Filamin A Is a Prognostic Serum Biomarker for Differentiating Benign Prostatic Hyperplasia from Prostate Cancer in Caucasian and African American Men.

Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, PSA's screening utility is diminished, resulting in many unnecessary biopsies. To address this issue, we previously identified a cleaved fragment of Filamin A (FLNA) protein (as measured with IP-MRM mass spectrometry assessment as a prognostic biomarker for stratifying BPH from prostate cancer and subsequently evaluated its expanded utility in Caucasian (CA) and African American (AA) men. All men had a negative digital rectal examination (DRE) and PSA between 4 and 10 ng/mL and underwent prostate biopsy. In AA men, FLNA serum levels exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.71 AUC and 12.2 OR in 48 men with BPH and 60 men with PCa) and outperformed PSA (0.50 AUC, 2.2 OR). In CA men, FLNA serum levels also exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.74 AUC and 19.4 OR in 191 men with BPH and 109 men with PCa) and outperformed PSA (0.46 AUC, 0.32 OR). Herein, we established FLNA alone as a serum biomarker for stratifying men with BPH vs. those with high Gleason (7-10) prostate cancers compared to the current diagnostic paradigm of using PSA. This approach demonstrates clinical actionability of FLNA alone without the requirement of prostate volume measurement as a test with utility in AA and CA men and represents a significant opportunity to decrease the number of unnecessary biopsies in aggressive prostate cancer diagnoses.

Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder.

BACKGROUND: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective ß3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence. METHODS: This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence. DISCUSSION: OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.

The patient burden of nocturnal polyuria in the United States: Results from the epidemiology of nocturnal polyuria (EpiNP) study.

OBJECTIVES: To explore the impact of nocturnal polyuria (NP) on health-related quality of life (HRQoL), work productivity, mental health, fatigue, bother, and daytime sleepiness. MATERIALS AND METHODS: This large-scale, US population-representative epidemiologic study was conducted in two parts: a web-based survey and 3-day bladder diary. Consenting participants completed the baseline Epidemiology of NP (EpiNP) survey online (Lower Urinary Tract Symptoms [LUTS] Tool, comorbidities, burden, and multiple HRQoL measures). Participants who reported ≥2 voids/night, and a random sample of 100 respondents each reporting 0 or 1 void/night, were sent urine measurement containers and asked to complete the 3-day bladder diary. NP was defined as Nocturnal Polyuria Index >0.33 (NPI33) or nocturnal urine production >90 ml/h (NUP90). Five subgroups were created: Idiopathic NP (NP with no underlying cause), NP associated with symptoms of overactive bladder (NPOAB) or bladder outlet obstruction (NPBOO; men only), NP associated with other comorbidities (NPCOM; e.g., diabetes, hypertension, heart disease, sleep apnea), and no NP (did not meet NP criteria). RESULTS: A total of 4893 men and 5297 women completed the EpiNP survey; mean age was 54.4 (SD = 14.7). Significantly greater patient burden (p < 0.0001) was evidenced in the nocturia group (≥2 voids/night) versus no nocturia group (0-1 void/night) on daily impact of nocturia, LUTS Bother, prostate symptoms (men only), work productivity, physical and mental health component scores, depression, fatigue, and daytime sleepiness. NP subgroup analyses showed men in the NPBOO group and women in the NPOAB group reported the greatest impact on LUTS bother, fatigue, physical health, work productivity impairment, daytime sleepiness, and depression (women only). CONCLUSION: This was the first large-scale, epidemiologic study to explore the impact of different forms of NP on patients' HRQoL. Findings demonstrate that NP associated with other urologic or comorbid conditions appears to have greater patient burden than idiopathic NP, in particular for women.

Nocturnal polyuria in women: results from the EpiNP study.

