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[Comparative evaluation of the effectiveness and safety of combined drug therapy of patients with benign prostatic hyperplasia with finasteride and alfuzozine].

A finasteride + alfuzozine combination was used in 3-year treatment of 138 patients with initial benign prostatic hyperplasia (BPH). The principle of the combination is in parallel administration of 5 alpha-reductase inhibitors which inhibit cell proliferation at the hormonal level and alpha-adrenoblockers affecting the smooth muscle component of prostatic stroma and detruzor blood supply. Patients participating in the study had enlanged prostate (at least 60 cm3) and pronounced symptoms (IPSS over 13 scores). Patients of two control groups received alfuzozine and finasteride monotherapy, respectively. Better micturition and relief of BPH symptoms were seen in 96% patients of the study group, 84 and 74% controls, respectively. Thus, compared to monotherapy, finasteride and alfuzozine were more effective in combination which is pathogenetically valid and perspective in BPH chemotherapy.

Drug Therapy, Combination↗

[Efficacy of finasteride in the treatment of hematuria associated with benign prostatic hypertrophy].

OBJECTIVE: To evaluate the efficacy of finasteride in the treatment of prostatic origin haematuria. METHODS: This is a prospective observational study in 29 patients with hematuria from a demonstrated prostatic-origin which were treated with finasteride 5 mg/day. 58.6% had undergone previous prostatic surgery. Both previous-to-treatment hematuria and response to treatment were evaluated under the Puchner & Miller's criteria. RESULTS: Response rate was 86.2% without additional haematuria episodes. The remaining patients had mild haematuria episodes during follow-up. No patient needed surgery. CONCLUSIONS: Finasteride is effective in the treatment of prostatic-origin haematuria.

5-alpha Reductase Inhibitors↗

Early diagnosis of prostate cancer in finasteride treated BPH patients.

A total of 37 patients with well-documented benign prostatic hypertrophy (BPH) were referred to finasteride. In all subjects the prostate volume was > 60 cc. Serum total PSA (TPSA) and free/total PSA (%FPSA) values were recorded at 3-month intervals. After 6 months of treatment, the patients were divided into two groups in accordance with the numerical values of these two parameters. In the first group (25 patients), a drop in TPSA approached 50% reduction while the %FPSA level remained at the initial level. No malignancy was detected in these patients after 9 months of finasteride treatment and in 4-18 months additional follow-up. The second group (12 patients), consisted of subjects with a less pronounced decrease in TPSA concentration (ca. 28%) and a significant reduction in %FPSA mostly to values < 18% (cut-off point dividing BPH from cancer) during a 6-month monitoring period. During the extended part of the investigation, prostate cancer was diagnosed in 7 out of 11 of these latter patients (63.6%), or overall in 7 out of 30 (23.3%) patients who reached the end-point of the study. Accordingly, serial assessments of total and free PSA are necessary and sufficient clinical means to detect early prostate cancer in patients with a large benign prostate referred to finasteride.

Aged↗

Comparison of finasteride and alpha-blockers as independent risk factors for erectile dysfunction.

There are insufficient data on the effects of alpha-blockers and finasteride on erectile function in men who have other risk factors for erectile dysfunction (ED). This study was conducted to compare the relative effects of these medications on ED in men who may be on other medications or have other risk factors for ED. Patients attending urology and primary care clinics were asked to complete an IRB-approved questionnaire that combined the validated Sexual Health Inventory for Men (SHIM) and a detailed medical history. A total of 123 patients completed the questionnaire. The age range was 28-88 years (mean: 68 years). Eighty-one per cent of patients had SHIM scores <21, indicating some degree of ED. The average SHIM scores in a population of patients with similar age and risk factors who had been on finasteride or alpha-blockers indicated the presence of ED but did not reveal a significant difference between the two groups. The scores were no different from an age-matched group of patients who were not on either medication, demonstrating the relatively greater importance of various other risk factors for ED. There was an inverse linear relationship between the number of ED risk factors and SHIM scores. There does not appear to be a significant difference between alpha-blockers and finasteride as independent risk factors for ED. Age and other risk factors (heart disease, diabetes, hypertension, smoking, and hypercholesterolaemia) tend to have a much stronger influence on the severity of ED as assessed by SHIM scores.

Adrenergic alpha-Antagonists↗

[Effects of finasteride on capillary in the ventral prostate of rat].

