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Objectives: To summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important., Methods: The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate glands. The initial 1-year placebo-controlled study was followed by a 5-year open-label extension. In total, 6-year finasteride data were available in 487 patients originally randomized to finasteride, and 5-year data were available on 238 patients originally randomized to placebo., Results: After 6 years of treatment with finasteride 5 mg, the mean quasi-American Urological Association Symptom Score improved by 4.0 points, the median prostate volume decreased by 24%, and the mean maximal urinary flow rate increased by 2.9 mL/s (P <0.001 for all parameters). Long-term finasteride treatment was well tolerated, with a low incidence of drug-related sexual adverse events occurring during the first year and even fewer occurrences during the 5-year open extension., Conclusions: Treatment with finasteride leads to durable improvement in urinary tract symptoms, flow rate, and prostate volume, with no increase in the prevalence of drug-related adverse events over time.

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.

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.

Objectives: To determine the long-term effects of finasteride treatment on prostate tissue composition; to relate these effects to clinical outcomes; and to test the hypothesis that finasteride exerts a selective or preferential action on the transition zone., Methods: Nineteen men with symptomatic benign prostatic hyperplasia (BPH) who completed a 6-month double-blind trial of finasteride were enrolled in a 24-month open-label extension study of drug responders. Magnetic resonance imaging and prostate biopsy for morphometric analysis were performed together 70 times: at baseline (n = 19), after treatment periods of intermediate duration (6 to 18 months, n = 32), and after long-term drug treatment (24 to 30 months, n = 19). At baseline, prostate volume averaged 51 cc, of which 57% was transition zone., Results: Decreases in symptom score, dihydrotestosterone and prostate-specific antigen levels, and prostate volume occurred at 6 months (P <0.01), stabilized, and were maintained without further long-term decreases. Prostate epithelium contracted progressively from baseline (19.2% tissue composition; 6.0-cc volume; 3.2 stroma/epithelial ratio) to intermediate (12.5%, 3.3 cc, and 5.6, respectively) to long-term treatment (6.4%, 2.0 cc, and 17.4, respectively, P <0.01 for all). Percent epithelial contraction was similar in the peripheral and transition zones (P = NS). The transition zone remained a relatively constant proportion (53% to 58%) of whole-prostate volume from baseline to long-term observation., Conclusions: Long-term finasteride treatment (24 to 30 months) results in a marked involution of the prostate epithelium, which continues to progress for many months after clinical effects stabilize. The effect on the epithelium is similar in the peripheral and transition zones for both morphometric and volumetric changes. Progressive contraction of the prostate epithelium appears to constitute the underlying mechanism for sustained action of finasteride.

Purpose: Finasteride therapy for benign prostatic hyperplasia (BPH) results in a marked lowering of serum prostate specific antigen (PSA) levels. However, little is known about the effect of finasteride on unbound or free serum levels of PSA. Such information would be important since percent free PSA may substantially improve the cancer specificity of PSA testing. Thus, we prospectively studied the effect of finasteride therapy on total and free serum PSA levels., Materials and Methods: In a randomized, placebo controlled, double-blind trial 40 men with histologically confirmed BPH (age range 52 to 78 years) were treated with either 5 mg. finasteride daily (26 patients) for 9 months or placebo (14) for 6 months. Prostate volume was assessed by transrectal ultrasound. Serum levels of free and total PSA were measured from archived serum samples stored at -70C at baseline and for as long as 9 months of treatment., Results: In the finasteride group mean total PSA levels declined from 3.0 ng./ml. at baseline to 1.5 ng./ml. after 6 months of treatment (50% decrease, p <0.01). In the placebo group, with similar baseline levels, no significant change was observed. PSA density declined significantly in finasteride treated men (p <0.01) but not in men receiving placebo. The mean percent free PSA (13 to 17% at baseline) was not altered significantly by finasteride or placebo., Conclusions: Total PSA serum levels decreased by an average of 50% during finasteride therapy but percent free PSA did not change significantly. This information is potentially useful in the interpretation of PSA data used for early detection of prostate cancer in men receiving finasteride. However, further studies are required to demonstrate the use of percent free PSA to detect the development of cancer.

