Superiority of dutasteride over fifi nasteride in hair regrowth and reversal of miniaturization in men with androgenetic alopecia: A randomized controlled open-label, evaluator-blinded study.

Background: Finasteride and dutasteride are inhibitors of the enzyme 5-alpha-reductase which inhibits the conversion of testosterone to dihydrotestosterone. Dutasteride inhibits both type I and type II 5-alpha-reductase while fi nasteride inhibits only the type II enzyme. As both isoenzymes are present in hair follicles, it is likely that dutasteride is more effective than fi nasteride. Aims: To compare the effi cacy, safety and tolerability of dutasteride and fi nasteride in men with androgenetic alopecia. Methods: Men with androgenetic alopecia between 18 and 40 years of age were randomized to receive 0.5 mg dutasteride or 1 mg fi nasteride daily for 24 weeks. The primary effi cacy variables were hair counts (thick and thin) in the target area from modifi ed phototrichograms and global photography evaluation by blinded and non-blinded investigators. The secondary effi cacy variable was subjective assessment using a preset questionnaire. Patients were assessed monthly for side effects. Results: Ninety men with androgenetic alopecia were recruited. The increase in total hair count per cm2 representing new growth was signifi cantly higher in dutasteride group (baseline- 223 hair; at 24 weeks- 246 hair) compared to fi nasteride group (baseline- 227 hair; at 24 weeks- 231 hair). The decrease in thin hair count per cm2 suggestive of reversal of miniaturization was signifi cantly higher in dutasteride group (baseline- 65 hair; at 24 weeks- 57 hair) compared to fi nasteride group (baseline- 67 hair; at 24 weeks- 66 hair). Both the groups showed a similar side effect profi le with sexual dysfunction being the most common and reversible side effect. Limitations: Limitations include the short duration of the study (6 months), the small sample size and the fact that it was an open-label study. Conclusions: Dutasteride was shown to be more effi cacious than fi nasteride and the side-effect profi les were comparable.

Long-term Combination Therapy With α-Blockers and 5α-Reductase Inhibitors in Benign Prostatic Hyperplasia: Patient Adherence and Causes of Withdrawal From Medication / 대한배뇨장애요실금학회지

PURPOSE: To investigate long-term therapeutic effects and patient adherence to a combination therapy of a 5α-reductase inhibitor and an α-blocker and to identify causes of withdrawal from medication in patients with clinical benign prostatic hyperplasia (BPH). METHODS: BPH patients with lower urinary tract symptoms (LUTS) receiving combination therapy with follow-ups for 1–12 years were retrospectively analyzed. Therapeutic effects were assessed at baseline and annually by measuring International Prostatic Symptoms Score, quality of life index, total prostate volume (TPV), maximal flow rate, voided volume, postvoid residual volume and prostate-specific antigen level. Causes of discontinued combination therapy were also investigated. RESULTS: A total of 625 patients, aged 40–97 years (mean, 73 years) were retrospectively analyzed. All measured parameters showed significant improvements after combination therapy. Three hundred sixty-nine patients (59%) discontinued combination therapy with a mean treatment duration of 2.2 years. The most common reasons for discontinued treatment were changing medication to monotherapy with α-blockers or antimuscarinics (124 patients, 19.8%), receiving surgical intervention (39 patients, 6.2%), and LUTS improvement (53 patients, 8.5%). Only 64 patients (10.2%) were loss to follow-up and 6 (1.0%) discontinued combined treatment due to adverse effects. Smaller TPV after short-term combination treatment caused withdrawal from combination therapy. CONCLUSIONS: BPH patients receiving long-term combination therapy showed significant improvement in all measured parameters. Changing medication, improved LUTS and choosing surgery are common reasons for discontinuing combination herapy. A smaller TPV after short-term combination treatment was among the factors that caused withdrawal from combination therapy.

