finasteride, Propecia
Effect of nonsteroidal anti-inflammatory agents and finasteride on prostate cancer risk.

Irani J, Ravery V, Pariente JL, Chartier-Kastler E, Lechevallier E, Soulie M, Chautard D, Coloby P, Fontaine E, Bladou F, Desgrandchamps F, Haillot O.

University Hospital of Poitiers, France.

PURPOSE: We examine the relationship of nonsteroidal anti-inflammatory drugs and finasteride on the risk of prostate cancer. MATERIALS AND METHODS: Participants in this case control study using a prospective collection of data were drawn from consecutive patients who underwent prostate biopsy at 12 different departments of urology from January 1999 to June 2000. Medication use was assessed by self-questionnaire as well as questions about dietary and lifestyle factors that might be relevant for prostate cancer risk. RESULTS: The study included 639 patients with prostate cancer and 659 cancer-free controls. Univariate analysis showed no significant impact of aspirin and finasteride on prostate cancer risk while the nonaspirin nonsteroidal anti-inflammatory drug users had a lower risk (OR 0.80, 95% CI 0.64-0.99). After adjusting for potential confounders, the protective effect of nonaspirin nonsteroidal anti-inflammatory drugs was no longer significant (OR, 0.84, 95% CI 0.66-1.07), while finasteride showed a significant protective effect (OR 0.58, 95% CI 0.37-0.92). CONCLUSIONS: The results suggest that finasteride could have a chemopreventive role in prostate cancer. While aspirin did not show any impact on prostate cancer risk, the role of nonaspirin nonsteroidal anti-inflammatory drugs warrants further studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12394690&dopt=Abstract finasteride Propecia



finasteride, Propecia
Finasteride and tamsulosin used in benign prostatic hypertrophy: a review of the prescription-event monitoring data.

Shakir S, Pearce G, Mann RD.

Drug Safety Research Unit, Bursledon Hall, Southampton, UK.

OBJECTIVE: To review the results of non-interventional observational cohort studies of 14 772 patients treated with finasteride and 12 484 patients treated with tamsulosin, both studies being of national proportions and undertaken in general medical practice in England. METHODS: Both studies were undertaken by prescription-event monitoring (PEM), whereby the exposure data are derived from information provided in strict confidence by the Prescription Pricing Authority of the National Health Service. The outcome data are derived from 'green form' questionnaires completed by the prescribing general practitioners (GPs). Additional data are obtained by medical follow-up with the attending practitioners. Adverse experience was measured in three ways; as reports of events which the doctors considered to represent adverse drug reactions; as reports of reasons for stopping the drug; and by studying the incidence density of each reported event. For these purposes a computerized dictionary containing 1430 higher level terms was used. The duration of exposure in the finasteride study was approximately 1 year and was approximately 6 months in the tamsulosin study. RESULTS: The outcome data on the 14 772 and 12 484 patients treated in the finasteride and tamsulosin studies were derived from the 63% and 57.4% of the green forms sent out and returned, respectively. The finasteride cohort included two women and the tamsulosin cohort 70 women. The mean (SD) age of the men in the two cohorts was, respectively, 69.0 (9.2) and 66.2 (11.7) years. Both drugs were well tolerated on long-term therapy and 69.6% (10 274 patients) of the total finasteride and 62.0% (7739 patients) of the total tamsulosin cohort were still receiving the drug at the end of 6 months. In the finasteride study, impotence or ejaculatory failure was reported in 2.0% of the patients still receiving the drug; there were reports of decreased libido in 1.0% and gynaecomastia was reported whilst the drug was still being prescribed in 39 patients (0.3% of the cohort). With tamsulosin, uncommon cases of dizziness, headache, malaise and hypotension (89 reports in 12 484 patients, i.e. 0.7% of the cohort) were common to the findings of reported adverse reactions, reasons for stopping the drug and events of highest incidence density. None of the deaths which occurred in either of these large cohorts was attributed by either the reporting GPs or the PEM medical staff to the drugs examined. Conclusion The GPs rated the drugs effective in most patients; tolerance and adverse experience was consistent with the known pharmacology of the two drugs. No serious, unexpected adverse effects were identified.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11412215&dopt=Abstract finasteride Propecia



finasteride, Propecia
Depression circumstantially related to the administration of finasteride for androgenetic alopecia.

Altomare G, Capella GL.

Department of Dermatology, Ospedale Maggiore IRCCS, University of Milan, Italy.

In this paper we report 19 patients (14 males, 5 females; mean age 28.16 years +/- 7.68 SD) out of a series of 23 (17 males, 5 females) who developed a mood disturbance (moderate to severe depression) during treatment with finasteride, 1 mg/day orally, for androgenetic alopecia (Hamilton subtypes III-V; Ludwig subtypes I-II). Depression, which significatively impaired sociofamilial relations, sleep and eating behaviour, was associated to marked anxiety in some cases, developed after 9-19 weeks of treatment with finasteride, and promptly resolved after suspension of the drug. Two patients accepted reintroduction of the drug, and depression relapsed within 2 weeks. Depression as an adverse effect of finasteride has been reported only once. Further studies are needed to confirm our circumstantial observations, which are based on a retrospective series of patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12433001&dopt=Abstract finasteride Propecia



finasteride, Propecia
5 alpha-reductase inhibition by a new synthetic steroid (PM-9) in cultures of Penicillium crustosum.

Cabeza M, Quiroz A, Bratoeff E, Garcia G, Ramirez E, Flores E.