Purpose: We sought to quantify prostate tissue changes induced by finasteride and to identify a predictor of finasteride response in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled, double-blind clinical trial., Materials and Methods: Men with symptomatic BPH (52 to 78 years old) were randomly assigned to 6 months of treatment with finasteride (26) or placebo (15). Outcome measures were clinical (urinary symptom score and flow rate), chemical (serum prostate specific antigen and dihydrotestosterone levels), volumetric (transrectal ultrasound, and magnetic resonance imaging for whole and zonal prostate volumes) and histological (morphometry of prostate sextant biopsies, separated into inner and outer gland segments, to measure the percent epithelium, stroma and glandular lumen)., Results: In the finasteride group we found a suggestion of decreasing symptom scores and increasing flow rates (not significant) with significant decreases (p < 0.01) in prostate specific antigen (48%), dihydrotestosterone (74%) and prostate volume (21%). Finasteride treatment induced a 55% decrease in inner gland epithelium (p < 0.01) with little effect on stroma or lumina. We also found a linear correlation between pretreatment inner gland epithelial content and prostate volume decrease induced by the drug (tau = 0.58, p = 0.01)., Conclusions: Finasteride treatment results in a major suppression of prostate epithelium, which is most pronounced in the inner gland. Moreover, a finasteride induced prostate volume decrease was predictable by quantification of epithelial tissues of the inner gland. These data lend additional support to the emerging concept of transition zone primacy in symptomatic BPH.

The effects of urinary symptoms on health-related quality of life (HRQL) are important in therapeutic decision making. Few have evaluated the treatment effects on HRQL in men with benign prostatic hyperplasia (BPH), even though increased urinary symptoms are associated with greater worry, bother, and interference with living activities. We report on patient assessments of such disease-specific measures as well as general HRQL measures from two placebo-controlled clinical trials of finasteride in the treatment of symptomatic BPH. Patients treated with finasteride appeared to have greater improvement than placebo-treated patients in disease-specific measures and in patient global assessment. The treated group appeared to have a greater mean increase in sexual domain scores. As expected, general measures (health rating, life satisfaction, ladder of life) changed little. Thus, treatment with finasteride appears to reduce bother, worry, and activity interference due to symptoms but in a small percentage of men may lead to slightly reduced sexual function.

Purpose: We reviewed the available data on the effect of finasteride on serum levels of prostate specific antigen (PSA), PSA velocity and PSA density in men with benign prostatic hyperplasia (BPH) and prostate cancer., Materials and Methods: To our knowledge all previously published analyses of PSA data from clinical trials of finasteride therapy for BPH and prostate cancer are reviewed., Results: The normal reference range of serum PSA levels in men with BPH and no evidence of prostate cancer who were treated with finasteride for 6 months or longer is half that in untreated men with BPH. The percent by which serum levels of PSA are suppressed after 6 months of treatment for prostate cancer does not tend to be greater than that for BPH., Conclusions: To interpret serum PSA levels in men with BPH treated with finasteride for 6 months or longer, the serum PSA level should be multiplied by 2 and compared to either age-independent or age-specific upper limits of normal for serum PSA in untreated men with BPH. On the basis of limited data the sensitivity and specificity of this approach appear to be similar to those of the corresponding PSA limits in untreated men with BPH.

Benign prostatic hyperplasia (BPH) is a disease diagnosed by the presence of prostatic enlargement and lower-tract urinary obstruction. Finasteride (Proscar), is a potent and specific inhibitor of 5alpha-reductase, which inhibits the conversion of testosterone (T) to dihydrotestosterone (DHT) an important promoter of prostatic growth. It has provided a new therapeutic alternative for the treatment of BPH. The safety and efficacy of finasteride in the treatment of symptomatic BPH have been demonstrated by two multi-center placebo-controlled studies. After 12 months of treatment with 5 mg finasteride daily, prostate volume, DHT and prostate-specific antigen (PSA) levels were reduced and maximum urinary flow rates and symptom scores were improved. Finasteride was well-tolerated. Upon completion of the controlled studies, patients were eligible to enter an open-label extension study in which all patients received 5 mg finasteride. Approximately half of the 543 patients randomized to the 5 mg finasteride group in the controlled studies have now been treated with 5 mg finasteride continuously for 3 years. The data provided by this group of patients on the long-term safety and efficacy of finasteride in the treatment of symptomatic BPH are reviewed.