Current Status of 5alpha-Reductase Inhibitors in Prostate Disease Management

The key enzyme in the androgen synthesis and androgen receptor pathways is 5alpha-reductase (5-AR), which occurs as three isoenzymes. Types I and II 5-ARs the most important clinically, and two different 5-AR inhibitors (5-ARIs), finasteride and dutasteride, have been developed. Several urology associations have recommended and upgraded the use of 5-ARIs for an enlarged prostate with lower urinary tract symptoms. In the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events Trial, 5-ARIs reduced the incidence of low-grade prostate cancer. However, despite the documented reductions in the overall incidence of prostate cancer, 5-ARIs are at the center of a dispute. The American Society of Clinical Oncology (ASCO) and the American Urology Association (AUA) presented clinical guidelines for the use of 5-ARIs for chemoprevention of prostate cancer in 2008. However, ASCO/AUA has eliminated these from the main "Clinical Guidelines" in 2012, because the U.S. Food and Drug Administration denied a supplemental New Drug Application for the use of dutasteride for prostate cancer chemoprevention. The 5-ARIs can also be used to manage hemospermia and prostatic hematuria, and to prevent intraoperative bleeding, although there is insufficient evidence for a standard strategy. This review summarizes the current use of 5-ARIs for prostate disease, including benign prostate hyperplasia, prostate cancer, prostate-related bleeding, and hemospermia.

The Change of Prostate-specific Antigen and Prostate-specific Antigen Density in Patients with Benign Prostatic Hyperplasia after Dutasteride Treatment / 대한비뇨기과학회지

PURPOSE: Dihydrotestosterone(DHT) is key to the initiation and maintenance of abnormal prostatic growth in benign prostatic hyperplasia (BPH). Five alpha-reductase inhibitor reduces prostatic growth and serum prostate-specific antigen(PSA) by blocking the conversion of testosterone to DHT. Dutasteride is a dual(type 1 and 2) 5alpha-reductase inhibitor. We evaluated the effects of dutasteride on prostate volume, PSA, and PSA density in men with BPH. MATERIALS AND METHODS: A total of 83 men with a clinical diagnosis of BPH were treated with dutasteride and an alpha-blocker. We investigated the change in prostate volume, PSA, and PSA density 6 and 12 months after initiation of dutasteride therapy. RESULTS: After 6 months of dutasteride therapy, the total prostate volume was reduced from baseline by a mean of 15.46%, the PSA was reduced by a mean of 48.24%, and the PSA density was reduced by a mean of 37.97%(p<0.001). After 12 months of dutasteride therapy, the total prostate volume was reduced from baseline by a mean of 23.3%, the PSA was reduced by a mean of 52.57%, and the PSA density was reduced by a mean of 36.2%(p<0.001). There were no differences in the regression rate of PSA and PSA density, in contrast to prostate volume, between 6 and 12 months of dutasteride therapy by repeated measures ANOVA. CONCLUSIONS: The findings in this study demonstrate that the actual PSA in men receiving dutasteride would be multiplied by 2 considering the PSA regression rate after 12 months.

Expression of Neuroendocrine Cells in Benign Prostatic Hyperplasia and the Effect of Dihydrotestosterone / 대한비뇨기과학회지

PURPOSE: Neuroendocrine (NE) cells of the prostate are considered to be involved in the pathogenesis of benign prostate hyperplasia (BPH). By a comparative analysis of NE cell density in BPH tissue of men who were either exposed to or not exposed to 5alpha-reductase inhibitor, we investigated the relationship between NE cells and BPH, and the effect of androgen deprivation on NE cells. MATERIALS AND METHODS: Prostate tissue specimens, obtained from 30 men by transurethral resection of the prostate or radical cystoprostatectomy, were used. Of the 30 patients, 10 had a prostate smaller than 25 ml (normal control), the other 20 had a prostate larger than 40ml, 10 of who had taken 5alpha-reductase inhibitor (finasteride) for 3 months before surgery (androgen blockade group), and 10 who had not (BPH group). The distribution of NE cells in the prostate was examined using the anti-chromogranin A (CgA) antibody, and the density of the CgA-positive cells was compared by an optical dissector method. Immunoblotting was performed using the neuron specific enolase (NSE) antibody. A Mann-Whitney U test was used in a statistical analysis. RESULTS: Most of the CgA-positive NE cells were localized between the acinar epithelial cells. The mean numbers of CgA-positive NE cells per acinus in the normal controls and the BPH groups were 1.67+/-0.78 and 4.45+/-2.54, respectively, and the difference was statistically significant (p<0.05). However, the mean number of CgA-positive NE cells in the androgen blockade group, was 4.93+/-2.17, which was similar to the BPH group. In a NSE immunoblotting study, a distinct band was observed in the BPH and androgen blockade groups, but the density of the band was higher in the androgen blockade group. CONCLUSIONS: Our results suggest that NE cells may be involved in the hyperplastic process of BPH. Inhibition of dihydrotestosterone, caused by the oral administration of the 5alpha-reductase inhibitor, failed to induce any significant change in the NE cells, probably due to the incomplete androgen blockade.

