disease-related, health-care-related, personal and social factors)., Conclusion: Adherence decision-making in bronchiectasis is complex, but there is the potential to enhance adherence by understanding patients' specific barriers and motivators to adherence and using this to tailor adherence strategies to individual patients and treatments., (© 2014 John Wiley & Sons Ltd.)

Objectives: To systematically review clinicians' knowledge and beliefs about the importance and causes of antibiotic resistance, and strategies to reduce resistance., Methods: Four databases were searched (until July 2014), without restrictions on language, setting or study design. Fixed responses (from surveys) were grouped into categories. The proportion of participants who agreed with each category was expressed as median, percentage and IQR. Qualitative data were coded into emergent themes. Quantitative categories and qualitative themes were grouped into four overarching categories that emerged from the data., Results: There were 57 included studies (38 quantitative, 14 qualitative, 5 mixed methods) of 11593 clinicians. Most clinicians (69%, IQR 63%-72%, n=5 studies) had heard of antibiotic resistance and 98% (IQR 93%-99%, n=5 studies) believed it was serious. The proportion who believed it was a problem for their practice (67%, IQR 65%-74%, n=13 studies) was smaller than the proportion who believed it was a problem globally (89%, IQR 85%-97%, n=5 studies) or nationally (92%, IQR 88%-95%, n=21 studies). Most believed excessive antibiotic use (97%, IQR 91%-98%, n=12 studies) and patient non-adherence (90%, IQR 82%-92%, n=7 studies) caused resistance. Most knew of strategies to reduce resistance (e.g. clinician education, 90%, IQR 85%-96%, n=7 studies). Qualitative findings support these data: they attributed responsibility for antibiotic resistance to patients, other countries and healthcare settings; resistance was considered a low priority and a distant consequence of antibiotic prescribing., Conclusions: Clinicians believe antibiotic resistance is a serious problem, but think it is caused by others. This needs to be accommodated in interventions to reduce antibiotic resistance., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Low patient adherence to treatment is associated with poorer health outcomes in bronchiectasis. We sought to use the Theoretical Domains Framework (TDF) (a framework derived from 33 psychological theories) and behavioural change techniques (BCTs) to define the content of an intervention to change patients' adherence in bronchiectasis (Stage 1 and 2) and stakeholder expert panels to define its delivery (Stage 3)., Methods: We conducted semi-structured interviews with patients with bronchiectasis about barriers and motivators to adherence to treatment and focus groups or interviews with bronchiectasis healthcare professionals (HCPs) about their ability to change patients' adherence to treatment. We coded these data to the 12 domain TDF to identify relevant domains for patients and HCPs (Stage 1). Three researchers independently mapped relevant domains for patients and HCPs to a list of 35 BCTs to identify two lists (patient and HCP) of potential BCTs for inclusion (Stage 2). We presented these lists to three expert panels (two with patients and one with HCPs/academics from across the UK). We asked panels who the intervention should target, who should deliver it, at what intensity, in what format and setting, and using which outcome measures (Stage 3)., Results: Eight TDF domains were perceived to influence patients' and HCPs' behaviours: Knowledge, Skills, Beliefs about capability, Beliefs about consequences, Motivation, Social influences, Behavioural regulation and Nature of behaviours (Stage 1). Twelve BCTs common to patients and HCPs were included in the intervention: Monitoring, Self-monitoring, Feedback, Action planning, Problem solving, Persuasive communication, Goal/target specified:behaviour/outcome, Information regarding behaviour/outcome, Role play, Social support and Cognitive restructuring (Stage 2). Participants thought that an individualised combination of these BCTs should be delivered to all patients, by a member of staff, over several one-to-one and/or group visits in secondary care. Efficacy should be measured using pulmonary exacerbations, hospital admissions and quality of life (Stage 3)., Conclusions: Twelve BCTs form the intervention content. An individualised selection from these 12 BCTs will be delivered to all patients over several face-to-face visits in secondary care. Future research should focus on developing physical materials to aid delivery of the intervention prior to feasibility and pilot testing. If effective, this intervention may improve adherence and health outcomes for those with bronchiectasis in the future.

