Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new proscar research articles will be listed here shortly after becoming available to us.
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Medical research on proscar
Eur J Dermatol. 2008 Jun 23; 18(4): 407-411
Kaufman KD, Girman CJ, Round EM, Johnson-Levonas AO, Shah AK, Rotonda J
Relatively little is known about the progression of androgenetic alopecia (AGA; male pattern hair loss) in untreated men. We evaluated the long-term (5-year) progression of AGA in men treated with placebo in a controlled clinical trial setting. We analyzed pooled data over 5 years from two replicate studies with finasteride 1 mg/day in men with predominantly vertex-pattern AGA. Each study consisted of an initial 1-year, randomized, double-blind, placebo-controlled base study and four consecutive, 1-year, double-blind, placebo-controlled extension studies. Change over time in scalp hair growth was evaluated by four predefined endpoints: scalp hair counts; assessment of standardized clinical photographs by an expert panel; investigator clinical assessment; and patient self-assessment. All four predefined endpoints demonstrated progressive scalp hair loss in men receiving placebo over the 5-year study period, with a loss of 239 hairs from baseline (26.3% decline in hair density) measured in the target area at 5 years (p < 0.001 vs. baseline). Similarly, visible progression of scalp hair loss was demonstrated by global photographic assessment, with 75% of placebo patients rated as worsened from baseline at 5 years. We found that scalp hair loss continued in a progressive manner over a 5-year period in placebo-treated men with AGA.
Eur J Dermatol. 2008 Jun 23; 18(4): 400-406
Kaufman KD, Rotonda J, Shah AK, Meehan AG
There are no reports on the effects of pharmacologic treatment on the likelihood of developing further visible hair loss in men with androgenetic alopecia (AGA). Our objectives were to examine whether finasteride 1 mg treatment decreases the likelihood of developing further visible hair loss in men with AGA. We conducted an analysis of global photographic assessment data from two Phase III trials in which 1553 men with AGA received finasteride 1 mg/day or placebo for up to 5 years. Finasteride 1 mg treatment led to a 93% decrease relative to placebo in the 5-year likelihood of developing further visible hair loss (95% CI: 89-97%; p < 0.001). We conclude that, in men with AGA, treatment with finasteride 1 mg/day over 5 years led to a marked and sustained decrease in the likelihood of developing further visible hair loss.
Alcohol Clin Exp Res. 2008 Jun 19;
Ford MM, Yoneyama N, Strong MN, Fretwell A, Tanchuck M, Finn DA
Background: Allopregnanolone (ALLO) is a physiologically relevant neurosteroid modulator of GABA(A) receptors, and it exhibits a psychopharmacological profile that closely resembles the post-ingestive effects of ethanol. The 5alpha-reductase inhibitor finasteride (FIN), which inhibits biosynthesis of ALLO and structurally related neurosteroids, was previously demonstrated to reduce the maintenance of limited-access ethanol consumption. The primary aim of the current work was to determine whether FIN would reduce the acquisition of drinking in ethanol-naïve mice. Methods: Male C57BL/6J (B6) mice were acclimated to a reverse light/dark schedule, and were provided ad libitum access to chow and water. Following habituation to vehicle injections (VEH; 20% w/v beta-cyclodextrin; i.p.) administered 22-hour prior to drinking sessions with water only, mice were divided into 3 treatment groups: vehicle control (VEH), 50 mg/kg FIN (FIN-50), and 100 mg/kg FIN (FIN-100). Twenty-two hours after the first treatment, mice were permitted the inaugural 2-hour limited access to a 10% v/v ethanol solution (10E) and water. The acquisition of 10E consumption and underlying drinking patterns were assessed during FIN treatment (7 days) and subsequent FIN withdrawal (13 days) phases. Results: FIN dose-dependently blocked the acquisition of 10E drinking and prevented the development of ethanol preference, thereby suggesting that the GABAergic neurosteroids may be important in the establishment of stable drinking patterns. FIN-elicited reductions in 10E intake were primarily attributable to selective and marked reductions in bout frequency, as no changes were observed in bout size, duration, or lick rates following FIN treatment. FIN-treated mice continued to exhibit attenuated ethanol consumption after 2 weeks post-treatment, despite a full recovery in brain ALLO levels. A second study confirmed the rightward and downward shift in the acquisition of ethanol intake following 7 daily FIN injections. While there were no significant group differences in brain ALLO levels following the seventh day of ethanol drinking, ALLO levels were decreased by 28% in the FIN-50 group. Conclusions: Although the exact mechanism is unclear, FIN and other pharmacological interventions that modulate the GABAergic system may prove useful in curbing ethanol intake acquisition in at-risk individuals.
