Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male pseudohermaphrodites with 5 alpha-reductase deficiency have ambiguous genitalia and nonpalpable prostates on rectal examination, suggesting the dihydrotestosterone dependency of these structures. To clearly delineate the status of the prostate, male pseudohermaphrodites with 5 alpha-reductase deficiency had transrectal sonography of the prostate performed, and the results were compared to that of age-matched male controls. In six male pseudohermaphrodites, magnetic resonance imaging studies of the prostate were also performed. Heterozygote fathers also had transrectal sonography of the prostate performed and the results compared to age-matched controls. The prostates of the male pseudohermaphrodites appeared as platelike soft tissue structures posterior to the urethra on both prostatic ultrasound and magnetic resonance imaging. Prostatic volume, as determined on prostatic ultrasound by two different methods, was significantly smaller (approximately one-tenth) than the volume of age-matched controls. Transurethral ultrasound guided biopsy of the prostate in two affected subjects revealed stromal tissue. These results correlate with undetectable prostate-specific antigen in affected subjects, suggesting atrophic epithelium or lack of epithelial differentiation. This study demonstrates the dihydrotestosterone dependence of the prostate for normal differentiation and growth. The presence of some prostatic tissue in the male pseudohermaphrodites may be due to the fact that there is a decrease and not an absence of 5 alpha-reductase activity, and/or that the increased level of testosterone in subjects with this condition partially compensates for the decreased level of dihydrotestosterone. There was no difference, however, in prostate size between heterozygous fathers and age-matched control males. The heterozygote fathers had dihydrotestosterone production sufficient for normal prostate growth and development.
 ...
PMID:Prostate visualization studies in males homozygous and heterozygous for 5 alpha-reductase deficiency. 140 Aug 66

Whole tissue dihydrotestosterone (DHT) and testosterone (T) concentrations have been measured after finasteride, a 5 alpha-reductase inhibitor, and this was compared to other methods of androgen inhibition. In 10 patients treated for 1 week with finasteride, whole tissue DHT decreased to a mean of 0.302 ng/g. This value was significantly less than DHT values in control patients (mean, 4.5 ng/g) and patients treated with either surgical castration (mean, 1.14 ng/g), megestrol (160 mg/day) plus diethylstilbestrol (0.1 mg), or megestrol plus ketoconazole (1200 mg/day; mean, 0.609). Tissue T levels were significantly increased in finasteride-treated patients (1.18 ng/g) compared to a mean of 0.171 ng/g in controls and 0.105 ng/g in megestrol-treated patients. Part of the prostate tissue obtained at surgery was mechanically separated into epithelium and stroma. The epithelial cells were homogenized, the supernate was assayed for prostate-specific antigen (PSA), an androgen-dependent protein, and the pellet was assayed for DHT and DNA. Epithelial cell PSA and DHT values significantly decreased in finasteride- and megestrol- plus estrogen-treated patients compared to controls. However, the slope and position of the regression lines for DHT vs. PSA in patients treated with megestrol plus low dose estrogen (r = 0.79) differed significantly (P less than 0.05) from the regression line relating epithelial DHT to PSA in patients treated with finasteride (r = 0.82). Since the regression slope for finasteride described a greater increase in PSA per unit change in DHT compared to the slope for megestrol plus estrogen, which lowers both DHT and T, finasteride, despite its drastic lowering of DHT, may have a modest residual androgenic effect related to its effect on tissue T.
 ...
PMID:Effect of finasteride, a 5 alpha-reductase inhibitor on prostate tissue androgens and prostate-specific antigen. 169 65

Luteinizing hormone-releasing hormone (LHRH) agonist, when administered in a continuous, nonpulsatile manner, causes desensitization of the LHRH receptor complex on the gonadotroph cells in the anterior pituitary gland. Biosynthesis and secretion of luteinizing hormone cease, and testicular androgenic production is inhibited. When used in this capacity, LHRH agonists can be an effective treatment for benign prostatic hyperplasia. After 4 to 6 months of therapy, prostatic volume decreases by 25% to 30%, voiding symptoms improve significantly in approximately 25% to 33% of patients, and the peak urinary flow rate increases substantially (more than 15 ml/second) in approximately 25% to 33% of patients. During the first month of treatment, serum luteinizing hormone, follicle-stimulating hormone, testosterone, dihydrotestosterone, 17 beta-estradiol, and prostate-specific antigen decline to low values and remain low throughout treatment. Prostatic 5 alpha-reductase activity and androgen receptor content also decrease with treatment. Side effects are significant: impotence, decreased libido, and hot flushes are the most common. Because the effect of LHRH agonist therapy on the serum testosterone concentration is reversible, treatment of benign prostatic hyperplasia with an LHRH agonist must be considered life-long therapy. Thus, this therapy should be reserved for patients who are impotent or who are poor surgical risks.
 ...
PMID:LHRH agonists. A nonsurgical treatment for benign prostatic hyperplasia. 172 94

