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PubMed2003

Hormonal and morphologic evaluation of the effects of antiandrogens on the blood supply of the rat prostate.

OBJECTIVES: To clarify the basic aspects of the regulation of the prostatic blood supply by antiandrogens, their effect on the prostatic blood supply was studied for both androgen content and morphology of true capillaries in the rat ventral prostate. The effectiveness of antiandrogens on the control of hemorrhagic status in prostatic diseases has been previously reported. METHODS: Androgen concentrations in the prostate were quantified after administration of chlormadinone acetate (CMA), finasteride, or flutamide. The prostatic blood supplies were measured after administration of CMA, finasteride, flutamide, or bicalutamide. The alpha-blockers, terazosin and tamsulosin, were included in the study as negative controls. The histologic changes in the capillaries of the ventral prostate were observed, and the luminal area was measured. RESULTS: The prostate dihydrotestosterone concentrations were decreased by the administration of all antiandrogens. Treatment with CMA, finasteride, flutamide, or bicalutamide reduced the prostatic blood supply by 50% to 65%. The parallel reduction in luminal areas of the true capillaries was observed in rats treated with CMA. Treatment with alpha-blockers did not affect the prostate androgen content, prostatic blood supply, or capillary luminal area. CONCLUSIONS: The reduction of the prostatic blood supply was suggested to be the result of a decrease in dihydrotestosterone content and the reduction in the luminal area of capillaries. The early reductive effect of antiandrogens on the prostatic blood supply suggests an alternative use for antiandrogens independent of their typical use for prostate volume regression. The results support the basic aspects of the advantage of preoperative treatment with CMA, flutamide, and bicalutamide, similar to finasteride, in reducing perioperative hemorrhage.

5-alpha Reductase Inhibitors↗
PubMed2002

Androgens and alopecia.

Androgens have profound effects on scalp and body hair in humans. Scalp hair grows constitutively in the absence of androgens, while body hair growth is dependent on the action of androgens. Androgenetic alopecia, referred to as male pattern hair loss (MPHL) in men and female pattern hair loss (FPHL) in women, is due to the progressive miniaturization of scalp hair. Observations in both eunuchs, who have low levels of testicular androgens, and males with genetic 5alpha-reductase (5alphaR) deficiency, who have low levels of dihydrotestosterone (DHT), implicate DHT as a key androgen in the pathogenesis of MPHL in men. The development of finasteride, a type 2-selective 5alphaR inhibitor, further advanced our understanding of the role of DHT in the pathophysiology of scalp alopecia. Controlled clinical trials with finasteride demonstrated improvements in scalp hair growth in treated men associated with reductions in scalp DHT content, and a trend towards reversal of scalp hair miniaturization was evident by histopathologic evaluation of scalp biopsies. In contrast to its beneficial effects in men, finasteride did not improve hair growth in postmenopausal women with FPHL. Histopathological evaluation of scalp biopsies confirmed that finasteride treatment produced no benefit on scalp hair in these women. These findings suggest that MPHL and FPHL are distinct clinical entities, with disparate pathophysiologies. Studies that elucidate the molecular mechanisms by which androgens regulate hair growth would provide greater understanding of these differences.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1998

PNU 157706, a novel dual type I and II 5alpha-reductase inhibitor.

