Distribution and associations of [-2]proenzyme-prostate specific antigen in community dwelling black and white men.

PURPOSE: We provide cross-sectional normative data on [-2]proenzyme-prostate specific antigen from the Olmsted County Study of Urinary Symptoms and Health Status among Men, and the Flint Men's Health Study. We also describe associations with clinical urological measures and the risk of prostate cancer diagnosis. MATERIALS AND METHODS: Measurements of [-2]proenzyme-prostate specific antigen were obtained from 420 white men from Olmsted County, Minnesota, and 328 black men from Genesee County, Michigan. Cross-sectional associations between [-2]proenzyme-prostate specific antigen and prostate enlargement/elevated prostate specific antigen were assessed. Cox proportional hazard models were used to assess associations between [-2]proenzyme-prostate specific antigen and the incident diagnosis of prostate cancer. RESULTS: Baseline [-2]proenzyme-prostate specific antigen was slightly higher in black men at a median of 6.3 pg/ml (25th, 75th percentiles 4.1, 8.9) than in white men at a median of 5.6 pg/ml (25th, 75th percentiles 3.9, 7.7, respectively, p = 0.01). Baseline [-2]proenzyme-prostate specific antigen was highly predictive of biopsy confirmed prostate cancer in the Olmsted County Study cohort. Relative to men in the [-2]proenzyme-prostate specific antigen lower quartile those in the upper quartile were at almost eightfold increased risk for prostate cancer (HR 7.8, 95% CI 2.2-27.8) after adjusting for age and baseline prostate specific antigen. CONCLUSIONS: In these cohorts of community dwelling black and white men [-2]proenzyme-prostate specific antigen was much lower than in previous studies. These data suggest that [-2]proenzyme-prostate specific antigen may help identify prostate cancer in men with serum prostate specific antigen in an indeterminate range, although the reference ranges for white and black men may differ slightly.

Benign prostate specific antigen distribution and associations with urological outcomes in community dwelling black and white men.

PURPOSE: We describe cross-sectional associations of benign prostate specific antigen with clinical urological measures and examined the risk of future urological outcomes in 2 population based cohorts of black and white men, respectively. MATERIALS AND METHODS: Two population based cohort studies were established to characterize the natural history of and risk factors for prostate disease progression in white and black male residents of Olmsted County, Minnesota, and Genesee County, Michigan, respectively. RESULTS: The benign prostate specific antigen distribution was similar in black men at a median of 32.9 pg/ml (25th, 75th percentiles 17.3, 68.0) and white men at a median of 32.2 pg/ml (25th, 75th percentiles 16.6, 68.9, respectively). However, it was much lower than in previous reports. For Olmsted County men in the upper quartile of benign prostate specific antigen there was a fifteenfold increased risk of prostate cancer (HR 14.6, 95% CI 3.1-68.6) and a twofold higher risk of treatment for benign prostatic hyperplasia (HR 2.2, 95% CI 1.2-4.2) after adjusting for age. After additional adjustment for baseline prostate specific antigen the association between benign prostate specific antigen and prostate cancer risk was attenuated but remained almost ninefold higher for men in the upper quartile of benign prostate specific antigen (HR 8.7, 95% CI 1.8-42.4). The twofold higher risk of treatment for benign prostatic hyperplasia also remained after adjusting for baseline prostate specific antigen for men in the upper benign prostate specific antigen quartile (HR 1.9, 95% CI 0.9-4.0). CONCLUSIONS: Results suggest that increased benign prostate specific antigen may help identify men with prostate cancer and those at risk for benign prostatic hyperplasia treatment.

Effectiveness of medical and surgical therapies for lower urinary tract symptoms in the community setting.

