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BackgroundMusculoskeletal pain, a possible marker of central sensitization, is associated with higher prevalence of lower urinary tract symptoms (LUTS) among older men. We investigated whether musculoskeletal pain is associated with LUTS progression.MethodsParticipants were 5 569 men age ≥65 years enrolled in the prospective, multicenter Osteoporotic Fractures in Men (MrOS) Study. Self-reported musculoskeletal pain within 12 months before baseline was categorized as any pain and multilocation pain. Pain interference within 4 weeks of baseline was assessed with the SF-12 questionnaire. LUTS were assessed repeatedly with the American Urological Association Symptom Index (AUA-SI). Men with severe LUTS at baseline were excluded. LUTS progression was defined as the first occurrence of a ≥4-point AUA-SI increase during a 2-year follow-up interval. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using multivariable pooled logistic regression.ResultsLUTS progression was 37% higher among men with any musculoskeletal pain compared with men without pain (IRR 1.37, 95% CI: 1.21, 1.54). Positive associations were also observed between LUTS progression and pain at 1 (IRR 1.31, 95% CI: 1.13, 1.48) and ≥2 locations (IRR 1.42, 95% CI: 1.24, 1.60). Compared with men without pain interference, men with quite a bit/extreme pain interference were most likely to experience LUTS progression (minimal interference IRR 1.15, 95% CI: 1.03, 1.26; moderate interference IRR 1.28, 95% CI: 1.11, 1.45; quite a bit/extreme interference IRR 1.47, 95% CI: 1.22, 1.71).ConclusionsAmong men initially without severe LUTS, musculoskeletal pain is associated with an increased risk of LUTS progression. Studies using validated measures of central sensitization and LUTS progression among men are warranted.

BackgroundLower urinary tract symptoms (LUTS) are associated with prevalent frailty and functional impairment, but longitudinal associations remain unexplored.ObjectivesTo assess the association of change in phenotypic frailty with concurrent worsening LUTS severity among older men without clinically significant LUTS at baseline.DesignMulticenter, prospective cohort study.SettingPopulation-based.ParticipantsParticipants included community-dwelling men age ≥65 years at enrollment in the Osteoporotic Fractures in Men study.MeasurementsData were collected at 4 visits over 7 years. Phenotypic frailty score (range: 0-5) was defined at each visit using adapted Fried criterion and men were categorized at baseline as robust (0), pre-frail (1-2), or frail (3-5). Within-person change in frailty was calculated at each visit as the absolute difference in number of criteria met compared to baseline. LUTS severity was defined using the American Urologic Association Symptom Index (AUASI; range: 0-35) and men with AUASI ≥8 at baseline were excluded. Linear mixed effects models were adjusted for demographics, health-behaviors, and comorbidities to quantify the association between within-person change in frailty and AUASI.ResultsAmong 3235 men included in analysis, 48% were robust, 45% were pre-frail, and 7% were frail. Whereas baseline frailty status was not associated with change in LUTS severity, within-person increases in frailty were associated with greater LUTS severity (quadratic P

BackgroundAdiposity increases risk for male lower urinary tract symptoms (LUTS), although longitudinal studies have produced conflicting results. No prior studies have evaluated longitudinal associations of changes in adiposity with concurrent LUTS severity among older men.MethodsWe used repeated adiposity measurements from dual-energy x-ray absorptiometry (DXA), body mass index (BMI), and American Urological Association Symptom Index (AUASI) measured at 4 study visits over a 9-year period among 5 949 men enrolled in the Osteoporotic Fractures in Men (MrOS) study. Linear mixed effect models adjusted for age, health-related behaviors, and comorbidities were created to evaluate the association between baseline and change in visceral adipose tissue (VAT) area, total fat mass, and BMI with change in LUTS severity measured by the AUASI.ResultsA nonlinear association was observed between baseline VAT area and change in AUASI: men in baseline VAT tertile (T) 2 had a lower annual increase in AUASI score compared to men in T1 and T3 (T2 vs T1: β = -0.07; 95% CI -0.12, -0.03; p = .008; T3 vs T1: NS) but differences were small. No significant associations were observed between change in VAT area and change in AUASI score. Neither baseline tertiles nor change in total fat mass or BMI were associated with change in AUASI score.ConclusionsChanges in VAT area, total fat mass, and BMI were not associated with change in LUTS severity in this cohort. Thus, despite other health benefits, interventions targeting adiposity alone are unlikely to be effective for preventing or treating LUTS among older men.