The effect of finasteride on spermatogenesis of Mesocricetus auratus.
Acta Cir Bras. 2008 Jun; 23(3): 282-286
Vidigal DJ, Silva AL, Fonseca LM, Vasconcelos AC, Resende DF, Vidigal FE
PURPOSE: To study the effect of finasteride on the spermatogenesis of adult Mesocricetus auratus. METHODS: Twenty adult hamsters were evaluated. The animals were one year-older, and were randomly divided in 2 different groups: control group with ten animals (n=10) and experimental group also with ten animals (n=10). The animals in the experimental group were shot 7.14 ng/mL (0.5mL) of finasteride by 100mg/Kg, subcutaneously in the dorsal region three times per week during 90 days. This dose correspondes to 5mg of the drug used in adult men for the treatment of benign prostatic hyperplasia (BPH). After three months, the animals were anesthetized through association of 200mg/kg ketamine chloridrate and 2.5 mg/kg of diazepan and were dead through hypovolemia.. The testis removed along with the whole genitourinary apparel were fixed with 10% formalin and submitted to histological analisys by optical microscopy. The hematoxilin-eosin (HE) method was used to stain the slides. RESULTS: The mean weight of animals in the control group before death was 129.0+/-18.8gr. The mean weight of animals in experimental group was 145.0+/-15.25gr. The mean age of animals in control group before death was 15.2+/-1.13 months. The mean age of animals in experimental group before death was 17.16+/-0.82 months. The mean difference in weight between both groups was not statistical significant (p=0.0514). The totality of animals in control group (100%) presented no tubular alterations and showed no disturbancy in the spermatogenesis stages. Four animals (40%) in the experimental group showed hypotrophy of the seminiferous tubules and six (60%) showed normal spermatogenesis, however reduced compared to control group. There was statiscally significant difference (p=0.043) between the control and experimental group related to testicular alterations. CONCLUSION: The animals that were administered finasteride showed significant tubules atrophy and spermatogenesis reduction compared to control group.
PCPT, MTOPS and the use of 5ARIs: a Canadian consensus regarding implications for clinical practice.
Can Urol Assoc J. 2007 Mar; 1(1): 17-21
Klotz L, Saad F,
OBJECTIVES: Two large, recently published, definitive trials evaluated the benefits of 5-alpha reductase inhibitors (5ARIs). The Prostate Cancer Prevention Trial (PCPT) tested the effect of finasteride for prostate cancer prevention and the Medical Therapy of Prostatic Symptoms (MTOPS) tested its effect in benign prostatic hyperplasia (BPH). Both trials were strongly positive. However, the role of 5ARIs in the clinical management of patients remains controversial. The consensus conference, which forms the basis for this report, attempted to develop an expert opinion, based on these studies, as to the optimal use of 5ARIs in patient management. METHODS: The Canadian Consensus Meeting, organized by the Canadian Urology Research Consortium and the Canadian Urologic Oncology Group, held in Toronto on May 7, 2006, focused on the new data from the PCPT and the MTOPS study. Internationally recognized experts and clinicians discussed the implications of these data on clinical practice and issued a recommendation on the optimal management of patients with BPH. RESULTS: The Consensus meeting agreed on the following recommendations: The overall results from the PCPT and MTOPS studies are of importance to the urologic, as well as to the greater medical, community.Prostate management guidelines should be updated to include the results from both the MTOPS and the PCPT studies.In the PCPT, the incidence of high-grade cancer was higher in the finasteride-treated group (6.4%), compared with the placebo group (5.1%). Subsequent analyses strongly suggest that this increased prevalence was owing to a detection bias caused by the reduction in prostate volume in patients taking finasteride, compared with patients taking placebo. This resulted in an improved detection at biopsy of high-grade cancer in the finasteride group.In men who have large prostates and lower urinary tract symptoms (LUTS), 5ARIs( section sign) should be considered, both for the treatment of BPH and for prostate cancer risk reduction.For men who are concerned about prostate cancer, it is appropriate to discuss chemoprevention with finasteride.Urologists are encouraged to disseminate these recommendations among other healthcare professionals.
