finasteride, Propecia
Comparison of microvessel densities in rat prostate tissues treated with finasteride, bicalutamide and surgical castration: A preliminary study.

Kaya C, Ozyurek M, Turkeri LN.

Department of Urology, Marmara University Medical Faculty Hospital, Istanbul, Turkey.

Abstract Background: A group of anti-androgens with different mechanisms of action and adverse effects have been investigated in patients with gross hematuria related to benign prostate hyperplasia; however, there is not yet any consensus about the standard management of these patients. The present study aims to identify if any one type of the hormonal intervention is superior in terms of the suppression of microvessel formation in the prostate. Materials and methods: A total of 28 mature, healthy male Sprague-Dawley rats (300 +/- 50 g) were used in this study. The rats were randomly assigned to one of four groups (n = 7 per group). The effects of three different hormonal therapies on angiogenesis and microvascularity in rat ventral prostate were compared. Groups 1 and 2 were treated for 28 days with finasteride and bicalutamide, respectively, and rats from Group 3 underwent surgical castration. Following treatment, all rats included in the study underwent dissection of the ventral prostate and immunohistochemical analysis of microvessel density by factor VIII-related antigen. Results: The mean number of microvessels in the finasteride and bicalutamide groups was 24.5 (+/-8.44 SE) and 27 (+/-9.89 SE) respectively. In contrast, the castration and control groups had microvessel numbers of 12.9 (+/-5.35 SE) and 40.3 (+/-5.03 SE) respectively. Differences were statistically significant between all three treatment groups and the controls (P < 0.005); the number of microvessels in rat prostate tissues of the control group was significantly higher than the treatment groups. Mean microvessel densities in the bicalutamide and finasteride groups were significantly higher than microvessel densities in the castration group (P < 0.005). There was no statistically significant difference between mean microvessel number in rat prostate tissue treated with finasteride or bicalutamide (P > 0.05). Conclusions: Even though finasteride was not as effective as castration in reducing microvessel number, its effect was equal to that of bicalutamide in terms of suppressing the angiogenesis in prostatic tissue. Based on the findings of the present study, finasteride might offer a viable option in the management of macroscopic hematuria by inhibition of microvessel formation within the prostatic tissue. Further clinical studies are warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15733115&dopt=Abstract finasteride Propecia



finasteride, Propecia
Influence of estrogens on the androgen metabolism in different subunits of human hair follicles.

Niiyama S, Happle R, Hoffmann R.

Department of Dermatology, Philipp University, Deutschhausstrasse 9, D-35033 Marburg, Germany.

The molecular pathways involved in estrogen-mediated induction of hair growth in androgenetic alopecia are unknown. Some authors found that estradiol (E) inhibited 5alpha-reductase (5alpha-R) activity and therefore we addressed the question whether 17alpha- or 17beta-E are able to modulate the activity of 5alpha-R, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) or 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in isolated compartments of human hair follicles. For this purpose, scalp biopsies from volunteers were taken and from each biopsy root sheaths, connective tissue sheaths and dermal papillae (DP) were dissected and incubated in the presence of 3H-testosterone (T) and, in addition, either 17alpha-E, 17beta-E, progesterone or finasteride for up to 48 hrs. Thereafter high-performance liquid chromatography analysis of culture supernatants was performed to detect T-metabolites. At the tested concentrations, finasteride was found to be a major inhibitor of dihydrotestosterone (DHT) formation. Even 1 nM finasteride inhibited DHT synthesis in DP by 86% and 1 nM progesterone by 75%. Estrogens were less able to inhibit the synthesis of DHT in DP (e.g. 100 nM 17alpha-E: 20%; 100 nM 17beta-E: 60%). Whether E directly inhibits 5alpha-R in DP's or whether the effect of estrogens might be explained by an increased conversion of T to the weaker androgens such as androstendione (via 17beta-HSD), androstenediol (via 3beta-HSD) or 17beta-E (via aromatase), thereby diminishing the amount of T available for the conversion to DHT, remains to be shown.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11358723&dopt=Abstract finasteride Propecia



finasteride, Propecia
Estimated impact of the Prostate Cancer Prevention Trial on population mortality.