ObjectiveTo evaluate the longitudinal association between plant-based diet index (PDI) score and incident erectile dysfunction (ED).Materials and methodsWe conducted a prospective analysis of 21 942 men aged 40 to 75 years who were enrolled in the Health Professionals Follow-Up Study. ED was assessed with questionnaires every 4 years starting in 2000. Dietary data were collected via validated food frequency questionnaires completed every 4 years and were used to calculate total PDI scores, as well as healthy (hPDI) and unhealthy (uPDI) subscores. Multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) for incident ED. All models were stratified by age (

AimsFeatures of central sensitization (CS) are present in almost all chronic pain conditions, including painful urinary conditions and back pain. Recently CS was proposed as a mechanism of nonpainful lower urinary tract symptoms (LUTS). Using musculoskeletal pain as an indicator of CS, we investigated whether the prevalence of musculoskeletal pain is greater among community-dwelling men with moderate or severe LUTS compared to those with mild LUTS.MethodsWe conducted a cross-sectional study of 5966 men ≥65 years who attended the Osteoporotic Fractures in Men Study baseline visit. LUTS were assessed with the American Urological Association Symptom Index (AUA-SI) and categorized as none/mild (0-7), moderate (8-19), or severe (≥20). Self-reported back, neck, hip, or knee pain within the 12 months before baseline was categorized as any pain and multilocation pain. We tested our hypothesis using odds ratios (OR) and 95% confidence intervals (CI) estimated from multivariable logistic regression models.ResultsThe adjusted odds of any pain were higher among men with moderate (OR 1.49, 95% CI: 1.29-1.72) and severe LUTS (OR 1.76, 95% CI: 1.28-2.40) compared to those with no/mild LUTS. The adjusted odds of pain at ≥ 2 locations were 69% higher among men with moderate (OR 1.69, 95% CI: 1.45-196) and more than double among men with severe LUTS (OR 2.24, 95% CI: 1.62-3.10) compared to men with no/mild LUTS.ConclusionsMusculoskeletal pain, especially at multiple locations, is associated with greater LUTS severity among older men. CS may represent a novel shared mechanism of pain and LUTS.

ObjectiveTo evaluate the association between non-neurogenic lower urinary tract symptoms (LUTS) and frailty among treatment-seeking older men.MethodsThis is a cross-sectional study of male patients age 65 years and older presenting to an academic urology practice between December 2015 and March 2019. Men with cancer, neurologic disease, indwelling catheter, or continuous leakage were excluded. Participants completed a Timed-Up-and-Go-Test (TUGT) which was used to categorize men as fast (≤10 seconds), intermediate (11-14 seconds), or slow (≥15 seconds). Participants with the following diagnoses were identified using billing codes extracted from the electronic medical record: overactive bladder (OAB), benign prostatic hyperplasia (BPH), mixed OAB/BPH, or non-LUTS urologic condition. Multivariable associations were evaluated using multinomial logistic regression models adjusted for age, race, and body mass index.ResultsAmong 2206 men included in our sample, 64% were fast (mean TUGT time: 8.3 ± 1.2 seconds), 25% were intermediate (mean TUGT time: 12.0 ± 1.0 seconds), and 11% were slow (mean TUGT time: 18.5 ± 4.7 seconds). Subjects with slow TUGT times were more likely to be older, non-White, and have LUTS. Compared to non-LUTS conditions, OAB (odds ratio [OR] = 2.62, 95% CI 1.74, 3.93), BPH (OR = 1.70, 95% 1.14, 2.55), and mixed OAB/BPH (OR = 1.82, 95% 1.14, 2.92) were all associated with increased odds of slow TUGT time. LUTS diagnosis was not significantly associated with intermediate TUGT time.ConclusionLUTS diagnosis, particularly OAB, is associated with increased odds of slow TUGT time, a surrogate of frailty, compared to non-LUTS conditions. Frailty is common among older men with LUTS and should be considered during the initial urological evaluation.

