Dutasteride in men receiving testosterone therapy: a randomised,double‐blind study

We investigate the impact of dutasteride on prostate specific antigen (PSA) and prostate volume in men receiving testosterone (T) therapy. Twenty‐three men on stable dose T therapy were randomised to receive either dutasteride or placebo for 12 months. Serum levels of PSA, T and dihydrotestosterone (DHT) and responses to the International Index of Erectile Function (IIEF) and Male Sexual Health Questionnaire (MSHQ) questionnaires were determined at baseline and at 3, 6, 9 and 12 months. Prostate volume (PV) was measured using transrectal ultrasound (TRUS) at baseline and again after 12 months. A total of 22 men (mean age 57.3) completed the study, with 11 men receiving placebo and 11 receiving dutasteride. Men receiving dutasteride had a significant decrease in PSA (?0.46 ± 0.81 ng ml^?1; P = 0.04) and in PV (?6.65 ± 11.0%; P = 0.03) from baseline over 12 months. DHT decreased significantly for men on dutasteride compared with men receiving placebo (P = 0.02). When compared with men who received placebo, men who received dutasteride demonstrated nonsignificant trends towards decreased PSA (?0.46 versus 0.21 ng ml^?1; P = 0.11), PV (?6.65% versus 3.4%; P = 0.08) and MSHQ scores (?10.2 versus 5.6; P = 0.06). Dutasteride reduces PSA and PV for men on T therapy, but perhaps less so than in men without T therapy.     

Low reduction of prostate volume is a significant predictor of prostate cancer at subsequent biopsy in patients with dutasteride: A retrospective study

Appropriate decision of prostate biopsy in men with 5α-reductase inhibitor (5AR inhibitor) is still unclear to avoid unnecessary biopsy. We retrospectively investigated patients with initial PSA 4.0 ng/ml or more and underwent subsequent prostate biopsy following dutasteride treatment. From September 2009 to August 2018, 399 cases of benign prostate hyperplasia (BPH) were treated with dutasteride in our department. Of the total, 36 cases with elevated pre-treatment PSA (4.0 ng/ml or more) and underwent subsequent prostate biopsy were included into this study. We evaluated PSA kinetics and changing prostate volumes (PV), and detection of prostate cancer. Overall, average PSA reduced by half at 6 months from dosing. Pre-treatment biopsy was performed in 17 of 36 cases, and all were diagnosed as having no malignancy. After treatment, prostate cancer was detected in 15 cases by subsequent biopsy. Fourteen of 15 cases were clinically significant cancer (Gleason score 7 or more). Logistic regression analysis detected a nominal association between prostate cancer detection and three variants, PSAD, PV reduction (1–Before/After PV) and abnormal MRI findings. In addition to abnormal MRI findings and pre-treatment of high PSAD, the case with low reduction of PV after treatment should consider performing prostate biopsy.     

5‐Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms,current concepts,comparative efficacy,and safety

Androgenetic alopecia (AGA) is a multifactorial disease that carries a significant psychological burden with it. Dihydrotestosterone, the main pathogenic androgen in AGA, is produced by conversion of testosterone, which is catalyzed by the 5‐alpha reductase (5‐AR) isoenzyme family. Finasteride and dutasteride are inhibitors of these enzymes. Finasteride, which is a single receptor 5‐alpha reductase inhibitor (5‐ARI), acts by blocking dihydrotestosterone (DHT). Dutasteride, a dual receptor DHT blocker, has a higher potency than its predecessor, finasteride. This review corroborates the evidence of superiority of dutasteride over finasteride, and its comparable safety profile concerning fertility, teratogenicity, neurotoxicity, and hepatotoxicity.     

Improvements in benign prostatic hyperplasia-specific quality of life with dutasteride,the novel dual 5alpha-reductase inhibitor

OBJECTIVES: To examine the effect of the dual-action 5alpha-reductase inhibitor dutasteride on benign prostatic hyperplasia (BPH)-specific health status, as measured by the BPH Impact Index (BII), and to identify baseline and treatment risk factors for those most bothered by their BPH symptoms at the end of the protocol. PATIENTS AND METHODS: Data were derived from three randomized, double-blind, placebo-controlled, 2-year studies conducted in 4325 men with lower urinary tract symptoms caused by benign prostatic enlargement. Each study comprised a 1-month single-blind placebo run-in period, followed by randomization to oral dutasteride 0.5 mg once daily or placebo for 2 years. Patients eligible for inclusion were consenting men aged >/= 50 years with moderate to severe symptoms (American Urological Symptom Index, AUA-SI, score >/= 12), a prostate volume of >/= 30 mL, a serum prostate-specific antigen (PSA) level of >/= 1.5 or < 10 ng/mL, and a maximum urinary flow rate (Qmax) of /= 5 (greatest symptomatic burden) treatment with dutasteride improved the scores by 2.41, while the scores in placebo-treated patients only improved by 1.64. Dutasteride-treated patients with a baseline BII score of < 5 (least symptom burden) had a clinically significant improvement in health status, while placebo-treated patients deteriorated. Regression analysis showed that men with a combination of a baseline BII item-3 score of 3 (bothered a lot) and a high symptom score (AUA-SI >/= 20) were more likely to be bothered by their symptoms at the end of the study. Men receiving placebo were also more likely to be bothered at the end of the study than were those receiving dutasteride. CONCLUSIONS: Dutasteride treatment is associated with clinically significant improvements in BII score, reflecting improvements in the quality of life of men with BPH. Taken together with previously reported improvements in prostate volume, lower urinary tract symptoms and urinary flow, and diminution of the risk of acute urinary retention and the need for BPH-related surgery, dutasteride offers demonstrable efficacy in the management of BPH.     

