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PubMed2005

[Effect of dutasteride on reduction of plasma DHT following finasteride therapy in patients with benign prostatic hyperplasia].

INTRODUCTION: Dihydrotestosterone (DHT) is a steroid hormone derived from testosterone, by the action of two distinct isoenzymes (type 1 and 2) of 5-alpha-reductase. Dutasteride is a specific selective inhibitor of the two isoenzymes, while finasteride is a selective inhibitor of type 2 -alpha-reductase. The working hypothesis is that the double 5-alpha-reductase inhibition induced by dutasteride therapy for 6 weeks should induce a supplementary reduction of plasma DHT levels compared to a parallel patient group continuing finasteride therapy over the same period. MATERIALS AND METHODS: In this prospective, two-centre, double-blind study, 21 patients previously treated by finasteride 5 mg for benign prostatic hyperplasia (BPH) for at least 6 months were randomized to receive either dutasteride 0.5 mg, or finasteride 5 mg daily for 6 weeks. RESULTS: The mean relative variation of plasma DHT was 67.3% +/- 16.16% in the dutasteride group and 30.3% +/- 59.8% in the finasteride group. The reduction of DHT was numerically greater and more constant in the dutasteride group than in the finasteride group at 6 weeks; such a tendency was already observed after two weeks of treatment with dutasteride. Nevertheless, these differences were not statistically significant. Both medications were well tolerated and the only treatment-related adverse event (epigastric pain) was reported in the finasteride group. CONCLUSIONS: The working hypothesis was therefore not statistically confirmed. It is difficult to conclude whether this reflects poor patient compliance with long-term finasteride for BPH or variability of response in patients with good compliance with treatment.

Aged↗
PubMedDate not supplied

Therapeutic effects of finasteride in benign prostatic hyperplasia: a randomized double-blind controlled trial.

The clinical effects of finasteride, a 5 alpha-reductase inhibitor, in patients with benign prostatic hyperplasia (BPH) were evaluated in a double-blind, placebo-controlled study. Forty-six patients with symptomatic BPH were randomly assigned to 2 groups, the finasteride group and the placebo group. The finasteride group received 5 mg of finasteride daily for 6 months. Prostate volume, urinary flow, urinary symptoms, serum prostate-specific antigen (PSA) and adverse events were determined before and after treatment. After 6 months of treatment the patients treated with 5 mg of finasteride per day had a 30% decrease in their total urinary symptom score, a 14% decrease in prostate volume and a 0.9 ng/dL decrease of PSA. Their maximal urinary flow rate increased by 1.42 mL per second and the mean urinary flow rate increased by 0.64 mL per second. The patients given placebo showed no significant changes in their prostate volume, serum PSA and maximal and mean urinary flow rate. However, the symptom scores in the placebo group also decreased significantly. When compared with the placebo group, those in the finasteride group had significantly lower prostate volume, serum PSA, maximal urinary flow rate and urinary symptoms, but not mean urinary flow rate. The frequency of adverse events was low in both the finasteride and placebo groups. These results show that finasteride may be an effective and safe alternative for the treatment of patients with BPH.

Aged↗
PubMed1997

[Treatment of benign prostatic hyperplasia with finasteride. Results after 7 years of follow-up].

Our centre took part in an international, multicentre, Phase III trial with Finasteride (MK-906) in the treatment of BPH. In the first year, this was a double-blind, randomised, placebo-controlled study which included 25 patients who were randomly assigned: 9 to treatment with placebo, 8 to finasteride 1 mg and 8 to finasteride 5 mg. After the first year, all patients were assigned to finasteride 5 mg as a single daily dose taken before breakfast. Of the 25 patients who started the trial, 7 have completed 7 years treatment (28%): 1 from the placebo group. 1 from finasteride 1 mg, and 5 who took finasteride 5 mg throughout the study. Total symptoms score, assessed by the modified Boyarsky questionnaire, improved during the first year 4.97 points (51%) and remained unchanged up to year 7 with a final reduction of 6.2 points (64%). Percentual increase in peak urinary flow during follow-up ranged between 21 and 45.9% with an absolute increase at 7 years of 4.2 mL/seg (47.5%) and a reduction in prostate volume of 26%. Finasteride tolerance was excellent at all times, and no serious clinical reaction was seen in laboratory parameters. Two patients reported decreased libido and sexual potency and 1 decreased libido. In summary, since after 7 years of treatment efficacy is maintained in at least 30% of patients with an excellent safety profile, finasteride can be considered an alternative in the medical treatment of BPH.

