finasteride, Propecia
The treatment of gross hematuria secondary to prostatic bleeding with finasteride.

Sieber PR, Rommel FM, Huffnagle HW, Breslin JA, Agusta VE, Harpster LE.

Urological Associates of Lancaster, Ltd., Pennsylvania, USA.

PURPOSE: We evaluate the use of finasteride to control gross hematuria secondary to prostatic bleeding. MATERIALS AND METHODS: We reviewed retrospectively 42 patients treated with finasteride to treat gross hematuria. RESULTS: There were 28 evaluable patients who had taken finasteride for at least 6 months to control gross hematuria and hematuria ceased in 25 (91%). In 1 patient clot retention developed requiring transurethral resection of the prostate and 2 patients had 1 or more minor episodes of bleeding that resolved spontaneously. CONCLUSIONS: Finasteride appears to be an effective agent for controlling gross hematuria secondary to prostatic bleeding.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9507842&dopt=Abstract finasteride Propecia



finasteride, Propecia
The role of transforming growth factor-beta1, -beta2, and -beta3 in androgen-responsive growth of NRP-152 rat prostatic epithelial cells.

Lucia MS, Sporn MB, Roberts AB, Stewart LV, Danielpour D.

Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

We have investigated the role of autocrine/paracrine TGF-beta secretion in the regulation of cell growth by androgens as demonstrated by its inhibition by two androgen response modifiers; the nonsteroidal antiandrogen hydroxyflutamide (OHF), believed to act by inhibiting androgen binding to androgen receptors, or finasteride, an inhibitor of 5alpha-reductase, the enzyme necessary for the conversion of testosterone to 5alpha-dihydrotestosterone (DHT), using the nontumorigenic rat prostatic epithelial cell line NRP-152. Growth of these cells was stimulated three- to sixfold over control by either testosterone or DHT under serum-free culture conditions. This was accompanied by a two- to threefold decrease in the secretion rate of TGF-beta1, -beta2, and -beta3. Finasteride reversed the ability of testosterone but not DHT to stimulate growth and downregulate expression of TGF-beta1, -beta2, and -beta3 in a dose-dependent fashion, suggesting that this activity of testosterone required its conversion to DHT. OHF antagonized the stimulatory effects of DHT on NRP-152 cell growth but could reverse the inhibitory effects of DHT only on TGF-beta2 and TGF-beta3 and not TGF-beta1 secretion. This suggests that either TGF-beta1 regulation by DHT or the androgen antagonism of OHF occurs independent of androgen receptor binding. Neutralizing antibodies to TGF-beta (pantropic and isoform-specific) were able to block the ability of finasteride to antagonize the effects of testosterone nearly completely while only partially inhibiting the antiandrogenic effects of OHF. Thus, the ability of androgens to stimulate growth of NRP-152 cells involves the downregulation of the production of TGF-beta1, -beta2, and -beta3 in addition to other growth-stimulatory mechanisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9525477&dopt=Abstract finasteride Propecia



finasteride, Propecia
Structure-function studies of human 5-alpha reductase type 2 using site directed mutagenesis.

Baxter FO, Trivic S, Lee IR.

School of Biomedical Sciences, Curtin University of Technology, GPO Box U1987, Perth, WA 6845, Australia.

Site directed mutagenesis of human steroid 5alpha-reductase types 1 (5AR1) and 2 (5AR2) has been used to identify residues involved in inhibitor/substrate binding by 5AR2. Replacing residues 21-24 (GALA) in 5AR2 with the analogous residues 26-29 (AVFA) from 5AR1 did not significantly alter either the Km for testosterone or the Ki for the competitive inhibitor Finasteride. Replacement of AVFA in 5AR1 with GALA from 5AR2 however, significantly decreased the Km and increased the resistance to Finasteride. These findings confirm that 5AR1 residues 26-29 are involved in inhibitor/substrate binding but suggest residues 21-24 of 5AR2 are not. Replacing residues 20-29 (QCAVGCAVFA) of 5AR1 with the analogous residues 15-24 (ATLVALGALA) from 5AR2, changed the Km and Ki to values approaching those for wild type 5AR2. Replacing residues VAL in wild type 5AR2 with VGC from 5AR1 did not change Km or Ki but replacing ATL in 5AR2 with QCA from 5AR1 significantly decreased the Km and increased the resistance to Finasteride. Conversely, replacing QCA with ATL in 5AR1 containing GALA in place of AVFA, increased the Km and decreased resistance to Finasteride. These findings indicate residues 15-17 of human 5AR2 participate in inhibitor/substrate binding whereas residues 18-20 do not.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11377983&dopt=Abstract finasteride Propecia



finasteride, Propecia
Effect of castration and finasteride on urinary oxalate excretion in male rats.