INTRODUCTION AND HYPOTHESIS: Data from a large US population-based, cross-sectional, epidemiological study (the EpiNP Study) were used to assess the symptoms and bother experienced by women with nocturnal polyuria (NP). METHODS: Consenting participants recruited from an online panel completed the baseline EpiNP survey online (Lower Urinary Tract Symptoms Tool and urological comorbidities). All reporting ≥2 voids/night and a random sample of 100 respondents, each reporting 0 or 1 void/night were asked to complete a 3-day web-based bladder diary recording time, volume, and urgency rating of each void. NP was calculated by the proportion of urine production that occurred during nocturnal hours using a Nocturnal Polyuria Index (NPI33) threshold of >0.33 or nocturnal urine production of >90 ml/h (NUP90). The frequency of participants reporting LUTS and bother was determined by age and NP: idiopathic NP, NP associated with overactive bladder (NPOAB), NP associated with comorbidities (NPCom), and no NP (did not meet NP criteria). RESULTS: A total of 5,290 women completed the baseline survey. Mean age (range) was 54.9 (30-95) years; 1,841 (34.8%) reported ≥2 nocturnal voids. The prevalence of LUTS increased across the lifespan; however, bother associated with each LUTS decreased with increasing age. The percentage of women rating bother by nocturia episodes ≥2 "> somewhat" ranged from 40.3% to 68.3%, with bother ratings highest in the NPOAB and No NP groups. CONCLUSIONS: NP is prevalent in women with considerable bother and is often associated with other urinary symptoms. Multifactorial causes and potential treatments of NP should be considered, particularly at a later age.

Vibegron for the Treatment of Patients with Dry and Wet Overactive Bladder: A Subgroup Analysis from the EMPOWUR Trial.

Background: Overactive bladder (OAB) is characterized by urgency and frequency with (OAB wet) or without (OAB dry) urge urinary incontinence (UUI). In the phase 3 EMPOWUR trial, vibegron-a selective ß 3-adrenergic receptor agonist for the treatment of OAB-significantly improved daily number of urgency episodes and micturitions vs. placebo (P < 0.01). These post hoc analyses aimed to compare the efficacy of vibegron vs. placebo in OAB dry and wet populations. Methods: Patients were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, for 12 weeks. Baseline criteria for OAB dry included an average of ≥8 micturitions, ≥3 urgency episodes, and <1 UUI episode per diary day and for OAB wet included an average of ≥8 micturitions and ≥1 UUI episode per diary day. Change from baseline in mean daily number of urgency episodes and micturitions was assessed in both populations. Results: Of the 1463 patients included in the full analysis set, 336 (23%) had OAB dry (vibegron, N = 123; placebo, N = 115; and tolterodine, N = 98), and 1127 (77%) had OAB wet (vibegron, N = 403; placebo, N = 405; and tolterodine, N = 319). Vibegron was associated with significant reductions (95% CIs of the least squares mean differences [LSMD] does not include 0) from baseline at week 12 vs. placebo in mean daily urgency episodes for the dry (LSMD [95% CI], ‒1.0 [‒2.0, ‒0.1]) and wet (‒0.6 [‒1.0, ‒0.1]) populations. Vibegron was associated with significant reductions from baseline at week 12 vs. placebo in mean daily micturitions for the dry (LSMD [95% CI], ‒0.8 [‒1.5, ‒ 0.1]) and wet (‒0.5 [‒0.8, ‒0.1]) populations. There were no significant differences in either outcome between tolterodine and placebo for either the dry or wet populations in this study. Conclusions: In this subgroup analysis from the EMPOWUR trial, vibegron was associated with significant reductions compared with placebo in urgency episodes and micturitions in both the OAB dry and wet populations, suggesting that vibegron is similarly efficacious for these endpoints in patients with and without UUI. This trial is registered with NCT03492281.

Differences in the Prevalence of Nocturnal Polyuria in the U.S. by Definition: Results from the Epidemiology of Nocturnal Polyuria Study.