Double-Blind Method↗
PubMed2003

Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia.

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.

5-alpha Reductase Inhibitors↗
PubMedDate not supplied

Long-term (5-year) multinational experience with finasteride 1 mg in the treatment of men with androgenetic alopecia.

BACKGROUND: Finasteride 1 mg (Propecia) is indicated for the treatment of men with androgenetic alopecia (male pattern hair loss, MPHL). However, the long-term (> 2 years) efficacy and safety of finasteride in this population has not been previously reported. Objectives. To assess the efficacy and safety of finasteride in men with MPHL compared to treatment with placebo over five years. METHODS: In two 1-year, Phase III trials, 1,553 men with MPHL were randomized to receive finasteride 1 mg/day or placebo, and 1,215 men continued in up to four 1-year, placebo-controlled extension studies. Efficacy was evaluated by hair counts, patient and investigator assessments, and panel review of clinical photographs. RESULTS: Treatment with finasteride led to durable improvements in scalp hair over five years (p 3/4 0.001 versus placebo, all endpoints), while treatment with placebo led to progressive hair loss. Finasteride was generally well tolerated and no new safety concerns were identified during long-term use. CONCLUSIONS: In men with MPHL, long-term treatment with finasteride 1 mg/day over five years was well tolerated, led to durable improvements in scalp hair growth, and slowed the further progression of hair loss that occurred without treatment.

Adult↗
PubMed1998

Morphological and hormonal changes in the ventral and dorsolateral prostatic lobes of rats treated with finasteride, a 5-alpha reductase inhibitor.

BACKGROUND: In rats, the prostate is divided into three distinct lobes, and the lobes are dependent on androgens [testosterone (T) and dihydrotestosterone (DHT)] as trophic hormones. However, the reasons for the difference in the incidence of proliferative changes reported are not well-understood. Administration of finasteride, a 5-alpha reductase (5alphaR) inhibitor which selectively inhibits the conversion of T to DHT, results in elevated intraprostatic T levels. However, long-term (2 years) administration of finasteride results in no increase in proliferative changes in the ventral lobes of the rat prostate. Therefore, studies were designed to determine the differences in intraprostatic hormonal levels, morphology, and 5alphaR activity in different lobes of the rat prostate. METHODS: Sexually mature male Sprague-Dawley rats were used in all studies. Finasteride was administered orally to rats. The methodology included determination of intraprostatic T and DHT levels by radioimmunoassay, qualitative and quantitative evaluation of prostatic morphology, and in vitro determination of 5alphaR activities in rat prostatic lobes. RESULTS: A significant amount of 5alphaR activity was observed in the dorsal, ventral, and lateral lobes of the rat prostate. Both 5alphaR isozymes (types 1 and 2) were present in all lobes, based on 5alphaR activities observed at both acidic and neutral pH. Oral administration of finasteride (160 mg/kg/day) for 15 days resulted in significant (P < or = 0.001) decreases in intraprostatic DHT levels and increases in T levels; when compared to controls, the mean decrease in DHT levels in the ventral and the dorsolateral lobes was 86% and 94%, respectively, and the mean increase in T levels in the ventral and the dorsolateral lobes was approximately 3 times and 20 times, respectively, higher than in controls. Chronic administration of finasteride (80 mg/kg/day) for 6 months resulted in significant (P < or = 0.001) decreases in the weights of the prostatic lobes, which correlated with significant (P < or = 0.001) decreases in the total number of epithelial and stromal cells per gland in both the ventral and dorsolateral lobes of the prostate. There were no qualitative differences in prostatic morphology between the control and finasteride-treated groups. A short-term study in control rats exposed to bromodeoxyuridine (Brdu) showed that the number of Brdu-labeled cells in the dorsolateral lobe was significantly (P < or = 0.05) greater than in the ventral lobe. CONCLUSIONS: This first comparative study has highlighted some of the similarities and differences among the prostatic lobes of the rat. Inhibition of conversion of T to DHT with finasteride resulted in a significant increase in intraprostatic T levels and a significant decrease in DHT levels in rats; despite a significant increase in intraprostatic T levels, the prostate remained atrophic, indicating that DHT alone has a trophic effect on the prostate.