PNU 157706 is a novel dual inhibitor of 5alpha-reductase (5alpha-R), the enzyme responsible for the conversion of testosterone (T) to 5alpha-dihydrotestosterone (DHT). Tested on a crude preparation of human or rat prostatic 5alpha-R, PNU 157706 caused enzyme inhibition with IC50 values of 20 and 34 nM, respectively, compared to the values of 32 and 58 nM shown by finasteride. Furthermore, PNU 157706 was highly potent in inhibiting human recombinant 5alpha-R type I and II isozymes, showing IC50 values of 3.9 and 1.8 nM and, therefore, it was several folds more potent than finasteride (IC50 values of 313 and 11.3 nM), particularly on the type I isozyme. PNU 157706 was shown to have no binding affinity for the rat prostate androgen receptor (RBA 0.009% that of DHT). In adult male rats, a single oral dose of 10 mg/kg of PNU 157706 caused a marked and longer lasting reduction of prostatic DHT than did finasteride (at 24 h inhibition by 89 and 47%, respectively). In prepubertal, T- or DHT-implanted castrated rats, PNU 157706, given orally for 7 days at the dose of 10 mg/kg/day, markedly reduced ventral prostate weight in T- but not in DHT-implanted animals, thus showing to be devoid of any anti-androgen activity. In adult rats treated orally for 28 days, PNU 157706 resulted markedly more potent (16-fold) than finasteride in reducing prostate weight, the ED50 values being 0.12 and 1.9 mg/kg/day, respectively. These results indicate that PNU 157706 is a promising, potent inhibitor of both type II and I human 5alpha-R with a very marked antiprostatic effect in the rat.

5-alpha Reductase Inhibitors↗
PubMed2002

A comparison of the relative efficacy of antiandrogens for the treatment of acne in hyperandrogenic women.

OBJECTIVES: To compare the relative effectiveness of two newer antiandrogens (flutamide and finasteride) with cyproterone acetate (CPA), at both low and high doses in the treatment of moderate to severe acne in hyperandrogenic women. SUBJECTS AND DESIGN: Forty-eight hyperandrogenic women were prospectively randomized to the following treatments for 1 year: CPA 2 mg with 35 micro g ethinylestradiol; CPA 50 mg with 25 micro g ethinylestradiol (reverse sequential regimen); flutamide 250 mg daily; and finasteride 5 mg daily. Assessment of Cook scores was the primary end-point of the trial. Blood for androgens was obtained at baseline in these women and 30 ovulatory age-matched controls. RESULTS: Serum androgens were elevated in all 48 women and was similar in each of the four treatment groups. Cook scores were significantly and equally decreased (59-71%) with flutamide and both low and high doses of CPA (P < 0.01). The decrease with finasteride (-36 +/- 2%) was statistically significant but lower than that obtained with the other agents. All treatments were well tolerated. CONCLUSIONS: In hyperandrogenic women with moderate to severe acne, low doses of certain antiandrogens appear to be effective. Low and high doses of CPA with ethinylestradiol were equally effective and were comparable to the effects of a low dose of flutamide. Finasteride was less beneficial.

Acne Vulgaris↗
PubMed2003

Effects of androgen deprivation on chronic bacterial prostatitis in a rat model.

BACKGROUND: Many attempts have been made to improve the treatment success rate of chronic bacterial prostatitis (CBP). However, no treatment modality has achieved complete cure. The growth and development of the prostate is under direct hormonal control, and it is possible that prostatitis may be directly influenced by its hormonal milieu in a similar fashion to benign prostatic hyperplasia and prostate cancer. Therefore, the effects of androgen deprivation on the treatment of CBP were investigated in rats. METHODS: Experimental CBP was induced in one hundred, male Wistar rats by instillation of bacterial suspension (Escherichia coli Z17, O2: K1: H-) containing 1 x 10(8) CFU/ microL into the prostatic urethra. Microbiologically and histologically proven CBP was demonstrated in 62% (62 of 100) of the rats after 4 weeks of bacterial instillation. The 62 rats demonstrating CBP were randomly divided into five groups: control; castration; finasteride; estrogen; and levofloxacin groups. All drug treatments were conducted over a period of 4 weeks. RESULTS: Microbiological cultures and histological findings of the prostate and urine samples demonstrated reduced bacterial growth and improved inflammatory responses in all four experimental groups compared with the control group. The castration and estrogen groups showed coherent trends of decrease in bacterial growth and improvements in prostatic inflammation compared with the control group, but not to a statistically significant degree (P > 0.05). However, the finasteride and levofloxacin groups did show statistically significant decreases in bacterial growth and improvements in prostatic inflammation compared with the control group (P < 0.05). CONCLUSION: These results suggest that androgen deprivation is an effective modality in CBP treatment. In particular, the finasteride treatment reduced the severity of CBP in the animal model without reducing the systemic testosterone level. The combination of finasteride and levofloxacin maybe one of the effective treatment modalities for CBP.