Objectives: We aimed to determine if beliefs about treatment, clinical factors and quality of life predicted adherence to treatment in patients with bronchiectasis., Methods: We recruited participants with confirmed bronchiectasis to a one-year study. We calculated adherence to treatment using medication possession ratios and self-report. Baseline Beliefs about Medicines, clinical, demographic and Quality of Life Questionnaire-Bronchiectasis data were collected. We used logistic regression to determine predictors of adherence to treatment during the subsequent year., Results: Seventy-five participants were recruited. Beliefs about harm, age and total number of prescribed medications were predictors of adherence to inhaled antibiotics. Concerns about medication, age and Quality of Life Questionnaire-Bronchiectasis Treatment Burden were predictors of adherence to other respiratory medicines. Beliefs about necessity of airway clearance and age were predictors of adherence to airway clearance., Conclusion: Beliefs about treatment, age, number of prescribed medications and perceived treatment burden predicted subsequent adherence in bronchiectasis, thereby, providing potential targets for future interventions in this population. Clinicians can use these data to identify patients with bronchiectasis who might be at risk of non-adherence i.e. those who are younger, have concerns about medications, who do not think airway clearance is necessary or who are prescribed numerous medications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Numerous opportunities are available in primary care for alleviating the crisis of increasing antibiotic resistance. Preventing patients from developing an acute respiratory infection (ARI) will obviate any need for antibiotic use downstream. Hygiene measures such as physical barriers and hand hygiene, and possibly vaccination and exercise, may be effective. Also, a large range of complementary and alternative medicines (e.g. zinc, vitamin C and probiotics) are proposed for preventing and treating ARIs, but evidence for efficacy is scarce. General practitioners' (GPs) attitudes towards antibiotic prescribing are a major factor in the prescribing for ARIs. Professional interventions with educational components are effective, although they have modest effects, and are expensive. GPs' perceptions - that mistakenly assume as a default that patients want antibiotics for their ARIs - are often wrong. Shared decision making might be a solution, as it enables clinician and patient to participate jointly in making a health decision, having discussed the options together with the evidence for their harms as well as benefits. Furthermore, GPs' diagnostic uncertainty - often leading to an antibiotic prescription "just in case" - might be addressed by exploiting strategies such as safety-netting, e.g., establishing with the patient a priori clearly defined actions to take if the course of the illness deviates from the expected. None of these strategies or interventions on their own will greatly improve the use of antibiotics for ARIs. However, used in concert, combinations are likely to enable clinicians and health care systems to implement the strategies that will reduce antimicrobial resistance in the future.

Background: We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months., Methods: Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as "adherent" to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses., Results: Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with FEV1 % predicted., Conclusions: Treatment adherence is low in bronchiectasis and affects important health outcomes including pulmonary exacerbations. Adherence should be measured as part of bronchiectasis management and future research should evaluate bronchiectasis-specific adherence strategies.

Introduction: Provoked and spontaneous nocturnal erections are thought to play a role in maintenance of male sexual health through oxygenation of the corpus cavernosa. Conversely, hypoxia is thought to be an etiological factor in the pathogenesis of cavernosal fibrosis and long-term erectile dysfunction. It has been hypothesized that the early penile hypoxia after radical prostatectomy (RP) may lead to fibrosis and consequently a decrease in stretched penile length and long-term erectile dysfunction., Aim: The aim of this study was to assess the changes in penile tissue oxygenation with vacuum erection device (VED) use., Methods: Twenty men between 2 and 24 months following RP were enrolled prospectively. Each man cycled a VED to achieve full erection 10 consecutive times over a period of approximately 2 minutes without constriction ring., Main Outcome Measures: Tissue oximetry was measured at baseline and immediately after VED using a tissue oximeter at five sites: right thigh, right corpora, glans, left corpora, and left thigh. Additional measurements were captured over the course of an hour., Results: Mean age and time from surgery was 58.2 years and 12.6 months, respectively, and the average Sexual Health Inventory for Men score was 7. Use of the VED significantly increased both glanular and corporal oximetry relative to the baseline values for the entire 60 minutes. An initial increase of 55% was seen in corporal oxygenation with VED use., Conclusions: This is the first study demonstrating that a single, brief application of the VED without a constriction ring results in significant improvement in penile oxygen saturation. The use of a VED has significant benefits for patients both with regard to cost and invasiveness when compared with other penile rehabilitation protocols., (© 2014 International Society for Sexual Medicine.)

