Antimuscarinics for treatment of storage lower urinary tract symptoms in men: a systematic review.

Despite potential benefits, primary care clinicians may avoid using antimuscarinics in men with overactive bladder (OAB) symptoms because of safety concerns. To review the efficacy and safety of antimuscarinics, alone or in combination with an α-blocker, for the treatment of men with OAB symptoms, we conducted a systematic review of articles published before 22 July 2010, using PubMed. Data from 12-week, randomised, double-blind, placebo-controlled trials of tolterodine extended release (ER), oxybutynin and solifenacin show that combined antimuscarinic+α-blocker treatment is generally more effective than monotherapy or placebo in men with OAB symptoms. The efficacy and safety of tolterodine ER+α-blocker treatment was not affected by prostate size or prostate-specific antigen (PSA) level. In men meeting entry criteria for OAB and benign prostatic obstruction trials, tolterodine ER alone was effective selectively in men with prostate size or PSA level below study medians. Incidence of acute urinary retention (AUR) in men receiving antimuscarinics with or without an α-blocker was ≤3% in all of these trials; changes in postvoid residual volume and maximum flow rate did not appear clinically meaningful. Post hoc analyses from double-blind, placebo-controlled trials and prospective studies of fesoterodine, oxybutynin, propiverine, solifenacin and tolterodine also suggest that antimuscarinics are generally safe and efficacious in men. A retrospective database study found that risk of AUR in men was the highest in the first month of treatment and decreased considerably thereafter. Antimuscarinics, alone or with an α-blocker, appear to be efficacious and safe in many men with predominant OAB symptoms or persistent OAB symptoms despite α-blocker or 5-α-reductase inhibitor treatment. However, antimuscarinics are not approved for the treatment of benign prostatic hyperplasia. Monitoring men for AUR is recommended, especially those at increased risk, and particularly within 30 days after starting antimuscarinic treatment.

Changes in amount and intracellular distribution of androgen receptor in human foreskin as a function of age.

To provide insight into the factors that control growth of the penis we measured the amount and intracellular distribution of specific high affinity androgen receptor in foreskins obtained at circumcision from 49 males varying in age from newborn to 59 yr. Total (cytosolic plus nuclear extract) androgen receptor decreased from approximately 40 fmol/g tissue weight in newborn foreskins to approximately 25 fmol/g by 1 yr of age. The amount of receptor rose in childhood to approximately 180 fmol/g in the late teenage years and fell thereafter to approximately 20-40 fmol/g in men older than 40 yr. The amount of receptor in the nuclear fraction increased at the time of puberty and subsequently decreased in parallel with the decline in total receptor level. These changes in androgen-receptor amount are similar when expressed per milligram DNA or per milligram protein.

Effects of alfuzosin 10 mg once daily on sexual function in men treated for symptomatic benign prostatic hyperplasia.

We evaluated the effects of extended-release alfuzosin HCl 10 mg once daily (q.d.) on sexual function in men with lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). In a randomized, double-blind, placebo-controlled study of men aged > or = 50 years, after a 28-day placebo run-in period, patients were randomized to receive alfuzosin 10 mg q.d. or matching placebo for 28 days. The mean change from baseline (day 1) in sexual function on day 29 was assessed using the Danish Prostate Symptom Score Sex (DAN-PSSsex) questionnaire. A total of 372 patients were randomized to receive alfuzosin (n=186) or placebo (n=186), with 355 completing the study. At baseline, 64% of the patients reported erectile dysfunction (ED) and 63% reported ejaculatory dysfunction (EjD). For the 320 patients who completed the DAN-PSSsex, alfuzosin treatment was associated with a significant improvement in the mean change from baseline in erectile function on day 29 compared with placebo (P=0.02). No significant difference was observed between the two treatment groups in the mean change from baseline in ejaculatory function on day 29. For patients with ED at baseline, a marginal improvement in erectile function was demonstrated with alfuzosin treatment (P=0.09 vs placebo). For patients with EjD at baseline, the mean change from baseline in ejaculatory function with alfuzosin was comparable to that with placebo. Dizziness was the most common adverse event with alfuzosin treatment (5 vs 0% with placebo), with other adverse events reported with comparable frequency in both treatment groups. After 1 month of treatment, alfuzosin 10 mg q.d. significantly improved erectile function in men with lower urinary tract symptoms/ benign prostatic hypertrophy and had no adverse effect on ejaculatory function.