UNLABELLED: Study Type - Therapy (outcomes research) Level of Evidence 2c. What's known on the subject? and What does the study add? It is known that benign prostatic hyperplasia is a common condition affecting most men by the age of 80 years. There are multiple treatment options available, including both medical and surgical interventions. However, what is not known is how affective the different types of interventions are in the general population. Previous studies have focused on centre-specific data. What is unique about our study is that it is a prospective cross-section analysis of a community cohort of men. Through this study we were able to assess the outcomes in the general population as opposed to in a high-volume surgical centre. Our findings show that in this community medical management was poor at symptomatic improvement, whereas surgical intervention produced the best improvement. OBJECTIVE: • To describe the use and symptomatic outcomes of different therapies for lower urinary tract symptoms (LUTS) in a community-based population of men followed for 17 years. PATIENTS AND METHODS: • Data from a randomly selected cohort of 2184 men, aged 40-79 years in 1990, from Olmsted County, Minnesota, USA were included in the study. Participants completed a questionnaire similar to the American Urological Association Symptom Index (AUASI) and reported on incontinence. • Men were followed biennially through 2007 (median follow-up: 13.7 years; Q1, Q3: 8.8, 15.7). Medical and surgical treatments for LUTS were reported on biennial questionnaires and abstracted from community medical records. RESULTS: • Overall, 610 (28%) men received medical or surgical therapy for treatment of LUTS. Patients undergoing vaporization and transurethral resection of the prostate (TURP) had the highest pre-intervention AUASI scores (P < 0.001) and the most rapid increase in scores over time (P= 0.002) compared with those treated with medications or no therapy. After intervention, symptom progression slowed in all treatment groups. • However, the greatest improvement in AUASI score (median % change) was observed in the TURP group: -27.45%. The TURP group also reported a significant decrease in incontinence after surgery (% change): TURP: -22.58%. CONCLUSION: • All therapies were effective at slowing the progression of LUTS, but only TURP patients reported a significant decrease in both LUTS and incontinence after therapy.

Nocturia is associated with an increased risk of coronary heart disease and death.

UNLABELLED: What's known on the subject? and What does the study add? Nocturia has been associated with multiple chronic conditions, however, previous studies have been conducted only at a single time. We found that nocturia preceded the development CHD in young men. Moderate nocturia may be an early marker of CHD in young men. OBJECTIVE: To determine whether nocturia is associated with the development of diabetes mellitus, hypertension, coronary heart disease (CHD) and occurrence of death. MATERIALS AND METHODS: We studied data obtained from a retrospective cohort of randomly selected men, aged 40-79 years in 1990, from Olmsted County, MN, USA. Moderate nocturia was defined as waking to urinate ≥2 times per night. Men were followed every 2 years through repeated questionnaires and community medical records to assess development of diabetes mellitus and hypertension, and occurrence of death. CHD was ascertained through ongoing surveillance of heart disease in Olmsted County. Cox proportional hazard models were used to estimate associations between baseline nocturia and each of the outcomes. RESULTS: A total of 2447 men were followed for a median of 17.1 years (25th and 75th percentiles: 15.0, 17.4 years). Moderate nocturia was not significantly associated with the later development of diabetes mellitus or hypertension in this study. Younger men (<60 years of age) with moderate nocturia were more likely to develop CHD later in life than younger men without nocturia (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.13, 2.49). This association was no longer significant when adjusted for age, body mass index (BMI) and urological medications (HR: 1.36; 95% CI: 0.87, 2.12). Older men (≥60 years of age) with moderate nocturia were more likely to die than older men without moderate nocturia, even after adjusting for age, BMI, urological medications and CHD (HR: 1.48; 95% CI: 1.15, 1.91). CONCLUSION: Nocturia may be a marker for increased risk of CHD in younger men, and death in older men.

Associations between longitudinal changes in serum estrogen, testosterone, and bioavailable testosterone and changes in benign urologic outcomes.