Introduction: Phosphodiesterase type 5 (PDE5) inhibitors have become standard treatment for erectile dysfunction (ED)., Aim: To prospectively evaluate the safety and efficacy of avanafil, a novel PDE5 inhibitor, in men with mild to severe ED., Methods: In this multicenter, double-blind, Phase 3 trial, 646 subjects were randomized to receive avanafil (50 mg, 100 mg, 200 mg) or placebo throughout a 12-week treatment period. Subjects were instructed to take study drug 30 minutes prior to initiation of sexual activity. At least a 12-hour separation time between doses was required; no restrictions were placed on food or alcohol intake., Main Outcome Measures: Improvement in erectile function (EF) was measured by Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3) and by the EF domain of the International Index of Erectile Function (IIEF) questionnaire., Results: Mean change in percentage of successful sexual attempts (SEP2 and SEP3) and IIEF-EF domain score significantly favored all doses of avanafil over placebo (P ≤ 0.001). Secondary analyses demonstrated achievement of successful intercourse by subjects within 15 minutes of dosing. Of the 300 sexual attempts made during this interval, 64% to 71% were successful in avanafil-treated subjects compared with 27% in placebo-treated subjects. Successful intercourse was also demonstrated >6 hours post dosing, with 59% to 83% of the 80 sexual attempts successful in avanafil-treated subjects compared with 25% of placebo-treated subjects. The most commonly reported adverse events in subjects taking avanafil included headache, flushing, and nasal congestion; there were no drug-related serious adverse events., Conclusion: Following 12 weeks of avanafil treatment without food or alcohol restrictions, significant improvements in sexual function were observed with all 3 doses of avanafil compared with placebo. Successful intercourse was observed as early as 15 minutes and >6 hours after dosing in some subjects. Avanafil was generally well tolerated for the treatment of ED., (© 2012 International Society for Sexual Medicine.)

Introduction: Implantable testosterone pellets were approved by the Food and Drug Administration in 1972 for the treatment of testosterone deficiency syndrome (TDS). Clinical use of this testosterone delivery modality has been limited until its recent reintroduction (Testopel(®) , Slate Pharmaceuticals, Durham, NC, USA). Six academic institutions collaborated and combined their databases to more fully characterize serum testosterone levels after the pellet implantations., Aims: To assess the time-dependent serum testosterone levels after subcutaneous testosterone pellets in clinical practice for the treatment of TDS., Methods: Data were retrospectively pooled and analyzed from data in six academic institutions. Variables included patient age, total testosterone concentrations before and after implantation, the number of testosterone pellets implanted, and the time from implantation to measurement of serum testosterone concentrations. Three hundred eighty men undergoing 702 insertions were included for analysis using JMP (version 4.0.4; SAS Institute, Cary, NC, USA)., Main Outcome Measures: Main outcome measures were postimplantation total testosterone levels and investigator-reported adverse events. Testosterone levels as a function of the number of pellets implanted and time from implantation were assessed., Results: Implantation of six to ≥10 testosterone pellets (450 to ≥750 mg) increased total testosterone into the therapeutic range at 1 month postimplantation and sustained therapeutic levels (>300) for 4-6 months. Higher pellet numbers (10-12 pellets) were associated with higher, more consistent, and longer maintenance of testosterone levels within the therapeutic range. Four extrusions and three hematomas were reported early in our experience; other investigator-reported adverse events were generally mild to moderate in nature and transient in duration. No subjects required analgesics., Conclusions: Testosterone pellets (Testopel(®) , Slate Pharmaceuticals) provide sustained levels of testosterone for at least 4 months and up to 6 months in men with TDS. Implantation of ≥8 pellets achieved optimal results with respect to peak mean testosterone level and duration of effect. Testosterone pellets were generally well tolerated., (© 2012 International Society for Sexual Medicine.)