Fan J, Glass MA, Chandhoke PS.

Division of Urology, University of Colorado Health Sciences Center, Denver 80262, USA.

We investigated the effects of castration and finasteride administration on urinary oxalate (Ox) excretion in a rat ethylene glycol (EG) model of urolithiasis. Male adult SD rats were divided into six groups. Group 1 were normal, untreated rats. The other five groups, all treated with 0.75% EG for 4 weeks; were as follows: group 2, non-castrated (intact) rats; group 3, castrated rats; group 4, castrated rats with a 4-cm testosterone implant; group 5, intact rats treated with high-dose finasteride (7.5 mg%); and group 6, intact rats treated with low-dose finasteride (0.75 mg%). Urinary Ox excretion increased 12.8-fold after 4 weeks of EG treatment (group 2 vs group 1). Both castration (group 3) and finasteride administration (groups 5 and 6) significantly decreased urinary Ox excretion compared with intact rats (group 2). We conclude that dihydrotestosterone is partially responsible for the exaggerated hyperoxaluria observed in the rat EG model of urolithiasis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9537700&dopt=Abstract finasteride Propecia



finasteride, Propecia
Erectile dysfunction following treatments of benign prostatic hyperplasia: a prospective study.

Uygur MC, Gur E, Arik AI, Altug U, Erol D.

Urology Clinic of the Ministry of Health, Ankara Hospital, Turkey.

The effects of open prostatectomy, transurethral resection, transurethral vaporization, doxazosin and finasteride on sexual functions of men were investigated in a total of 305 patients with benign prostatic hyperplasia. The sexual functions of the patients were assessed with a questionnaire before treatment and 3 and 6 months after the treatment. A total of 212 (70%) patients were judged to be potent before the treatment. At 3 months, open prostatectomy and transurethral resection caused erectile dysfunction in 2 of 40 (5%) and 5 of 89 (6%) potent patients, respectively. At 6 months, one of the patients from the former and 2 of the patients from the latter groups who developed erectile dysfunction at 3 months stated improvement. Transurethral vaporization caused loss of erectile functions in 4 of 14 potent patients (29%) at the 3-month follow-up and, one of these patients recovered erectile functions at 6 months. Only one of the 33 patients (3%) using doxazosin stated that he lost his erectile functions both at 3 months and 6 months. At 3 months follow-up, finasteride caused loss of erectile functions in 8 of 36 potent patients (22%). Four of these patients underwent surgery (transurethral resection) after 3 months of finasteride use. At the 6-month follow-up, 4 more patients suffered from loss of erectile functions. We suggest that finasteride and transurethral vaporization have the greatest potential of impairing the sexual functions among the treatment options investigated in this study and that they must be carefully offered to the potent patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9567164&dopt=Abstract finasteride Propecia



finasteride, Propecia
[Histomorphometry study of the effect of an inhibitor of 5-alpha reductase on the coating of human prostate explants in tissue culture]

[Article in Spanish]

Lopez Munoz A, Larran Lopez J, Salido Peracaula M, Aparicio Patino J, Vilches Troya J.

Departamento de Biologia Celular, Facultad de Medicina, Universidad de Cadiz.

Histomorphometric study of hyperplastic human prostate explants coating grown "in vitro" to evaluate the response to a 5-alpha-reductase inhibitor (finasteride). Explants were grown for four weeks in three groups, one in growth medium alone (RPM1-1640), one supplemented with testosterone and one supplemented with testosterone plus finasteride. Explants underwent histological studies, quantifying the surface and thickness of the coating epithelium. Study of the values obtained from the different samples show significant differences (p < 0.001) for the coated surface and its thickness between groups supplemented with testosterone and testosterone + finasteride, and so it can be inferred that this compound (finasteride) would blockade basal cells proliferation and their migration on the explant surface.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9580265&dopt=Abstract finasteride Propecia