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Ovariectomized adult female rats received estrogen for five days or estrogen for three days followed by two days peanut oil or testosterone either alone or in the presence of flutamide or finasteride. At the end of treatment, uteri were perfused with perfusate containing CFTRinh-172. The rate of fluid and Cl(-) secretion were determined. Dose-dependent effect of testosterone and effect of forskolin on fluid secretion rate were measured. Animals were sacrificed and uteri were removed for CFTR protein and mRNA expression analyses, histology and cAMP measurement. Morphology of uterus, levels of expression of CFTR protein and mRNA and distribution of CFTR protein were observed.
Healthy men (n = 48) received doses of 0.1 to 40 mg GI198745 (n = 4 subjects per dose), 5 mg finasteride (n = 8), or placebo (n = 8) in a parallel-group study. Plasma concentrations of GI198745, finasteride, and DHT were measured frequently up to 8 weeks after dosing. Models were fitted with mixed-effects modeling with the NONMEM program.
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We evaluated the efficacy and safety of alpha 1--blocker doxazosin for treatment of lower urinary tract symptoms (LUTS) compatible with benign prostatic hypertrophy (BPH). Fourteen randomized controlled trials enrolled 6261 men, average age 64 years, who had moderately severe LUTS and flow impairment. Compared with baseline measures and placebo effect, doxazosin resulted in a statistically significant improvement in both LUTS and flow. However, when compared with placebo, the average magnitude of symptom improvement (International Prostate Symptom Score [IPSS] improvement < 3 points) typically did not achieve a level detectable by patients. Combined doxazosin and finasteride therapy improved LUTS and reduced the risk of overall clinical progression of BPH compared to each drug separately in men followed over 4 years. Reported mean changes from baseline in the IPSS were -7.4, -6.6, -5.6, and -4.9 points for combination therapy, doxazosin, finasteride, and placebo, respectively. Combination therapy reduced the need for invasive treatment for BPH and the risk of long-term urinary retention. The absolute reductions compared with placebo were less than 4% and primarily seen in men with prostate gland volume > 40 mL or PSA levels > 4 ng/mL. Efficacy was comparable with other alpha 1--blockers. Withdrawals from treatment for any cause were comparable to placebo. Dizziness and fatigue occurred more frequently with doxazosin compared to placebo.
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A high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make diagnosis and therapy of prostate cancer a special challenge for urologists. Effective prevention of the disease may help to resolve some of the problems mentioned above. Two randomised, controlled studies prove that effective chemoprevention of prostate cancer is possible using 5-α reductase inhibitors (finasteride, dutasteride) (LoE 1) both in individuals at low and those at high risk developing prostate cancer. Furthermore, there is evidence that other compounds, e.g. selective estrogen receptor modulators (SERMs), non-steroidal anti-inflammatory drugs (NSAIDs) and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economic aspects. The authors conclude that chemoprevention in a high risk cohort using 5-α reductase inhibitors is a viable option and may even be cost effective. In consequence, the options of chemoprevention in prostate cancer should be further explored in an open and unbiased way.
In comparison with men, women have a better prognosis when experiencing aortic valve stenosis, hypertrophic cardiomyopathy, or heart failure. Recent data suggest that androgens like testosterone or the more potent dihydrotestosterone contribute to the development of cardiac hypertrophy and failure. Therefore, we analyzed whether antiandrogenic therapy with finasteride, which inhibits the generation of dihydrotestosterone by the enzyme 5-α-reductase, improves pathological ventricular remodeling and heart failure.
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[corrected] Due to the ageing and longevity of the population, the costs associated with the management of LUTS suggestive of BPO will rise in the future, whereas healthcare budgets will be relatively restricted. In order to improve cost-effective management of LUTS, more and better studies are needed in real life practice in primary care. These studies should not only be based on classical efficacy and safety data, but also on effectiveness of treatment in the long-term and the associated costs.
5 α-reductase inhibitors such as finasteride and dutasteride have been studied for the treatment of hair loss in men, with finasteride being the only Food and Drug Administration-approved treatment. Increasingly, in recent years, off-label use of these drugs has been employed in the treatment of female pattern hair loss (FPHL) and frontal fibrosing alopecia (FFA) in women. Side effects with 5 α-reductase inhibitors can include changes in sexual function, and recent publications have characterized an increasing prevalence of these in men. A review of 20 peer-reviewed articles found that very few side effects, or adverse events, related to sexual function have been reported in studies in which dutasteride or finasteride has been used to treat hair loss in women. Future publications should investigate not only the efficacy of these drugs in treating FPHL and FFA, but the side effect profile in patients as well.
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837 patients referred to the Instituto Nacional de Cancerología, Mexico City, Mexico, between 2005 and 2009 were used to validate the finPCPTRC by examining various measures of discrimination and calibration. Net benefit curve analysis was used to gain insight into the use of the finPCPTRC for clinical decisions.
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Sexual adverse experiences such as erectile dysfunction (ED), loss of libido, and ejaculation disorders have been consistent side effects of finasteride in a maximum percentage of 15% after 1 year of therapy. Such data could be seen as far from reality, if compared to a higher percentage that may be found in any common clinical practice.
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The coadministration of tadalafil/finasteride provides early improvement in lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement. Tadalafil/finasteride coadministration also improves erectile function in men who have comorbid erectile dysfunction.