Animals↗
PubMed1999

Finasteride in association with either flutamide or goserelin as combination hormonal therapy in patients with stage M1 carcinoma of the prostate gland. International Prostate Health Council (IPHC) Trial Study Group.

BACKGROUND: It was very reasonable to consider that the combination of the 5alpha-reductase, finasteride, and a pure antiandrogen such as flutamide should provide an effective form of maximal androgen blockade (MAB). Finasteride decreases intraprostatic levels of 5alpha-dihydrotestosterone (DHT), and the antiandrogen would restrain the biological action of the residual DHT by interfering with its association with androgen receptor. This form of MAB should sustain the concentration of testosterone in plasma, thereby maintaining sexual function and reasonable quality of life. In order to investigate this, a randomized multicenter phase II clinical trial of patients with untreated M1 cancer of the prostate was developed and undertaken. METHODS: Patients were randomly allocated to one of three treatment schedules: 1) goserelin, 3.6 mg, s.c., monthly in combination with flutamide, 250 mg., t.i.d. and a placebo, daily, in the image of 2 x 5 mg finasteride; 2) goserelin, 3.6 mg., s.c., monthly in combination with finasteride, 10 mg (2 x 5 mg, daily) and a placebo (t.i.d.) in the image of flutamide; and 3) finasteride, 10 mg (2 x 5 mg, daily) in combination with flutamide (250 mg, t.i.d.). The reduction in concentration of serum PSA at 24 weeks was the endpoint of interest. RESULTS: Baseline prostate-specific antigen (PSA) levels of the patients in the three groups were very similar. There was a substantial decrease in levels of PSA in the three groups prior to the end of the study, the percent decrease in the groups being: 1) goserelin and flutamide combination, 99.1% (95% Confidence interval (CI), 97.7, 99.6); 2) goserelin and finasteride combination, 98.75% (95% CI, 97.1, 99.5); and 3) finasteride and flutamide combination, 97.6%, 95% CI, 94.5, 98.9). In the Generalized linear model (GLM) analysis, there was no center by treatment group interaction (P = 20), and there were no significant differences between centers (P = 0.059) nor among the three treatment groups (P = 0.16). CONCLUSIONS: The decrease in levels of PSA in such a group of patients with M1 cancer of the prostate over a 24-week period was surprisingly large, and the differences in these decreased levels between the three treatment arms were remarkably small. There were no apparent differences in bone scan scores, World Health Organization (WHO) performance status, and pain scores between the arms. With regard to sexual function associated with quality of life, there were the understandable difficulties of data collection from patients treated with goserelin.

5-alpha Reductase Inhibitors↗
PubMed1994

Leydig cell hyperplasia and adenomas in mice treated with finasteride, a 5 alpha-reductase inhibitor: a possible mechanism.

Finasteride is a selective inhibitor of the enzyme 5 alpha-reductase which is responsible for the conversion of testosterone (T) to dihydrotestosterone (DHT). Finasteride is indicated for the treatment of benign prostatic hyperplasia in man (approximately 0.1 mg/kg/day). The effect of long-term treatment was studied in mice given high doses (2.5, 25, and 250 mg/kg/day) of finasteride for 83 weeks. In finasteride-treated mice, increased incidences of testicular Leydig cell hyperplasia (52% compared to 24% in control group) at doses equal to or greater than 25 mg/kg/day and Leydig cell adenomas (32% compared to 0.5% in control group) at 250 mg/kg/day were observed. There were no drug-related effects on the seminiferous tubules. Since luteinizing hormone (LH) is a trophic hormone for Leydig cells, short-term studies (5 to 14 weeks) were done to investigate the relationship between Leydig cell hyperplasia and serum LH levels in finasteride-treated mice. In these studies, there was a positive correlation between the drug-related increased incidence of Leydig cell hyperplasia and a statistically significant (p < or = 0.05) increase in serum LH levels in finasteride-treated (250 mg/kg/day) mice. Furthermore, studies in castrated male mice showed that the suppression of serum LH levels by T is reversible by inhibition of conversion of T to DHT with finasteride (250 mg/kg/day), supporting the hypothesis that DHT is involved in the regulation of LH release in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1997

[Combination of Sabal and Urtica extract vs. finasteride in benign prostatic hyperplasia (Aiken stages I to II). Comparison of therapeutic effectiveness in a one year double-blind study].