OBJECTIVE: To investigate the effects of finasteride on capillary in the ventral prostate of rat and study the mechanisms therein involved, METHODS: Male SD rats were given via gavage finasteride 40 mg/kg per day for 7 days (group B) and for 14 days (group C). The changes of capillary infused with Chinese ink were observed with the use of HE staining. Immunohistochemical (IHC) SP-method was adopted in measuring the protein expression of VEGF and eNOS in rat prostatic tissue. RESULTS: In comparison with the relevant values measured in the control group (group A), the microvessel density (MVD) values in group B and group C decreased by 35.2% and 56% respectively, the protein expression of VEGF in group B and group C decreased by 31.7% and 62.6% respectively, the protein expression of eNOS in group B and group C decreased by 15.7% and 52.5% respectively. CONCLUSION: Finasteride can inhibit the protein expression of VEGF and eNOS and thereby can suppress angiogenesis of capillary in the ventral prostate of rat.

Animals↗

Combination finasteride and flutamide in advanced carcinoma of the prostate: effective therapy with minimal side effects.

PURPOSE: The efficacy of the combination of finasteride and flutamide in select patients with advanced prostatic cancer is determined. MATERIALS AND METHODS: A total of 22 sexually active patients with stages C and D1 carcinoma of the prostate was treated with finasteride plus flutamide. Mean followup was 22 months. RESULTS: Initial mean prostate specific antigen level was 42.9 ng./ml. At 3 and 6 months, the mean prostate specific antigen level was 3.6 ng./ml. and 2.9 ng./ml., respectively. The results appear durable at 24 months. Side effects were minimal, with 86% of the men maintaining sexual function. CONCLUSIONS: Finasteride plus flutamide should be considered in sexually active patients with minimal volume advanced prostate cancer.

Aged↗

Finasteride: the first 5 alpha-reductase inhibitor.

Finasteride is a synthetic 4-azasteroid that is a specific competitive inhibitor of 5 alpha-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone (DHT). It has no binding affinity for androgen receptor sites and itself possesses no androgenic, antiandrogenic, or other steroid hormone-related properties. It is well absorbed after oral administration, with absolute bioavailability in humans of 63% (range 34-108%). The mean time to maximum concentration is 1-2 hours, and it is approximately 90% plasma protein bound. The elimination half-life averages 6-8 hours. The agent is metabolized to a series of five metabolites, of which two are active and possess less than 20% of the 5 alpha-reductase activity of finasteride. Little is known about potential drug interactions, although they appear to be minimal and not clinically relevant. The drug is indicated for the treatment of symptomatic benign prostatic hyperplasia. Its efficacy in regression of prostate gland enlargement is rapid and predictable, although correlation with subsequent improvement in urinary flow and symptoms is highly variable. Dosages of 0.5-100 mg/day regress prostate enlargement; the recommended dosage is 5 mg once/day. Finasteride may hold promise for other DHT-mediated disorders such as acne, facial hirsutism, frontal lobe alopecia, and prostate cancer, but its use in these conditions remains investigational. The frequency of adverse drug events is low, with the most common side effects being impotence, decreased libido, and decreased volume of ejaculate. No reports of intentional overdose have been reported, and dosages of up to 80 mg/day for 3 months have been taken without adverse effect.

5-alpha Reductase Inhibitors↗

Evaluation of prostatic intraepithelial neoplasia after treatment with a 5-alpha-reductase inhibitor (finasteride). A methodologic approach.

OBJECTIVE: To develop a methodology applicable to the morphologic study of the efficacy of finasteride on prostatic intraepithelial neoplasia (PIN), a putative precursor of prostate cancer. STUDY DESIGN: Three PIN foci were reviewed in two simple prostatectomy specimens from patients with clinical diagnoses of benign prostatic hyperplasia and treated with finasteride for six months. The feasibility of PIN diagnosis and grading based on "diagnostic distance" was investigated. It is a measure of the "extent" to which the observed features are different from those of the untreated prototypes representing the following diagnostic categories: normal prostate, low and high grade PIN and prostatic adenocarcinoma with a cribriform or large acinar pattern. Uncertainty in the PIN diagnosis and grading was dealt with by means of a Bayesian belief network (BBN). RESULTS: The distance measure values of the three PIN foci from the prototype of untreated, nonneoplastic prostate were 9, 7 and 8, respectively, in relative, arbitrary units. Their distance from the two prostate cancer patterns (large acinar and cribriform) was as high as 8-10. The distance of these foci from either low or high grade PIN were as low as 5, 3 and 2, and 3, 5 and 4, respectively. BBN produced the highest belief values for PIN, thus confirming the morphology-based and diagnostic distance-supported diagnosis; however, the belief values were low for both grades. CONCLUSION: The results provided by BBN analyses and diagnostic distance measures support the conclusion that this methodology is applicable to assessing the efficacy of finasteride treatment of PIN.