Rapid onset of action with alfuzosin 10 mg once daily in men with benign prostatic hyperplasia: a randomized, placebo-controlled trial.

This randomized, double-blind, placebo-controlled study was conducted to investigate whether alfuzosin 10 mg once daily improves the maximum flow rate (Q(max)) and lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) after 1 week and 1 month of treatment. A total of 372 men aged > or = 50 years with symptomatic BPH received alfuzosin or placebo for 28 days. Q(max) increased significantly from baseline at day 8 with alfuzosin (P<0.001 versus placebo); this improvement was evident within 24 h after the first dose and was maintained at day 29. LUTS improved from baseline with alfuzosin at day 8 (P=0.07 versus placebo) and day 29 (P=0.003 versus placebo). Alfuzosin 10 mg once daily exhibits a rapid onset of action, with improvements in Q(max) and LUTS maintained through 1 month of treatment.

Formalin disinfection of prostate biopsy needles may reduce post-biopsy infectious complications.

BACKGROUND: We sought to determine whether formalin disinfection of prostate biopsy needles between cores reduces post-biopsy urinary tract infections (UTIs). METHODS: We reviewed a single-surgeon experience of transrectal prostate biopsies from 2010 to 2014. Biopsies were performed in either an operative suite, where 10% formalin was used to disinfect the needle tip between each biopsy core, or an outpatient clinic, where formalin was not used. Our primary outcome was post-biopsy UTI rates, defined as a positive urine culture within 30 days of biopsy. Infection severity was characterized by the need for admission. Patient demographics, prostate size, prior biopsies, prior UTIs, pre-biopsy antibiotics and cultures and post-biopsy cultures were analyzed. Logistic regression was used to assess predictors of post-biopsy UTIs. Statistical significance was defined as P<0.05. RESULTS: A total of 756 patients were included for analysis, including 253 who received formalin disinfection and 503 who did not. Of these, 32 patients (4.2%) experienced post-biopsy UTIs, with 8 requiring admission (all without formalin use). Infection rates were more than double in the group that did not receive formalin (5.2% vs 2.3%, P=0.085). More patients in the formalin group had undergone prior biopsies (73.9% vs 31.8%, P<0.001). On multivariable analysis, prior UTI (odds ratio (OR) 3.77, P=0.006) was a significant predictor for post-biopsy infection, whereas formalin disinfection trended towards a protective effect (OR 0.41, P=0.055). CONCLUSION: Infectious complications following prostate biopsy may be mitigated by the use of formalin disinfection of the biopsy needle between cores.

Three months' treatment with the alpha1-blocker alfuzosin does not affect total or transition zone volume of the prostate.

Treatment with alpha(1)-adrenergic receptor blockers improves lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia. This study was conducted to test the hypothesis that induction of apoptosis in prostate tissue could be a mechanism underlying the observed clinical benefit. This placebo-controlled, double-blind, randomized trial enrolled 536 men with LUTS who were treated with alfuzosin (10 or 15 mg) once daily or placebo for 3 months. Total prostate and transition zone volume was measured by standardized transrectal ultrasound measurements at baseline and 3 months. Total prostate volume increased by 0.4 ml from baseline in placebo patients but decreased by -0.25 ml in the combined alfuzosin groups. Percentage change was not statistically significantly different between the placebo and alfuzosin groups. Changes in transition zone volumes from baseline were similar in both treatment arms; percentage change was not statistically significantly different between the placebo and alfuzosin groups. Volume changes did not correlate with prostate volumes at baseline. Overall, neither total prostate nor transition zone volume increased or decreased systematically within the 3-month treatment period. If alfuzosin-induced apoptosis in prostate tissue, it was not evident by a measurable change in prostate volume after 3 months' treatment. Further analysis at 1 and 2 years will determine the effect of longer-term treatment.

Efficacy and tolerability of the dual 5alpha-reductase inhibitor, dutasteride, in the treatment of benign prostatic hyperplasia in African-American men.

