Johnny B. Roy

SERUM PROSTATE SPECIFIC ANTIGEN IS A STRONG PREDICTOR OF FUTURE PROSTATE GROWTH IN MEN WITH BENIGN PROSTATIC HYPERPLASIA

PURPOSE We analyze patterns of prostate growth in men diagnosed with benign prostatic hyperplasia (BPH) and treated with placebo during 4 years, and determine which baseline parameters were the strongest predictors of growth. MATERIALS AND METHODS A total of 3,040 men were enrolled in the 4-year randomized, placebo controlled Proscar Long-Term Efficacy and Safety study. Of these men a subgroup of 10% underwent pelvic magnetic resonance imaging prostate volume measurement at baseline and yearly thereafter. Absolute and percent volume changes during 4 years were calculated in the 164 placebo treated men in the subgroup. The ability of age, baseline prostate volume and prostate specific antigen (PSA) to predict prostate growth in placebo treated patients was assessed by multiple linear regression analyses, receiver operator characteristics curves, and evaluations of growth stratified by tertiles of baseline serum PSA and decades of life. RESULTS In placebo treated patients a steady increase in mean plus or minus standard deviation prostate volume from year to year was noted (2.5+/-6.1, 4.9+/-6.8, 6.4+/-8.5 and 7.2+/-8.8 ml. at years 1, 2, 3 and 4, respectively). Mean volume changes at 4 years ranged from -9 to +30 ml. Mean percent change from baseline ranged from 12.5% to 16.6% for men 50 to 59 years old to those 70 to 79 years old. Baseline serum PSA was a strong predictor of growth with 7.4% to 22.0% change at 4 years from the lowest to highest PSA tertiles. Annualized growth rates from baseline were 0.7 ml. per year for PSA 0.2 to 1.3, 2.1 for PSA 1.4 to 3.2 and 3.3 for PSA 3.3 to 9.9 ng./ml. Multiple linear regression analysis showed that serum PSA was a stronger predictor of prostate growth than age or baseline prostate volume. All but 1 man with baseline serum PSA greater than 2.0 ng./ml. had prostate growth during 4 years, and 32.6% of men with serum PSA less than 2.0 exhibited a decrease in volume. CONCLUSIONS Serum PSA is a stronger predictor of growth of the prostate in placebo treated patients than age or baseline prostate volume. Since prostate volume is a risk factor for acute urinary retention and the need for BPH related surgery, the ability of PSA to predict prostate growth may be an important factor when considering individual treatment options for BPH. Such use of PSA represents a shift in paradigm away from focusing solely on symptoms of BPH toward a more comprehensive approach with consideration of predicting and preventing risk factors of BPH related outcomes.

Doxazosin for the treatment of benign prostatic hyperplasia in patients with mild to moderate essential hypertension: a double-blind, placebo-controlled, dose-response multicenter study.

A total of 248 hypertensive patients 45 years old or older with benign prostatic hyperplasia (BPH) was included in this 16-week, multicenter, double-blind, placebo-controlled, parallel-group dose-response study. Doxazosin, a selective alpha 1-adrenoceptor antagonist, produced a significant increase in maximum urinary flow rate (2.3 to 3.6 ml. per second) at doses of 4 mg., 8 mg. and 12 mg., and in average flow rate (8 mg. and 12 mg.) compared with placebo. The increase in maximum flow rate was significant with doxazosin versus placebo within 1 week of initiating double-blind therapy. Doxazosin compared to placebo significantly decreased patient-assessed total, obstructive and irritative BPH symptoms. Blood pressure was significantly lower with all doxazosin doses compared with placebo. Adverse events, primarily mild to moderate in severity, were reported in 48% of patients on doxazosin and 35% on placebo. Our results strongly support the use of doxazosin as a nonoperative therapeutic alternative in the management of uncomplicated BPH. Doxazosin would also be particularly useful in the management of patients who have BPH and hypertension.