Androgen Antagonists↗
PubMed2005

A cost comparison of medical management and transurethral needle ablation for treatment of benign prostatic hyperplasia during a 5-year period.

PURPOSE: We performed an analysis comparing the cost of medical management with TUNA therapy for a 5-year period. MATERIALS AND METHODS: Published costs for tamsulosin, finasteride, transurethral needle ablation (TUNA, Medtronic, Inc., Minneapolis, Minnesota) and transurethral resection of the prostate were used to construct a cost analysis model comparing medication with TUNA. The model analyzed monotherapy with an alpha-blocker (tamsulosin) and a 5alpha-reductase inhibitor (finasteride), combination therapy using both medications, and a mixed scenario using monotherapy and combination therapy. Published data were used to estimate the rate of surgical intervention in patients initially treated with medications or TUNA. RESULTS: Tamsulosin monotherapy was less expensive than TUNA for 5 years ($3,485 for tamsulosin vs $4,811 for TUNA year 5). Finasteride monotherapy reaches a break-even point with TUNA during year 5 ($4,867 for finasteride vs $4,811 for TUNA). Combination therapy reaches a break-even point with TUNA after approximately 2 years 7 months of treatment ($4,515 for combination therapy vs $4,572 for TUNA) and the mixed scenario breaks even with TUNA at approximately year 4 ($4,696 for medical management vs $4,645 for TUNA). CONCLUSIONS: The TUNA procedure compares favorably to combination medical therapy for the treatment of benign prostatic hyperplasia on a cost basis. alpha-Blocker monotherapy is less costly than TUNA while 5alpha-reductase inhibitor monotherapy is approximately equivalent to TUNA for 5 years. The TUNA procedure is less expensive than combination medical management for 5 years, with a break-even point at approximately 2 years 7 months.

Aged↗
PubMedDate not supplied

Erectile dysfunction following treatments of benign prostatic hyperplasia: a prospective study.

The effects of open prostatectomy, transurethral resection, transurethral vaporization, doxazosin and finasteride on sexual functions of men were investigated in a total of 305 patients with benign prostatic hyperplasia. The sexual functions of the patients were assessed with a questionnaire before treatment and 3 and 6 months after the treatment. A total of 212 (70%) patients were judged to be potent before the treatment. At 3 months, open prostatectomy and transurethral resection caused erectile dysfunction in 2 of 40 (5%) and 5 of 89 (6%) potent patients, respectively. At 6 months, one of the patients from the former and 2 of the patients from the latter groups who developed erectile dysfunction at 3 months stated improvement. Transurethral vaporization caused loss of erectile functions in 4 of 14 potent patients (29%) at the 3-month follow-up and, one of these patients recovered erectile functions at 6 months. Only one of the 33 patients (3%) using doxazosin stated that he lost his erectile functions both at 3 months and 6 months. At 3 months follow-up, finasteride caused loss of erectile functions in 8 of 36 potent patients (22%). Four of these patients underwent surgery (transurethral resection) after 3 months of finasteride use. At the 6-month follow-up, 4 more patients suffered from loss of erectile functions. We suggest that finasteride and transurethral vaporization have the greatest potential of impairing the sexual functions among the treatment options investigated in this study and that they must be carefully offered to the potent patients.

Adrenergic alpha-Antagonists↗
PubMed1999

Prostate Cancer Prevention Trial (PCPT) update.