PURPOSE: Prevalence data on nocturnal polyuria (NP), nocturia caused by overproduction of urine during sleep, is primarily limited to men and varies by NP definition. This U.S.-representative epidemiological study of men and women ≥30 years old assessed the prevalence of NP. MATERIALS AND METHODS: Consenting participants completed the baseline EpiNP (Epidemiology of Nocturnal Polyuria) survey (eg Lower Urinary Tract Symptoms Tool, comorbidities). All reporting ≥2 voids/night and a target of 100 random respondents reporting 0 or 1 void/night were asked to complete 3-day bladder diaries. NP was defined as nocturnal polyuria index (NPI) >0.33 (NPI33) and nocturnal urine production >90 ml/hour (NUP90). Extrapolated prevalence was stratified by sex and subgroups: idiopathic (without underlying causes), associated with overactive bladder (NPOAB), bladder outlet obstruction (NPBOO; men) and comorbidities. Voided volumes and timing, including first uninterrupted sleep period, were assessed by subgroup. RESULTS: A total of 10,190 individuals completed the baseline survey; mean age (range) was 54.4 (30-95). A total of 3,938 individuals were invited to complete the diary; 1,763 (49.3%) completed 3-day bladder diaries. Urine production (maximum nighttime volume, total volume, nocturnal urine production, nocturia index) was higher in both men and women with idiopathic NP and comorbidities. The median number of nighttime voids was greatest for NPBOO in men and NPOAB in women. Bother associated with nighttime voiding differed by NP subgroup but was highest in NPBOO for men (NPI33: 69.6%; NUP90: 71.1%) and NPOAB for women (NPI33: 67.5%; NUP90: 66.0%). CONCLUSIONS: This population-based NP prevalence study including men and women characterizes NP subgroups and provides insights into nocturia treatment by emphasizing factors influencing urine production versus factors influencing bladder capacity.

The Prevalence of Nocturnal Polyuria in the United States: Results from the Epidemiology of Nocturnal Polyuria Study.

BACKGROUND: The prevalence of nocturnal polyuria (NP), which is passing large volumes of urine during the main sleep period, has been investigated primarily in middle-aged to older men. There is thus a gap in the NP evidence base for women and for younger individuals. OBJECTIVE: To estimate the prevalence of nocturia due to NP in the USA. DESIGN, SETTING, AND PARTICIPANTS: This large epidemiologic study used a US population-representative sample of men and women aged ≥30 yr to assess the prevalence of NP (NCT04125186). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consenting participants completed an online survey (Lower Urinary Tract Symptoms Tool and comorbidities). All who reported two or more voids per night and 100 random respondents each reporting no or one void per night were asked to complete a 3-d bladder diary. Two NP definitions were used: nocturnal urine production >90 ml/h (NUP90) and Nocturnal Polyuria Index >0.33 (NPI33). Crude and population-adjusted prevalence results were calculated from completed diaries for the following subgroups by sex and age: idiopathic NP; NP with overactive bladder (NP-OAB) or bladder outlet obstruction (NP-BOO; men only); NP associated with other comorbidities; and no NP (did not meet the NPI33 or NUP90 definition). RESULTS AND LIMITATIONS: Among the 10,190 respondents who completed the survey, the mean age was 54.4 yr (range 30-95); 3,339 reported two or more nocturnal voids and 1,763 completed the 3-d diary (response rate 49.3%). The adjusted overall NP prevalence was 31.5% among men and 38.5% among women using the NPI33 definition, and 23.8% among men and 18.1% among women using NUP90. The adjusted idiopathic NP prevalence was lower among men (NPI33: 5.2%; NUP90: 1.4%) than among women (NPI33: 9.8%; NUP90: 4.0%). The prevalence of idiopathic NP decreased with age as NP associated with other possible causes increased with age in men (most common, BOO) and women (most common, OAB). CONCLUSIONS: This is the first population-based study of NP prevalence to include men, women, and young adults. NP is common; a multifactorial etiology should be considered, particularly as age increases. PATIENT SUMMARY: In this population-based US study, we examined the frequency of nighttime urination among men and women aged ≥30 y and older. We found that nighttime urination is common among men and women. Many conditions can lead to increased nighttime urination as people age.