Background/objectivesTo estimate associations between lower urinary tract symptoms (LUTS) and phenotypic frailty in older men.DesignCross-sectional study.SettingCommunity-dwelling men recruited from 2000 to 2002 from six U.S. academic centers for the Osteoporotic Fractures in Men Study.ParticipantsA total of 5,979 men aged 65 and older.MeasurementsThe independent variable was LUTS severity (none/mild, moderate, or severe) assessed with the American Urologic Association Symptom Index. Participants were categorized as frail, intermediate stage, or robust using an adapted Cardiovascular Health Study index (components: low lean mass, weakness, exhaustion, slowness, and low physical activity). Associations were estimated with odds ratios and 95% confidence intervals (CIs) from multivariable multinomial logistic regression models adjusted for potential confounders of age, other demographics, health-related behaviors, and comorbidities.ResultsThe prevalence of frailty was 7%, 11%, and 18% among men with none/mild, moderate, and severe LUTS, respectively. Moderate and severe LUTS, overall and by storage and voiding subscores, were associated with higher odds of both intermediate stage and frailty in all models. After adjustment for confounders, the odds of frailty was 1.41 times higher among men with moderate LUTS (95% CI = 1.14-1.74) and 2.51 times higher among men with severe LUTS (95% CI = 1.76-3.55), compared with none/mild LUTS. Severe LUTS was associated with a greater odds of individual frailty components exhaustion and low physical activity.ConclusionThe prevalence of phenotypic frailty is higher among older community-dwelling men with moderate or severe LUTS compared with those with mild or no LUTS. The positive association between LUTS severity and frailty among older men appears independent of age and known frailty risk factors. Although the temporal direction of this association and the utility of LUTS or frailty interventions in this population remain unclear, the high co-occurrence of these conditions could lead to earlier identification of frailty when clinically appropriate.

PurposeMost international practice guidelines recommend screening for chronic kidney disease among older men with lower urinary tract symptoms. However, prior studies supporting these guidelines are insufficient due to incomplete assessments of kidney function and inadequate adjustment for confounding factors.Materials and methodsWe conducted a cross-sectional study among 5,530 American men older than 65 years in the multicenter Osteoporotic Fractures in Men Study. Chronic kidney disease was defined per international guidelines as estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 based on serum creatinine or cystatin C, or urinary albumin-to-creatinine ratio 30 mg/gm or greater. Lower urinary tract symptoms were assessed with the American Urological Association Symptom Index. Associations were estimated using multivariable linear and modified Poisson regression models.ResultsChronic kidney disease prevalence was 16% among 5,530 men with serum creatinine, 24% among 1,504 men with serum cystatin C and 14% among 1,487 men with urinary albumin-to-creatinine measurements. Lower urinary tract symptoms were not associated with lower estimated glomerular filtration rate based on serum creatinine or cystatin C. Although symptom severity was modestly associated with a higher prevalence of chronic kidney disease in age/site adjusted analyses, confidence intervals were wide and associations using all 3 definitions were not statistically significant after adjustment for important confounders, including cardiovascular disease and analgesic use.ConclusionsLower urinary tract symptoms are not independently associated with multiple measures of kidney dysfunction or prevalence of chronic kidney disease among older community dwelling men. Our results do not support recommendations for kidney function testing among older men with lower urinary tract symptoms.

