finasteride, Propecia
The novel drug CS-891 inhibits 5alpha-reductase activity in freshly isolated dermal papilla of human hair follicles.

Niiyama S, Kojima K, Hamada T, Happle R, Hoffmann R.

Department of Dermatology, Philipp University, Deutschhausstrasse 9, D-35033 Marburg, Germany. niiyama mailer.uni-marburg.de

The local conversion of testosterone (T) to the more potent androgen dihydrotestosterone (DHT) by 5alpha-reductase (5aR) is implicated in the pathogenesis of androgenetic alopecia (AGA). Recently, the clinical effectiveness of finasteride, a selective type II 5aR inhibitor, in treating AGA has been documented, and these clinical studies have shown that circulating DHT is lowered by 60-70% in men taking finasteride. The source of the residual circulating DHT is presumed to be due to type I 5aR activity which is not affected by finasteride. Several novel compounds with potent dual inhibitory activity on both isoenzymes have been described and CS-891 is one of them. This compound may be likewise effective in the prevention or treatment of AGA. As a prerequisite for such an action CS-891 should be able to inhibit 5aR activity in its target tissue: the hair follicles (HF). Here we report on the capability of CS-891 to inhibit 5aR activity in dermal papillae (DP) of human HF.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11125319&dopt=Abstract finasteride Propecia



finasteride, Propecia
Comparison of histological compositions and apoptosis in canine spontaneous benign prostatic hyperplasia treated with androgen suppressive agents chlormadinone acetate and finasteride.

Shibata Y, Fukabori Y, Ito K, Suzuki K, Yamanaka H.

Department of Urology, Gunma University School of Medicine, Maebashi, Japan.

PURPOSE: Chlormadinone acetate and finasteride are androgen suppressive agents clinically used for benign prostatic hyperplasia but their mechanism for inducing prostatic atrophy differs. We investigated the effect of these androgen suppressive agents on prostatic histology and apoptosis using the spontaneous canine benign prostatic hyperplasia model. MATERIALS AND METHODS: Animals were treated with oral chlormadinone acetate or finasteride for 25 weeks. The prostatic volumes were analyzed every 5 weeks. Prostatic androgen and estrogen concentrations, histological composition and apoptosis were determined at the end of treatment. Apoptosis was measured by in situ labeling of 3' hydroxy ends of the DNA breaks using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling method. RESULTS: There was a similar volume reduction effect with 0.3 mg./kg. chlormadinone acetate daily and 1 mg./kg. finasteride daily. Chlormadinone acetate decreased testosterone and dihydrotestosterone but finasteride decreased only dihydrotestosterone in the prostate gland. The concentration ratio of estradiol-to-total androgen in the prostate was significantly increased in finasteride treated canines. Chlormadinone acetate and finasteride decreased the epithelial and stromal components. The extent of apoptosis observed in the prostate was significantly higher in the chlormadinone acetate group compared to that of the control and finasteride groups. CONCLUSIONS: Although a similar effect of chlormadinone acetate and finasteride was observed in the induction of prostatic regression and composition of the histological components, the sustained increase in apoptosis was observed only in chlormadinone acetate treated canines. We suggest that different intraprostatic endocrine environments created by chlormadinone acetate or finasteride, which have different intraprostatic testosterone levels and estradiol-to-androgen ratios, may be responsible for the different outcomes in the extent of apoptosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11125427&dopt=Abstract finasteride Propecia



finasteride, Propecia
Effects of the anti-androgen finasteride on the modulatory actions of oestradiol on androgen metabolism by human gingival fibroblasts.

Tilakaratne A, Soory M.

Department of Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka.

5 alpha-Reduction of androgen substrates results in the formation of the biologically active androgen 5 alpha-dihydrotestosterone (DHT), while 17 beta-hydroxysteroid dehydrogenase metabolises androgen substrates to 4-androstenedione or testosterone. The aim here was to study the effect of the anti-androgen finasteride on 5 alpha-reduction of androgens by human gingival fibroblasts (HGF) and its modulation by oestradiol-17 beta. Duplicate cultures of HGF were incubated with [14C]testosterone/[14C]4-androstenedione in Eagle minimum essential medium (n=6) in the presence or absence of oestradiol-17 beta (O) or finasteride (F; 0.1-3 microg/ml) for 24 h. The steroid metabolites were analysed and quantified using a radioisotope scanner. With [14C]testosterone as substrate, oestradiol stimulated the formation of DHT by 63% (n=6; P<0.01). In contrast, finasteride inhibited this activity by 61% (n=6; P<0.01). The combination of O+F produced 43% less inhibition than finasteride alone (n=6; P<0.01). There were 200-300% increases in the formation of 4-androstenedione in response to O and F, being less pronounced in combination. Oestradiol stimulated the formation of DHT from [14C]4-androstenedione by 300-600% and finasteride reduced the yield of DHT by 40-64%; there was less inhibition in combination with O. There were 300-700% increases in the formation of testosterone in response to F and O alone and in combination (n=6; P<0.01). Oestradiol-induced stimulation of 5 alpha-reductase activity on androgen substrates by HGF is suggestive of hormone modulatory mechanisms in the healing periodontium of both sexes. Its inhibition by finasteride is suggestive of type 2 isoenzyme activity, confirming target-tissue functions in the gingiva.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11163318&dopt=Abstract finasteride Propecia



finasteride, Propecia
Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-beta expression in benign prostatic hyperplasia.