The Prostate Cancer Prevention Trial is an intergroup effort in the USA managed by the Southwest Oncology Group (SWOG) in collaboration with the Eastern Cooperative Oncology Group (ECOG) and the Cancer and Leukemia Group B (CALGB). This 10-year study began approximately 5 years ago and will achieve its primary endpoint in October 2004. At the start of the study, 18,882 men, aged over 55 years, and with normal digital rectal examination (DRE) and serum prostate-specific antigen (PSA) levels of </=3.0 ng/ml were randomized to take finasteride (5 mg/day) or placebo (1 tablet/day). DRE and PSA have been determined yearly (PSA in a central laboratory). When DRE is abnormal or PSA rises to >4.0 ng/ml, a biopsy is recommended. Because of the effect finasteride has on PSA, the PSA value has been indexed to equalize the number of biopsies in both arms. At 7 years all survivors will undergo a sextant biopsy to determine the period prevalence of prostate cancer. The critical assumptions are: (1) finasteride-induced PSA changes result in a simple downward shift; (2) the assessment of adherence is sensitive enough to detect nonadherence affecting PSA level interpretation: (3) factors affecting biopsy loss will be equal in both arms; (4) finasteride does not affect the sensitivity or specificity of DRE on transrectal ultrasound nor the sensitivity of biopsy; (5) bias resulting from transurethral resection of the prostate in benign prostate hyperplasia cases will be negligible.

Aged↗
PubMed1997

Treatment of benign prostatic hyperplasia. A pharmacoeconomic perspective.

Men with moderate symptoms of benign prostatic hyperplasia (BPH) are the best candidates for medical treatment, while surgery is usually indicated for patients with severe symptoms. Men with mild symptoms do not usually need treatment, but they might be re-evaluated annually if desirable. Finasteride, which produces selective hormonal deprivation, is now established as a well tolerated drug for the long term medical therapy of BPH. Recent studies suggest that finasteride is most effective in men with large prostates (> 40 ml), and the drug should probably be reserved for these patients. alpha-Blockers work in men with small or large prostates, and their rapid onset of action facilitates the identification of responders. alpha-Blockers are more effective than finasteride during the first year of treatment, but only finasteride induces regression of the prostate and offers increased efficacy over time. Even if drug therapy reduces the need for prostate surgery, the total economic cost of BPH treatment is likely to rise because of the increasing application of medical treatment. The magnitude of this increase depends largely on what percentage of the male population embark on long term therapy, at what age treatment is started, and how successful it is. At present, the answers to these questions are largely unknown. The personal economic expenses for men who begin long term medical therapy will probably be an important factor in deciding how common drug treatment for BPH will become in the future. For many men, the main benefit of drug treatment will be the relief of urinary symptoms, but whether this improvement is substantial enough to improve their overall quality of life has not yet been clearly demonstrated in controlled studies.

Adrenergic alpha-Antagonists↗
PubMed2001

Inhibition of 5alpha-reductase in rat prostate reveals differential regulation of androgen-response gene expression by testosterone and dihydrotestosterone.

The growth and development of some of the male sex accessory organs such as the prostate requires the conversion of testosterone to dihydrotestosterone (DHT) by 5alpha-reductase. To provide insights into the role of testosterone versus DHT in the prostate, we studied the impact of finasteride, a potent and specific inhibitor of 5alpha-reductase, on the expression of prostatic androgen-response genes in testis-intact rats and in 7-day castrated rats. Finasteride inhibition of the conversion of testosterone to DHT was confirmed by measuring serum and intraprostatic androgens. As expected, finasteride treatment caused a reduction in the wet weight of the prostate in the testis-intact rats and inhibited the testosterone-stimulated prostatic regrowth in the 7-day castrated rats. Although finasteride treatment had little or no effect on the expression of the surveyed androgen-response genes in testis-intact rats, its administration enhanced the expression of many androgen-response genes during the testosterone-stimulated regrowth of the regressed prostate in castrated rats. These observations suggest that testosterone is more potent than DHT in stimulating the expression of many androgen-response genes in the regressed prostate. The expression of androgen-response genes is mainly prostate specific and thus is likely to be associated with androgen-dependent prostatic differentiation. Therefore, testosterone is more potent than DHT in inducing differentiation and weaker in stimulating proliferation during prostate regrowth. The fact that testosterone is a strong inducer of prostatic differentiation has potential clinical implications.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1995

[Effects of androgen regulation system on bladder carcinogenesis in male mice].