5-alpha Reductase Inhibitors↗

[Treatment of prostate adenoma with finasteride. Contribution of cases].

During recent years more and more researchers and clinicians have become interested in HPB in order to identify a medical therapy instead of surgery. The aim of our study was to find the value of finasteride in HPB therapy. We wanted to know if finasteride was able to improve the symptomatology and blood tests of patients afflicted with HPB. Every patient was agreed with the course of action of the 1991 Paris Urology Congress. All patients were treated with finasteride 5 mg/die for one year and inspected by prostatic echography and blood tests. The results of our study are every interesting and are discussed in the article.

Adult↗

Effect of finasteride (Proscar MSD) on seminal composition, prostate function and fertility in male dogs.

This study reports the long-term effects and reversibility of the administration of Finasteride, a 5 alpha-reductase inhibitor, on the prostate, prostatic fluid composition and volume, sperm output and characteristic, and fertility of adult beagle dogs treated for 21 weeks at a dose of 1 mg kg-1 body weight. Finasteride was not associated with any side effects. After 5 to 15 weeks of treatment, it induced a marked decrease in the size of the prostate and a fall in its secretions and in the production of spermatozoa. Sperm concentration increased and was inversely correlated with the decrease in the volume of prostatic secretions. At maximum effect, the calculated prostate volume was reduced to 30% of the initial value, and together with the reduced prostatic secretion, no ejaculate could be collected despite normal behaviour. These effects were reversible in 6 to 8 weeks after the cessation of treatment. Matings at 20 to 22 weeks after the start of treatment were fertile, demonstrating the absence of long-term effects of this treatment on male fertility. As fertility was not impaired and prostatic benign hyperplasia successfully regressed. Finasteride treatment in this preliminary study appears to be an interesting alternative therapy in valuable breeding dogs with benign prostatic hyperplasia.

5-alpha Reductase Inhibitors↗

[Finasteride and flutamide in the treatment of hirsutism].

BACKGROUND: The aim of this work was to evaluate the efficacy of two new antiandrogen drugs, finasteride and flutamide, in 80 hirsute patients: 44 with Polycystic Ovary Syndrome (PCOS) and 36 with Idiopathic Hirsutism (IH). METHODS: The study was conducted in a randomized way and randomization was carried out according to hospitalization. Before and after the treatment, all of the patients underwent hematochemical tests, hormone assays and assessment of hirsutism with the Ferriman Gallway score (F.G. score) and with measurement of the hair diameter in four different body areas. Finasteride was administered per os to 40 women at the dose of 5 mg/die; flutamide per os to 40 women at the dose of 250 mg twice daily. Both drugs were employed for 6 consecutive months. RESULTS: Both finasteride and flutamide significantly reduced the F.G. score and hair diameter. CONCLUSIONS: Abdominal hairs were more sensitive to the therapy.

Administration, Oral↗

Combined analysis of two multicenter studies of finasteride 5 mg in the treatment of symptomatic benign prostatic hyperplasia.

The purpose of this paper is to examine effects of finasteride 5 mg across different age groups in an ethnically diverse population of men with symptomatic benign prostatic hyperplasia (BPH) seen in community urology and primary care practices. Data were combined from two previous placebo-controlled randomised trials of finasteride that evaluated changes in urinary symptoms, blinded global assessments of urologic status, adverse experiences, and effects on dihydrotestosterone (DHT) and prostate-specific antigen (PSA) in over 4500 men. Finasteride showed a favourable efficacy and tolerability profile in this large ethnically diverse population and was similarly effective in middle-aged and older men with BPH and prostate gland enlargement.

Journal Article↗

Decreased gene expression of steroid 5 alpha-reductase 2 in human prostate cancer: implications for finasteride therapy of prostate carcinoma.

BACKGROUND: Steroid 5alpha-reductase 2 (SRD5A2) catalyzes the conversion of testosterone to the more potent androgen, DHT, in the prostate. The therapeutic influence of SRD5A2 inhibitor finasteride on prostate cancer is currently unknown. The direction and extent of changes in SRD5A2 expression in disease tissues is a relevant issue in this regard. METHODS: The expression differences of SRD5A2 in tissues representative of normal, benign, and malignant growth in the human prostate were examined in parallel by comparative analysis of relevant microarray gene expression data. Semiquantitative RT-PCR was used to further verify the gene expression differences of SRD5A2. RESULTS: Consistently decreased expression of SRD5A2 was observed in 25 prostate cancer samples when compared to 25 matched normal samples and nine BPH samples. Expression differences among these samples for six other genes were presented in parallel as indicators of the direction and extent of expression changes. These additional genes include SRD5A1, Hepsin (overexpressed in prostate cancer), AMACR (overexpressed in prostate cancer), Keratin 8 (epithelial marker), smooth muscle actin (stromal marker), Nell2 (overexpressed in BPH). Semiquantitative RT-PCR verified the expression differences for SRD5A2 in six normal, six BPH, and six prostate cancer samples. CONCLUSIONS: Results from this study, combined with those from previous studies, indicate an association of prostate cancer with reduced 5alpha-reductase enzymatic activity as a result of remarkably decreased expression of the SRD5A2 gene. The implications of this study for finasteride therapy of prostate cancer are discussed.