The efficacy and tolerability of dutasteride (0.5 mg daily for 2 years) in African-Americans (n=161), compared with Caucasians (n=3961), was assessed in a post hoc analysis of data from three Phase III clinical trials. Dutasteride significantly reduced serum dihydrotestosterone levels by >90% and significantly improved subjective (symptom score) and objective (prostate volume, peak urinary flow rate, risk of benign prostatic hyperplasia-related surgery and acute urinary retention) outcomes in both African-Americans and Caucasians. For all efficacy measures, there was no statistically significant treatment-by-race interaction and dutasteride was well tolerated in both racial groups. Therefore, dutasteride demonstrated similar efficacy and safety profiles in African-Americans and Caucasians.

Enlarged prostate: a landmark national survey of its prevalence and impact on US men and their partners.

This questionnaire-based survey evaluated the frequency and severity of lower urinary tract symptoms (LUTS) and the prevalence of enlarged prostate (EP) diagnosis and its impact on quality of life and spousal relationships among >1000 American men aged >50 years. A quarter of men suffered moderate to severe LUTS and 55% of those consulting a doctor had EP. EP negatively affected patient quality of life and caused relationship strain with spouses. These findings confirm that LUTS and EP are prevalent in the US population, affecting both patient and spouse, and may help in developing management strategies for EP.

Estrogen receptor beta agonist LY500307 fails to improve symptoms in men with enlarged prostate secondary to benign prostatic hypertrophy.

BACKGROUND: To assess the efficacy and safety of LY500307, a selective estrogen receptor beta agonist, on lower urinary tract symptoms (LUTS) in patients with enlarged prostate secondary to BPH. METHODS: In a randomized, double-blind, placebo-controlled, parallel phase 2, efficacy and safety study, eligible patients with moderate to severe LUTS and prostatic enlargement (⩾30 ml) were randomized to placebo or LY500307 at 1, 3, 10 and 25 mg once daily for 24 weeks. Primary efficacy end point was change in total International Prostate Symptoms Score (IPSS) after 24 weeks. Secondary end points included changes in total prostate volume (TPV) that served as a proof of concept end point, as well as IPSS quality of life, maximum peak urine flow rate (Qmax) and PSA and safety (adverse events, laboratory test). RESULTS: A total of 414 patients were randomized when the study was terminated because of insufficient TPV reduction, based on a priori defined interim analysis. The IPSS mean change from baseline to end point was -3.4±6.8 in the placebo group and -1.3±6.6, -2.6±7.0, -3.7±6.7 and -4.4±5.7 in the 1, 3, 10 and 25 mg LY500307-treated groups, respectively (P>0.05). Similarly, no treatment effect was observed for any of the secondary efficacy measures. Incidence of adverse events was comparable between treatment groups, and no clinically meaningful changes in laboratory tests were observed. CONCLUSIONS: LY500307 was well tolerated in BPH patients with LUTS at doses up to 25 mg once daily for 24 weeks. The study was terminated early because of inadequate efficacy.

Do baseline estrogen and testosterone affect lower urinary tract symptoms (LUTS) prior to or after pharmacologic treatment with tadalafil?

Little is known about how total testosterone and estradiol-17ß influence lower urinary tract symptoms (LUTS) in men with benign prostatic hypertrophy (BPH). We analyzed data from a subset of men aged ≥18 years randomized to tadalafil 5 mg once-daily or placebo who had ≥6 month history of LUTS and an International Prostate Symptom Score (IPSS)≥13 enrolled in one of three randomized, placebo-controlled tadalafil clinical trials (N = 958). Three specific aims were addressed, as follows: (i) To characterize enrolled men by treatment randomization and testosterone level; (ii) to assess cross-sectional associations of estradiol-17ß, testosterone, and LUTS prior to treatment with tadalafil; and, (iii) to assess longitudinal associations between baseline estradiol-17ß and testosterone and improvements or worsening of LUTS during a 12-week period of tadalafil or placebo administration. LUTS were assessed by total IPSS, IPSS voiding sub-score (IPSS-V) and IPSS storage sub-score (IPSS-S) for cross-sectional analyses, and change in total IPSS (ΔIPSS), ΔIPSS-V, and ΔIPSS-S between baseline and 12-week visit for longitudinal analyses. Correlation analyses and linear regression examined associations. Baseline testosterone was not significantly associated with IPSS. In contrast, estradiol-17ß was inversely correlated with IPSS (r = -0.08; p < 0.05) and IPSS-S (r = -0.14; p < 0.05). Tadalafil treatment resulted in greater IPSS improvements in men with lower baseline estradiol-17ß versus those with higher baseline estradiol-17ß. Lower baseline estradiol-17ß was significantly associated with modestly improved ΔIPSS-V (p = 0.04) and Δtotal IPSS (p = 0.05) but not with ΔIPSS-S, following treatment which may substantiate the role of bladder dysfunction because of nerve and smooth muscle changes in the bladder in addition to benign prostatic enlargement in LUTS. Circulating baseline testosterone did not predict ΔIPSS. Men with lower baseline estradiol-17ß levels showed greater responsiveness to tadalafil 5 mg treatment than those with higher baseline estradiol-17ß levels when responsiveness was measured using total IPSS and IPSS-V.