Some men have rapid increases in benign prostatic enlargement and lower urinary tract symptoms (LUTS), and it is not clear how sex steroid hormones contribute to the rates of change in these urologic outcomes. Therefore, the authors conducted a population-based cohort study of 648 men residing in Olmsted County, Minnesota, from 1990 to 2007, to examine associations between baseline sex steroid hormones, the rate of change in these hormones, and the rates of change in LUTS, maximum urinary flow rate, and prostate volume. Annual changes in hormone levels and urologic outcomes were calculated using mixed-effects regression models. Associations between hormone variables and rates of change in urologic outcomes were assessed with linear regression models. Higher baseline estradiol levels and rapid declines in estradiol over time were associated with rapid increases in LUTS and rapid decreases in maximum flow rate. Lower baseline bioavailable testosterone levels and more rapid declines in bioavailable testosterone were associated with more rapid increases in prostate volume. These results suggest that both absolute sex steroid hormone levels and the rates at which the levels change may be important in the development of urologic conditions in aging men.

Associations between variants in the cyclooxygenase 2 enzyme gene (PTGS2) and development of benign prostate enlargement.

OBJECTIVE: To determine if polymorphisms in the cyclooxygenase 2 (COX-2) enzyme gene (prostaglandin synthase 2; PTGS2) were associated with development of benign prostate enlargement (BPE), and whether associations were modified by use of nonsteroidal anti-inflammatory drugs (NSAIDs). MATERIALS AND METHODS: Participants were men residing in Olmsted County, MN, who were between 40 and 79 years of age in 1990 (N= 356). Prostate volume was measured by transrectal ultrasound and men reported all the medications that they were taking at the time of the examination. Men were followed biennially for 16 years. Ten tagging single nucleotide polymorphisms (SNPs) in the PTGS2 gene were typed using the Illumina GoldenGate(TM) Assay. Associations between SNPs and development of BPE (volume >30 mL) were assessed by Cox proportional hazards models. Models were also stratified by NSAID use. RESULTS: We observed significant associations between four polymorphisms in the PTGS2 gene and development of BPE (all P < 0.05). These associations were not observed among men who used NSAIDs. CONCLUSION: Variants in the PTGS2 gene may increase the risk of prostate enlargement, but the increased risk may be minimized by use of NSAIDs.

Statin use and decreased risk of benign prostatic enlargement and lower urinary tract symptoms.

OBJECTIVE: To determine whether statin use is associated with a decreased risk of developing benign prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS). SUBJECTS AND METHODS: We conducted a retrospective, population-based cohort study of 2447 men, 40-79 years of age, residing in Olmsted County, MN, USA, in 1990, and followed these men biennially through 2007. Cox proportional hazard models were used to assess associations between statin use and new onset of moderate/severe LUTS (American Urological Association Symptom Index score >7), a decreased maximum urinary flow rate (<12 mL/s) or BPE (prostate volume >30 mL). RESULTS: Statin use was inversely associated with new onset of LUTS (Hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.31-0.49), a decreased maximum flow rate (HR 0.53; 95% CI 0.34-0.82) and BPE (HR 0.40; 95% CI 0.23-0.69) after adjustment for baseline age and body mass index, diabetes, hypertension, coronary heart disease, smoking, alcohol use, activity level and non-steroidal anti-inflammatory use. The longest duration of statin use was associated with the lowest risk of developing each outcome (all tests for trend: P < 0.001). CONCLUSION: In this study, statin use was associated with a 6.5- to 7-year delay in the new onset of moderate/severe LUTS or BPE. While men typically take statin medications to prevent coronary heart disease events and related outcomes, these data suggest that men who use statins may also receive urologic benefits.

Measures of autonomic nervous system activity and lower urinary tract symptoms.

Autonomic nervous system (ANS) activity may play an important role in the development of lower urinary tract symptoms (LUTS). Men with severe LUTS and men with mild or no LUTS completed the Valsalva maneuver, quantitative sudomotor axon reflex test, tilt-table, and deep breathing tests. There were no differences between men with severe LUTS compared to men with mild or no LUTS (all P values > 0.05). Systemic ANS tests may not be useful in detecting the underlying physiologic changes that lead to LUTS in aging men.

Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

CONTEXT: The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. OBJECTIVE: To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011. INTERVENTIONS: Oral selenium (200 µg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer incidence. RESULTS: This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination. CONCLUSION: Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00006392.