Interpretation of the Meaningfulness of Symptom Reduction with Vibegron in Patients with Overactive Bladder: Analyses from EMPOWUR.

INTRODUCTION: Reductions in bothersome symptoms of overactive bladder (OAB) demonstrate improvement in clinical trials, but patient perception of meaningfulness of such improvement is lacking. In the 12-week phase 3 EMPOWUR trial, vibegron significantly reduced average daily number of micturitions, urgency episodes, and urge urinary incontinence (UUI) episodes vs placebo (P < 0.01 each). This analysis assessed meaningfulness of reductions in clinical endpoints observed in EMPOWUR using patient perception of improvement. METHODS: An anchor-based approach using Patient Global Impression of Change (PGI-C) applied to phase 2 data allowed predefining phase 3 responder definitions. To confirm in phase 3, median change from baseline at week 12 in average daily number of micturitions, urgency episodes, and UUI episodes was generated for each PGI-C category and pooled across treatments. Based on predefined meaningful responder definitions, percentages of patients achieving ≥ 15% reduction in micturitions (post hoc), ≥ 50% reduction in urgency episodes (predefined), and ≥ 75% (predefined) and ≥ 90% (post hoc) reduction in UUI episodes were determined for patients receiving vibegron or placebo. RESULTS: Across treatments, for micturitions, urgency episodes, and UUI episodes, median change from baseline to week 12 increased with greater subjective improvement based on PGI-C scores, and median reductions pooled across treatment groups were higher than the responder definitions that patients perceived as improved. Significantly more patients receiving vibegron vs placebo achieved ≥ 15% reduction in micturitions (56.3% vs 44.6%, respectively), ≥ 50% reduction in urgency episodes (39.5% vs 32.8%), ≥ 75% reduction in UUI episodes (49.3% vs 32.8%), and ≥ 90% reduction in UUI episodes (35.2% vs 23.5%) at week 12 (P < 0.05 each). CONCLUSION: Significantly more patients treated with vibegron vs placebo in EMPOWUR achieved meaningful reductions in micturitions, urgency episodes, and UUI episodes that were associated with patient-perceived improvement. Results of these analyses support the meaningfulness of reductions in clinical endpoints observed in the 12-week EMPOWUR trial. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier, NCT03492281.

Role of urinary cations in the etiology of interstitial cystitis: A multisite study.

OBJECTIVE: To determine whether patients with interstitial cystitis have elevated levels of toxic urinary cations, to identify and quantify these cationic metabolites, and to assess their cytotoxicity. METHODS: Isolation of cationic fraction was achieved by solid phase extraction using an Oasis MCX cartridge on urine specimens from interstitial cystitis patients and controls. C18 reverse phase high-performance liquid chromatography was used to profile cationic metabolites, and they were quantified by the area under the peaks and normalized to creatinine. Major cationic fraction peaks were identified by reverse phase high-performance liquid chromatography and liquid chromatography-mass spectrometry. HTB-4 urothelial cells were used to determine the cytotoxicity of cationic fraction and of individual metabolites. RESULTS: The reverse phase high-performance liquid chromatography analysis was carried out on cationic fraction metabolites isolated from urine samples of 70 interstitial cystitis patients and 34 controls. The mean for controls versus patients was 3.84 (standard error of the mean 0.20) versus 6.71 (0.37) mAU*min/µg creatinine, respectively (P = 0.0001). The cationic fraction cytotoxicity normalized to creatinine for controls versus patients in mean percentage was -7.79% (standard error of the mean 3.32%) versus 20.03% (standard error of the mean 2.75%; P < 0.0005). The major toxic cations were 1-methyladenosine, 1-methylguanine, N2 ,N2 -dimethylguanosine and L-tryptophan. CONCLUSIONS: These data confirm significant elevation of toxic cations in the urine of interstitial cystitis patients. These toxic cations likely represent a primary cause of interstitial cystitis, as they can injure the bladder mucus and initiate an epithelial leak.

Taking OAB seriously: A qualitative evaluation of primary care education on overactive bladder syndrome management.