Expression and characterization of full-length and partial human androgen receptor fusion proteins. Implications for the production and applications of soluble steroid receptors in Escherichia coli.

We have expressed fusion proteins encoding defined segments of the coding segment of the human androgen receptor (hAR) in Escherichia coli using the pGEX-2T expression vector. Large quantities of fusion proteins containing glutathione-S-transferase (GST) linked to the amino or carboxy terminal region of the receptor and a fusion protein containing the complete amino acid sequence of the androgen receptor were produced in soluble form. The GST hAR fusion proteins containing the hormone-binding domain of the androgen receptor exhibit high affinity specific binding for a variety of natural and synthetic androgens. Analysis of the binding properties of the complete and truncated androgen receptor fusion proteins revealed that the amino terminus affects the Kd of the fusion proteins for mibolerone (0.89 vs. 3.43 nM for the truncated and complete fusion proteins, respectively). Despite these differences, both the truncated and complete hAR fusion proteins exhibit a higher affinity for dihydrotestosterone than for testosterone, implying that the preferential affinity for dihydrotestosterone observed in androgen receptor prepared from native sources is a measure of the inherent structure of the hormone-binding domain. Furthermore, the ligand-receptor complex is stable, as the ligand is not easily displaced with unlabelled competitor and is stable to mild heat denaturation. Fusion proteins containing the DNA-binding domain demonstrate specific DNA binding, as evidenced by studies using segments of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) and synthetic glucocorticoid response elements. These studies establish that GST hAR fusion proteins exhibit physical properties similar to those of native androgen receptor. Affinity purification using a glutathione affinity resin and cleavage of the fusion proteins at a thrombin cleavage site permits a marked enrichment using a two-step purification. The use of such methods will facilitate the study of the normal and mutant receptor proteins.

Accurate determination of prostate size via digital rectal examination and transrectal ultrasound.

Previously, prostate size did not play a significant role in the choice of treatment for benign prostatic hyperplasia (BPH). It has been postulated that prostate size does not correlate with symptom severity, flow rate, or the presence or absence of obstruction. However, in a published study of community-dwelling men, the odds of having moderate to severe symptoms were five times higher for men with enlarged prostates than for those with normal prostates. Response to certain types of BPH therapy, especially finasteride, depends on actual prostate volume. Therefore, it is important to have a simple way to accurately determine if a patient's prostate is enlarged. In an analysis of four studies, there was a distinct underestimation of prostate size by digital rectal examination (DRE) when compared with transrectal ultrasound (TRUS) measurement. The underestimation of prostate volume increased with increasing TRUS volume, particularly if the volume was greater than 30 mL. The average underestimation was between 9% and 12% for prostate volumes 30 to 39 mL and between 17% and 27% for prostate volumes 40 to 49 mL. Because of these results, a prospective study is currently in progress to develop models or visual aids to assist physicians in more accurately predicting a threshold prostate volume via DRE.

Meta-analysis of randomized clinical trials of finasteride.

A meta-analysis was recently published based on six randomized clinical trials of at least one year duration involving finasteride 5 mg and placebo in the treatment of men with clinical benign prostatic hyperplasia (BPH). In a pooled analysis, mean improvement in symptoms and urinary flow rate with finasteride were found to increase with increasing prostate size. This article reviews the previous publication of this meta-analysis, which indicated prostate volume is a key predictor of outcomes with finasteride treatment and suggested that finasteride is most effective in men with large prostates.