The association between statin use and the diagnosis of prostate cancer in a population based cohort.

PURPOSE: The effect of statin medication use on the risk of prostate cancer is unknown. MATERIALS AND METHODS: We examined data from a longitudinal, population based cohort of 2,447 men between 40 and 79 years old who were followed from 1990 to 2007. Information on statin use was self-reported and obtained by biennial questionnaires. A randomly selected subset of men (634, 26%) completed biennial urological examinations that included serum prostate specific antigen measurements. Information on prostate biopsy and prostate cancer was obtained through review of community medical records. RESULTS: Of 634 statin users 38 (6%) were diagnosed with prostate cancer vs 186 (10%) of 1,813 nonstatin users. Statin use was associated with a decreased risk of undergoing prostate biopsy (HR 0.31; 95% CI 0.24, 0.40), receiving a prostate cancer diagnosis (HR 0.36; 95% CI 0.25, 0.53) and receiving a high grade (Gleason 7 or greater) prostate cancer diagnosis (HR 0.25; 95% CI 0.11, 0.58). Statin use was also associated with a nonsignificantly decreased risk of exceeding a prostate specific antigen threshold of 4.0 ng/ml (HR 0.63; 95% CI 0.35, 1.13). In addition, a longer duration of statin use was associated with a lower risk of these outcomes (all tests for trend p <0.05). CONCLUSIONS: Statin use is associated with a decreased risk of prostate cancer diagnosis. This association may be explained by decreased detection or cancer prevention.

Natural history of benign prostatic enlargement: long-term longitudinal population-based study of prostate volume doubling times.

OBJECTIVES: To measure prostate volume doubling times (PVDTs) for a large sample of community men followed serially by transrectal ultrasonography (TRUS), and to determine whether specific characteristics are associated with a rapid PVDT. SUBJECTS AND METHODS: A subsample of 446 subjects from a larger cohort of American white men aged 40-79 years were evaluated biennially for a median (range) follow-up of 10 (3-14) years. Mixed-effects regression models were used to estimate prostate growth rates and PVDT for subjects with three or more or with five or more serial biennial TRUS PV measurements. RESULTS: The median (25-75th percentile) PVDT was 32.6 (24.6-44.0) years. The average annual increase in PV was 2.2%. The PVDT distribution was constant in men of all age groups studied (r < 0.001, P = 0.99). The factor most strongly associated with PVDT was baseline transition zone volume (r = -0.55, P < 0.001). Baseline total prostate-specific antigen (PSA) level, free PSA and total PV were also significantly inversely associated with PVDT (r = -0.30, -0.44 and -0.32, respectively, all P < 0.001). Age, baseline anthropomorphic measurements, hormone levels and specific lifestyle characteristics were not significantly correlated with PVDT. CONCLUSION: These data indicate that PVDT might be a useful future measure of benign prostatic growth. They provide a basis to forecast PV at 10, 20, or 30 years later, after one baseline TRUS measurement of prostate volume, and can be presented in a simple nomogram.

Associations between C-reactive protein and benign prostatic hyperplasia/lower urinary tract symptom outcomes in a population-based cohort.

Inflammation may play a role in the development of benign prostatic hyperplasia and/or lower urinary tract symptoms (LUTS). Higher levels of C-reactive protein (CRP) may therefore be associated with the development of these outcomes. The authors examined the association of CRP levels measured in 1996 with rapid increases in prostate volume, prostate-specific antigen levels, and LUTS as well as rapid decreases in peak flow rates (through 2005) in a population-based cohort of men residing in Olmsted County, Minnesota. Men with CRP levels of > or =3.0 mg/L were more likely to have rapid increases in irritative LUTS (odds ratio (OR) = 2.14, 95% confidence interval (CI): 1.18, 3.85) and rapid decreases in peak flow rates (OR = 2.54, 95% CI: 1.09, 5.92) compared with men with CRP levels of <3.0 mg/L. CRP levels were not significantly associated with rapid increases in prostate volume, obstructive LUTS, or prostate-specific antigen levels. Associations were attenuated after adjusting for age, body mass index, hypertension, and smoking history (irritative LUTS: OR = 2.00, 95% CI: 1.04, 3.82; peak flow rate: OR = 2.45, 95% CI: 0.73, 8.25). These results suggest that rapid increases in irritative LUTS and rapid decreases in peak flow rates may be due to inflammatory processes.

