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Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease.
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The results of our study showed a strong correlation between the organ DHT concentration and blood flow in rat seminal vesicles. Of the various androgens, the most active androgen in the regulation of seminal vesicle blood flow was DHT.
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This study aimed to radiolabel finasteride, a novel 5α-reductase inhibitor, to evaluate its cancer targeting potential in experimental model of prostate carcinogenesis. Finasteride was effectively radiolabeled with (99m)Tc and showed >90% labeling efficiency. The radiopharmaceutical was found to be stable up to 6 hours in rat serum at 37°C. The blood kinetics of the (99m)Tc-finasteride followed a biphasic release pattern, whereby fast-release phase was observed at 15 seconds and a slow-release phase was observed after 30 minutes of administration. The plasma protein binding of the radio complex observed was 83.89%. For biodistribution studies, the rats were divided into two groups. Group I served as normal controls, while group II was subjected to carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (T) for induction of prostate carcinogenesis, which was confirmed histopathologically. The biodistribution studies on control and carcinogen-treated rats revealed a significant percent-specific uptake in prostate, which was found to be increased significantly as a function of time. The most significant finding of the study was an increase in the percent-specific uptake in prostate of carcinogen-treated animals when compared to the percent-specific uptake in prostate of normal rats after 2 and 4 hours postinjection. The study concludes that (99m)Tc-finasteride possesses selectively toward prostate cancer tissue and can be explored further for its role in detection of prostate cancer.
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Topiramate alone or combined with 17β-estradiol produced antidepressant-like actions; and 17β-estradiol shortened the onset of the antidepressant-like effects of topiramate.
The balance between glutamate- and GABA-mediated neurotransmission in the brain is fundamental in the nervous system, but it is regulated by the "tonic" release of a variety of endogenous factors. One such important group of molecules are the neurosteroids (NSs) which, similarly to benzodiazepines (BDZs), enhance GABAergic neurotransmission. The purpose of our work was to investigate, at in vivo physiologically relevant concentrations, the effects of NSs and BDZs as GABA modulators on dissociated neocortical neuron networks grown in long-term culture. We used a multi-electrode array (MEA) recording technique and a novel analysis that was able to both identify the action potentials of engaged excitatory and inhibitory neurons and to detect drug-induced network up-states (burst). We found that the NSs tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) applied at low nanomolar concentrations, produced different modulatory effects on the two neuronal clusters. Conversely, at high concentrations (1 μM), both NSs, decreased excitatory and inhibitory neuron cluster excitability; however, even several hours after wash-out, the excitability of inhibitory neurons continued to be depressed, leading to a network long-term depression (LTD). The BDZs clonazepam (CLZ) and midazolam (MDZ) also decreased the network excitability, but only MDZ caused LTD of inhibitory neuron cluster. To investigate the origin of the LTD after MDZ application, we tested finasteride (FIN), an inhibitor of endogenous NSs synthesis. FIN did not prevent the LTD induced by MDZ, but surprisingly induced it after application of CLZ. The significance and possible mechanisms underlying these LTD effects of NSs and BDZs are discussed. Taken together, our results not only demonstrate that ex vivo networks show a sensitivity to NSs and BDZs comparable to that expressed in vivo, but also provide a new global in vitro description that can help in understanding their activity in more complex systems.
Finasteride, 5 mg once daily, was given for 12 months.
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The aim of this study was to determine the relationship between body mass index, biochemical parameters, and 5-hydroxytryptamine (5-HT) genetic polymorphisms and prostate dysfunction in an elderly general male population.
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In the Prostate Cancer Prevention Trial (PCPT), men receiving finasteride had a 24.8% lower risk of prostate cancer than men receiving placebo but a higher risk of high-grade cancer. We examined the impact of finasteride on the sensitivity and area under the receiver operating characteristic curve (AUC) of prostate-specific antigen (PSA) for detecting prostate cancer.
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To review the available data on contemporary management of symptomatic benign prostatic hyperplasia (BPH) within the German healthcare system.
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Low posttreatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer.
Hormones and androgens play an important role in the pathogenesis of acne. Multiple hormonal modulators are now available for the treatment of acne. The efficacies and side effects of currently available hormonal agents are reviewed here including the use of oral contraceptives, spironolactone, flutamide, cyproterone acetate, finasteride, and cortexolone 17α-propionate. Hormonal therapies are an efficacious treatment option for acne among females. With the growing need to reduce antibiotic exposures, hormonal therapies should be more widely studied and incorporated into acne treatment strategies.