ImportanceErectile dysfunction, especially in younger men, is an early sign of cardiovascular disease and may decrease quality of life. Men may be motivated to adopt a healthy dietary pattern if it lowers their risk of erectile dysfunction.ObjectiveTo assess the association between adherence to a diet quality index based on healthy dietary patterns and erectile dysfunction in men.Design, setting, and participantsThis population-based prospective cohort study included men from the Health Professionals Follow-up Study with follow-up from January 1, 1998, through January 1, 2014. Participants included US male health professionals aged 40 to 75 years at enrollment. Men with erectile dysfunction or a diagnosis of myocardial infarction, diabetes, stroke, or genitourinary cancer at baseline were excluded. Analyses were completed in February 2020.ExposuresA food frequency questionnaire was used to determine nutrient and food intake every 4 years.Main outcomes and measuresDiet quality was assessed by Mediterranean Diet score and the Alternative Healthy Eating Index 2010 score, with higher scores indicating healthier diet. Dietary index scores were cumulatively updated from 1986 until men developed erectile dysfunction, cardiovascular disease, died, or were lost to follow-up. Incident erectile dysfunction was assessed with questionnaires in 2000, 2004, 2008, and 2012. Hazard ratios (HRs) by prespecified categories or quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses stratified by age.ResultsAmong 21 469 men included in analysis, mean (SD) age at baseline was 62 (8.4) years. During a mean (SD) follow-up of 10.8 (5.4) years and 232 522 person-years, there were 968 incident erectile dysfunction cases among men younger than 60 years, 3703 cases among men aged 60 to less than 70 years, and 4793 cases among men aged 70 years or older. Men younger than 60 years and in the highest category of the Mediterranean Diet score had the lowest relative risk of incident erectile dysfunction compared with men in the lowest category (HR, 0.78; 95% CI, 0.66-0.92). Higher Mediterranean diet scores were also inversely associated with incident erectile dysfunction among older men (age 60 to

PurposeIn younger men lower body mass is associated with fewer urinary symptoms, including incontinence and nocturia. However, lower body mass may have different implications in older men due to age associated muscle atrophy and decreased strength.Materials and methodsWe performed a prospective analysis of community dwelling men 70 to 79 years old in the multicenter Health ABC (Aging and Body Composition) study who underwent measurement of body mass on physical examination, composition using dual x-ray absorptiometry and strength according to grip and lower leg dynamometry. We evaluated associations with prevalent incontinence and nocturia on structured questionnaires as well as concurrent changes in urinary symptoms during 3 years using multivariate logistic regression.ResultsOf the 1,298 men analyzed 22% reported incontinence and 52% reported nocturia at baseline. Higher body mass index, fat mass and lower appendicular lean mass, and grip and quadriceps strength corrected for body mass index were associated with an increased prevalence of incontinence (each p

BackgroundMen with prostate cancer often experience urinary and sexual dysfunction after treatment. Previous studies have demonstrated a relationship between dietary factors and these symptoms among men with diabetes or metabolic syndrome. However, there are limited data on whether diet after prostate cancer diagnosis, including a Mediterranean dietary pattern, affects urinary and sexual function among prostate cancer survivors.MethodsMen diagnosed with non-metastatic prostate cancer in the Health Professionals Follow-up Study (n = 2960) from 1986 to 2012 were prospectively followed for a median of 8.3 years after treatment. Participants completed validated dietary questionnaires every 4 years and a health-related quality of life assessment in 2010 or 2012. We used generalized linear models to examine associations between post-diagnosis Mediterranean Diet Score (including individual score components and dietary fat subtypes) and quality of life domains (sexual functioning, urinary irritation/obstruction, urinary incontinence) assessed using the Expanded Prostate Cancer Index Composite Short Form (score 0-100; higher scores indicate better function).ResultsNo statistically significant relationships were observed between the Mediterranean Diet Score after prostate cancer diagnosis and urinary or sexual function. However, the associations did vary depending on pre-diagnosis urinary and sexual dysfunction for urinary irritation/obstruction and sexual function scores, respectively (P-interactions