Clinical Significance of Prostatitis in Patients with Benign Prostatic Hyperplasia / 대한비뇨기과학회지

PURPOSE: The clinical significance of prostatitis associated with benign prostatic hyperplasia (BPH) remains to be determined. We determined the differences in the prevalence, pattern, clinical symptoms and outcome in BPH patients both with, and without prostatitis. MATERIALS AND METHODS: This prospective study included 134 consecutive patients with lower urinary tract symptoms related to BPH. The patients were divided into 2 groups relating to the expressed prostatic secretion caused by prostate massage (group 1: more than 10 leukocytes per high power field, group 2: less than 10 leukocytes per high power field). Tamsulosin, a selective alpha1-blocker, and finasteride were administered at doses of 0.2 and 5mg, respectively, once a day for one year. The primary efficacy criteria included, symptomatic improvement (International Prostate Symptom Score: I-PSS), maximum flow rate (Qmax) and residual urine volume. RESULTS: Prostatitis was identified in 67 of 119 patients (56.3%); the other 15 patients failed the prostatic massage. Of the patients with associated prostatitis, 8 (11.9%) showed bacterial growth. The serum PSA level was higher in group 1 than in group 2, but there were no significant differences in the other clinical parameters. There was no significantly difference in the improvement of the total I-PSS after treatment between the two groups. However, in group 1, the rritative symptom was significantly less improved (p<0.05). CONCLUSIONS: Prostatic inflammation is a common finding in patients with symptoms of BPH. In such cases, the response to medical treatment for irritative symptoms was inferior in the BPH only cases. There is a need for more studies to distinguish chronic prostatitis and BPH, and to ascertain any additional treatment requirements.

The Efficacy of Combination Therapy of 5 alpha -Reductase Inhibitor and of-Adrenergic Blocker in Benign Prostate Hyperplasia / 대한비뇨기과학회지

PURPOSE: Benign prostate hyperplasia(BPH) can be treated with alpha1-adrenergic blocker that relaxes prostate smooth muscle or 5 alpha-reductase inhibitor that reduces serum dirtydrotestosterone. The efficacy of the combination of 5 alpha -reductase inhibitor(finasteride) and alpha1-adrenergic blocker(doxazosin) was evaluated in patients with benign prostate hyperplasia. MATERIALS AND METHODS: Eighty five patients with BPH was treated and followed over 6 months and divided into three groups: Group 1(doxazosin 3mg/day), Group 2(finasteride 5mg) and Group 3(combination of both drugs). Initially, all patients were evaluated by international Prostatic Symptom Score(IPSS: irritative, obstructive, sum, life quality), uroflowmetry, residual urine, serum prostate specific antigen(PSA) and prostate weight by transrectal ultrasonography. IPSS, uroflowmetry and complications were evaluated every month. Residual urine and PSA were assessed at every 3 months, prostate weight at every 6 months. RESULTS: In Group 1 and 3, IPSS were more decreased than In Group 2 immediately(p < 0.001). In Group 1 and 3, maximal flow rate was more increased than in group 2 immediately(p < 0.001). There was no difference of mean change of residual urine among three group. In Group 2 and 3, serum prostate specific antigen and prostate weight were more decreased than in Group 1 (p < 0.001). CONCLUSIONS: In medical treatment of BPH, the combination therapy of alpha1-adrenergic blocker and 5alpha-reductase inhibitor shows early symptomatic improvement and decreased prostate weight without significant complications.