Therapeutic equivalence should be demonstrated in a randomised, reference-controlled multicentric double blind clinical trial with PRO 160/120, a combination of Sabal- and Urtica-Extract, and Finasteride, respectively, in patients suffering from benign prostatic hyperplasia (BPH, Stage I to II according to Aiken). The study involved 543 patients, who were treated for 48 weeks with two capsules of PRO 160/120 or one capsule of Finasteride per day, in a double dummy design. Primary variable was the change of the maximum urinary flow after 24 weeks of therapy in comparison to therapy start. As secondary variables urodynamic parameters such as average urinary flow, miction volume and miction time were monitored. Urinary symptoms were recorded by the International-Prostate-Symptom-Score (I-PSS, Paris 1993). Additionally, the impacts of the symptoms on quality of life had been assessed by a quality of life questionnaire according to The American Urological Association Measurement Committee (1991). An increase of the urinary flow rate could be observed in both treatment groups (1.9 ml/s with PRO 160/ 120; 2.4 ml/s with Finasteride). During the trial, the average urinary flow increased, whereas the miction time decreased in both groups in a similar extent. The miction volume did not show any relevant differences after treatment with either PRO 160/120 or Finasteride. The I-PSS decreased from 11.3 at the therapy start to 8.2 after 24 weeks and 6.5 (week 48) under PRO 160/120 and from 11.8 to 8.0 and 6.2, under Finasteride, respectively. Accordingly, life quality improved between therapy start and therapy end from 7.5 to 4.3 with PRO 160/120 and from 7.7 to 4.1 with Finasteride. In terms of safety aspects less adverse events occurred with the Sabal/Urtica-Extract as with Finasteride. Especially less cases of diminished ejaculation volume, erectile dysfunction and headache have been reported.

Aged↗
PubMed1994

Qualitative and quantitative evaluation of prostatic histomorphology in rats following chronic treatment with finasteride, a 5-alpha reductase inhibitor.

OBJECTIVE: To determine any potential direct and/or indirect effects of elevated intraprostatic T levels on the prostates of rats chronically (1-2 years) exposed to high doses (160 mg/kg/day) of finasteride, a selective inhibitor of 5-alpha reductase. METHODS: Sprague-Dawley male rats were administered daily finasteride by oral gavage. Prostates from all rats were weighed, fixed in 10% neutral buffered formalin, and processed for light microscopic examination. The volume fractions of the prostatic glandular and stromal compartments were quantitated by morphometric analysis. RESULTS: Administration of finasteride at doses of 20, 40, and 80 mg/kg/day for one year resulted in a significant (P < or = 0.05) decrease in prostatic weight; prostatic atrophy was evident by light microscopy. Morphometric analysis of the prostate showed that chronic finasteride administration resulted in a significant (P < or = 0.001) decrease in the absolute volume of both glandular (-65.2%) and stromal (-57.1%) compartments of the prostate. Furthermore, the total number of epithelial and stromal cells per gland were significantly (P < or = 0.002) decreased in finasteride-treated rats compared with vehicle controls; the magnitude of mean decrease was 69.8 percent and 50.6 percent of controls in epithelial and stromal cells, respectively. In addition, prostates from all two hundred fifty rats in a two-year study were qualitatively evaluated by light microscopy. Administration of finasteride at doses ranging from 2.5 mg/kg/day to 160 mg/kg/day for two years did not result in an increase over the background incidence of prostatic focal hyperplasia or adenoma. No malignant tumors of the prostate were seen in any of the groups. CONCLUSIONS: These studies have demonstrated that the expected pharmacologic effects of finasteride on the prostate are maintained following chronic treatment and that there was no evidence of a direct and/or an indirect effect of elevated intraprostatic T on prostatic morphology in rats.

5-alpha Reductase Inhibitors↗
PubMedDate not supplied

Age-related changes in brain and pituitary 5 alpha-reductase with finasteride (Proscar) treatment.