Case-Control Studies↗

Picogram determination of finasteride in human plasma and semen by high-performance liquid chromatography with atmospheric-pressure chemical-ionization tandem mass spectrometry.

A method based on high-performance liquid chromatography (HPLC) with atmospheric-pressure positive-ion chemical ionization (APCI)-tandem mass spectrometric (MS-MS) detection for the determination of finasteride (MK-906, I) in human plasma and semen has been developed. The drug and internal standard (II) were extracted from biological matrices using a single solid-phase cyano cartridge. The eluent from the cartridge was injected directly onto the a 33 x 4.6 mm I.D. C18, 3-microns column coupled with a base deactivated C18 20 x 4.6 mm I.D., 5-microns guard column. The column eluate was passed into the corona discharge APCI source by means of a heated nebulizer interface. The analyte and its internal standard were detected using multiple reaction monitoring (MRM) mode for enhanced selectivity and sensitivity. The chromatographic run time was 3 min, and the method had sufficient sensitivity, precision, accuracy and selectivity for the analysis of clinical samples containing finasteride at concentration of 0.2 ng/ml. The assay methodology confirms the versatility of APCI-MS-MS detection, combined with HPLC, for the quantitation of selected drugs in the sub-ng/ml range in biological fluids.

Chromatography, High Pressure Liquid↗

Finasteride: a clinical review.

Finasteride is the first of a new class of 5 alpha-reductase inhibitors which allows selective androgen deprivation affecting dihydrotestosterone (DHT) levels in target organs such as the prostate and scalp hair without effecting circulating levels of testosterone thus preserving the desired androgen mediated effects on muscle strength, bone density and sexual function. Finasteride has been demonstrated to produce significant effects in men with an enlarged prostate gland. The long-term data now emerging suggests that progression of benign prostatic hyperplasia (BPH) may be arrested providing additional long term benefits. Experimental uses in prostate cancer prevention and male pattern baldness offer new and exciting possibilities for this class of compounds.

Alopecia↗

The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride.

BACKGROUND: Male pattern hair loss (MPHL) is a potentially reversible condition in which dihydrotestosterone is an important etiologic factor. OBJECTIVE: Our aim was to evaluate the efficacy of the type 1 and 2 5alpha-reductase inhibitor dutasteride in men with MPHL. METHODS: Four hundred sixteen men, 21 to 45 years old, were randomized to receive dutasteride 0.05, 0.1, 0.5 or 2.5 mg, finasteride 5 mg, or placebo daily for 24 weeks. RESULTS: Dutasteride increased target area hair count versus placebo in a dose-dependent fashion and dutasteride 2.5 mg was superior to finasteride at 12 and 24 weeks. Expert panel photographic review and investigator assessment of hair growth confirmed these results. Scalp and serum dihydrotestosterone levels decreased, and testosterone levels increased, in a dose-dependent fashion with dutasteride. LIMITATIONS: The study was limited to 24 weeks. CONCLUSION: Dutasteride increases scalp hair growth in men with MPHL. Type 1 and type 2 5alpha-reductase may be important in the pathogenesis and treatment of MPHL.

5-alpha Reductase Inhibitors↗

The anxiolytic effect of pregnancy in rats is reversed by finasteride.

Several studies have shown the influence of the oestrous cycle on anxiety levels and the important role of progesterone in this effect. The metabolism of this steroid hormone yields neuroactive steroids among them allopregnanolone (alloP) and allotetrahydrodeoxycorticosterone (alloTHDOC), which bind to GABAA receptors and have anxiolytic effects. Considering that during pregnancy there is an increase in levels of both progesterone and its metabolites, the main objectives of this work were: (1) to assess changes in anxiety levels during pregnancy and (2) to verify the role of alloP and alloTHDOC in this process using finasteride, an inhibitor of 5alpha-reductase, the enzyme responsible for their synthesis. The results showed a significant reduction in anxiety levels on the 19th day of pregnancy, which was reversed by finasteride, suggesting a role for alloP and alloTHDOC in the anxiolytic process.

5-alpha Reductase Inhibitors↗