In an attempt to maximize the quality of life of advanced prostate cancer patients on prolonged total androgen ablation and to minimize side effects, we have devised a strategy of 'sequential androgen blockade'. Animal studies have demonstrated that the combination of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide was as effective as a luteinizing hormone-releasing hormone analog and flutamide in inhibiting the growth of the prostate. In a pilot trial, 10 potent patients with clinical stage C and D1 prostate cancer were given the combination of finasteride (5 mg b.i.d.) and flutamide (125-250 mg t.i.d.). Eight of ten men remained potent. At 3 months the mean prostate-specific antigen level of all patients was 3.8 ng/ml (34 ng/ml prior to therapy). In all patients serum testosterone increased and those with the highest increase demonstrated gynecomastia. The combination was easily tolerable and side effects were few. This treatment regime appears to offer the benefits of total androgen blockade, is less expensive and has fewer side effects. Further trials are warranted.
 ...
PMID:Treatment of advanced prostate cancer with the combination of finasteride plus flutamide: early results. 750 29

Prostate-specific antigen (PSA) is a kallikrein-like serine protease that, for all practical purposes, is specific for prostatic tissue. PSA is usually detected at low concentrations (0.0-4.0 ng/ml) in the serum and is the most important tumor marker for detecting otherwise unsuspected prostate cancer; it also useful for monitoring the response of prostate cancer to various types of therapy. Androgen deprivation therapy (ADT) includes bilateral orchiectomy, luteinizing hormone-releasing hormone (LHRH) agonists, antiandrogens, and 5-alpha-reductase inhibitors. Treatment of benign prostatic hypertrophy (BPH) or prostate cancer with ADT usually decreases the serum PSA concentration. Recent basic science research has demonstrated that the expression of the PSA gene is controlled by androgens acting via the androgen receptor. Therefore, in some patients a low serum PSA concentration will be the result of hormonal down-regulation of the genetic expression of PSA and not the result of the antitumorigenic activity of the therapy. Nevertheless, in spite of the direct effect of ADT on PSA expression, PSA remains a valuable prostate cancer tumor marker for prognosticating the response to ADT and portending clinical progression after this type of treatment for most patients.
 ...
PMID:Prostate-specific antigen and androgen deprivation therapy. 750 89

The clinical effects of finasteride, a 5 alpha-reductase inhibitor, in patients with benign prostatic hyperplasia (BPH) were evaluated in a double-blind, placebo-controlled study. Forty-six patients with symptomatic BPH were randomly assigned to 2 groups, the finasteride group and the placebo group. The finasteride group received 5 mg of finasteride daily for 6 months. Prostate volume, urinary flow, urinary symptoms, serum prostate-specific antigen (PSA) and adverse events were determined before and after treatment. After 6 months of treatment the patients treated with 5 mg of finasteride per day had a 30% decrease in their total urinary symptom score, a 14% decrease in prostate volume and a 0.9 ng/dL decrease of PSA. Their maximal urinary flow rate increased by 1.42 mL per second and the mean urinary flow rate increased by 0.64 mL per second. The patients given placebo showed no significant changes in their prostate volume, serum PSA and maximal and mean urinary flow rate. However, the symptom scores in the placebo group also decreased significantly. When compared with the placebo group, those in the finasteride group had significantly lower prostate volume, serum PSA, maximal urinary flow rate and urinary symptoms, but not mean urinary flow rate. The frequency of adverse events was low in both the finasteride and placebo groups. These results show that finasteride may be an effective and safe alternative for the treatment of patients with BPH.
 ...
PMID:Therapeutic effects of finasteride in benign prostatic hyperplasia: a randomized double-blind controlled trial. 754 9