Smoking and acute urinary retention: the Olmsted County study of urinary symptoms and health status among men.

BACKGROUND: Previous reports have suggested an inverse relationship between smoking and surgery for benign prostatic hyperplasia (BPH). We hypothesized that acute urinary retention (AUR), an adverse outcome of this disease and indication for surgical treatment, may be related to smoking. METHODS: Study subjects were randomly selected from Olmsted County men aged 40-79 identified through the Rochester Epidemiology Project. Of the 3,854 eligible men, 2,089 (54%) completed a questionnaire that included the American Urological Association Symptom Score and assessed smoking status. Community medical records were examined for occurrence of AUR with documented catheterization in the subsequent 10 years and occurrence of BPH surgery. Proportional hazard models were used to assess the relationship between baseline smoking status and subsequent retention. RESULTS: In the 18,307 person-years of follow-up, 114 men had AUR. When compared to 727 never-smokers, there was a trend among the 336 current smokers to be at lower risk (Relative risk (RR) = 0.62, 95% Confidence Interval (CI) = 0.33, 1.18) whereas the 1,026 former smokers were at similar risk to non-smokers (RR = 1.0, 95%CI = 0.67, 1.46). Among men with moderate-severe symptoms at baseline, current smokers were at lower risk of retention compared to non-smokers (RR = 0.65, 95%CI = 0.22, 1.91) but the association approached the null among those with none-mild symptoms (RR = 0.91, 95% CI = 0.40, 2.06). CONCLUSIONS: Community-dwelling men who currently smoke may be at a modestly reduced risk of AUR. The magnitude of this association is sufficiently small that it seems unlikely that this explains a sizable proportion of the inverse association between smoking and surgically treated BPH.

Intravesical prostatic protrusion in men in Olmsted County, Minnesota.

PURPOSE: Ultrasonically measured intravesical prostatic protrusion may be a promising noninvasive method of assessing bladder outlet obstruction. Previous investigations of this technique focused on patients with acute urinary retention and symptomatic men identified in urology clinics, which may not reflect the distribution of intravesical prostatic protrusion in community dwelling men. MATERIALS AND METHODS: In 2006 a total of 322 white men residing in Olmsted County, Minnesota underwent transrectal ultrasound examination which permitted direct measurement of intravesical prostatic protrusion. Cross-sectional associations between lower urinary tract symptoms/benign prostatic enlargement and intravesical prostatic protrusion were measured. Rapid increases in lower urinary tract symptoms/benign prostatic enlargement measures as predictors of severe intravesical prostatic protrusion were also assessed. RESULTS: Overall 10% of these men had an intravesical prostatic protrusion of 10 mm or greater. Greater intravesical prostatic protrusion was weakly correlated with greater prostate volume (r(s) = 0.28), higher obstructive symptoms (r(s) = 0.18) and lower peak urinary flow rate (r(s) = -0.18). Men with the most rapidly growing prostate before intravesical prostatic protrusion measurement were 3 times more likely to have an intravesical prostatic protrusion of 10 mm or greater. Men with an intravesical prostatic protrusion of 10 mm or greater were more likely to use medications for lower urinary tract symptoms/benign prostatic enlargement compared to those with an intravesical prostatic protrusion less than 10 mm (adjusted OR 2.95, 95% CI 1.23-7.06). CONCLUSIONS: These population based data provide reference ranges for future studies of intravesical prostatic protrusion as a predictor of adverse urological outcomes. Intravesical prostatic protrusion is significantly correlated with greater prostate volume, higher obstructive symptoms and lower peak urinary flow rate, suggesting that it may have clinical usefulness in predicting the need for treatment.