BackgroundObservational studies suggest an inverse association between selenium and risk of prostate cancer. However, randomized controlled trials of selenium supplementation have reported conflicting results. Thus, we examined plasma selenium and selenium-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with non-metastatic disease.MethodsWe measured plasma selenium and genotyped 73 single nucleotide polymorphisms in TXNRD1, TXNRD2, GPX1, GPX3, GPX4, SEP15, SEPP1, SELENBP1, OGG1, and CAT among 568 men with non-metastatic prostate cancer who underwent radical prostatectomy. We examined associations between plasma selenium, genotypes, and risk of high-grade prostate cancer (Gleason grade ≥8 or 7 with primary score ≥4; n = 111) using logistic regression, and risk of prostate cancer recurrence (61 events; 3.8 y median follow-up) using Cox proportional hazards regression.ResultsPlasma selenium was not associated with risk of high-grade prostate cancer or prostate cancer recurrence. Less common alleles of rs11913319 in TXNRD2 and rs125701 in OGG1 were associated with an increased risk of high-grade prostate cancer. We observed associations between the risk of prostate cancer recurrence and multiple SNPs in TXNRD1, TXNRD2, GPX3, and SEP15. These associations were no longer statistically significant after adjustment for multiple comparisons.ConclusionsAmong men with non-metastatic prostate cancer, there is suggestive evidence that genetic variation in selenoproteins and related antioxidant enzymes may be associated with risk of high-grade disease at diagnosis and prostate cancer recurrence.

BackgroundObservational studies suggest an inverse association between vitamin E and risk of prostate cancer, particularly aggressive tumors. However, three large randomized controlled trials have reported conflicting results. Thus, we examined circulating vitamin E and vitamin E-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with clinically organ-confined disease.MethodsWe measured circulating α- and γ-tocopherol and genotyped 30 SNPs in SOD1, SOD2, SOD3, TTPA, and SEC14L2 among 573 men with organ-confined prostate cancer who underwent radical prostatectomy. We examined associations between circulating vitamin E, genotypes, and risk of high-grade prostate cancer (Gleason grade ≥ 8 or 7 with primary score ≥ 4; n = 117) using logistic regression, and risk of recurrence (56 events; 3.7 years median follow-up) using Cox proportional hazards regression.ResultsCirculating γ-tocopherol was associated with an increased risk of high-grade prostate cancer (Q4 v. Q1 odds ratio [OR] = 1.87; 95% confidence intervals [CI]: 0.97-3.58; P trend =0.02). The less common allele in SOD3 rs699473 was associated with an increased risk of high-grade disease (T > C: OR = 1.40, 95% CI: 1.04-1.89). Two independent SNPs in SOD1 were inversely associated with prostate cancer recurrence in additive models (rs17884057 hazard ratio [HR] = 0.49, 95%CI: 0.25-0.96; rs9967983 HR = 0.62, 95% CI: 0.40-0.95).ConclusionsAmong men with clinically organ-confined prostate cancer, genetic variation in SOD may be associated with risk of high-grade disease at diagnosis and disease recurrence. Circulating γ-tocopherol levels may also be associated with an increased risk of high-grade disease at diagnosis.

BackgroundStatins are a common medication for cholesterol control that may also have effects on cancer-related pathways. The evidence of an association between statins and prostate cancer risk remains ambiguous.MethodsWe examined statin use in a prospective cohort of 5,069 elderly U.S. men and the risk of incident total, low/high stage, and low/high grade prostate cancer diagnosed between 2000 and 2008. We used multivariate logistic regression models to estimate relative risks and 95% confidence intervals, adjusting for demographic and lifestyle characteristics.ResultsThere was no evidence of an association between statin use and any of the prostate cancer endpoints (total, low/high stage, low/high grade prostate cancer), adjusting for age, study site, race, body mass index, marital status, family history of prostate cancer, number of comorbidities, physical activity, and smoking history.Conclusions and impactIn this study of elderly U.S. men, we observed a null association between statin use and risk of prostate cancer.