The pharmacology and pharmacokinetics of finasteride are reviewed, and finasteride's clinical efficacy, adverse effects, and dosage in patients with benign prostatic hyperplasia (BPH) are described. Finasteride is a member of a new class of medications, the azasteroids, that have antiandrogenic activity limited to certain tissues, including the prostate gland. Finasteride inhibits the activity of 5 alpha-reductase, the enzyme necessary for converting testosterone to dihydrotestosterone in the prostate and other tissues. BPH is androgen dependent, and dihydrotestosterone is necessary for the hyperplasia to occur. Finasteride is well absorbed after oral administration; peak plasma concentration is reached in as little as one hour. Finasteride is approximately 90% bound to plasma proteins, is widely distributed, and is extensively metabolized by the liver. In clinical studies, finasteride has been effective in decreasing prostatic volume, increasing urinary flow rate, and decreasing the obstructive and irritative symptoms of BPH. Because of the heterogeneity of BPH, however, treatment is successful in only one third to one half of patients. Finasteride's adverse effects include decreased libido, ejaculatory disorders, and effects on prostate-specific antigen. The recommended dosage of finasteride is 5 mg/day orally. Therapy should be continued for at least six months before the clinical response is evaluated. Finasteride provides a pharmacologic alternative to surgery in patients with BPH.
 ...
PMID:Finasteride: a 5 alpha-reductase inhibitor. 767 63

The effects of finasteride, a potent 5 alpha-reductase inhibitor, were assessed in 750 patients with benign prostatic hyperplasia (BPH) in a multicenter, double-blind, placebo-controlled study. Patients were randomized to finasteride, 1 or 5 mg, or placebo, daily for 12 months. The following changes were seen with finasteride 5 mg after 12 months: (1) Serum dihydrotestosterone decreased by 62% compared to no change with placebo (P < 0.001); (2) serum prostate-specific antigen (PSA) decreased by 46% compared to no change with placebo (P < 0.001); (3) prostate volume was reduced by 22% compared to a 5% decrease with placebo (P < 0.001); (4) maximum urinary flow rate increased by 1.7 ml/sec compared to a 0.4 ml/sec increase with placebo (P < 0.025); (5) total urinary symptom scores decreased by 3.3 points compared to a 2.0 point decrease with placebo (P = 0.005), and (6) obstructive symptom scores decreased by 2.1 points compared to a 1.4 point decrease with placebo (P = 0.017). The effects of finasteride 1 mg were similar to 5 mg, except in urinary symptoms, where no significant differences between 1 mg and placebo were seen. Patients treated with 5 mg finasteride demonstrated significantly greater improvements in urological status (assessed by the investigator) and the troublesome symptom score, compared to placebo. Treatment with finasteride was well tolerated. We conclude that finasteride is an effective medical therapy for a significant proportion of patients with BPH.
 ...
PMID:Finasteride (MK-906) in the treatment of benign prostatic hyperplasia. The Finasteride Study Group. 768 24

A group of 69 men with bladder outflow obstruction due to benign prostatic hyperplasia (BPH) were treated in a double-blind placebo-controlled study with finasteride (Proscar), a 5 alpha-reductase inhibitor, 5 mg or 10 mg/day, or an identical placebo for 3 months; subsequently, 20 patients received finasteride 5 mg/day in an open extension study. Ten of these patients have now completed 3 years of therapy and have been reevaluated with pressure/flow urodynamics. In finasteride-treated patients dihydrotestosterone (DHT) declined by over 60%, remaining unchanged with placebo. Symptom scores fell in both groups of patients, maximum flow rate values decreased on placebo but improved by a mean of 1.5 ml/s in the 10-mg group and 3.3 ml/s in the 5-mg group. After 1 year of therapy, the reduction in symptom score was well maintained and the flow rate had increased by a mean of 2.7 ml/s; the mean prostate volume was reduced by 14% and prostate-specific antigen (PSA) had declined by 28%. In the 10 patients treated for 3 years who consented to further urodynamic study, the maximum urinary flow rate had improved from a mean baseline value of 8.7 ml/s to a mean of 13.8 ml/s, while maximum subtracted voiding pressure had decreased from a mean baseline value of 72 cm H2O to an unobstructed mean value of 44 cm H2O. Side effects were minimal and reversible on stopping the medication.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Long-term urodynamic effects of finasteride in benign prostatic hyperplasia: a pilot study. 768 71

We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH.
 ...
PMID:Proscar: five-year experience. 857 97


1 2 3 4 5 6 7 Next >>