Department of Biological Systems, Metropolitan University-Xochimilco, Mexico D. F., Mexico. marisa cueyatl.uam.mx

The conversion of testosterone (T) to 5 alpha-dihydrotestosterone (DHT), plus the presence of 5 alpha-reductase enzyme, which is responsible for this reduction, had been demonstrated in P. crustosum broth. This enzyme is also present in androgen-dependent animal and human tissues such as prostate and seminal vesicles. The increase in the conversion of T to DHT has been implicated in androgen-dependent diseases such as benign prostate hyperplasia and prostate cancer. The use of 5 alpha-reductase inhibitors could mitigate these illnesses by inhibiting the DHT-receptor complex formation. The purpose of this study is to determine the inhibition pattern of 5 alpha-reductase by finasteride and PM-9 in P. crustosum broth. Km and Vmax values were determined in the broth by Lineweaver-Burk plots using different testosterone concentrations. The Km value was 0.22 microM and Vmax 0.833 pmol of DHT/mg of mycelium/day. The inhibition pattern of finasteride and PM-9 was also determined by Lineweaver-Burk plot, using different concentrations of T and inhibitors. The results of this study show that both finasteride and PM-9 inhibit 5 alpha-reductase in a competitive manner.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12434569&dopt=Abstract finasteride Propecia



finasteride, Propecia
Apoptotic and proliferative index after Alpha-1-adrenoceptor antagonist and/or finasteride treatment in benign prostatic hyperplasia.

Erdogru T, Ciftcioglu MA, Emreoglu I, Usta MF, Koksal T, Ozbilim G, Gulkesen KH, Baykara M.

Department of Urology, Faculty of Medicine, Akdeniz University, Antalya, Turkey. drtibet netone.com.tr

INTRODUCTION: The induction of apoptosis has emerged as a potential target for optimization of the medical management of benign prostatic hyperplasia (BPH), recently. The influence of alpha1-adrenoceptor antagonist (alpha1-ARA), 5-alpha reductase inhibitor and their combination on prostatic cell apoptotic and proliferative indices of benign hyperplastic prostate gland were investigated. MATERIALS AND METHODS: A total of 49 male patients with BPH (mean age: 66.5 years) treated with alpha1-ARA and/or finasteride were retrospectively evaluated. Patients treated with alpha1-ARA (doxazosin n = 12 and terazosin n = 10), finasteride (n = 9) and combination of finasteride and alpha1-ARA (n = 9) were enrolled in the study. Primary antibodies were Ki-67 and proliferating cell nuclear antigen for the evaluation of proliferation in prostate stromal and epithelial cells. In situ apoptotic DNA fragmentation was evaluated using TUNEL assay. RESULTS: All treatment groups had no significant changes in the rate of prostate stromal and epithelial cell proliferation. Epithelial apoptotic index (AI) was not statistically significant for finasteride vs. alpha1- ARA, alpha1-ARA vs. finasteride + alpha1-ARA and finasteride + alpha1-ARA vs. finasteride groups. While alpha1-ARA was more effective than finasteride on stromal apoptosis, alpha1-ARA-induced stromal apoptosis was not significantly different from alpha1-ARA plus finasteirde treatment. CONCLUSION: Not only androgen variabilities but also alterations in sympathetic neurotransmission with age could have important implications for pathophysiological prostate growth. The combination of finasteride and alpha1-ARA is not superior to alpha1-ARA therapy with their similar epithelial and stromal apoptotic effects with unaffected cell proliferation. Copyright 2002 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12444285&dopt=Abstract finasteride Propecia



finasteride, Propecia
Phenytoin-mediated androgen metabolism in gingival fibroblasts. Effects of the antiandrogen finasteride and the alkaline phosphatase inhibitor levamisole.

Soory M, Suchak A.

Division of Periodontology, Guy's, King's and St Thomas' Dental Institute, King's Dental Hospital, London, UK. mena.soory kcl.ac.uk

OBJECTIVES: This investigation attempts to identify the role of the alkaline phosphatase inhibitor levamisole (L) and the antiandrogen finasteride (F) on 5alpha-reductase activity in gingival fibroblasts, to elucidate mechanisms for phenytoin-induced gingival overgrowth. MATERIAL AND METHODS: Human gingival fibroblasts were incubated with Eagle's MEM and 14C-testosterone/14C-4-androstenedione as substrates; effective concentrations of phenytoin (Ph), levamisole (L) and finasteride (F), alone and in combinations of (Ph + F) (Ph + L) were added to the incubate. After 24 h, the medium was analysed for steroid metabolites and quantified using a radioisotope scanner. RESULTS: The metabolites isolated were 5alpha-dihydrotestosterone (DHT), 4-androstenedione (4-A) or testosterone (T) from each substrate. With 14C-T as substrate, Ph stimulated DHT synthesis by 1.7-fold, while F and L inhibited this activity by 1.8-fold and 34%, respectively (n = 6; P < 0.001). The combination of Ph + F reduced yields by 2.7-fold compared with Ph alone and Ph + L reduced DHT synthesis by 2.4-fold compared with Ph alone (n = 6; P < 0.001). When 14C-4-androstenedione was used as substrate, similar trends were identified. CONCLUSION: These results suggest that the alkaline phosphatase inhibitor levamisole and the 5alpha-reductase inhibitor finasteride can substantially decrease the yields of DHT in fibroblasts, stimulated by phenytoin. This could be a potential target for reducing the gingival overgrowth caused by phenytoin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12445228&dopt=Abstract finasteride Propecia