Glassman DT, Chon JK, Borkowski A, Jacobs SC, Kyprianou N.

Division of Urology, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

BACKGROUND: Medical treatment of benign prostatic hyperplasia (BPH) targets relief of symptoms by causing either relaxation of the prostatic smooth muscle with alpha1 adrenergic blockade, or shrinkage of the gland with 5alpha-reductase inhibitors. We recently demonstrated that alpha1-blockers, such as terazosin, induce apoptosis in prostatic cells. In this study, we examined the combined effect of finasteride and terazosin on the rate of apoptosis and cellular proliferation to investigate their potential synergy at the cellular level. METHODS: Prostate specimens were obtained from men who were treated with either finasteride (n = 24), terazosin (n = 42), or combination therapy (n = 10) for varying time periods (1 week to 36 months) for the relief of the symptoms of BPH. The proliferative and apoptotic indices of both stromal and epithelial prostatic cell populations were determined. Antibodies against TGF-beta1 and TbetaRII were used to examine the immunoreactivity of TGF-beta1 and TbetaRII, respectively, in all prostate tissue sections. RESULTS: The apoptotic index in both prostate cell populations was significantly higher following the combination treatment compared to terazosin or finasteride alone. There were no significant changes in the rate of cellular proliferation with any treatment. Furthermore, there was a significant increase in TGF-beta1 expression in the prostates of patients treated with terazosin or combination therapy, while there was no change in TbetaRII expression. CONCLUSIONS: These results support the concept that induction of prostate apoptosis is a potential molecular mechanism underlying the combination effect of alpha1 blockade with 5alpha-reductase inhibitors in the effective treatment of BPH. The upregulation of TGF-beta1 implies a role for this ligand as an effector of apoptosis induction in response to alpha1-blockade or finasteride therapy of BPH patients. Copyright 2001 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11170131&dopt=Abstract finasteride Propecia



finasteride, Propecia
Management of lower urinary tract symptoms of elderly men in Austria.

Madersbacher S, Haidinger G, Struhal G; Prostate Study Group of the Austrian Society of Urology.

Department of Urology, University of Vienna, Austria. madersbacher hotmail.com

OBJECTIVES: The aim of this nation-wide study was to determine the current management of elderly men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE) in Austria, and to assess changes over a 4-year study period from 1995 to 1998. METHODS: The annual figures of prostatectomies performed in Austria from 1995 to 1998 were collected from the Austrian Institute for Health Affairs. Sales figures for finasteride, alpha(1)-receptor blockers and plant extracts were obtained from IMS market sales and Austrian regional compulsory insurance companies. These data were correlated with the number of males living in Austria during the study period and to the estimated numbers of elderly men with moderate and severe LUTS in this country. RESULTS: The annual number of transurethral resections of the prostate (TURPs) decreased from 6,302 in 1995 to 5,297 in 1998 (-16%), and the number of open prostatectomies from 506 to 469 (-7%). Extrapolation of these data to 100,000 men aged > or = 55 years revealed that 0.76% underwent TURP in 1995, this figure decreased to 0.59% in 1998. Market sales of alpha(1)-receptor blockers increased by 497% during the study period and those of finasteride by 1.6%, while plant extract market sales declined by 18.2%. In 1998, plant extracts comprised 43.3% of the total BPH market, alpha(1)-receptor blockers 41.5% and finasteride 15.2%. CONCLUSIONS: During the years 1995-1998, significant changes in medical and surgical BPH therapy were observed in Austria. These data provide the basis for a comparison to the situation in other countries and serve as a baseline investigation for future studies in this country.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11223673&dopt=Abstract finasteride Propecia



finasteride, Propecia
Finasteride. Does it affect spermatogenesis and pregnancy?

Pole M, Koren G.

Hospital for Sick Children, Toronto, Ont.

QUESTION: A few women have asked me whether finasteride, taken by their partners for male pattern baldness, will affect their pregnancies. The product monograph is very alarming: it sounds as if even handling the medication could cause harm, especially to a male fetus. Should a man stop taking finasteride if his partner is planning pregnancy or is pregnant? What is the risk to the fetus if its mother accidentally handles crushed or broken tablets? ANSWER: To date, there are no reports of adverse pregnancy outcomes among women exposed to finasteride. Taking 1 mg of finasteride daily did not have any clinically significant effect on men's semen. Absorption through the skin while handling tablets is extremely unlikely to cause fetal exposure or harm. There is no reason to discontinue the drug. Motherisk is currently following up women who are pregnant or planning pregnancy and whose partners are taking finasteride.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11785276&dopt=Abstract finasteride Propecia