Finasteride (Proscar), a 5 alpha-reductase inhibitor, was administered with or without 5 alpha-dihydrotestosterone (DHT) in juvenile (28), peripubertal (48), or young adult (68-day-old) male rats. Luteinizing hormone (LH) levels and ventral prostate (VP) weights monitored the efficacy of the treatments. For each postnatal day tested, LH hormone levels were not significantly altered by finasteride, suggesting that 5 alpha-reductase inhibition does not modulate LH in male rats using this protocol. Finasteride plus DHT treatment significantly decreased LH levels. Conversely, VP weights were significantly decreased in finasteride-treated animals while finasteride plus DHT treatment significantly increased VP values. Finasteride plus DHT treatment significantly decreased pituitary, but not brain, 5 alpha-reductase for each postnatal day tested. In finasteride-treated animals, hypothalamic and pituitary 5 alpha-reductase were significantly inhibited in young adult animals, whereas the activities were not altered in juvenile or peripubertal male rats. These data suggest that a different mechanism may regulate 5 alpha-reductase with the aging of the central nervous system and pituitary.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2005

Evaluation of male sexual function in patients with Lower Urinary Tract Symptoms (LUTS) associated with Benign Prostatic Hyperplasia (BPH) treated with a phytotherapeutic agent (Permixon), Tamsulosin or Finasteride.

OBJECTIVES: Sexual function is one of the aspects in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) that has gained increasing attention. We compared the influence on men's sexuality of Permixon, a lipido-sterolic extract of Serenoa Repens, with Tamsulosin and Finasteride using a specific validated questionnaire exploring patient's sexual functions. METHODS: A database was created comprising patients from 3 main double-blind, randomized studies - Permixon vs. Finasteride, Permixon vs. Tamsulosin and Permixon 160 mg vs. 320 mg including a total of 2511 patients. Three hundred fifty four were on Tamsulosin, 545 on Finasteride and 1612 patients on Permixon. LUTS were assessed using the I-PSS questionnaire. Peak flow rates and prostate volume were recorded. The MSF-4 questionnaire, including 4 items that explore the patient's interest in sex, quality of erection, achievement of orgasm and ejaculation, was used across the studies. This questionnaire was demonstrated as highly reproducible and both psychometrically and clinically valid across different cultures. Correlation coefficients were given to assess the linear relationship between continuous variables. RESULTS: At 3 months, there were no statistically significant differences between the three treatment groups in terms of I-PSS or Qmax evolutions (all p values > 0.05). At 6 months, as compared to pretreatment data, there was a slight increase in sexual disorders in Tamsulosin (+0.3) and Finasteride (+0.8) treated patients while it slightly improved with Permixon therapy (-0.2). Ejaculation disorders were the most frequently reported side effects after Tamsulosin or Finasteride (both +0.2 on the specific MSF-4 question 4). There was no correlation between the evolution of the MSF-4 scores and the evolution in I-PSS neither in patients treated with Permixon, Finasteride or Tamsulosin. However, there was a slight correlation between the MSF-4 score at baseline and the I-PSS at baseline (r2 = 0.032). Although there was a correlation between the MSF-4 and age at baseline (r2 = 0.1452), there was no correlation between the evolution in MSF-4 during therapy and the age of the patients. CONCLUSION: The present study demonstrates that Permixon therapy has no negative impact on male sexual function. Both Finasteride and Tamsulosin had a slight impact on sexual function, especially on ejaculation, although these effects were rare and in line with previous reports about these two drugs.

Adrenergic alpha-Antagonists↗
PubMed2001

Comparison of Diane 35 and Diane 35 plus finasteride in the treatment of hirsutism.

OBJECTIVE: To compare the clinical efficacy and safety of the combination of Diane 35 (2 mg of cyproterone acetate, and 35 microg of ethinyl estradiol) plus finasteride (5 mg), and Diane 35 alone in the treatment of hirsutism. DESIGN: Prospective randomized clinical study. SETTING: Outpatients in Erciyes University Medical School. PATIENT(S): Forty women with hirsutism were selected. INTERVENTION(S): For 1 year, group 1 patients (n = 20) were treated with Diane 35 alone (2 mg of cyproterone acetate and 35 microg of ethinyl estradiol) daily on days 5 to 25 of the menstrual cycle and group 2 patients (n = 20) with Diane 35 plus finasteride (5 mg daily). MAIN OUTCOME MEASURE(S): Hirsutism was graded at 6-month intervals using the Ferriman-Gallwey method. The basal hormone levels of total and free testosterone (T), androstenedione, DHEAS, and sex-hormone-binding globulin (SHBG) were measured by radioimmunoassay before the study. Total T, free T, SHBG, and DHEAS were also measured at 6-month intervals for 1 year. Multiscreen blood chemistry and side effects were evaluated during the treatment. RESULT(S): Thirty-four patients completed the 12-month study period. A significant decrease in the hirsutism score as compared to baseline was observed after 12 months with both Diane 35 treatment (mean +/- SD, 15.62 +/- 4.89 vs. 9.75 +/- 3.97) and Diane 35 plus finasteride treatment (16.27 +/- 6.90 vs. 8.38 +/- 4.44). The percentage decreases in the hirsutism score (mean percent +/- SD) were 30.26 +/- 14.56 vs. 34.70 +/- 11.60 at 6 months, 38.09 +/- 11.46 vs. 48.14 +/- 14.27 at 12 months in the Diane 35 and the Diane 35 plus finasteride groups, respectively. The percentage reduction in the hirsutism score in the Diane 35 plus finasteride group at 12 months was greater than in the Diane 35 group (P <.05). CONCLUSION(S): The percentage decrease in the hirsutism score at 12 months was higher in the Diane 35 plus finasteride group than in the Diane 35 group. We believe that Diane 35 plus finasteride is an effective and safe combination for the treatment of hirsutism.

