finasteride, Propecia
Who should be treated and how? Evidence-based medicine in symptomatic BPH.

Speakman MJ.

Department of Urology, Taunton and Somerset Hospital, Taunton, UK. speakmanmj aol.com

The management of benign prostatic hyperplasia (BPH), although based on the best available evidence, should be individualised to patients' circumstances and personal choices. Subjective symptoms (LUTS), bothersomeness and negative impact on the quality of life are the main reasons for the patient to seek treatment for BPH. Therefore, the improvement of this subjective discomfort ought to be an important treatment goal and criterion of appraisal. Although transurethral resection of the prostate (TURP) remains the most effective and definite way of treatment, it is less attractive from the patients' perspective, especially after medical treatments with better tolerability have become available. For this reason, the indication for surgery is nowadays set on more stringent criteria of 'appropriateness'. Several new, less-invasive surgical techniques have been introduced, but their ultimate position is difficult to appraise because of the lack of appropriate long-term data from prospective, properly designed, controlled trials, also in terms of lack of data on cost-efficiency. Therefore, medical therapy with either finasteride or alpha(1)-blockers remains an attractive therapeutic alternative: both approaches are effective, reasonably well tolerated and in the 'shorter' term more cost-efficient than TURP. Available evidence suggests that finasteride is mainly effective on a long-term basis in patients with substantially enlarged prostates. In the shorter term, alpha(1)-blockers have consistently been shown to be more effective than finasteride, irrespective of prostate size. In addition, alpha(1)-blockers have the important advantage of a rapid alleviation of subjective discomfort. To date, the combination of an alpha(1)-blocker and finasteride seems to offer no more than an alpha(1)-blocker alone. Among the alpha(1)-blockers, tamsulosin is particularly suited because of its clinical selectivity (i.e. its low risk of safety relevant cardiovascular effects) and its ease of use (once daily administration without the need for stepwise dose increments on treatment initiation). Copyrightz1999S.KargerAG,Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10559630&dopt=Abstract finasteride Propecia



finasteride, Propecia
Immunohistochemical expression of pi class glutathione S-transferase in the basal cell layer of benign prostate tissue following chronic treatment with finasteride.

Montironi R, Mazzucchelli R, Pomante R, Thompson D, Duval da Silva V, Vaught L, Bartels PH.

Institute of Pathological Anatomy and Histopathology, School of Medicine, University of Ancona, Ospedale Regionale, Italy. r.montironi popcsi.unian.it

BACKGROUND: Glutathione S-transferases (GST) may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Treatment directed at the induction or preservation of GST-pi expression in normal epithelium could have a profound impact on the prevention of prostate neoplasia. Finasteride, a 5-alpha-reductase inhibitor, is used as a chemopreventive agent because it blocks the conversion of testosterone to its byproduct which promotes prostate tumour growth. OBJECTIVE: To investigate GST-pi expression immunohistochemically in benign prostate tissue from untreated patients and from patients chronically treated with finasteride. MATERIALS: Immunostaining with anti-GST-pi antibody was performed on 10 (cysto-) prostatectomy, eight simple prostatectomy, and three transurethral prostatectomy specimens. The first set of 10 prostates was from untreated patients operated on for bladder cancer. The other cases were from patients with benign prostatic hyperplasia and chronically treated with finasteride. None of the specimens in either group showed prostatic cancer, prostatic intraepithelial neoplasia, urothelial carcinoma, or chronic prostatitis. Specimens were evaluated for the presence, intensity, and distribution of immunostaining. RESULTS: Diffuse cytoplasmic immunostaining was observed in the basal cell layer of the untreated specimens. Some variability in the expression of GST-pi was seen within each zone and also between the prostate zones. Only a minority of the secretory cells was stained weakly, mainly in the subnuclear region of the cells facing an uninterrupted basal cell layer. Staining was more homogeneously diffuse in the cytoplasm of the luminal cells facing the basement membrane directly. In the benign epithelium of the finasteride treated specimens the circumferential staining of the basal cells appeared to be more continuous than in the untreated cases, the gaps in the stained basal cell layer being fewer, shorter, or even absent in some ducts and acini. There was no variability in the intensity of staining of the basal cell layer, all the cells being intensely stained in a uniform way. The intensity of staining of the secretory cells was not influenced by finasteride treatment. CONCLUSIONS: Following chronic treatment with finasteride the immunohistochemical expression of pi class glutathione S-transferase in the benign prostate ducts and acini is upregulated in relation to an expanded basal cell layer. This could indicate that finasteride acts as a GST-pi inducer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10560354&dopt=Abstract finasteride Propecia



finasteride, Propecia
Androgen receptor gene alterations and chromosomal gains and losses in prostate carcinomas appearing during finasteride treatment for benign prostatic hyperplasia.

Koivisto PA, Schleutker J, Helin H, Ehren-van Eekelen C, Kallioniemi OP, Trapman J.

Laboratory of Cancer Genetics, Tampere University Hospital, Finland. blpako uta.fi

Finasteride is commonly used for the treatment of benign prostatic hyperplasia and has been suggested to prevent prostate cancer development. To gain insight to the molecular effects of finasteride on prostate cancer development, we studied six prostate cancers diagnosed during finasteride treatment for benign prostatic hyperplasia. Comparative genomic hybridization detected genetic alterations in four tumors (1-5 changes/tumor). Xq gains and 6q losses were the most common alterations. The recurrent Xq gains motivated us to study the involvement of the androgen receptor (AR) gene. One tumor with Xq gain had a 3-fold amplification of the AR gene, suggesting that tumor development in finasteride-treated patients may require increased AR copy number and expression, as has previously been shown for prostate cancers recurring during hormonal therapy. Furthermore, in another tumor, an Arg726Leu mutation of the AR gene was found. This mutation was also present in the germ-line DNA of the patient. Arg726Leu mutation has previously been reported to affect the transactivational properties of the AR. In summary, prostate cancers developing during finasteride therapy may have distinct biological properties, such as a low number of chromosomal alterations and frequent involvement of the AR gene. Further studies are needed to explore the role of germ-line AR mutations in these patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10589774&dopt=Abstract finasteride Propecia



finasteride, Propecia
New topical antiandrogenic formulations can stimulate hair growth in human bald scalp grafted onto mice.