Purpose: To our knowledge we report the first large, randomized, prospective penile rehabilitation clinical trial to compare the effectiveness of nightly intraurethral alprostadil vs sildenafil citrate after nerve sparing prostatectomy., Materials and Methods: We performed a prospective, randomized, open label, multicenter American study in men with normal erectile function who underwent bilateral nerve sparing radical prostatectomy. The International Index of Erectile Function erectile function domain was the primary end point. Subjects initiated nightly treatment within 1 month of surgery with intraurethral alprostadil or oral sildenafil citrate (50 mg) for 9 months. After 1-month washout and before sexual activity subjects self-administered sildenafil citrate (100 mg) for a total of 6 attempts in 1 month. Secondary end points were the global assessment question, sexual encounter profile, Erectile Dysfunction Inventory of Treatment Satisfaction and measured stretched penile length., Results: Of 139 men who started intraurethral alprostadil and 73 who started sildenafil citrate, 97 and 59, respectively, completed the trial. There were no statistically significant differences in International Index of Erectile Function erectile function domain and intercourse success rates to intraurethral alprostadil. The global assessment question was significantly better only at 6 months for intraurethral alprostadil (p <0.028). At completion there were no differences between treatments for any of the end points., Conclusions: This is the first study to directly compare the ability of alprostadil and a phosphodiesterase-5 inhibitor to enhance penile recovery subsequent to bilateral nerve sparing radical prostatectomy. The use of nightly subtherapeutic intraurethral alprostadil is well tolerated after radical prostatectomy. The benefit to return of erectile function of nightly sildenafil citrate and subtherapeutic intraurethral alprostadil appears to be comparable within the first year of surgery., (Copyright 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Context: Erectile dysfunction (ED) after radical prostatectomy (RP) has a significant negative impact on a patient's health-related quality of life. Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently been utilized not only as a treatment of ED in this population but also as a preventive strategy in penile rehabilitation programs., Objective: To elucidate the pathophysiologic mechanisms of post-RP ED, to assess the need for rehabilitation following surgery, and to analyze the basic scientific evidence and clinical applications of PDE5-Is for the prevention and treatment of ED., Evidence Acquisition: A systematic review of the literature using Medline, Cancerlit, and the Cochrane Library was conducted for the period between January 1997 and June 2008 using the keywords erectile dysfunction, radical prostatectomy, and phosphodiesterase inhibitors. Efficacy and safety of PDE5-Is in the randomized, placebo-controlled trials are evaluated in this review, and the limitations of the remaining studies are also discussed., Evidence Synthesis: Post-RP ED has many factors. Cavernosal nerve injury induces pro-apoptotic factors (ie, loss of smooth muscle) and pro-fibrotic factors (ie, an increase in collagen) within the corpora cavernosa. Cavernosal changes may also be attributed to poor oxygenation due to hemodynamic changes. Experimental data support the concept of cavernosal damage and suggest a protective role for daily dosage of a PDE5-I; however, similar data have not yet been replicated in humans. Penile rehabilitation programs are common in clinical practice, but there is no definitive evidence to support their use or the best treatment strategy. PDE5-Is are efficacious and safe in young patients with normal preoperative erectile function who have undergone bilateral nerve-sparing radical prostatectomy. On-demand use of a PDE5-I may be at least as efficacious as daily use. PDE5-I use in penile rehabilitation programs is not supported by rigorous level 1 evidence-based medicine., Conclusions: PDE5-Is are an efficacious and safe treatment for post-RP ED in properly selected patients. The experimental results on the protective role of daily dosages of PDE5-Is, while robust, have not been replicated in humans. With current human data, the role of a PDE5-I alone as a rehabilitation strategy is unclear and deserves further investigation.

Four weeks after bilateral nerve-sparing radical retropubic prostatectomy, men with normal erectile function before surgery were randomized to double-blind sildenafil (50 or 100 mg) or placebo nightly for 36 weeks, followed by an 8-week drug-free period before assessment of erectile function. Enrollment was prematurely ceased and only 76 men completed because, assuming a placebo response rate similar to the published literature (for example, 34% in meta-analysis), the 25% response at blinded interim review suggested a lack of treatment effect. On the contrary, spontaneous erectile function (a combined score of >or=8 for questions 3 and 4 of the International Index of Erectile Function and a positive response to 'Were erections good enough for satisfactory sexual activity?') occurred in only 4% of the placebo group (n=1 of 25) versus 27% (n=14 of 51, P=0.0156, Fisher's exact test) of the sildenafil group. Nightly sildenafil administration for 36 weeks after surgery markedly increased the return of normal spontaneous erections.

In two randomized, double-blind, placebo-controlled trials of 100 mg sildenafil citrate, men (N=601) with mild to moderate erectile dysfunction (ED) attempted intercourse 8 h (range, 7-9 h) postdose. The baseline to end-of-treatment improvement in the sildenafil groups vs placebo was greater (P<0.001) for the per-patient proportion (PPP) of 'yes' responses to the Sexual Encounter Profile question 3 (SEP3: successful intercourse (primary outcome)) (odds ratio (OR)=3.2 (trial 1), 7.6 (trial 2) and 5.6 (pooled data)); PPP of erection hardness score 4 (EHS 4, completely hard and fully rigid) (OR=6.2 (trial 1) and 10.9 (trial 2)); scores on the International Index of Erectile Function; and other EHS and SEP outcomes. Two to three times as many men were satisfied with sildenafil vs placebo treatment (Erectile Dysfunction Inventory of Treatment Satisfaction Index >50). Thus, responsiveness to 100 mg sildenafil may persist for 8 h postdose in men with mild to moderate ED.