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Finasteride at 1 mg/day and 5% topical minoxidil are effective in male androgenetic alopecia (MAGA). However, studies describing their effects in Chinese individuals are scarce. 450 Chinese MAGA patients were randomly assigned to receive finasteride (n = 160), minoxidil (n = 130) and combined medication (n = 160) for 12 months. The patients returned to the clinic every 3 months for efficacy evaluation. And efficacy was evaluated in 428 men at treatment end, including 154, 122, and 152 in the finasteride, 5% minoxidil, and combination groups, respectively. All groups showed similar baseline characteristics, including age at enrollment, and duration and severity of alopecia (p > 0.05). At 12 months, 80.5, 59, and 94.1% men treated with finasteride, 5% minoxidil and the combination therapy showed improvement, respectively. Adverse reactions were rare (finasteride, 1.8%; minoxidil, 6.1%), and disappeared right after drug withdrawal. In conclusion, finasteride is superior to 5% minoxidil, while the combined medication showed the best efficacy.
Improvement of investigative methods and especially the Dynamic Multifactorial Classification makes it easier for a patient to follow the results of treatment adapted to their case.
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The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of gamma-aminobutyric acidA (GABAA) receptors that can modulate ethanol (EtOH) withdrawal. The 5alpha-reductase inhibitor finasteride blocks the formation of ALLO from progesterone and was recently found to reduce certain effects of EtOH. Using the Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) selected lines, in the present studies we examined the effect of finasteride on acute and chronic EtOH withdrawal severity.
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About one-quarter of men aged 50 years and older experience voiding problems due to benign prostatic hyperplasia (BPH). Until about 10 years ago, surgery (particularly transurethral resection of the prostate) was the only effective treatment for symptomatic BPH. Over the last decade, several new treatments have been introduced. These include different types of medication (alpha-blockers and finasteride), thermotherapy, laser prostatectomy, needle ablation and vaporisation methods. The diffusion of these less invasive treatment modalities has resulted not only in a decrease in the age-adjusted surgery rates, but also in an increase of the total number of men treated for BPH. A large number of studies on clinical benefits and risks reveal that the conventional types of surgery remain the most effective treatments, whereas new interventional therapies require a shorter hospital stay and result in fewer short term complications. The efficacy of medication is lower than that of interventional treatments. Adverse effects include dizziness and orthostatic hypotension (alpha-blockers) and decreased sexual function (finasteride), but are generally mild. There is some evidence that medication and minimally invasive treatments may preclude eventual surgical treatment, but the precise effect is difficult to estimate because of differences in the study populations and the relatively short study periods. As a result of the dynamic nature of BPH treatment and the lack of long term data, the cost effects of the introduction of the various new treatments are also difficult to assess. Given the aging of the population and the growing percentage of patients with BPH for whom any type of treatment can be considered, a considerable increase of total costs can be expected. Long term prospective studies are necessary to gain insight into the most cost-effective treatment for different patient groups.
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Since July 2007 to June 2009, a total of 790 patients with BPH were prospectively collected in this study, including 390 outpatients with pharmaceuticals who were randomly classified into 3 groups of finasteride, tamsulosin and combined therapy, 140 inpatients with transurethral 2 micron laser resection of the prostate and 260 inpatients with TURP. The costs and effectiveness of each group were compared.
These guidelines are intended to provide a framework for health professionals involved in BPH management in order to facilitate decision-making in all areas and at all levels of healthcare.
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Based on these behavioral and pharmacological findings, we suggest that THP withdrawal in the mouse may serve as a rodent model of PMDD.
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In the light of post-marketing reports of persistent sexual dysfunction with the use of finasteride, analysis of the extent of risk associated with 5α-reductase inhibitor treatment for androgenetic alopecia (AGA) is warranted. This study sought to evaluate the efficacy of 5α-reductase inhibitors using the outcomes hair count, global photographic assessment and patient self-assessment and evaluate the benefits of treatment versus the risk of global sexual dysfunction.