Can Urol Assoc J. 2008 Feb; 2(1): 16-21
Nickel JC, Barkin J, Koch C, Dupont C, Elhilali M
OBJECTIVE: Our Canadian multicentre open-label study sought to evaluate, in patients with moderate/severe lower urinary symptoms (LUTS) secondary to benign prostatic hyperplasia, the effect on symptoms of 9 months of monotherapy with finasteride 5 mg following 9 months of combination treatment (finasteride with an alpha-blocker) as quantified according to the International Prostate Symptom Score (IPSS). METHODS: The primary outcome measure for efficacy was the maintenance of IPSS response after cessation of the alpha-blocker. Subjects were treated with a combination of finasteride and an alpha-blocker for 9 months and then with finasteride alone for 3 or 9 months. RESULTS: Results showed that the IPSS scores after 3 months of monotherapy were within the criteria for equivalence to those after 9 months of combination therapy. Symptom control equivalence was also found after 9 months of monotherapy. The IPSS response rate was also similar for combination and monotherapy. The safety profile was similar and as expected with these medications. CONCLUSION: Control of LUTS associated with BPH thus appears to be maintained for at least 9 months with finasteride alone, following a 9-month course of combination therapy with finasteride and an alpha-blocker, with similar safety profiles.
Neuroscience. 2008 May 3;
Martín-García E, Darbra S, Pallarés M
Recent findings indicate that neurosteroids could act as important keys during the brain development. Fluctuations in neonatal allopregnanolone (AlloP) could result in altered pharmacological properties of the GABA(A) receptor system in adulthood. Recent studies demonstrated that neurosteroids play a critical role in regulating normal neurodevelopment in the hippocampus. The aim of the present work is to screen whether developmentally altered neurosteroid levels influence the behavioral response to adult intrahippocampal administration of AlloP, a GABA(A) positive modulating neurosteroid, and pregnenolone sulfate (PregS), a GABA(A) negative modulator in rats. For this purpose, pups received AlloP (10 mg/kg, s.c.), a 5alpha-reductase inhibitor (finasteride, 50 mg/kg, s.c.) or vehicle from the fifth to the ninth postnatal day. At maturity (i.e. 90 days old) a bilateral cannula was implanted into the hippocampus. After recovery from surgery, animals received an administration of AlloP (0.2 mug/0.5 mul), PregS (5 ng/0.5 mul) or vehicle in each hippocampus 5 min before they were tested in the elevated plus maze (EPM) and immediately after the passive avoidance training session, and retention was tested 24 h later. Results indicated that neonatal finasteride treatment deteriorated passive avoidance retention and elicited an anxiogenic-like effect in the EPM test in adulthood, as seen by the reduction of open arm entries and in the time spent in the open arms. Intrahippocampal PregS administration also disrupted passive avoidance, possibly related to its anxiogenic profile. Fluctuations in neonatal AlloP affect the aversive learning and the anxiety-related behavior in adulthood, and this effect could be in part mediated by alterations of the mature functions of the hippocampus, possibly via the GABA(A) receptor. These data point to the role of GABAergic neurosteroids in critical periods of vulnerability that influence normal development of GABAergic pathways in the CNS.