The Clinical Effects of a 5α-Reductase Inhibitor, Finasteride, on Benign Prostatic Hyperplasia

AbstractFinasteride (Proscar—an orally active 5α -reductase enzyme inhibitor) blocks the conversion of testosterone to dihydrotestosterone. The effects of finasteride in patients with benign prostatic hyperplasia were investigated in 2 double-blind, placebo-controlled studies. In study 1, 86 patients were treated with placebo or finasteride (5 to 80mg. per day) for 12 weeks, followed by a 12-week drug-free period. After 12 weeks of treatment all doses of finasteride showed significant decreases in prostate volume. However, 12 weeks after discontinuation of finasteride prostate volume returned to near baseline values. In study 2, 104 patients were treated with placebo or finasteride (0.2 to 40mg. per day) for 24 weeks. After 24 weeks of finasteride treatment prostate volume showed a mean decrease of 24% and 28% (p <0.01) in the 1 and 5mg. groups, respectively. Lower doses had a lesser effect on prostate shrinkage. Maximum urinary flow showed a mean increase of 3.7cc per second when the 1 and 5mg. groups we...

Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia.

OBJECTIVES To evaluate the incidence and resolution of sexual adverse experiences (AEs) in men with benign prostatic hyperplasia treated with finasteride 5 mg compared with placebo. METHODS The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men, aged 45 to 78 years, with symptomatic benign prostatic hyperplasia, enlarged prostates, and no evidence of prostate cancer. Patients completed a questionnaire at screening regarding their history of sexual dysfunction. During treatment, spontaneously self-reported sexual AEs were recorded. RESULTS At screening, 46% of patients in each treatment group reported some history of sexual dysfunction. During year 1 of the study, 15% of finasteride-treated patients and 7% of placebo-treated patients had sexual AEs that were considered drug related by the investigator (P <0.001). During years 2 to 4, no between-group difference was noted in the incidence of new sexual AEs (7% in each group). The drug-related sexual AE profile for finasteride was similar for men with or without a history of sexual dysfunction. Sexual AEs resolved while continuing therapy in 12% of finasteride patients and 19% of placebo patients. Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively. CONCLUSIONS Compared with placebo, men treated with finasteride experienced new drug-related sexual AEs with an increased incidence only during the first year of therapy.

CHRONIC TREATMENT WITH FINASTERIDE DAILY DOES NOT AFFECT SPERMATOGENESIS OR SEMEN PRODUCTION IN YOUNG MEN

PURPOSE Finasteride, an oral type 2, 5alpha-reductase inhibitor, is used in 1 mg. daily doses for the treatment of male pattern hair loss. A dose of 5 mg. finasteride daily reduces ejaculate volume by approximately 25%, and reduces prostate volume by approximately 20% and serum prostate specific antigen (PSA) by approximately 50% in men with benign prostatic hyperplasia. To our knowledge no data exist on the effect of 1 mg. finasteride daily on ejaculate volume or other semen parameters, or on the prostate in young men. Therefore, we studied the potential effect and reversibility of effect of 1 mg. finasteride daily on spermatogenesis, semen production, the prostate and serum PSA in young men. MATERIALS AND METHODS In this double-blind, placebo controlled multicenter study 181 men 19 to 41 years old were randomized to receive 1 mg. finasteride or placebo for 48 weeks followed by a 60-week off-drug period. Of the 181 men 79 were included in a subset for the collection and analysis of sequential semen samples. RESULTS There were no significant effects of 1 mg. finasteride on sperm concentration, total sperm per ejaculate, sperm motility or morphology. Ejaculate volume in subjects on finasteride decreased 0.3 ml. (-11%) compared to a decrease of 0.2 ml. (-8%) for placebo, with a median between treatment group difference of -0.03 ml. (1%, 90% confidence interval -10.4 to 13.1, p = 0.915). There were significant but small decreases in prostate volume (-2.6%) and serum PSA (-0.2 ng./ml.) in the finasteride group, which reversed on discontinuation of the drug. CONCLUSIONS Treatment with 1 mg. finasteride daily for 48 weeks did not affect spermatogenesis or semen production in young men. The effects of 1 mg. finasteride daily on prostate volume and serum PSA in young men without benign prostatic hyperplasia were small and reversible on discontinuation of the drug.

Urinary Glycosaminoglycan Excretion as a Laboratory Marker in the Diagnosis of Interstitial Cystitis

Urinary macromolecular uronate and glycosaminoglycan uronate concentrations were determined in 209 urine specimens obtained from 192 interstitial cystitis patients, 47 asymptomatic normal individuals and 32 spinal cord injury patients. As a group the concentration of macromolecular uronate or glycosaminoglycan uronate was significantly less in the interstitial cystitis patients than in the normal controls. Some interstitial cystitis patients showed low values of macromolecular uronate and glycosaminoglycan uronate. Analysis of the population distributions suggested that macromolecular uronate may have significant value in diagnosis of interstitial cystitis.

Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia

OBJECTIVES To evaluate the effects of finasteride, a specific type II 5-alpha-reductase inhibitor, on symptoms of benign prostatic hyperplasia, prostate volume, and urinary flow during a 7 to 8-year period. METHODS A total of 190 men with symptomatic benign prostatic hyperplasia and enlarged prostates entered one of two Phase II double-blind 3 to 6-month studies. Of these, 156 patients continued taking open-label finasteride, and more than 70 patients completed 7 to 8 years of treatment. The symptoms were scored using a patient self-administered modified Boyarsky symptom questionnaire. Prostate volume was measured by magnetic resonance imaging or ultrasonography, and the maximal urinary flow rate was assessed noninvasively. RESULTS Treatment with finasteride for 7 to 8 years led to sustained improvement in symptoms, reduction in prostate volume (28% from baseline), and increased urinary flow (median 2.5 mL/s from baseline). Decreases in dihydrotestosterone (86%) and prostate-specific antigen (54%) levels were also maintained. Long-term finasteride treatment was safe and generally well tolerated. CONCLUSIONS Long-term treatment with finasteride was well tolerated and resulted in durable symptom relief and improvement in prostate volume and urinary flow.

Proscar: five-year experience

We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH.

Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years

OBJECTIVES The purpose of this open-label study extension was to assess the long-term safety and efficacy of finasteride in the treatment of men with benign prostatic hyperplasia (BPH). METHODS A Phase III North American BPH trial originally enrolled 895 men, 297 of whom were randomized to receive finasteride 5 mg. An enlarged prostate gland by digital rectal examination, symptoms of urinary obstruction, and a maximal urinary flow rate of less than 15 mL/s were required for entry. Patients who completed the initial 12-month, double-blind, placebo-controlled study were invited to participate in an open-label extension for 4 additional years. RESULTS Of the 297 patients initially randomized to receive finasteride 5 mg, 259 completed 12 months in the double-blind period and 186 completed 48 months of open-label therapy. Prostate volume reached a nadir of -24.6% at month 24, and the effect was maintained through month 60. Compared with baseline values, month 60 prostate volume was decreased by 22.7% (P<0.001), the quasi-American Urological Association symptom score was decreased by 4.3 points, and maximal urinary flow was increased by 2.3 mL/s (P<0.001) on average. Finasteride was well tolerated, with no significant increase in the prevalence of sexual adverse events over time. CONCLUSIONS Patients treated with finasteride 5 mg maintained an initial decrease in prostate volume and improvement in symptom score and maximal urinary flow rate over 5 years.

Biologic Variability of Prostate-Specific Antigen and its Usefulness as a Marker for Prostate Cancer: Effects of Finasteride

OBJECTIVES The effects of finasteride on prostate-specific antigen (PSA) variability and usefulness in prostate cancer detection were examined. METHODS Percent change and crossover of PSA levels between the low (1.0 to 3.9 ng/mL) and high (4.0 to 10.0 ng/mL) ranges were evaluated in 72 men with benign prostatic hyperplasia (BPH) and 77 men with both BPH and prostate cancer (PCa) treated with finasteride or placebo for 6 months. Patients with PCa were studied as a model for evaluating the effects on PSA levels in patients with BPH and latent PCa. As recommended on the product label, PSA levels for finasteride-treated patients were doubled for interpretation. RESULTS In patients with BPH, most placebo- and finasteride-treated patients with low PSA levels at baseline had subsequent PSA levels below 4.0 ng/mL throughout the study. Among patients with high baseline PSA levels, only 1 of 17 finasteride-treated patients compared with 8 of 13 placebo-treated patients crossed into the low range. In the BPH/PCa study, most placebo-treated patients maintained PSA levels in the same range (15 of 19 less than 4.0 ng/mL; 14 of 16 greater than 4.0 ng/mL). Almost one third of finasteride-treated patients with low PSA levels at baseline crossed into the high range (8 of 22), whereas most patients with high PSA levels at baseline were not masked with treatment, with PSA levels remaining high (12 of 15). CONCLUSIONS PSA levels cross between the low and high PSA ranges in both finasteride- and placebo-treated patients with BPH and those with both BPH and PCa. Doubling the PSA levels in finasteride-treated patients allows appropriate interpretation of PSA values and does not mask the detection of PCa.