The drug proskar (finasterid) has been developed and synthetized in "Merck Sharp & Dohme" research laboratories and tried initially in healthy male volunteers. Proskar is highly active as a blocker of 5-alpha-reductase blocking conversion of testosteron in dehydrotestosteron (DHT). The assessment of proskar effect on the prostate has been performed in 2000 patients throughout the world, including Russia. Follow-up studies (up to 5 years) demonstrate that proskar in the dose 5 mg/day produces a reduction in the levels of specific prostatic antigen, serum DHT and prostatic size, an increase in urination rate, life quality. In benign prostatic hyperplasia proskar realizes its effect in hormonal nature of the disease. The advantages are also safety and rare occurrence of side effects. The response became noticeable on the treatment month 6.

Finasteride, a 5 alpha-reductase inhibitor, does not bind to the androgen receptor and has no other known hormonal activity. To determine what effect, if any, it has on adrenal steroidogenesis, 10 healthy men received 5 mg finasteride daily for 28 days. Adrenocorticotropic hormone (ACTH) stimulation tests were performed before and after 4 weeks of finasteride administration (5 mg daily). Serum levels of 17-hydroxypregnenolone, 17-hydroxyprogesterone, deoxycorticosterone, corticosterone, aldosterone, cortisol, dehydroepiandrosterone, and androstenedione were measured before and 60 minutes after i.v. ACTH. Finasteride decreased serum dihydrotestosterone levels from 31 +/- 5 to 4.4 +/- 1.2 ng/dl (P < 0.001). There were no significant changes in basal or ACTH-stimulated serum levels of adrenal steroids. There was also no significant decrease in the product to precursor ratio for the seven adrenal enzymes tested. Finasteride increased mean serum androstenedione levels by 17% (P = 0.10) and significantly increased the androstenedione to 17-hydroxyprogesterone ratio (P = 0.02 before ACTH and 0.05 after ACTH). These changes are most likely due to inhibition of androstenedione metabolism by 5 alpha-reductase. In conclusion, finasteride has no detectable effect on adrenal steroidogenesis, other than that which can be explained by inhibition of the 5 alpha-reductase enzyme.

The clinical experience relating to the detection of prostate cancer in patients participating in 2 large multicenter clinical trials of finasteride in the treatment of benign prostatic hyperplasia is reviewed. A total of 1,645 patients 40 to 83 years old with benign prostatic hyperplasia was randomized to receive 1 or 5 mg finasteride or placebo once a day for 12 months in a double-blind fashion followed by an open extension study in which all patients were treated with 5 mg finasteride daily. At entry, all patients were to have a maximum urinary flow rate of 15 ml per second or less with a voided volume of 150 ml or more, an enlarged prostate and symptoms of urinary obstruction. Patients with a prostate specific antigen level of 40 ng/ml or more, or any finding suggestive of prostate cancer were excluded. During the study period 32 cases of prostate cancer were diagnosed: 12 were detected during the 12 months of the controlled study and were evenly distributed among the treatment groups (4 on placebo, and 3 on 1 mg and 5 on 5 mg finasteride) and 20 cases were detected in the extension study. From these results we conclude that finasteride-treated patients should be evaluated periodically by digital rectal examination, careful monitoring of prostate specific antigen levels and appropriate investigation of any suspicious findings.

Objective: To assess the long-term safety and efficacy of finasteride in the treatment of symptomatic benign prostatic hyperplasia in patients treated with finasteride 5 mg for thirty-six months., Methods: Two large multicenter studies were used. Patients were randomly assigned to treatment with finasteride, 1 or 5 mg, or placebo for twelve months. After completing twelve months of therapy, patients were invited to enter an open extension to the study in which all patients received finasteride 5 mg. Urinary symptoms, urinary flow rate, prostate volume, and serum concentrations of prostate-specific antigen and dihydrotestosterone were measured periodically during the study., Results: After thirty-six months of treatment with finasteride 5 mg, prostate volume was reduced from baseline by approximately 27 percent, maximum urinary flow rate improved by approximately 2.3 mL/second, and symptom scores improved by 3.6 points. Forty-two percent of patients had a 30 percent or greater decrease in prostate volume, 40 percent of patients showed an increase of 3 mL/second or more in maximum urinary flow rate, and 48 percent of patients experienced a 50 percent or greater improvement in symptom scores. Finasteride was well tolerated and there was no evidence of increased adverse experiences with increased duration of treatment., Conclusions: The excellent safety profile and sustained clinical efficacy, over thirty-six months, of daily treatment with finasteride 5 mg recommend finasteride as a low-risk medical option for the treatment of symptomatic benign prostatic hyperplasia.