Unger JM, Thompson IM Jr, Leblanc M, Crowley JJ, Goodman PJ, Ford LG, Coltman CA Jr.

Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.

BACKGROUND: The potential public health impact of the recently completed Prostate Cancer Prevention Trial (PCPT) is debated. The results indicated that the period prevalence of prostate cancer was reduced by 24.8% due to finasteride, whereas an increase in the rate of high-grade tumors (Gleason score 8-10) among men who were diagnosed with cancer also was found (5.0% in the PCPT placebo arm vs. 11.9% in the PCPT finasteride arm). Whether the increased Gleason score was valid or was a histologic artifact is under investigation. METHODS: The authors estimated the number of person-years saved assuming a 24.8% reduction in the incidence of prostate cancer for 5 years among United States males age >/= 55 years. Scenarios for different proportions of patients with high-grade Gleason scores also were considered. RESULTS: With a 24.8% reduction in the number of men with newly diagnosed prostate cancer, the authors estimated that 316,760 person-years would be saved due to finasteride in the United States. An absolute increase of 6.9% in the proportion of men with high-grade tumors in the United States cancer population (corresponding to the difference between the rates on the placebo and finasteride arms of the PCPT) would reduce the number of person-years saved to 262,567. For each absolute increase of 5% in the proportion of patients with high-grade tumors, the number of person-years saved would be reduced by approximately 39,000. CONCLUSIONS: The results of the PCPT may have a major impact on population mortality from prostate cancer if they are applied clinically. The potential detrimental effects of an increased rate of patients who have prostate cancer with high-grade Gleason scores would be outweighed by a reduction in incidence. Cancer 2005. (c) 2005 American Cancer Society.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15739207&dopt=Abstract finasteride Propecia



finasteride, Propecia
Nodular hyperplasia of the prostate. Quantitative evaluation of secretory cell changes after treatment with finasteride.

Pomante R, Santinelli A, Muzzonigro G, Montironi R.

Institute of Pathological Anatomy and Histopathology, University of Ancona, Italy.

OBJECTIVE: To quantitatively evaluate the changes in the secretory cells in nodular hyperplasia of the prostate after treatment with finasteride. STUDY DESIGN: Secretory cell nuclear and nucleolar measurements were performed with an image analyzer in hematoxylin-and-eosin-stained sections of 20 untreated and 20 finasteride-treated cases of nodular hyperplasia. An immunoperoxidase method was used to stain the secretory cells with a monoclonal antibody-directed, anti-prostate specific antigen (PSA). The size of prostates was determined by transrectal ultrasound. For both groups the serum PSA values were determined. RESULTS: After six months of treatment with finasteride, the prostates shrank by approximately 20% with the therapeutic regimen (as determined by transrectal ultrasound), whereas the serum PSA values decreased by 30% (before therapy, < 4.00 ng/mL). The secretory cells appeared smaller than those from the untreated group of patients, and the cytoplasm staining of the PSA marker was slightly diminished. Karyometric analyses showed that the nuclear and nucleolar size were smaller in comparison with the controls. In particular, the mean nuclear and nucleolar area in the treated group were, respectively, 34.12 and 1.424 micron 2, whereas in the untreated group the values were 40.46 and 2.261. CONCLUSION: Reduced androgen stimulation after treatment with finasteride induces involution of secretory cells. This may be responsible for the decrease in the serum PSA level and may contribute to the reduction in prostate size.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10068778&dopt=Abstract finasteride Propecia



finasteride, Propecia
Evidence for the regulation of prostatic oxytocin by gonadal steroids in the rat.

Jenkin L, Nicholson HD.

Department of Anatomy, School of Medical Sciences, University of Bristol, United Kingdom.