Presumed circle area ratio of the prostate in a community-based group of men.

OBJECTIVE To determine the normal values for the presumed circle area ratio (PCAR) in a group of community-based men, and to determine whether PCAR is associated with specific urological outcomes. PATIENTS AND METHODS The study was a cross-sectional analysis among 328 Caucasian men (94% participation) residing in Olmsted County, Minnesota, USA. The PCAR was measured during prostatic ultrasonography. Lower urinary tract symptoms (LUTS) were measured using the American Urologic Association Symptom Index. The peak urinary flow rate was measured by a uroflowmeter, and the postvoid residual volume (PVR) was assessed using the BladderScan(TM) BVM 6500 (Verathon, Bothell, WA, USA). Correlations between PCAR and presence of LUTS, peak urinary flow rate, and PVR were determined using Spearman correlation coefficients. Unadjusted and adjusted odds ratios (ORs) were calculated using logistic regression to determine the associations between PCAR thresholds and categorical urological outcomes. RESULTS The median (interquartile range) PCAR was 0.85 (0.81-0.88). After adjusting for age and total prostate volume, men who had PCARs of >0.90 were more likely to have elevated overall and obstructive symptom scores (OR 2.95, 95% confidence interval 1.39-6.25, and 3.47, 1.63-7.39, respectively). CONCLUSION PCAR might add further information beyond total prostate volume when predicting the development of obstructive LUTS.

Longitudinal evaluation of sexual function in a male cohort: the Olmsted county study of urinary symptoms and health status among men.

INTRODUCTION: The presence of erectile or ejaculatory dysfunction may indicate physical problems; however, individual perceptions (e.g., sexual satisfaction) may reflect the degree of concern about these changes. Long-term data showing how changes in multiple sexual function domains track together may be useful in understanding the importance of physical declines vs. sexual satisfaction. AIM: The aim of this study was to describe changes in sexual function among a population-based sample of aging men. METHODS: A population-based cohort study using data from the Olmsted County Study of Urinary Symptoms and Health Status among Men. Sexual function was assessed biennially from 1996 to 2004 using a previously validated questionnaire in a random sample of 2,213 men. MAIN OUTCOME MEASURES: Changes in erectile function, libido, ejaculatory function, sexual problems, and sexual satisfaction. RESULTS: Overall, we observed declines in all of the sexual function domains, ranging from an annual decrease of 0.03 point per year for sexual satisfaction to an annual decrease of 0.23 point per year in erectile function. Moderate correlations were observed among all longitudinal changes in sexual function (range in age-adjusted r(s) = 0.14-0.43); however, significantly smaller correlations between changes in the functional domains and changes in sexual satisfaction and problem assessment were observed among older men (range in age-adjusted r(s) = 0.03-0.29). CONCLUSION: Overall, these results demonstrate that longitudinal changes in five sexual function domains change together over time in our community-based cohort. Erectile function, ejaculatory function, and sexual drive decrease over time with greater rates of decline for older men. However, older men may be less likely to perceive these declines as a problem and be dissatisfied. These data may prove helpful to patients and clinicians in understanding and discussing changes in multiple aspects of sexual function.

Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

CONTEXT: Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer. OBJECTIVE: To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer. INTERVENTIONS: Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer. RESULTS: As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group. CONCLUSION: Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00006392.

The induction and maintenance of in vitro plant morphogenesis as viewed from a new perspective, with theoretical and constructive implications.