Int J Cosmet Sci. 2000 Dec; 22(6): 397-407
Bernard FX, Barrault C, Deguercy A, de Wever B, Rosdy M
The steroid 5alpha-reductase isoenzymes (5alphaR) transform testosterone into 17beta-hydroxy-5alpha-androstan-3-one (5-dihydrotestosterone, DHT), which exerts a much stronger biological activity than does testosterone. Briefly, the two 5alphaR isoenzymes are differentially expressed in the two major target organs of steroid action, the prostate (isoenzyme 2, 5alphaR2) and the skin (isoenzyme 1, 5alphaR1). We analysed the potential of a human epidermal tissue reconstituted by cell culture (RHE, provided by SkinEthic Laboratories, Nice, France) as a model for assessing 5alphaR activity. The epidermal model was found to express the type-1 (skin) isoform of 5alphaR and thus could be used as an enzyme source for the screening of 5alphaR modulators for dermatological/cosmetic purposes. A reproducible and convenient assay method was developed, allowing both the evaluation of testosterone transformation into DHT (5alphaR activity) and an outlook on the general metabolism process of testosterone. This could be important for the detection of any compound that could act mainly on another target enzyme than 5alphaR. The assay gave evidence of the inhibitory activity of finasteride against type-1 5alphaR, which is now established both in vitro and in clinical studies. In addition to enzyme inhibitors, this in situ cellular assay can detect transcriptional modulators of 5alphaR gene expression, or any compound that could modulate enzyme processing or post-translational activation. RT-PCR analysis of RNA samples from RHE failed to show any notable effect of finasteride, testosterone, or DHT treatment on the expression of 5alphaR1 at the transcriptional level.
J Urol. 2008 Jul; 180(1): 367-72
Festuccia C, Gravina GL, Muzi P, Pomante R, Angelucci A, Vicentini C, Bologna M
PURPOSE: The profound decrease in serum dihydrotestosterone observed with the dual 5alpha-reductase inhibitor dutasteride makes it an attractive agent for prostate cancer therapy. To our knowledge we compared for the first time the antitumor effect of dutasteride with that of the specific 5alpha-reductase-1 inhibitor MK386 and the specific 5alpha-reductase-2 inhibitor finasteride in human prostate primary cultures. MATERIALS AND METHODS: Biochemical markers of the cellular response to 5alpha-reductase inhibitors were evaluated in primary cultures of prostate epithelial cancer cells from 54 patients with prostate carcinoma. RESULTS: In our cohort of 54 patients prostate cancer cell growth decreased with dutasteride in 42 (about 78%), whereas in 21 (39%) it decreased with finasteride or MK386 alone. We observed a relationship between the levels of 5alpha-reductase enzymes in cell culture extracts and those revealed by immunohistochemistry in sections of samples from which we established primary cultures. Finasteride effects depended on 5alpha-reductase-2 levels and they were higher when the 5alpha-reductase-1:2 ratio was low. However, dutasteride effects were related to 5alpha-reductase-1 and 2 levels, and were not influenced by the 5alpha-reductase-1:2 ratio. Conversely the effects of MK386 were related to 5alpha-reductase-1 levels and they were higher when the 5alpha-reductase-1:2 ratio was high. CONCLUSIONS: Our data may provide a rationale for the use of a dual 5alpha-reductase inhibitor rather than a mono specific inhibitor for the prevention or treatment of early prostate cancer. This finding appears to confirm some preliminary clinical results and it could be due to the simultaneous presence of each 5alpha-reductase isoenzyme in prostate tumor cells.
Causes of hair loss and the developments in hair rejuvenation.
Int J Cosmet Sci. 2002 Feb; 24(1): 17-23
Rushton DH, Norris MJ, Dover R, Busuttil N
Hair is considered to be a major component of an individual's general appearance. The psychological impact of hair loss results in a measurably detrimental change in self-esteem and is associated with images of reduced worth. It is not surprising that both men and women find hair loss a stressful experience. Genetic hair loss is the major problem affecting men and by the age of 50, up to 50% will be affected. Initial attempts to regenerate the lost hair have centred on applying a topical solution of between 2% to 5% minoxidil; however, the results proved disappointing. Recently, finasteride, a type II 5alpha reductase inhibitor has been found to regrow a noticeable amount of hair in about 40% of balding men. Further developments in treatments have lead to the use of a dual type I and type II inhibitor where 90% of those treated regrow a noticeable amount of hair. In women the major cause of hair loss before the age of 50 is nutritional, with 30% affected. Increased and persistent hair shedding (chronic telogen effluvium) and reduced hair volume are the principle changes occurring. The main cause appears to be depleted iron stores, compromised by a suboptimal intake of the essential amino acid l-lysine. Correction of these imbalances stops the excessive hair loss and returns the hair back to its former glory. However, it can take many months to redress the situation.