5-alpha Reductase Inhibitors↗
PubMed2003

The effect of finasteride on the expression of vascular endothelial growth factor and microvessel density: a possible mechanism for decreased prostatic bleeding in treated patients.

PURPOSE: Several studies have confirmed the benefit of finasteride in limiting hematuria from benign prostatic hyperplasia. Vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, and microvessel density have been independently evaluated in the mechanism of decreased bleeding observed in patients treated with finasteride. We evaluated the expression of VEGF and suburethral prostatic microvessel density in patients with benign prostatic hyperplasia treated with finasteride. MATERIALS AND METHODS: The study included 24 patients undergoing prostatic surgery for benign disease, of whom 12 were given finasteride for a minimum of 6 weeks before surgery and the remaining 12 served as controls. Sections from the prostatic urothelium and hyperplastic prostate were individually stained for CD34 specific for nascent blood vessels and VEGF. Analysis of each specimen was performed in a blinded fashion. Microvessel density was calculated by counting the number of positively stained blood vessels on 10 consecutive, nonoverlapping, high power fields within the suburethral and hyperplastic prostate compartments. VEGF expression was examined by immunohistochemistry. Statistical analysis of the results was performed using Student's t test. RESULTS: Prostatic suburethral VEGF expression and microvessel density were significantly lower in the finasteride group compared to controls (p <0.05). Differences in VEGF expression and microvessel density at the level of the hyperplastic prostate were not found to be significantly different between the 2 groups. CONCLUSIONS Decreased expression of VEGF by finasteride inhibits angiogenesis and significantly decreases microvessel density in prostatic suburethral tissue. This sequential relationship provides histochemical insight into the mechanism by which finasteride reduces prostatic urethral bleeding.

Aged↗
PubMed1992

Multicenter, randomized, double-blind, placebo controlled study to investigate the effect of finasteride (MK-906) on stage D prostate cancer.

A total of 28 untreated patients with asymptomatic, stage D prostate cancer was randomized in a double-blinded fashion to receive finasteride (10 mg. per day), a 5 alpha-reductase inhibitor or placebo. Patients were evaluated at 3-week intervals by rectal examination, and serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) levels, and at 6-week intervals by bone scan and transrectal ultrasound determinations of prostatic volume. Patients stopped the medication at week 6 at the discretion of the investigator when PSA levels increased from baseline. After 12 weeks all patients were reevaluated. Of the patients 13 received finasteride and 15 received placebo. The 2 groups did not differ statistically with respect to patient age, initial PSA and PAP level, or the extent of metastases on initial bone scan. A statistically significant decrease in the median percentage change from baseline in PSA at weeks 3 and 6 occurred in the finasteride group compared to the placebo group (-22.9% versus -2.9% and -15.1% versus +11.7%, respectively, p less than 0.05). Finasteride had no effect upon PAP, serum testosterone, prostatic volume or appearance of bone scans. A decrease in serum PSA in the finasteride treatment group suggests that finasteride exerts a minor effect in patients with prostate cancer. This effect does not approach that seen with medical or surgical castration yet because of the potency preserving feature and the lack of toxicity finasteride may warrant further study in the treatment of prostate cancer.

5-alpha Reductase Inhibitors↗
PubMed2001

Blood loss during transurethral resection of the prostate after 3 months of treatment with finasteride.