Can transabdominal ultrasound estimation of postvoiding residual (PVR) replace catheterization?

In 81 outpatients the postvoiding residual urine (PVR) using real-time B-mode ultrasonography (3.5 MHz transducer) was measured. For the calculation of the bladder volume the formula for an ellipsoid (V = 4/3 pi X r1 X r2 X r3) was found to be most accurate in predicting the actual volume measured by in-and-out catheterization (r = 0.982). Other volume formulas, using only one diameter of the bladder, were found to be much less accurate. For any arbitrary value of PVR, used in determining clinical management, the incidence of misjudgment by ultrasound was negligibly low. We conclude, that sonographic measurement of the PVR as a quick, noninvasive method, should replace catheterization, if the basic equipment is available. Additional information, e.g., prostate size, bladder configuration, diverticula, etc., can be obtained during the procedure without additional costs or loss of time.

Antimicrobial prophylaxis prior to shock wave lithotripsy in patients with sterile urine before treatment: a meta-analysis and cost-effectiveness analysis.

OBJECTIVES: To determine the efficacy and cost-effectiveness of routine antimicrobial prophylaxis prior to shock wave lithotripsy (SWL) in patients with a sterile pretreatment urine culture. METHODS: A structured MedLine search revealed eight prospective, randomized, controlled trials (RCTs) of active treatment versus placebo or no treatment (n = 885) and six clinical series (non-RCTs; n = 597) addressing the use of antimicrobial prophylaxis for SWL. A meta-analysis was performed on the eight RCTs, with the primary outcome being the diagnosis of a urinary tract infection (UTI) post-SWL. A cost analysis was performed comparing a prophylactic strategy (prophylaxis for every patient and treatment for post-SWL UTIs) with a treatment-only strategy for post-SWL UTIs using various antimicrobial combinations and the median probability of post-SWL UTIs determined by meta-analysis. RESULTS: The incidence of post-SWL UTIs ranged from 0% to 28% in the control group and from 0% to 7.7% in the patients who underwent prophylaxis. Combining the placebo/no-drug treatment arms in the six RCTs by meta-analysis (Bayesian analysis) resulted in a median probability of a post-SWL UTI of 5.7% (95% confidence interval [CI] 3.8% to 8.4%). For the drug treatment arms, the median probability of a UTI was 2.1% (95% CI 0.9% to 3.6%). Relative risk (RR) analysis resulted in an overall RR of post-SWL UTIs with prophylaxis versus without prophylaxis of 0.45 (95% CI 0.22 to 0.93) (P = 0.0005). Depending on the antimicrobial regimen used for prophylaxis and treatment, a prophylactic strategy added minimally to the overall treatment cost of SWL, and proved cost beneficial when taking into consideration serious UTIs requiring inpatient treatment. CONCLUSIONS: A policy of antibiotic prophylaxis prior to SWL in patients with sterile pretreatment urine cultures is efficacious in reducing the rate of post-SWL UTIs. Discounting inpatient episodes for sepsis and acute pyelonephritis, however, the strategy is not cost-effective. In contrast, using literature-derived incidence estimates for post-SWL urosepsis or pyelonephritis necessitating inpatient treatment, prophylaxis becomes both efficacious and cost-effective, and thus constitutes a dominant strategy.

Pedicled preputial patch in repair of minor penile chordee with or without hypospadias.

A pedicled preputial patch is described which provides coverage of the ventral skin defect resulting from the release of the ventral skin during the repair of milder forms of hypospadias. The results have been reviewed in 32 consecutive cases, and have been shown to be satisfactory.

Safety and efficacy of doxazosin in benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies.