Background: Finasteride, a 5 alpha-reductase inhibitor, has been shown to have beneficial effects in the treatment of benign prostatic hyperplasia. The long-term safety and efficacy of finasteride in the treatment of benign prostatic hyperplasia was assessed., Methods: In two multicenter, double-blind, placebo-controlled studies (North American and international), patients with symptomatic benign prostatic hyperplasia were randomly assigned to receive finasteride, 1 or 5 mg, or placebo for 1 year followed by an open-extension study in which all patients were treated with finasteride, 5 mg, regardless of original therapy. Men aged 40 to 80 years, in good physical and mental health, were eligible to enter the study. All patients were to have a maximum urinary flow rate of 15 mL/s or less with a voided volume of 150 mL or more, an enlarged prostate, and symptoms of urinary obstruction. Patients with a prostate-specific antigen level of 40 mg/mL or more or any finding suggestive of prostate cancer were excluded., Results: Two hundred ninety-eight patients received finasteride, 5 mg, continuously for 24 months. At the end of 24 months of finasteride therapy, the median prostate volume was reduced by 25%, and 60% of patients had a 20% or greater reduction in prostate volume. Maximum urinary flow rate was improved by at least 2 mL/s, and symptoms were improved by approximately 3.5 points. Decreased libido and ejaculation disorders were the only drug-related adverse experiences reported in more than 1% of patients., Conclusion: These studies support the long-term safety and tolerability of finasteride, while demonstrating its continuing clinical efficacy in the treatment of patients with symptomatic benign prostatic hyperplasia.

Objective: Prostate-specific antigen density (PSAD) has been proposed as a diagnostic marker for prostate cancer. Because treatment with finasteride may affect PSAD differently in men with BPH compared with men with BPH plus prostate cancer, we evaluated the diagnostic utility of PSAD in men treated with finasteride for twelve months., Methods: Data for this analysis were obtained from 895 men with BPH enrolled in a twelve-month placebo-controlled North American study. Prostate volume was measured by magnetic resonance imaging and PSA was measured by the Hybritech immunoradiometric assay., Results: Treatment with finasteride for twelve months increased the positive predictive value of PSAD for identifying the presence of prostate cancer from 14 percent to 30 percent. Using PSA values alone with a cutoff of 10 ng/mL at baseline and 5 ng/mL after twelve months of treatment, similar specificity and sensitivity could be achieved., Conclusion: The data suggest that adjustment of PSA values during treatment with finasteride can be used to maintain the diagnostic accuracy for prostate cancer while PSAD can be used to provide additional reassurance without requiring adjustment for treatment.

The efficacy and safety profiles of finasteride were tested in 1,645 patients with benign prostatic hyperplasia (BPH) over a 12-month period. The following effects were observed: (1) a 60-80% reduction in serum dihydrotestosterone levels; (2) a 20% reduction in prostate volume; (3) significant increases in the maximum urinary flow rate compared with placebo; and (4) significant improvement in urinary symptoms, particularly obstructive symptoms. All effects were well maintained for the entire duration of the study. Finasteride had a good safety profile and was well tolerated.

Finasteride, a 5-alpha reductase inhibitor recently introduced for the treatment of symptomatic benign prostatic hyperplasia, reduces prostate size and decreases serum PSA concentration. To interpret PSA in men treated with finasteride, it is necessary to take the reduction into account. This article describes the effect of finasteride on the serum PSA concentration in the North American Phase III clinical trial and discusses implications of these findings for the interpretation of serum PSA in men treated with finasteride.