Objectives: To clarify the period of responsiveness to sildenafil., Methods: Under a double-blind protocol, men with mild to moderate erectile dysfunction (International Index of Erectile Function [IIEF] Erectile Function domain score, 11 to 25) were randomized to sildenafil (100 mg) or placebo and attempted intercourse 8 hours (range, 7 to 9 hours) postdose (first 4-week phase) and 12 hours (11 to 13 hours) postdose (second 4-week phase after treatment crossover). The primary outcome was the per-patient proportion (PPP; least squares means [95% confidence interval]) of affirmative responses to the Sexual Encounter Profile question 3 (SEP3: "Did your erection last long enough for you to have successful intercourse?")., Results: For sildenafil (n = 174) versus placebo (n = 177), baseline values were similar but the PPP of successful intercourse attempts increased to 76% (69% to 82%) versus 50% (43% to 57%) in phase 1 (odds ratio [OR] = 3.2) and 79% (72% to 85%) versus 52% (44% to 60%) in phase 2 (OR = 3.5), and the PPP of Erection Hardness Score 4 erections (completely hard and fully rigid) was 41% (34% to 48%) versus 10% (7% to 15%) in phase 1 (OR = 6.2) and 44% (37% to 51%) versus 17% (12% to 23%) in phase 2 (OR = 4.0). Thus, at 12 hours, the odds of successful intercourse tripled and of a completely hard erection quadrupled. The sildenafil group achieved greater (P <0.001) PPP of successful penetration (SEP2), satisfaction with erection hardness (SEP4), and satisfaction with the sexual experience (SEP5); improvement in IIEF domain scores; and treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction., Conclusions: In men with mild to moderate ED, responsiveness to sildenafil may persist much longer than 4 hours.

Introduction: After bilateral nerve-sparing radical retropubic prostatectomy (BNSRRP), nocturnal and sexually mediated erections may help to preserve normal erectile function (EF)., Aim: To investigate nocturnal penile tumescence and rigidity (NPTR) in a subset (N = 54 men) from a randomized, double-blind trial (N = 76) of nightly sildenafil after BNSRRP., Methods: Inclusion required preoperative "normal" EF (defined as a combined score of >/=8 for International Index of Erectile Function questions 3 (penetration) and 4 (maintained erection after penetration) and NPTR testing (>/=10 continuous minutes of >/=55% rigidity [R >/= 55%] at the base). Postoperative assessments were at weeks 4 (pretreatment), 16, 28, 40 (during 36 weeks of nightly prophylaxis: sildenafil 50 mg [N = 17], 100 mg [N = 18] or placebo [N = 19]), and 48 (after 8 weeks of no erectile dysfunction therapy, when "responders" were delineated by the defined normal EF and a "yes" response to "Over the past 4 weeks, have your erections been good enough for satisfactory sexual activity?"). Base and tip rigidity and tumescence were measured using penile plethysmography., Main Outcome Measures: Duration of R >/= 55% and area under the curves for rigidity and tumescence., Results: Postoperatively, rapid profound reduction in nocturnal EF was noted in all groups. There was a gradual dose-dependent improvement in base and tip rigidity in the sildenafil groups but little improvement in the placebo group. Eight weeks after treatment termination (48 weeks postoperatively), 24% (4/17) of 50-mg sildenafil recipients, 33% (6/18) of 100-mg sildenafil recipients, and 5% (1/19) of placebo recipients were responders. Tip R >/= 55% was the most discriminating NPTR measure between nonresponders and responders to sildenafil, in whom it regained baseline (preoperative) levels (whereas base R >/= 55% did not). It was most prolonged in responders to sildenafil 100 mg., Conclusions: In our subset analysis, nightly sildenafil for 9 months post-BNSRRP objectively improved nocturnal erections and pharmaceutically unassisted EF.

The concept of muscle rehabilitation after nerve injury is not a novel idea and is practiced in many branches of medicine, including urology. Bladder rehabilitation after spinal cord injury is universally practiced. The erectile dysfunction (ED) experienced after radical prostatectomy (RP) is increasingly recognized as being primarily neurogenic followed by secondary penile smooth muscle (SM) changes. There is unfortunately no standard approach to penile rehabilitation after RP because controlled prospective human studies are not available. This article reviews the epidemiology, experimental pathophysiological models, rationale for penile rehabilitation, and currently published rehabilitation strategies.

We investigated the effect of early sildenafil dose optimization and personalized instructions on sexual intercourse success in 1109 men beginning sildenafil therapy for erectile dysfunction. In phase 1 (4 weeks), patients followed the instructions contained in the sildenafil (50 mg) sample pack and had 1.4 sexual intercourse attempts per week with 82% success. Patients (17%) had a second intercourse attempt (80% successful): 58% occurred within 4 h, 20% within 5-8 h, and 22% within 9-24 h of the first attempt. In phase 2 (4 weeks), sildenafil was adjusted as needed (53% to 100 mg, and 2% to 25 mg), and investigators provided personalized instructions to facilitate patient success. Sexual intercourse attempts increased to 1.7 per week, with 91% success, and 18% were followed by a second attempt, of which 91% were successful. Most patients requested the 100-mg dose, which helped improve sexual intercourse frequency, flexibility and success.