OBJECTIVES: To study whether pretreatment with finasteride, compared with placebo, reduces the blood loss, operating time, amount of irrigating fluid absorbed, resources used, and other exploratory indexes of extensive surgery during transurethral resection of the prostate (TURP). METHODS: This double-blind, randomized, placebo-controlled, single-center, 6-month pilot study was designed to study the effects of 3 months of finasteride (5 mg daily) on blood loss during surgery in 60 men who required TURP. The prostate size was measured by transrectal ultrasonography, the surgical blood loss was measured by a HemoCue photometer, and fluid absorption was determined by the ethanol method. The microvessel density was counted using microscopic staining and immunoperoxidase techniques. RESULTS: Finasteride significantly reduced the prostate size before TURP (P <0.001 versus placebo). No significant between-group differences were found in blood loss (geometric mean 257 and 268 mL for finasteride versus placebo), fluid absorption, operating time, resection weight, or microvessel density. A positive correlation was found between the blood loss and the resection weight. Exploratory analyses indicated that finasteride might reduce the proportion of patients with high blood loss volumes. For prostates with resection weights greater than or equal to the median (18.6 g), finasteride was associated with less blood loss (median 324 mL, n = 14) than in the controls (median 547 mL, n = 14, P <0.01). CONCLUSIONS: Pretreatment with finasteride may help reduce the blood loss in TURP, except in the smallest resections.

Absorption↗
PubMed1996

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.

Enzyme Inhibitors↗
PubMed1997

Finasteride and flutamide as potency-sparing androgen-ablative therapy for advanced adenocarcinoma of the prostate.

OBJECTIVES: Androgen ablation with luteinizing hormone-releasing hormone (LHRH) agonists, orchiectomy, or oral estrogens has significant untoward sexual side effects. We evaluated a combination of finasteride and flutamide as potency-sparing androgen ablative therapy (AAT) for advanced adenocarcinoma of the prostate. In addition, we evaluated whether finasteride provided additional intraprostatic androgen blockade to flutamide. METHODS: Twenty men with advanced prostate cancer were given flutamide, 250 mg orally three times daily. Serum prostate-specific antigen (PSA) values were measured weekly. At a nadir PSA value, finasteride, 5 mg orally every day, was added. PSA values were then measured weekly until a second nadir PSA value was achieved. Sexual function was evaluated at baseline, at the second nadir PSA value, and every 3 months thereafter. Testosterone, dihydrotestosterone (DHT), and dehydroepiandrostenedione (DHEA) levels were measured at baseline and at the first and second nadir PSA values. RESULTS: The median follow-up period was 16.9 months. Therapy failed in 1 patient with Stage D2 disease at 12 months, but an additional response to subsequent LHRH agonist therapy was observed. One patient developed National Cancer Institute grade 3 diarrhea and was withdrawn from the study. Seven of 20 men developed mild gynecomastia, and 3 of 20 developed mild transient liver function test elevations. Mean PSA levels were 94.6 +/- 38.2 ng/mL at baseline and 7.8 +/- 2.7 and 4.7 +/- 2.2 ng/mL at the first and second PSA nadir values, respectively (P = 0.034). Mean percent decline in PSA value from baseline was 87.0 +/- 3.1% with flutamide alone and 94.0 +/- 1.9% with both flutamide and finasteride (P = 0.001). Eleven of 20 men were potent at baseline. At the second nadir PSA value, 9 (82%) of 11 were potent, whereas 2 (18%) of 11 were impotent. With longer follow-up (median 16.4 months), 6 (55%) of 11 men were potent, 2 (18%) of 11 were partially potent, and 3 (27%) of 11 were impotent. With flutamide alone, testosterone rose a mean of 77 +/- 14.7% of baseline (P = 0.0001), DHEA fell a mean of 32.4 +/- 4.6% (P = 0.0001), and DHT was unchanged. With the addition of finasteride, testosterone rose another 14 +/- 6% (P = 0.06, not significant), DHEA was unchanged, and DHT fell a mean of 34.8 +/- 4.7% (P = 0.0009). CONCLUSIONS: Finasteride and flutamide were safe and well tolerated as AAT for advanced prostate cancer. Finasteride provided additional intraprostatic androgen blockade to flutamide, as measured by additional PSA suppression. Sexual potency was preserved initially in most patients, although there was a reduction in potency and libido in some patients on longer follow-up. Further evaluation of this therapy is needed.

Adenocarcinoma↗