Sintov A, Serafimovich S, Gilhar A.

Ben-Gurion University of the Negev, The Institutes for Applied Research, PO Box 653, Beer-Sheva, Israel. asintov bgumail.bgu.ac.il

The purpose of this study was to test the ability of topical formulations of finasteride and flutamide to re-enlarge hair follicles in male-pattern baldness. This was evaluated by an experimental model of human scalp skin graft transplanted onto SCID mice. A comparison was made between formulations containing finasteride and flutamide, and a vehicle formulation in terms of the mean hairs per graft, length, diameter of the shafts, and structures of the growth stages of the hair. Flutamide and finasteride had a significantly higher effect (P<0.05) than the placebo in all the tested parameters, but flutamide demonstrated more hair per graft and longer hair shafts than finasteride (P<0.05). The number of hairs per graft for flutamide and finasteride groups were 1.22+/-0. 47 and 0.88+/-0.95 hairs/0.5 mm2 graft, respectively, versus 0. 35+/-0.6 hairs/graft for vehicle-treated graft. Similarly, hair lengths for flutamide and finasteride were 5.82+/-0.50 and 4.50+/-0. 32 mm, respectively, versus 2.83+/-0.18 mm for the vehicle-treated grafts. An in vitro diffusion study of flutamide gel using hairless mouse skin demonstrated the beneficial effect of the vehicle composition in comparison with a hydroalcoholic solution or a gel containing no penetration enhancer. It is therefore suggested that this topical composition containing flutamide or finasteride may effectively result in regression of male-pattern baldness.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10601691&dopt=Abstract finasteride Propecia



finasteride, Propecia
A pilot study of a bioabsorbable self-reinforced poly L-lactic acid urethral stent combined with finasteride in the treatment of acute urinary retention from benign prostatic enlargement.

Isotalo T, Talja M, Valimaa T, Tormala P, Tammela TL.

Department of Surgery, Paijat-Hame, Central Hospital, Lahti, Finland.

OBJECTIVE: To assess whether patients with acute urinary retention from benign prostatic enlargement can be treated with a combined therapy comprising a bioabsorbable self-reinforced poly L-lactic acid (SR-PLLA) urethral stent and finasteride. PATIENTS AND METHODS: Eleven men in acute urinary retention were treated as outpatients; they had a suprapubic catheter inserted and the SR-PLLA stent placed cystoscopically. The patients were allowed to attempt to void spontaneously after 2 days. RESULTS: All patients started to void spontaneously within 2 weeks. There was a steady improvement in urinary flow rates up to 9 months, followed by a slight impairment after the bioabsorption of the stent. During the mean (range) follow-up of 24 (23-26) months only three patients required surgical treatment. CONCLUSION: The bioabsorbable SR-PLLA stent combined with finasteride therapy provides a promising new alternative in the treatment of acute urinary retention, especially in patients unfit for surgical therapy. Larger, placebo-controlled studies are needed to establish the efficacy of this combined therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10619952&dopt=Abstract finasteride Propecia



finasteride, Propecia
Ventral tegmental area infusions of inhibitors of the biosynthesis and metabolism of 3alpha,5alpha-THP attenuate lordosis of hormone-primed and behavioural oestrous rats and hamsters.

Frye CA, Vongher JM.

Department of Psychology, Biological Sciences and the Center for Neuroscience Research, The University at Albany-SUNY, Albany, New York 12222, USA. cafrye cnsunix.albany.edu

The importance of progesterone biosynthesis and metabolism to 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), which exerts its effects via GABAA/benzodiazepine receptor complexes (GBRs) rather than intracellular progestin receptors (PRs), was investigated for its effects on sexual receptivity. Epostane, a 3beta-hydroxysteroid dehydrogenase inhibitor, blocks progesterone and 3alpha,5alpha-THP biosynthesis. Finasteride, a 5alpha-reductase inhibitor, blocks the metabolism of progesterone to dihydroprogesterone (DHP), which is subsequently metabolized to 3alpha,5alpha-THP. Indomethacin, a 3alpha-hydroxysteroid oxidoreductase inhibitor, blocks DHP's metabolism to 3alpha,5alpha-THP, and its oxidation to DHP. Epostane, finasteride, indomethacin or vehicle were infused intracranially in the ventral tegmental area (VTA) of hormone-primed or naturally receptive rats and hamsters and sexual behaviour was recorded. Epostane, finasteride and indomethacin to the VTA significantly reduced lordosis, compared to vehicle infusions, in hormone-primed and behavioural oestrous rats and hamsters. Radioimmunoassay revealed that concentrations of midbrain 3alpha,5alpha-THP were reduced following epostane, finasteride or indomethacin infusions that significantly decreased lordosis. Immunocytochemistry for 3alpha,5alpha-THP revealed the number of immunoreactive cells were significantly reduced in the VTA following epostane, finasteride or indomethacin infusion to the VTA, but not other midbrain sites. These data suggest that biosynthesis of progestins, and the metabolism of progesterone to 3alpha,5alpha-THP in the VTA, are important for progestin-facilitated sexual receptivity of rats and hamsters.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11722704&dopt=Abstract finasteride Propecia