It is believed that a chronic state of corporal oxygen desaturation or hypoxemia secondary to the loss of nocturnal erections is a fundamental pathophysiological cause of erectile dysfunction (ED). Limited invasive blood gas measurements in human models have shown decreased oxygen tension in vasculogenic impotence. Normative data on flaccid and erect oxygen saturation (StO(2)) levels are lacking due to the invasive nature of blood gas determinations. Our objective was to determine StO(2) in the flaccid and erect penis in men with and without ED using a tissue oximeter. This FDA-approved instrument provides instantaneous, noninvasive, painless local tissue StO(2) measurements, which highly correlate to blood gas data. The study population included 171 men (18-90 years) who presented to one andrologist. They completed the Sexual Health Inventory for Men (SHIM) based on pharmacologically unassisted erectile function and had penile StO(2) measurements taken. 64 of these men had repeat measurements after PGE-1 induced erections. There are significant differences (P<.001) in corporal and glanular StO(2) in the flaccid (right corpora, 45.23%; left corpora, 52.50%) and erect state (right corpora, 76.58; left corpora, 80.42). Men with ED (right corpora, 45.04% vs 53.58%; P=.02; and left corpora, 50.95% vs 58.78%; P=.03) have significantly lower corporal penile StO(2). Future prospective data collection can correlate penile StO(2) in specific populations, such as diabetics and RRP patients. This may help further elucidate the relationship between corporal hypoxia and the development and progression of ED and possibly its treatment and prevention.

Our objective was to assess the effects of customized instructions and dose optimization on treatment satisfaction and improvement in erectile function (EF) with sildenafil citrate in men with erectile dysfunction (ED) who had not been previously treated with a phosphodiesterase-5 inhibitor. This 8-week, multicenter, open-label, flexible-dose (25, 50, or 100 mg sildenafil) study included 2 phases. During phase 1, patients took 50 mg sildenafil and followed the sildenafil sample package instructions. In phase 2, sildenafil dose could be adjusted on the basis of efficacy and tolerability, and investigators provided additional customized instructions. The primary efficacy variable was the satisfaction rate (defined as patients responding "very" or "somewhat" satisfied to the Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS] Question 1). Other efficacy assessments included the International Index of Erectile Function (IIEF) and the percentage of successful sexual intercourse attempts. Of 1109 men (mean age, 54+/-13 years) treated, 867 completed the study. In phase 1, 75% of patients were very or somewhat satisfied with treatment. Mean EF domain score on the IIEF increased from 14.3 at baseline to 23.5, and 79% of sexual intercourse attempts were successful. In phase 2, 53% of patients increased their sildenafil dose to 100 mg and 2% decreased to 25 mg. Satisfaction with sildenafil increased to 86%, 91% of sexual intercourse attempts were successful, and mean IIEF EF domain score increased to 25.7. Of the 196 men who were not initially satisfied at the end of phase 1, 64% became very or somewhat satisfied with treatment by the end of phase 2. Initially high levels of efficacy and satisfaction with sildenafil were achieved when patients were provided with only the sample package instructions and the recommended 50-mg starting dose. These results were enhanced with dose optimization, individual patient counseling, and customized instructions.

Sexual dysfunction associated with radical retropubic prostatectomy (RRP) may start before the surgery. Men undergoing RRP frequently have some degree of sexual dysfunction. In addition to the psychological stress of the diagnosis, the biopsy may itself have a detrimental effect. After surgery, all men will experience loss of ejaculate, because the organ responsible for ejaculate has been removed. Orgasm quality is adversely affected in many men. Erectile dysfunction is immediate and recovery from it is slow. Initially, phosphodiesterase (PDE)-5 inhibitors do not work, and they take up to 18 months for their effect to be maximized. Younger men who have had bilateral nerve-sparing procedures respond the best. Combination treatment with prostaglandin E1 or high-dose PDE-5 inhibitors may provide salvage therapy when initial PDE-5 inhibitor therapy has failed.