PURPOSE: In several previous reports, it has been suggested that the androgen system is related to bladder carcinogenesis. In this study, to understand the mechanism underlying this relationship, we administered a LH-RH agonist depot (Leuprolide depot), a pure-antiandrogen (flutamide) or a 5 alpha-reductase inhibitor (finasteride) to the mice in the promotion state of bladder carcinogenesis by N-butul-N-(4-hydroxybutyl) nitrosamine (BBN). MATERIALS AND METHODS: 177 C3H/He male mice were divided into 7 groups. All mice were treated with 0.05% BBN for 10 weeks and were maintained over the subsequent 12 weeks with the following treatments. Group 1 was a control group; in group 2, castration was performed at the 11th week; in group 3, finasteride was administered starting the 11th week; in group 4, a LH-RH agonist depot was administered starting the 11th week; in group 5, flutamide was administered starting the 11th week; in group 6, both finasteride and a LH-RH agonist depot were administered simultaneously starting the 11th week; and in group 7, both flutamide and a LH-RH agonist depot were administered simultaneously starting the 11th week. RESULTS AND CONCLUSIONS: (1) We confirmed that castration significantly suppressed bladder carcinogenesis. (2) Finasteride or flutamide administration as monotherapy had no effect on the results; however, the dosages of these drugs may have been too low, so we are planning a study with higher doses. (3) Conversely, the LH-RH agonist depot significantly promoted bladder carcinogenesis, we believe that the high levels of testosterone immediately after the administration were responsible for this promotion. (4) Simultaneous administration of flutamide suppressed this LH-RH induced promotion of carcinogenesis.

5-alpha Reductase Inhibitors↗
PubMedDate not supplied

Androgen responsive genes as they affect hair growth.

Finasteride has been shown to be an effective treatment for men with androgenetic alopecia (AGA) as it restores hair growth to miniaturized hair follicles on the top of the scalp [1]. Caspases are regulators of programmed cell death, and very likely some specific caspases may function as mediators of the hair growth cycle. It is unclear whether finasteride influences the regulation of apoptosis via caspases in the hair follicle. Very little information is available regarding the role of caspases present in human hair follicles in normal scalp and in androgenetic alopecia. In this study we have analyzed the family of caspases, 1-10 along with usurpin, and XIAP, in men with normal scalp and in men with androgenetic alopecia before and after 6 months treatment with 1 mg oral finasteride treatment. Caspases 1, 3, 8 and 9 were detected predominantly within the isthmic and infundibular hair follicle area for both normal and AGA patients, however the expression of all factors, especially caspase 3 was greater in the AGA group than in the normal scalp group. AGA men had the same caspase factors but with greater expression. In the same AGA men treated with finasteride for 6 months, the expression of these factors was similar to levels in the normal group. Results from our study indicate caspase 3 to be of primary importance in normal hair homeostasis and that DHT may be signaling greater expression of caspases, inducing apoptosis in androgenetic alopecia. In conclusion, DHT may selectively regulate the caspase genes which play an important role in signaling programmed cell death, affecting the hair growth cycle.

5-alpha Reductase Inhibitors↗
PubMed1996

The American Urological Association symptom score in the evaluation of men with lower urinary tract symptoms: at 2 years of followup, does it work?