In plant tissue culture research, the non-traditional growth regulators, methylglyoxal and ascorbic acid, have been used to induce and promote in vitro morphogenesis from plant callus, generally having the initial characteristics of a type of neoplasm, and in many cases overcoming recalcitrant morphogenesis. In other investigations methylglyoxal, most likely with ascorbic acid, also promoted such morphogenesis. In the various investigations, low concentrations of methylglyoxal were used and proved to be the most effective in promoting in vitro morphogenesis. In many cases, the growth of such neoplastic-like calli was concurrently inhibited on culture media containing these chemicals. When methylglyoxal was present in high concentration, morphogenesis was also inhibited. Such chemicals, it would appear likely, allowed for the generation of cohesive forces within regions of the calli, reversing the neoplastic state in such regions, due to very low internal cohesion, and through such cohesive forces of particular magnitude, morphogenesis ensued, as an adaptive response to the stress of such cohesive forces. This would suggest a deeper, underlying biological process, with developmental features, that is perhaps universal among plants and perhaps in all biological organisms. This particular, consistent avenue and theme of plant tissue culture research, manifested over four decades and across four continents, may have revealed a unifying, dynamical process in both the biological and physical worlds, with constructive implications for agriculture and medicine.

Psychosocial factors associated with an increased frequency of prostate cancer screening in men ages 40 to 79 years: the Olmsted County study.

Prostate cancer is the second leading cause of cancer deaths among U.S. men. Early detection is associated with drastically improved 5-year survival rates. It is unclear, however, what psychosocial factors motivate or discourage men from taking advantage of both prostate-specific antigen (PSA) testing and digital rectal examination (DRE). The goal of the current study was to identify psychosocial factors that influence screening behavior for prostate cancer in a cohort of 2,447 men. In 1990, a randomly selected cohort of Caucasian men, ages 40 to 79 years, from Olmsted County, Minnesota, were enrolled in the study. These men completed a questionnaire containing queries on family history of prostate cancer, concern about getting prostate cancer, and marital status. Medical and laboratory records were reviewed to determine the number DREs (1989-1996) and PSA tests (1989-1998). Frequent screening was defined as the upper 25th percentile for number of DREs (>4) or PSAs (>3). Men who have a family history and men who worry or have concern about prostate cancer were more likely [odds ratio (OR), 1.5; 95% confidence interval (95% CI), 1.2-2.0 and OR, 1.9; 95% CI, 1.4-2.5] to seek screening compared with those without a family history or worry. The association between family history and frequent screening was similar in men who were married or living with someone (OR, 1.7; 95% CI, 1.2-2.2); however, it was reduced among men who live alone (OR, 0.6; 95% CI, 0.2-1.8). These data suggest that psychosocial factors such as family history, worry, or concern about prostate cancer and marital status may play an important role in men's decisions about prostate cancer screening.

The associations between serum sex hormones, erectile function, and sex drive: the Olmsted County Study of Urinary Symptoms and Health Status among Men.

INTRODUCTION: Testosterone replacement therapy has been used in the treatment of sexual dysfunction; however, its use remains controversial, and the effectiveness and long-term health implications are unknown. AIM: To evaluate the association between sex hormone serum levels, erectile function, and sexual drive in a population-based sample of men. METHODS: A stratified random sample of men residing in Olmsted County, Minnesota, completed a questionnaire containing questions from the Brief Male Sexual Function Inventory (BMSFI), and participated in a clinical exam, which included serum hormone measurements. MAIN OUTCOME MEASURES: Levels of sexual drive (libido) and erectile function as assessed by the BMSFI and serum testosterone, bioavailable testosterone, and estradiol measurements. RESULTS: Out of 414 men, 294 had a regular sexual partner and androgen measurements at the 14th year of follow-up. Total testosterone and erectile function were significantly correlated even after adjustment for age (r = 0.12, P = 0.04). Conversely, total testosterone was not significantly correlated with sex drive (r = 0.08, P = 0.17). Bioavailable testosterone was significantly correlated with both erectile function and sex drive (r = 0.16, P = 0.01 and r = 0.20, P = 0.001, respectively). However, these associations disappeared after age adjustment (r = 0.04 and r = 0.09). CONCLUSIONS: These cross-sectional results suggest the relationship between sex hormones and sexual function is complex, and that the age-related decline in sexual function may be due to age-related declines in levels of bioavailable testosterone rather than total testosterone levels.