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Benign prostatic hyperplasia (BPH) can impact significantly on a patient's quality of life (QOL), including sexual functioning. With increased life expectancy, this aspect of the disease is becoming increasingly important. Symptom severity can be measured using a number of instruments, the most common one being the International Prostate Symptom Score (IPSS). A number of studies have shown that symptom severity is correlated with decreased QOL, i.e. the more severe the symptoms, the greater the impact on QOL. Specific questionnaires have been developed to address the issue of sexual function, including the Brief Sexual Function Inventory and the International Index of Erectile Function. Importantly, these instruments can usefully be applied to assess the effect of the various therapies for BPH on sexual function. In general, the alpha(1)-blockers have minimal impact on sexual function, compared with finasteride, which can affect libido, ejaculation and erectile function itself.
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The Delta(4)-3-ketosteroid functionality is present in nearly all steroid hormones apart from estrogens. The first step in functionalization of the A-ring is mediated in humans by steroid 5alpha- or 5beta-reductase. Finasteride is a mechanism-based inactivator of 5alpha-reductase type 2 with subnanomolar affinity and is widely used as a therapeutic for the treatment of benign prostatic hyperplasia. It is also used for androgen deprivation in hormone-dependent prostate carcinoma, and it has been examined as a chemopreventive agent in prostate cancer. The effect of finasteride on steroid 5beta-reductase (AKR1D1) has not been previously reported. We show that finasteride competitively inhibits AKR1D1 with low micromolar affinity but does not act as a mechanism-based inactivator. The structure of the AKR1D1.NADP(+)*finasteride complex determined at 1.7 A resolution shows that it is not possible for NADPH to reduce the Delta(1-2)-ene of finasteride because the cofactor and steroid are not proximal to each other. The C3-ketone of finasteride accepts hydrogen bonds from the catalytic residues Tyr-58 and Glu-120 in the active site of AKR1D1, providing an explanation for the competitive inhibition observed. This is the first reported structure of finasteride bound to an enzyme involved in steroid hormone metabolism.
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After culturing DuCaP cells 20 passages with additional 1 nM R1881, DuCaP-N(aive) cell line was developed and validated for testing endocrine therapy combinations. Cell viability, apoptosis and cell cycle distribution were assessed in DuCaP and DuCaP-N when interfering with the hormonal content.
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In a large cohort of men ages 66 years or older, we did not demonstrate an increased risk of suicide associated with 5α-reductase inhibitor use. However, the risk of self-harm and depression were increased compared with unexposed men. This is in keeping with postmarketing experience and patient concerns, and discontinuation of the medication in these circ umstances may be appropriate.
Medical therapy for the treatment of benign prostatic hyperplasia (BPH) became an accepted standard of care in the 1990s following the reports of randomized, double-blind, placebo-controlled studies showing that finasteride, a 5-α reductase inhibitor, and terazosin, an α-blocker, significantly improved lower urinary tract symptoms and increased peak urinary flow rates in men with BPH. This article reviews novel approaches to the pharmacological treatment of BPH.
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Androgenetic alopecia is by far the most common cause of hair loss. It affects approximately 50% of men by the age of 50 and 20 to 53% of women by the age 50. Although it is a medically benign condition, it is a significant psychosocial issue for many patients. Various different treatment options are now available for androgenetic alopecia. The best treatment option for women with androgenetic alopecia Ludwig stage I and II is minoxidil 5% solution. If it is not effective after 1 year, antiandrogens can be tried, but there are no large studies showing their efficacy and they have considerable adverse effects. Also, for patients with alopecia that is unresponsive to treatment or with Ludwig stage III, hair transplantation can be offered if the occipital donor area is sufficient. For men, we always offer minoxidil or finasteride therapy and leave the choice of therapy to the patient. Some patients may prefer a systemic agent, whereas others may favor a topical agent. If the condition is not stabilized after 1 year or if the patient wants greater hair density, hair transplantation can be discussed. There have been tremendous advances in the treatment of hair loss in recent years and the future is very encouraging. As our knowledge of androgenetic alopecia pathophysiology increases, novel targeted treatments will potentially be developed.
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At week 24, hair counts were increased from baseline in both groups. However paired t-test revealed statistical difference only in MFX group (p = 0.044). Unpaired t-test revealed no statistical difference between two groups with respect to change of hair counts at 24 weeks from baseline (p = 0.503). MFX showed significantly higher efficacy than MNX by global photographic assessment (p = 0.003). There was no significant difference in side effects between both groups.