BACKGROUND: Overactive bladder (OAB) syndrome has a diverse etiology that disrupts quality of life domains in affected patients. OAB is significantly under-recognised and undertreated, especially in the primary care setting. In order to educate primary care providers about OAB recognition, evaluation and management, we created a virtual live-streamed and enduring education program. METHODS: We evaluated the impact of education on provider knowledge and self-efficacy via qualitative interviews with a sample of education participants. We analysed participant responses via constant comparative method, an iterative approach that allows for exploration of a priori issues and identification of emergent themes. RESULTS: We identified four key themes: (a) taking OAB seriously; (b) variations in therapy; (c) patient motivation; and (d) education value. Participants were proactive about screening for and managing OAB and recognised urgency as a key symptom; some participants used diagnostic tests that are not are not considered necessary in the workup of uncomplicated OAB patients. Participants varied in their descriptions of initial approaches to treatment and most participants described a longer-than-recommended follow-up window to monitor patients. Some participants characterised patients as looking for a "quick fix" in ways that could lead to provider inaction in relation to behavioural/lifestyle interventions. Overall, participants felt that the education validated their current practice and provided new knowledge about evaluation, initiating behavioural treatment, and combination therapy. CONCLUSIONS: Participant responses were congruent with education messages, which likely reflect their "readiness to learn". The rationale for diagnostic tests and evidence on the effectiveness of behavioural regimens represent ongoing areas of unmet educational need.

Cardiovascular risk with androgen deprivation therapy.

BACKGROUND: From the primary care perspective, many urologists and oncologists appear to be ignoring an FDA warning to assess patients' cardiovascular (CV) risk before instituting androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists. A growing body of data suggest an association between ADT and CV/cardiometabolic risk, particularly for GnRH agonists. METHODOLOGY: The author examined available evidence regarding CV side effects with GnRH agonists and antagonists to determine what urologists, medical oncologists, primary care physicians (PCPs) and patients need to know about these risks. RESULTS: Data are inconclusive and somewhat conflicting-for example, both low testosterone and testosterone replacement have been associated with elevated CV risk. But the distinction between GnRH agonists and antagonists is becoming clearer, as agonists appear to be more strongly linked with CV risk, perhaps due to the transient testosterone surge they cause upon administration. Moreover, adverse CV events associated with GnRH agonists can emerge relatively quickly, within weeks to months. Conversely, two studies show that GnRH antagonists may significantly reduce CV risk compared to GnRH agonists. CONCLUSIONS: Both GnRH agonists and antagonists carry some degree of CV risk. Although the risk appears to be lower with GnRH antagonists, urologists and oncologists should communicate with PCPs to determine patients' baseline CV risk levels before implementing ADT with either type of agent.

A practical primary care approach to overactive bladder.

The evaluation and treatment of overactive bladder (OAB) starts in the primary care office and can be accomplished efficiently, effectively and, most importantly, safely. With appropriate knowledge of the disease and an understanding of what to look for the primary care physician (PCP) can readily make the empiric diagnosis and initiate treatment. The key for the PCP is to be able to distinguish the uncomplicated patient from the complicated one and know when to refer, if necessary. It is also essential to be able to able to identify confounding conditions that could either be the cause of the symptoms or, in fact, make them worse. The algorithm presented in this paper describes a simplified, yet complete, approach to the patient presenting with lower urinary tract symptoms (LUTS) consistent with OAB. In the paper, we explain the disease itself, its prevalence and impact, the evaluation as well as the different treatment modalities that are available for the patient. Appropriate follow up, therapy adherence techniques and referral recommendations are also discussed.

A practical primary care approach to lower urinary tract symptoms caused by benign prostatic hyperplasia (BPH-LUTS).