Erectile dysfunction (ED) has only within the past 25 years been recognized as being largely organic in cause. The introduction of phosphodiesterase-5 inhibitor therapy represents a major breakthrough in the treatment of ED and has resulted in a fast-growing body of knowledge regarding the etiology of the disorder, including its close association with cardiovascular disease. ED symptoms are often an early manifestation of endothelial dysfunction and, as such, should prompt further evaluation of not only the sexual dysfunction but also cardiovascular risk. This article discusses the importance of recognizing ED as much more than a quality-of-life issue.

Since its approval in 1998, sildenafil citrate (Viagra) has been shown to be efficacious in >100 clinical trials involving >8000 men with erectile dysfunction (ED). In clinical practice, however, many men do not continue long-term use of sildenafil for a variety of reasons; thus, 6 different aspects of optimizing treatment with sildenafil are described here. (1) Intercourse success rates, considered a reflection of real-world effectiveness, were assessed in 1276 patients with ED. Results indicated that the cumulative probability of achieving intercourse success with sildenafil increased with the number of attempts, reaching a plateau after approximately 8 attempts. (2) A comprehensive disease management approach that included a medical history, physical examination, educational material about ED, modifications of risk factors/lifestyle changes, and counseling resulted in successful intercourse in 74% of 111 patients taking sildenafil. (3) A survey conducted among primary care physicians revealed that almost 50% did not routinely question their patients about ED symptoms, although it is known that most patients would prefer their physician to take the initiative. (4) Overall, 55% of 137 men who were previously not successful with sildenafil became successful after reeducation and counseling, which included information on patient and partner expectations, how to properly take the drug, titration to maximum dose, and a minimum trial of 8 attempts for efficacy assessment. (5) Many men with ED have underlying comorbidities or take multiple medications that are risk factors for ED. Controlling these risk factors in 521 men from a multispecialty clinic led to an overall intercourse success rate of 82%; patients with multiple risk factors were less likely to have intercourse success than men with only 1 risk factor. (6) Finally, treatment satisfaction is a pivotal factor in maintaining long-term ED therapy. In an open-label trial, 82% of 443 subjects reported treatment satisfaction with sildenafil. In summary, these findings highlight how important it is for physicians to take a more comprehensive, proactive approach when treating men with ED, including control of risk factors, instructions on how to properly take the drug, partner involvement, and follow-up visits. Using these recommended measures, most men with ED, including those whose treatment was previously unsuccessful, can be treated successfully with sildenafil.

Within 6 months of approval by the U.S. Food and Drug Administration (FDA), 5.3 million prescriptions were written for sildenafil citrate. It represented the first clearly effective and FDA-approved oral therapy for the treatment of ED. The chemical structure of sildenafil is very similar to the cyclic guanosine monophosphate molecule with which it competes, in the enzyme phosphodiesterase type-5. Sildenafil binds to the phosphodiesterase-5 enzyme, preventing the breakdown of cyclic guanosine monophosphate through competitive inhibition. The onset of action for sildenafil can be as short as 20 minutes and the duration of action may be as long as three half-lives (18 hours). Anecdotal evidence suggests that many men describe an erectogenic effect for almost 24 hours. The safety of sildenafil has been established in many pre- and postapproval studies at doses as high as eight times the maximum recommended dose. It is likely that the rare instance of myocardial infarction after taking sildenafil as directed, is due more to the activity of sexual intercourse rather than the medication itself. Efficacy have been established in patients with diabetes, parkinsonism, spinal cord injury, and those on antihypertensive (single- and multiple-therapy) agents. It has also been shown to be effective in reversing selective serotonin reuptake inhibitor-induced sexual side effects. Initial concerns about sildenafil with respect to ocular safety were based on misinterpretation of the FDA submission data. The two most common side effects are headache and flushing, both of which are short-lived and easily treated.

Most studies indicate general satisfaction rates of greater than 80% after radical retropubic prostatectomy. Nonetheless, erectile dysfunction remains the most common problem postoperatively, with rates ranging from 100% to 10% depending on the experience of the surgeon, the frequency with which he or she performs the surgery, the nerve-sparing nature of the procedure, the stage of the disease, and the age and preoperative potency of the patient. The natural recovery of erection function takes as long as 24 months and can be expedited by early treatment with intracorporal injection therapy. The treatment of erectile dysfunction after radical retropubic prostatectomy is highly successful despite the finding that fewer than 50% of patients seek treatment. Sildenafil does not seem to be effective early in the recovery phase but increases in efficacy as the nerves recover from intraoperative injury. Other modalities in the early recovery phase in the order of increasing effectiveness are intraurethral prostaglandin, the vacuum erection device, and intracorporal injection therapy. After 2 years from surgery, the recovery of natural function and improved sildenafil responsiveness are unlikely, and the implantation of a prosthesis is reasonable if other modalities are ineffective or unacceptable for the patient. Animal studies and human trials are underway to examine ways to expedite and maximize the return of erectile function.