PURPOSE: The American Urological Association (AUA) benign prostatic hyperplasia (BPH) guidelines committee established criteria for the diagnosis and treatment of patients with BPH. In a prospective study we determined the usefulness of these guidelines in 145 previously untreated patients with BPH symptoms. MATERIALS AND METHODS: Patients were evaluated initially by AUA symptom score, digital rectal examination, urinalysis, serum creatinine and prostate specific antigen. Based on symptom score, patients with mild symptoms were treated with watchful waiting, while those with moderate and severe symptoms were offered watchful waiting, finasteride alpha-blockers, or laser or transurethral prostatectomy. Minimum followup was 2 years. Patients were offered a change in therapy if they had an intolerable adverse event or no improvement. Analysis included maintenance of therapy at 1 and 2 years, number of office visits and diagnostic tests performed. In addition, all patients were queried regarding which factors influenced their therapeutic choice. RESULTS: Of 37 patients with mild symptoms 31 (81%) remained on watchful waiting at 2 years and 6 advanced to medical therapy. Among 71 patients with moderate symptoms 9 of 15 (60%) remained on watchful waiting, 27 of 36 (75%) remained on alpha-blockers and 12 of 20 (60%) remained on finasteride at 2 years. Of the 37 patients with severe symptoms 1 of 5 (20%) remained on watchful waiting, 1 of 6 (17%) remained on finasteride and 9 of 15 (60%) remained on alpha-blockers, while 3 of 5 (60%) who underwent laser prostatectomy and all 6 (100%) who underwent transurethral prostatectomy received no further treatment. At 2 years 83% of the men who selected either finasteride or alpha-blockers as either the primary or secondary therapeutic choice were still on medications. Most patients with mild (61%) or moderate (51%) symptoms cited adverse events as the predominant concern when selecting therapeutic options. In contrast, efficacy was the overriding concern (70%) in patients with more severe symptoms. CONCLUSIONS: Overall, with these guidelines and the AUA symptom score 110 men (76%) were still on original therapy at 1 year and 99 (68%) at 2 years. Additionally, 31 patients (21%) changed to an alternative, nonoperative therapy. These results suggest that the AUA BPH guidelines provide a rational and balanced approach for evaluation and management of patients with symptomatic BPH. Patients can reasonably expect to remain on the initial therapeutic option for at least 2 years.

Adrenergic alpha-Antagonists↗
PubMed1996

[The effect of 5-alpha-reductase inhibitors on benign prostatic hyperplasia].

The prevalence of BPH is high in elderly men with more than 60% of patients over the age of 60 experiencing some form of prostatism. Balancing the superior benefit of TUR/P are the small but significant risks and complications of surgery and the high cost of the procedure. The WHO guidelines recommend finasteride or alpha-blockers as treatment options for men with bothersome symptoms. Finasteride therapy reduces the volume of the hyperplastic prostate gland by more than 20%, improves the urinary flow rate and the symptoms associated with bladder outlet obstruction. Although statistically significant, results obtained with finasteride are just slightly better than placebo and TUR/P still offers the greatest improvement of symptoms. Finasteride is well tolerated and adverse events are rare. However, it decreases serum PSA (prostate specific antigen) by 50%, suggesting careful monitoring and exclusion of prostate cancer before initiation and during therapy. Current research is focusing on developing new 5-alpha-reductase inhibitors (type I and II) using polyunsaturated fatty acids and nonsteroidal inhibitors. Given the multifactorial nature of BPH, further clinical trials combining 5-alpha-reductors inhibitors and 5-alpha-receptor blockers are still needed.

5-alpha Reductase Inhibitors↗
PubMed1998

[Histomorphometry study of the effect of an inhibitor of 5-alpha reductase on the coating of human prostate explants in tissue culture].

Histomorphometric study of hyperplastic human prostate explants coating grown "in vitro" to evaluate the response to a 5-alpha-reductase inhibitor (finasteride). Explants were grown for four weeks in three groups, one in growth medium alone (RPM1-1640), one supplemented with testosterone and one supplemented with testosterone plus finasteride. Explants underwent histological studies, quantifying the surface and thickness of the coating epithelium. Study of the values obtained from the different samples show significant differences (p < 0.001) for the coated surface and its thickness between groups supplemented with testosterone and testosterone + finasteride, and so it can be inferred that this compound (finasteride) would blockade basal cells proliferation and their migration on the explant surface.

5-alpha Reductase Inhibitors↗
PubMed2006

The efficacy of drugs for the treatment of LUTS/BPH, a study in 6 European countries.