In the primary care office the evaluation of prostate related lower urinary tract symptoms (BPH-LUTS) in the male can be confusing. Are the symptoms, in fact, from the prostate or is there another etiology such as the bladder or medical conditions causing or contributing to the problems? If the cause is the prostate, how does the physician choose from the multitude of available treatment options and when is referral appropriate? The prevalence of BPH-LUTS is high and commonly encountered by the primary care physician (PCP). An understanding of the normal prostate is essential to identifying the patient when symptoms do occur. Then the evaluation and treatment of the affected patient can occur effectively and efficiently in the PCP setting. In this article we present the background information needed for the PCP to provide this evaluation of the patient with BPH-LUTS. We explain the various treatment options that are best suited for the individual which are based on symptom severity, sexual dysfunction and risk of progression. We also identify follow up parameters and reasons for referral.

Erectile dysfunction in primary care: a focus on cardiometabolic risk evaluation and stratification for future cardiovascular events.

An association between erectile dysfunction (ED) and cardiovascular disease has long been recognized, and studies suggest that ED is an independent marker of cardiovascular disease risk and even further, a marker for the burden of both obstructive and non-obstructive coronary artery disease. Therefore, the primary care physician (PCP) must assess the presence or absence of ED in every man > 39 years of age, especially if that man is asymptomatic of signs and symptoms of coronary artery disease. Assessment and management of ED may help identify and reduce the risk of future cardiovascular events, particularly in younger middle-aged men. The initial ED evaluation should distinguish between predominantly vasculogenic ED and ED of other etiologies. For men believed to have predominantly vasculogenic ED, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with ED who are at low risk for cardiovascular disease should focus on risk factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of selected prognostic markers to further understand cardiovascular risk in men with ED, particularly CT calcium scoring. In conclusion, we support cardiovascular risk stratification and risk factor management in all men with vasculogenic ED.

Testosterone deficiency: myth, facts, and controversy.

Testosterone deficiency (TD) afflicts approximately 30% of men ages 40-79 years, with an increase in prevalence strongly associated with aging and common medical conditions including obesity, diabetes, and hypertension. There appears to be a strong relationship between TD and metabolic syndrome, though the relationship is not certain to be causal. Several studies have suggested that repletion of testosterone in deficient men with these comorbidities may indeed reverse or delay their progression. While testosterone repletion has been largely thought of in a sexual realm, we discuss its potential role in general men's health concerns: metabolic, body composition, and its association with decreased all-cause mortality. Recent guidelines and studies have suggested variable prevalence statistics and expanded uses of testosterone repletion in certain populations with both biochemical and clinical signs of testosterone deficiency. Yet, this is not done without risk. A recent randomized placebo-controlled trial of testosterone repletion in elderly frail men with limited mobility has suggested potential negative cardiovascular risks in this older, sicker group of men. Two more recent retrospective studies of variable clinical design and interpretation suggest testosterone poses an increased cardiovascular risk in older men than 65 years and younger men with heart disease. This review examines these and other studies, with practical recommendations for the diagnosis of testosterone deficiency and repletion in middle aged and older men, including an analysis of treatment modalities and areas of concern and uncertainty.

A guide to the management of urologic dilemmas for the primary care physician (PCP).

Patients with urologic conditions may present to a primary care physician (PCP) in the emergency department or in the PCP's office. Some conditions are true emergencies that require immediate surgical intervention. Others may require medical treatment or possibly simply reassuring the patient that there is no serious medical problem. Sometimes the diagnosis can be easily made, whereas other times the PCP needs to be able to rule out serious causes for a presenting problem and execute a guideline-recommended patient work up, to make a final diagnosis. Sometimes recommended diagnostic tests may not be readily available. When a PCP believes that a patient may have a serious urologic condition and is unsure of the appropriate patient management strategy, then he or she must quickly refer the patient to a urologist. This article describes common urology-related issues-hematuria, prostate-specific antigen (PSA) test interpretation, phimosis and paraphimosis, acute scrotal pain and masses in the child and adult, urinary tract infection, renal colic, and castration-treatment-induced bone loss. It provides insights into decision-making processes for patient management of some urologic conditions, and information about managing sequelae and side effects of long term treatment. It includes practical diagnostic suggestions and patient management strategies based on the authors' years of urologic clinical practice experience.