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Androgenetic alopecia is the most common type of hair loss in men and women. The disorder represents a quantitative phenotype with an underlying genetic disposition. So far none of the causative genes have been identified. Under the influence of androgens there is a shortening of the anagen phase as well as a reduction of the cellular hair matrix volume in the involved scalp area. This results in the transformation of thick terminal hair follicles into thin vellus-like hair follicles. Clinically, patients present with an alopecia that follows a defined pattern (pattern baldness) and progresses continuously but in varying degrees. In advanced cases, men may develop baldness with remaining hair exclusively in the temporal and occipital regions. Women are prone to exhibit a more diffuse type of hair loss with pronounced thinning in the parietal region. Whereas the diagnosis of androgenetic alopecia is easy, its treatment is often difficult. The physician is commonly confronted with high patients' expectations regarding hair regrowth. Today, with minoxidil and finasteride, effective therapies are available which can lead to cessation of hair loss. The identification of underlying genes will make a more specific therapy easier to achieve.
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Medical treatment is effective in treating symptomatic BPH. Combination dibenyline and finasteride provides a weak synergistic clinical effect without additive side effects.
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Mean microvessel density plus or minus standard deviation in finasteride treated patients was significantly lower in the suburethral portion of the prostate versus untreated controls (14.0 +/- 2.8 versus 20.2 +/- 5.3 vessels per high power field, p <0.05). In the nodular hyperplasia there was no statistically significant difference in the treatment and control groups (mean 17.5 +/- 2.8 and 16.7 +/- 4.6 vessels per high power field, respectively).
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As severe alcohol intoxication impairs memory function, a high concentration of ethanol (60 mM) acutely inhibits long-term potentiation (LTP), a cellular model of learning and memory, in rat hippocampal slices. Neurosteroids are involved in this LTP inhibition. We recently reported that the inhibitory effects of 60 mM ethanol are blocked by 4-methylpyrazole (4MP), an inhibitor of alcohol dehydrogenase, suggesting that acetaldehyde locally generated within the hippocampus participates in LTP inhibition.
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PCPT has and will continue to yield valuable information regarding future strategies for prostate cancer prevention and detection, benign prostatic hyperplasia, and other matters of public health importance.
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The "natural history" of prostate cancer may bedevil the development of guidelines for chemoprevention interventions. Can strategies be designed to direct agents to those lesions which have the potential to develop localized extension that may become symptomatic or metastatic disease? Of necessity our interventions will focus on the identification and quantification of appropriate biomarkers as intermediate endpoints, although no reliable endpoints for prostate cancer have yet been identified. The reduction of prostate cancer incidence may be the ultimate objective, but a decrease in the progression of microfocal or "latent" cancer may well be just as effective as prevention when the age of the target population and competing causes of death are taken into account. Early intervention strategies must focus on the analysis of the interactions of the chosen chemopreventive agents upon precancerous and cancerous cellular dynamics in the prostate. Whether the requirements of such molecular epidemiology necessitate a more deliberate strategy of Phase II studies or a high risk-high gain strategy of a broad Phase III study is open to debate. Factorial designs for proposed randomized chemoprevention trials may be desirable to test multiple chemopreventive agents simultaneously, provided knowledge of the biochemical synergism of the agents is solid. Stratification of study participants by degree of risk will ameliorate concerns regarding the precision targeting of lesions at different stages in the precancer/cancer continuum.
To review all the available data on the effect of 5ARIs on sexual function and assess whether 5ARIs increase the risk of sexual dysfunction.
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We conducted an observational study to evaluate prospectively the effectiveness of four modes of treatment for benign prostatic hyperplasia (BPH)-watchful waiting, alpha-blocker therapy, finasteride therapy, and surgery (transurethral prostatectomy). A total of 1459 men aged 48 to 84 years, who were diagnosed for the first time by physicians as having BPH in 1994 and who had not received treatment, participated in the study. During 1 year of follow-up, 1064 (72.9%) men remained on no treatment (watchful waiting), 156 (10.7%) were treated with finasteride, 198 (13.6%) were treated with an alpha-blocker, and 41 (2.8%) underwent prostatectomy. The American Urological Association (AUA) Symptom Index was administered to the cohort before the initiation of treatment in 1994, as well as 1 year later. Improvements in lower urinary tract symptoms, as measured by the AUA Symptom Index, were assessed using linear and logistic regression, adjusting for age and baseline. Men who underwent prostatectomy reported the biggest improvements in lower urinary tract symptoms, whether assessed by mean changes in symptom scores relative to no treatment (-5.44; 95% confidence interval [CI]-6.91 to -3.97) or by the odds of improving by 5 or more points on the AUA Symptom Index (odds ratio, 12.66; 95% CI, 5.93 to 27.0). Irrespective of the initial degree of symptom severity, prostate surgery resulted in larger improvements than those reported for either finasteride or alpha-blocker therapy. In this prospective, observational study, prostatic surgery was associated with statistically and clinically significant improvements in BPH symptoms.
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Patients were randomly allocated to one of three treatment schedules: 1) goserelin, 3.6 mg, s.c., monthly in combination with flutamide, 250 mg., t.i.d. and a placebo, daily, in the image of 2 x 5 mg finasteride; 2) goserelin, 3.6 mg., s.c., monthly in combination with finasteride, 10 mg (2 x 5 mg, daily) and a placebo (t.i.d.) in the image of flutamide; and 3) finasteride, 10 mg (2 x 5 mg, daily) in combination with flutamide (250 mg, t.i.d.). The reduction in concentration of serum PSA at 24 weeks was the endpoint of interest.
Systematic analysis of clinical expertise can offer a meaningful contribution to the refinement of indications for BPH treatments.