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A eucaryotic cell assay was established to identify novel, dual and selective inhibitors of human 5alpha-reductase. For this purpose the cDNAs encoding 5alpha-reductase type I and type II were inserted into a pRcCMV vector and expressed in human embryonic kidney (HEK293) cells. Single cell clones with substantially high enzymatic activity were selected and established as permanent cell lines. KM values were determined for both isozymes. The inhibitory potency of several steroidal and non-steroidal compounds synthesized in our group, as well as finasteride and 4MA as controls, were tested by measuring the conversion of [3H]androstenedione. Reaction products were quantified by a HPLC reversed phase technique. Using the new cell assays, selective as well as novel dual 5alpha-reductase inhibitors with IC50 values between 1.0 and 2.5 microM were identified.
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Two drugs are available for the treatment of balding in men. Minoxidil, a topical product, is available without a prescription in two strengths. Finasteride is a prescription drug taken orally once daily. Both agents are modestly effective in maintaining (and sometimes regrowing) hair that is lost as a result of androgenic alopecia. The vertex of the scalp is the area that is most likely to respond to treatment, with little or no hair regrowth occurring on the anterior scalp or at the hairline. Side effects of these medications are minimal, making them suitable treatments for this benign but psychologically disruptive condition.
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While the lipidosterolic extract (LSESr) of Serenoa repens--Permixon--has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin.
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Whereas the embryological development of the human prostate is clearly dependent on steroid 5 alpha-reductase (5 alpha-R) type 2 expression, the respective expression of the two known isoforms (types 1 and 2) of 5 alpha-R in the adult human prostate remains unclear.
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Clinical trials of alpha-blockers in men with enlarged prostate have reported improvements in total symptom scores of 10% to 20% compared with placebo; however, these agents were not shown to reduce the risk of long-term complications or disease progression. Studies of the 5ARIs have reported significant reductions compared with placebo in the relative risk for AUR and enlarged prostate-related surgery, slowing of disease progression, and relief of symptoms. In studies of dutasteride, improvements in symptom scores were greater after 4 years of therapy compared with 2 years (-6.4 vs -4.3 points, respectively) and flow rates were better (2.6 vs 2.3 mL/sec). Six-year data for finasteride showed maintenance of the decreased risk for AUR and enlarged prostate-related surgery. Use of combination therapy with an alpha-blocker and a 5ARI may be of benefit in patients who require immediate relief of symptoms, with discontinuation of the alpha-blocker after several months of therapy. 5ARIs were generally well tolerated, with sexual dysfunction the most frequently reported adverse effect, although in only a small proportion of men (1%-8%).
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To assess the additive benefit of combining an alpha1-blocker and a 5alpha-reductase inhibitor.
Androgenetic alopecia is a common dermatological condition, with potentially adverse psychosocial sequelae. The present review critically examines scientific evidence concerning the effects of androgenetic hair loss on social processes and psychological functioning, as well as the psychosocial outcomes of medical treatments. Research confirms a negative but modest effect of visible hair loss on social perceptions. More importantly, androgenetic alopecia is typically experienced as a moderately stressful condition that diminishes body image satisfaction. Deleterious effects on self-esteem and certain facets of psychological adjustment are more apparent among women than men and among treatment-seeking patients. Various 'risk factors' vis-à-vis the psychological adversity of androgenetic alopecia are identified. Medical treatments, i.e. minoxidil and finasteride, appear to have some psychological efficacy. A conceptual model is delineated to explain the psychological effects of hair loss and its treatment. Directions for needed research are discussed. Strategies are presented for the clinical management of psychological issues among these patients.
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To review available evidence on the safety and efficacy of finasteride in the treatment of alopecia in women.
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5α-reductase inhibitors (5α-RIs) (finasteride and dutasteride) have been proven useful in treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). However, these inhibitors exert undesirable sexual side effects and, in some cases, these effects are persistent. There is considerable disagreement with regard to whether the adverse side effects resolve with continuous treatment.
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These findings suggest that both DOC and its metabolites may contribute to the anticonvulsant effects seen in young rats, perhaps acting via interactions with several different receptors.