OBJECTIVES: To present the results of a pooled analysis of three double-blind, placebo-controlled studies of doxazosin in benign prostatic hyperplasia (BPH). Heterogeneous symptom and bother score data collected using different symptom indices were transformed to enable a comparison of the data and to conduct a pooled, in-depth analysis. METHODS: Urinary flow rates, and symptom and bother score data were shown by analysis of covariance methods to give consistent estimates of the efficacy of doxazosin across different studies, thus confirming the validity of pooling the results. Prior to analysis, symptom and bother score data were transformed so that all scales started from zero (least symptoms or bother) and were expressed as a percentage of the maximum score. RESULTS: Doxazosin produced a significantly greater improvement than placebo in peak urinary flow rate (P = 0.0017), symptom severity (P < 0.0001), and bother caused by symptoms (P < 0.0001). Stratification showed that a greater improvement was obtained during doxazosin treatment by those with more severe symptoms at baseline (P = 0.0001). Stratification by age showed that age did not affect the capacity to benefit from treatment. Analysis of the pooled peak flow-rate data showed that doxazosin produced a consistently greater increase in flow compared with placebo. Doxazosin was well tolerated, with 10% of patients having withdrawn due to adverse events versus 4% with placebo (P < 0.05). CONCLUSIONS: Doxazosin is well tolerated and effective in the treatment of BPH. Pooling of data has enabled more extensive and robust conclusions to be drawn than was possible for each one of the individual three studies.

Variability of repeated serum prostate-specific antigen (PSA) measurements within less than 90 days in a well-defined patient population.

OBJECTIVES: To determine the variability of repeated serum prostate-specific antigen (PSA) measurements within less than 90 days in a well-defined patient population. METHODS: A retrospective review of the PSA database at the Dallas Veterans Affairs Medical Center in Dallas was performed to identify patients who had two serum PSA measurements within less than 90 days, with the first PSA being less than 10 ng/mL (monoclonal assay, Abbott IMx). Patients' age and the dates and results of the PSA 1 and 2 measurements were captured in a database. Charts were reviewed on all patients, and those who had undergone a manipulation likely to alter the PSA value either before PSA 1 or between the two PSA measurements were excluded. The results of digital rectal examination (DRE) were classified as follows: no pathologic condition, benign prostatic hyperplasia, or suspected carcinoma of the prostate. The data were stratified in a variety of ways and analyzed to determine the variability of repeated PSA measurements under varying conditions. RESULTS: A total of 295 men were identified who fulfilled the conditions. Mean age was 66.3 +/- 8.3 (standard deviation [SD]) years, and the mean PSA 1 was 2.7 +/- 2.4 (SD) ng/mL. When stratified by whether PSA 1 was 4.0 or less or from 4.1 to 10.0 ng/mL, the mean values (1.41 versus 1.43 and 6.00 versus 5.89 for PSA 1 and 2, respectively) were not significantly different. Similarly, when stratified by whether PSA 2 was obtained within 30 days, 30 to 60 days, or 60 to 90 days, there was no significant difference between the mean values for PSA 1 and 2. When stratified by decade of life, there were no differences between PSA values for any decade, although a clear relationship was seen between mean PSA and age (less than 50 years: 1.39 versus 1.06; 50 to 60 years: 1.89 versus 1.70; 60 to 70 years: 2.47 versus 2.48; 70 to 80 years: 3.65 versus 3.70; more than 80 years: 3.45 versus 3.56). A stratification by results of the DRE (1 = normal, 2 = benign prostatic hyperplasia, 3 = prostate cancer suspected) yielded the following values: DRE 1: 2.40 versus 2.47; DRE 2: 2.99 versus 2.75; DRE 3: 3.64 versus 3.81; the difference was not significant for all three groups. Forty-six percent of patients either had an identical PSA or an increase in the PSA, and 54% had a decrease. One third of the patients had a difference of greater than +/- 1.0 ng/mL. The largest differences noted were -5.3 and +7.5 ng/mL. Cumulative distributions of differences were calculated, and the patients were stratified by time intervals, age, DRE findings, and PSA 1 values. With the exception of the latter, there were no significant differences noted in the other three stratifications. CONCLUSIONS: There is a significant variability between two serum PSA measurements obtained within a short-time interval, which is due to chance alone. These results highlight the problem when relying on a single PSA measurement and using either a single cutoff, age-specific reference ranges, or a rate of change to trigger further diagnostic tests, such as a biopsy. Furthermore, they raise the question whether two measurements and in case of discrepancy a third measurement should precede any further recommendation or invasive testing. Decision aids are offered to physicians to select ranges of PSA within which they may wish to repeat a PSA test, depending on calculated probabilities for the second PSA to cross the predefined cutoff value.

Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials.

OBJECTIVES: Six randomized clinical trials have compared at least 1 year of 5 mg finasteride to placebo in the treatment of clinical benign prostatic hyperplasia (BPH). The findings for the 2601 men in these trials provide an opportunity to investigate the heterogeneity of the effects seen in the individual studies and to identify pretreatment predictors of outcomes as expressed by symptoms or peak urinary flow rates. METHODS: A formal meta-analysis using an Empirical Bayes approach employed data from all finasteride studies which included the Phase III trials in North America and Internationally, the Prospect, Early Intervention, and SCARP trials, and the Veterans Administration Cooperative Study which compared terazosin, finasteride, and the combination of these two drugs. A pooled analysis was also undertaken on the combined dataset. RESULTS: The effect of finasteride treatment on improvements in total symptom severity, frequency score, and peak urinary flow rate was consistent across all six trials and similar among men with similar prostate volumes at baseline. Symptom severity improved by 1.8 points (95% confidence interval [CI], 0.7 to 2.9) in men with prostate volumes less than 20 cc (n = 72), while the improvement was 2.8 points (95% CI, 2.1 to 3.5) for men with volumes greater than 60 cc (n = 272) on the Quasi-IPSS Scale (range 0 to 30). Similarly, improvements in peak urinary flow rate ranged from 0.89 mL/s (95% CI, -0.05 to 1.83) for men with prostate volumes less than 20 cc to 1.84 mL/s (95% CI, 1.37 to 2.30) in men with volumes greater than 60 cc. The difference in the magnitude of improvement between finasteride and placebo becomes significant (that is, no overlap in 95% CI) for men with a baseline prostate volume assessed by either transrectal ultrasonography or magnetic resonance imaging of greater than 40 cc, which encompasses approximately 50% of the entire population. Baseline prostate volume is a key predictor of treatment outcomes: approximately 80% of the variation in the treatment effects noted between studies could be attributed to differences in mean prostate volumes at baseline. Variation in entry criteria results in large differences in baseline symptom severity status, prostate volume, and consequently apparent inconsistencies in the overall outcomes of these trials. CONCLUSIONS: This meta-analysis suggests that finasteride is most effective in men with large prostates. Men with small prostates may not be suitable candidates for finasteride therapy for BPH. The need for a careful reevaluation of the definitions and terminology used when discussing urination problems is apparent.

Effect of scrambling on the short-term reliability of the American Urological Association Symptom Index.

OBJECTIVES: To determine the degree of attention patients pay to the wording of symptom scoring instruments and to determine the short-term reliability of the American Urological Association Symptom Index (AUA SI). METHODS: The AUA SI was administered to 111 volunteers with a mean age+/-SD of 50.8+/-16.4 years (range 23 to 83) in the standard formatting. Without debriefing, the same volunteers were given the AUA SI a second time within 2 weeks. By sequential assignment, 65 of the subjects were given the AUA SI in the same standard format, and for the remaining 46, the sequence of the questions was scrambled and the order of the answers reversed for the second administration. In addition, the Benign Prostatic Hyperplasia Impact Index (BPH II) and the quality of life (QOL) question were answered and urinary flow rates were performed on both occasions to compare the short-term variability between the "subjective" symptom score and the "objective" flow rate recordings. RESULTS: In this group of volunteers with a mean age of 50.8 years, the mean AUA SI was 11.7 points. The mean values in the unscrambled group were 12.4 and 12.9 (NS) and in the scrambled group 10.5 and 10.2 (NS) for the two administrations. Cumulative frequency distribution of differences were nearly identical. Similarly, there were no differences in the mean values for the two administrations in either group for the BPH II, the QOL question, or the peak flow rate. The reproducibility was excellent for each of the individual seven questions in both groups. There was no effect of age (younger or older than 50 years) on the reproducibility, although in general the variability of the scores was higher in older men, presumably due to a higher score in the first assessment. CONCLUSIONS: Subjects pay relatively close attention to the questions of symptom score questionnaires. The reproducibility for each individual question, as well as for the entire score, was very high in the original unscrambled and in the scrambled version. In addition, the short-term variability of the AUA SI is comparable to that of the flow rate recording. These observations should give confidence to those using such scores in clinical practice and clinical research.