Purpose: The response to sildenafil after radical retropubic prostatectomy (RRP) has been reported to be approximately 40% by the Sildenafil Study Group. We undertook a study in a large cohort of post-RRP erectile dysfunction (ED) patients in order to examine the relationship between satisfaction with sildenafil and time from surgery to start of sildenafil treatment., Methods: Pre- and post-operative erectile function was assessed by the O'Leary Brief Sexual Function Inventory questionnaire. Patient satisfaction with sildenafil before and after sildenafil treatment was assessed by the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. Between April and October 1998, EDITS questionnaires were given to 579 patients who had undergone RRP between 1994 and 1998. 316 (55%) patients returned questionnaires. Of these, 198 (63%) had sildenafil treatment and completed post-treatment questionnaires and were included in the study group., Results: In the study group, mean age was 61y. Pre-operatively, 92% had erections sufficient for vaginal penetration, 95% had bilateral nerve-sparing (NS) RRP. There was a significant increase in the treatment satisfaction rate with increasing time from surgery. Between zero and six months after surgery, the treatment satisfaction rate was 26%, which improved with time, peaking at 60% between 18 months and 2y. Self-perceived erectile function as determined by post-RRP pre-sildenafil treatment O'Leary questionnaires was not as predictive of response to sildenafil as time from surgery., Conclusions: The response to sildenafil appears to be dependent upon the interval between RRP and the start of sildenafil. The treatment satisfaction rate was found to peak at 60% between 18 months and 2y. Early nonresponders to sildenafil should not be disheartened, as they will more likely later respond.

There have been anecdotal reports of a decrease in penile size in men with erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy (NSRRP). Penile circumference and length measurements are obtained by one physician from 100 men, age 47 to 74, who presented at various intervals (1.7&endash;27.6 months) for the treatment of ED after NSRRP from 1994 through 1997. All patients were asked to complete a brief male sexual function inventory at their initial visit. Penile measurements were obtained both in the flaccid and erect states, with erections being induced with intracorporal injections of Trimix. The sexual inventory scores were compared with those of an age-matched control cohort of 130 men presenting for evaluation of ED during the same time period and 132 age-matched men who completed the inventory at the time of a prostate screening. By self-report, men experiencing ED after NSRRP had better libido but more severe ED than men presenting with ED of other causes. There was a decrease in all penile dimensions after NSRRP. The flaccid and erect measurements of length and circumference decreased 8% and 9%, respectively after surgery (p > 0.05). The most substantial change occurred between the first 4 and 8 months postoperatively. The average change in volume between the first 4 and 8 months was 19% to 22% in the flaccid and erect state, respectively. There is a significant decrease in penile size in men with ED after NSRRP. The etiology may be denervation smooth muscle atrophy, apoptosis, or hypoxia-induced damage to the corpora. Further research is needed to elucidate the nature of these postoperative changes.

We report case 10 of a gonadal stromal tumor of the testis in a neonate. This tumor may occur in the testis or ovary, and is defined as a tumor of any of the specialized supporting structures of the male or female gonad. All neonatal tumors reported to date have been benign. The serum alpha-fetoprotein level, although elevated for adults, was within the normal range for an infant.

This paper is a cross-sectional study of spontaneous benign prostatic hyperplasia (BPH) in a single canine species. The effects of aging and hormonal changes on the growth, histology, and glandular secretory function of the canine prostate were studied in 42 male beagles ranging in age from 8 mo to 9 yr. The beagle prostate enlarges for at least 6 yr, whether normal or hyperplastic. In contrast, prostatic secretory function, determined by ejaculate volume and total ejaculate protein, declines markedly after 4 yr of age. These reciprocal growth and functional changes in the prostate are closely associated with a progressive increase in the incidence of BPH, which is already apparent in some dogs by age two. With age there is a modest decrease in serum androgen levels with no apparent change in serum 17 beta-estradiol levels. This suggests that the growth and functional changes that are associated with the development of BPH and are initiated very early in life reflect an altered sensitivity of the prostate to serum androgens or a response to the relative decrease in the serum androgen to estrogen ratio.

Cutaneous horns of the penis are rare lesions, only seventeen previous cases having been reported in the English literature. The lesions usually appear following adult circumcision for long-standing phimosis. Frequently they are unusual presentations for squamous cell carcinoma of the penis. One third of the cases of penile horns were associated with underlying malignancies; therefore prompt surgical intervention is warranted.