Oxytocin and its receptor are present in the mammalian prostate, and the peptide has been shown to increase prostatic growth, 5alpha-reductase activity, and contractility. This study was performed to investigate whether local concentrations of the peptide were regulated by gonadal steroids in order to establish whether oxytocin has a physiological role in the prostate. Both intact and castrated adult Wistar rats were treated daily for 7 days with either testosterone propionate or the antiandrogen cyproterone acetate. Animals were then killed, and plasma hormone and prostatic oxytocin concentrations were measured. A separate group of rats was treated with the 5alpha-reductase inhibitor finasteride to investigate whether testosterone or dihydrotestosterone (DHT) was involved in regulating oxytocin concentrations. In a further series of experiments, rats were treated with diethylstilbestrol (DES) or the antiestrogen tamoxifen. Treatment with testosterone significantly decreased prostatic oxytocin, whereas reduction of androgens by castration or by administration of cyproterone acetate increased prostatic peptide concentrations without altering circulating levels of the peptide. Treatment with finasteride increased plasma testosterone but decreased DHT concentrations. Prostatic oxytocin concentrations were higher in finasteride-treated animals than in control animals with comparable testosterone levels. The data suggest that both testosterone and DHT are capable of decreasing prostatic oxytocin concentrations. Treatment with DES did not significantly alter prostatic oxytocin, but administration of tamoxifen decreased concentrations of the peptide, suggesting that low levels of estrogen may be necessary for oxytocin production. These data provide evidence that oxytocin is regulated by androgens, and we hypothesize that this regulatory mechanism may be involved in controlling prostatic growth.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10100477&dopt=Abstract finasteride Propecia



finasteride, Propecia
A pharmacoeconomic analysis of patients with symptoms of benign prostatic hyperplasia.

Cockrum PC, Finder SF, Ries AJ, Potyk RP.

Center for Pharmacoeconomic Studies and Outcomes Research, University of South Carolina, Columbia, USA. cockrump aa.wl.com

A pharmacoeconomic analysis of therapies for patients with benign prostatic hyperplasia (BPH) was conducted. The therapies compared were androgenic hormone inhibition (finasteride) and alpha-blockade (doxazosin, prazosin and terazosin). This was a cost-effectiveness analysis from the perspective of the US military. The 36-month decision-tree model considered the aforementioned drugs as initial therapy for BPH following an unsuccessful period of watchful waiting. Therapy was continued toward a successful response. All patients who did not respond to therapy received secondary interventions, including transurethral resection of the prostate (TURP). The main outcome measures were clinical effectiveness and incurred costs. A Monte Carlo sensitivity analysis was performed on all cost-effectiveness ratios. The model and sensitivity analysis supported prazosin as the most cost effective alpha-blocker over finasteride: the mean difference was $US381.65 (1994 values) per successfully treated patient, with a range of $US57.83 to $US675.53, in favour of prazosin. If prazosin was used as initial drug therapy after watchful waiting for a man over 50 years of age with classical symptoms of prostatism and no other severe or confounding comorbid conditions, a cost of $US578.15 per treatment could be expected, with clinical effectiveness of 70.3%. Patients who cannot tolerate prazosin should be considered for terazosin therapy before moving on from alpha-blockers. Subsequent treatment with finasteride would cost $US1426.53, with an additional clinical effectiveness of 9.9%. For the small number of patients who fail both therapies, the cost effectiveness of a first TURP as 'third-line' intervention [$US4321.36 for an additional effectiveness of 8.62% and a repeat TURP as 'fourth-line' ($US7650.54 for 0.59%) interventional] was calculated in a similar manner. Costs were cumulative, and effectiveness was derived from the total number of patients who started prazosin therapy. Pharmacological therapy was more cost effective than surgical intervention, and alpha-blockers were more cost effective than finasteride. Among the alpha-blockers, prazosin was by far the most cost effective followed by terazosin, then doxazosin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10168095&dopt=Abstract finasteride Propecia