Short-term pretreatment with finasteride and dutasteride has similar efficacy and significantly reduces perioperative bleeding during TURP and has minimal negative impact on sexual function. According to our findings, a 4 weeks' prior administration of 5-ARIs may reduce operative blood loss and prostatic MVD in TURP, thus potentially decreasing blood loss- related complications and the requirement of blood transfusion.
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Prior to initiating finasteride treatment, one patient reported having had 6 episodes of acute priapism, while the remaining patients had more than 10 episodes. One of the patients reported having stuttering priapism almost daily. With a mean follow-up of 20 months, four patients had no episodes and only one patient complained of sporadic and shorter duration episodes.
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Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses.
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Finasteride is a 5-alpha-reductase inhibitor used in the medical treatment of benign prostatic hyperplasia (BPH) and appears to be effective in treating prostatic bleeding secondary to BPH. The exact mechanism of this effect is not known. The aim of this study was to evaluate the effects of finasteride on the vascular surface density (VSD), number of microvessels (NVES) and vascular endothelial growth factor (VEGF) expression of the rat prostate.
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The methanolic extract of the fruits of Torilis japonica showed a potent inhibition against 5 alpha-reductase activity in vitro. Bioassay-guided fractionation of the methanol extract of the fruits followed by repeated silica gel chromatography led to the isolation of an active principle and its structure was identified as torilin on the basis of spectroscopic data. Torilin (IC50 = 31.7 +/- 4.23 microM) showed a stronger inhibition of 5 alpha-reductase than alpha-linolenic acid (IC50 = 160.3 +/- 24.62 microM) but was weaker than finasteride. (IC50 = 0.38 +/- 0.06 microM). Simple guaiane-type compounds, such as (-)-guaiol and guaiazulene showed weak inhibitory effects on the 5 alpha-reductase activity with IC50 values of f 81.6 microM and 100.8 microM, respectively, while azulene was not active. These results suggest that both degrees of unsaturation and the side-chain in the guaiane skeleton are important for the manifestation of 5 alpha-reductase inhibition.
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In this article, we review the current literature regarding the pathophysiology and management of RIP and discuss the risks and benefits associated with each option, which includes ketoconazole (KTZ), 5-α-reductase inhibitors and other hormonal therapies, phosphodiesterase type 5 (PDE5) inhibitors, intracavernosal sympathomimetic injection, oral sympathomimetic agents, and other investigational therapies.
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Cases were men with a confirmed diagnosis of PCa after visit 2 (n = 614), and controls were men not diagnosed with PCa during the trial who also had a negative end-of-study biopsy (n = 616). Controls were frequency-matched to cases by age, treatment arm, and family history of PCa. Sera from visit 2 were tested for CMV IgG antibodies.
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Finasteride has been associated with reversible adverse sexual side effects in multiple randomized, controlled trials for the treatment of male pattern hair loss (MPHL). The Medicines and Healthcare Products Regulatory Agency of the United Kingdom and the Swedish Medical Products Agency have both updated their patient information leaflets to include a statement that "persistence of erectile dysfunction after discontinuation of treatment with Propecia has been reported in post-marketing use."
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A total of 4498 patients met selection criteria, with comparable demographics between treatment cohorts. Patients taking dutasteride incurred $51 less per month in medical expenses than finasteride-treated patients ($122 vs $173; P <.001), attributable to lower monthly inpatient hospitalization costs ($55.84 vs $70.34), outpatient costs ($22.07 vs $44.25), and physician office visit costs ($40.69 vs $51.10).
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A simple spectrophotometric method for the assay of steroid 5α-reductase (5α-SR) was developed in which 5α-dihydrotestosterone (5α-DHT) and 5α-androstane-3α,17β-diol (5α-diol), metabolites formed in the NADPH-dependent reduction of testosterone with enzyme sources of 5α-SR, were measured by enzymatic cycling using 3α-hydroxysteroid dehydrogenase in the presence of excess thionicotinamide-adenine dinucleotide (thio-NAD) and NADH. It was found that 5α-SR activity was proportional to the accumulated thio-NADH having an absorption maximum at 400 nm. Because of the high cycling rate (> 600 cycle per min) and no interference from testosterone, enzymatic cycling can determine the sum of 5α-DHT and 5α-diol at the picomole level without separation from excess testosterone. The present method was readily applicable to the assay of 5α-SR activity of rat liver and prostate microsomes as well as to the assay of inhibitory activity of finasteride, a synthetic inhibitor of 5α-SR.