OBJECTIVES: This paper profiles the usage and effectiveness of various LUTS/BPH drugs in real-life practice. METHOD: The TRIUMPH study recorded the treatment and outcomes of 2351 newly-presenting LUTS/BPH patients in 6 European countries over a 1-year follow-up period. At each visit the clinician recorded the treatment, co-morbidities, complications and drugs prescribed, and the patient completed an IPSS questionnaire. The results were analysed using change in IPSS as the primary outcome measure. RESULTS: Over the study period 74.9% of patients were prescribed medication, the majority (83% of those medicated) were prescribed only a single drug. Tamsulosin was the most commonly prescribed drug in all countries (38% of medicated cases), although with national variation from 24% in Poland to 70% in Italy. The alpha-blockers were the most effective, with a mean reduction of 6.3 IPSS points. Finasteride was slightly less effective (4.1 points). Significant improvements were seen in 43% of patients on phytotherapy with Serenoa repens or Pygeum africanum compared to 57% of those on finasteride and 68% on alpha-blockers. The only combination therapy found to produce a statistically significant improvement over the use of individual drugs was finasteride+tamsulosin (8.1 points compared to 6.7 for tamsulosin alone and 4.2 for finasteride alone). CONCLUSIONS: All drug treatments showed some improvement over watchful-waiting for most patients over the study period: the alpha-blockers were found to be the most effective. There were marked national differences in prescribing patterns, both in individual drug choice and in the use of combination therapies.

Europe↗
PubMed1998

Long-term implications of medical therapy on benign prostatic hyperplasia end points.

There is a progression over time of relevant measurable benign prostatic hyperplasia (BPH) end points including symptoms, flow rates, prostate size, complications such as acute urinary retention (AUR), and surgical rates. Only two classes of medical therapy, the alpha-blockers and a 5-alpha-reductase inhibitor, have shown unequivocal and consistent efficacy over placebo in 1-year studies. Both of these classes of medications have demonstrated relative long-term safety. Finasteride has been shown in three large, 2-year, randomized, controlled studies to be superior to placebo, and both finasteride and the alpha-blockers have demonstrated long-term efficacy and safety in open-label studies. The efficacy of finasteride is significantly enhanced when it is used in patients with large prostates. Long-term finasteride therapy also results in a significant reduction in the incidence of AUR and the need for surgery. Long-term medical therapy for BPH is effective and safe. Data are now available that allow clinicians to analyze the long-term risks and benefits of the various medical options and subsequently rationalize long-term therapy for individual patients.

Acute Disease↗
PubMed2001

Structure-function studies of human 5-alpha reductase type 2 using site directed mutagenesis.

Site directed mutagenesis of human steroid 5alpha-reductase types 1 (5AR1) and 2 (5AR2) has been used to identify residues involved in inhibitor/substrate binding by 5AR2. Replacing residues 21-24 (GALA) in 5AR2 with the analogous residues 26-29 (AVFA) from 5AR1 did not significantly alter either the Km for testosterone or the Ki for the competitive inhibitor Finasteride. Replacement of AVFA in 5AR1 with GALA from 5AR2 however, significantly decreased the Km and increased the resistance to Finasteride. These findings confirm that 5AR1 residues 26-29 are involved in inhibitor/substrate binding but suggest residues 21-24 of 5AR2 are not. Replacing residues 20-29 (QCAVGCAVFA) of 5AR1 with the analogous residues 15-24 (ATLVALGALA) from 5AR2, changed the Km and Ki to values approaching those for wild type 5AR2. Replacing residues VAL in wild type 5AR2 with VGC from 5AR1 did not change Km or Ki but replacing ATL in 5AR2 with QCA from 5AR1 significantly decreased the Km and increased the resistance to Finasteride. Conversely, replacing QCA with ATL in 5AR1 containing GALA in place of AVFA, increased the Km and decreased resistance to Finasteride. These findings indicate residues 15-17 of human 5AR2 participate in inhibitor/substrate binding whereas residues 18-20 do not.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