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Based on published GPs and original GPs obtained at our clinical research facility, we developed a training set in order to allow European Union (EU) observers to practice and compare with ratings by the US experts.
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To test the hypothesis that in patients with benign prostatic hyperplasia (BPH), the outcome of drug therapy with finasteride may be predictable from the baseline prostate volume and that positive clinical effects might be expected only in patients with prostate volumes of > 40 mL, using a subgroup analysis of results from a previously reported clinical trial of finasteride and phytotherapy.
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An oral 5-mg dose of finasteride, a 5 alpha-reductase inhibitor, was administered for 3 months to 10 hirsute women to determine the effect on gonadotropin secretion, on basal and stimulated androgen secretion, and on hair growth. Hair growth was assessed by the Ferriman-Gallwey score. All of the above determinations were evaluated before and after 1 and/or 3 months of finasteride treatment. Basal and GnRH-stimulated gonadotropin secretions were not affected. Indeed, finasteride did not modify the pulsatility of LH secretion. No change was seen in estradiol, PRL, free testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone-binding globulin concentrations. Serum concentrations of cortisol (F) were significantly reduced after 1 month of finasteride treatment. The F levels returned to pretreatment levels after 3 months. Plasma levels of dihydrotestosterone and 3 alpha-androstanediol glucuronide significantly decreased during finasteride treatment. A significant increase in testosterone concentrations was observed after 3 months. Finasteride did not modify the responses of testosterone, androstenedione, and dehydroepiandrosterone sulfate to ACTH-(1-24) injection. Conversely, finasteride blunted the F response to corticotropin stimulation. Three months of finasteride treatment significantly decreased the Ferriman-Gallwey score. In conclusion, finasteride significantly decreased dihydrotestosterone and hair growth in hirsute women without negatively affecting gonadotropin secretion.
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It has long been recognised that neural factors are of considerable importance in lower urinary tract function. Whilst reduction in the bulk of the human prostate is feasible, experience on this therapeutic approach proved to be disappointing. Existing trial data with the agent finasteride are reviewed. A number of formulations derived from plant extracts have been advocated but their mechanism of action remain largely obscure and there is a dearth of placebo controlled information to support their efficacy. Experience over the last 10 years has demonstrated efficacy with the use of alpha adrenoceptor blockade in the management of BPH. Alpha adrenoceptor antagonists relax the prostatic smooth muscle by interrupting the sympathetic pathway at the receptor level. Recent developments in this field include the recognition that there are alpha I adrenoceptor subtypes. The functional adrenoceptor in the human prostate is predominantly the alpha IA - subtype. Of the alpha 1-adrenoceptor antagonists only tamsulosin discriminates between the alpha 1-adrenoceptor subtypes. Alpha 1-blockers should be used in first-line medical therapy for BPH and 5-alpha-reductase inhibitors reserved for those patients in whom alpha-blocker therapy fails. Alpha I-blockers such as doxazosin, tamsulosin, terazosin, alfuzosin are effective in the treatment of BPH both in younger and in older men. The drugs are well tolerated. The majority of side effects were classified as minor and mild. The most common complaints, as with other alpha-blockers, are dizziness, fatigue and headache, and these are often transient. In contrast, finasteride can lead to impotence, reduced libido. gynaecomastia or ejaculatory disorders. Men with small prostates may not be suitable candidates for finasteride therapy.
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Since 1992 the number of TURP operations per year has dropped from its peak of about 560 to around 270 in 1999. This is more than a 50% reduction in eight years. The number of patients being treated for BPH has multiplied since the introduction of drugs and the total cost of BPH treatment has doubled since 1984. There was a trend but not a significant change in indications for TURP when the two periods were compared.
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Vascular endothelial growth factor (VEGF) plays a critical role in the pathogenesis of diabetic microvascular complications. Finasteride has been confirmed to decrease VEGF expression in prostate and prostatic suburethral tissue resulting in limiting hematuria from human benign prostatic hyperplasia. The purpose of this study was to evaluate the effects of finasteride on microvessel density (MVD), VEGF protein and mRNA expressions in the renal tissue of diabetic rats.