A broader role for 5ARIs in prostate disease? Existing evidence and emerging benefits

5ARIs are recommended for men who have moderate‐to‐severe lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) secondary to benign prostatic hyperplasia. Studies have confirmed the utility of combining 5ARIs with alpha‐blockers; the MTOPS study showed that risk of overall clinical progression was significantly reduced after 4.5 years with combination therapy (finasteride/doxazosin) in comparison with either monotherapy, while the ongoing CombAT trial (dutasteride/tamsulosin) has for the first time shown benefit in improving symptoms for combination therapy over monotherapies within 12 months of treatment. Data also suggest roles for 5ARIs in prostate cancer. Several studies indicate that treatment with a 5ARI improves the performance of PSA testing for identifying men with prostate cancer, while the PCPT showed a significant reduction in the risk of developing prostate cancer with finasteride. However, widespread use of finasteride in this setting has been tempered by an apparent increase in high‐grade disease observed in the study. The ongoing REDUCE study will provide further insight into prostate cancer prevention with 5ARIs. 5ARI‐containing regimens may have utility as less aggressive treatment options for patients who only have rising PSA after definitive local therapy, and in patients with disease resistant to androgen deprivation therapy who have PSA progression. Current evidence therefore shows that 5ARIs are effective in treating LUTS/BPE and preventing disease progression, and may also have a role in the prevention of prostate cancer. The overlap between BPE and prostate cancer may allow a more unified approach to managing these conditions, with 5ARIs having a central role. Prostate 69: 895–907, 2009. © 2009 Wiley‐Liss, Inc.     

The effect of dutasteride on the peripheral and transition zones of the prostate and the value of the transition zone index in predicting treatment response

PURPOSE: We determined the effects of dutasteride on transition and peripheral zone volume, and the clinical value of the transition zone index in men with benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 2,802 men 50 years or older with diagnosed benign prostatic hyperplasia, American Urological Association symptom index score 12 or greater, total prostate volume 30 cc or greater, prostate specific antigen 1.5 ng/ml or greater and 10 ng/ml or less, and peak urinary flow rate 15 ml per second or less were randomized to receive 0.5 mg dutasteride daily or placebo for 2 years. Total prostate and transition zone volume was measured with transrectal ultrasound at baseline and 4 times during the 2-year period. Peripheral zone volume (total prostate volume minus transition zone volume) and the transition zone index (transition zone volume/total prostate volume) were calculated. Patients were stratified into tertiles according to baseline total prostate and transition zone volume, and the transition zone index. RESULTS: At 24 months dutasteride significantly decreased total prostate volume from baseline (p <0.0001). There were similar decreases in transition and peripheral zone volume (approximately 25%). In men receiving placebo high baseline total prostate and transition zone volume, and transition zone index were associated with poor 2-year outcomes, ie a low peak urinary flow rate, high American Urological Association symptom index scores, and an increased frequency of acute urinary retention and benign prostatic hyperplasia related surgery. Improvements in outcomes with dutasteride vs placebo were greatest in men with the highest baseline total prostate and transition zone volume, and transition zone index. In men with low (30 to less than 42 cc) and intermediate (42 to less than 58 cc) baseline total prostate volume the benefits of dutasteride therapy were only significant in the intermediate (0.4 to less than 0.55) and high (0.55 to less than 1.0) transition zone index tertiles. CONCLUSIONS: Total prostate and transition zone volume, and the transition zone index are directly related to benign prostatic hyperplasia progression. The transition zone index may add value to transition zone volume alone for predicting outcomes. Dutasteride decreased transition and peripheral zone volume equally, supporting a known therapeutic role in benign prostatic hyperplasia and a possible preventive role in prostate cancer.     

5α-还原酶抑制剂治疗良性前列腺增生现况

良性前列腺增生（BPH）是中老年男性的常见疾病,它与男性下尿路症状密不可分.近年来药物治疗BPH不断被人们重视,已逐渐成为BPH一线治疗方案.其中5α-还原酶抑制剂和α-阻滞剂长期以来成为研究的热点.作者就5α-还原酶抑制剂进行综述,着重分析非那雄胺和度他雄胺两种药物在治疗BPH的临床研究进展,进而阐述5α-还原酶抑制剂在临床治疗中的应用.     

Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study

Study Type – Prognostic (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Previous studies used the decrease in PSA after 6 months of dutasteride treatment as a new ‘baseline’ PSA value from which subsequent rises may serve as a warning for prostate cancer; however, PSA tends to continue to decrease as dutasteride treatment continues. By comparing positive biopsy rates in the REDUCE study using any rise from nadir in the dutasteride arm and standard PSA decision criteria (NCCN) in the placebo arm, we demonstrated that the ability to detect prostate cancer and high grade prostate cancer is maintained with dutasteride treatment.

OBJECTIVES

? To determine if dutasteride‐treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. ? To analyse whether the use of treatment‐specific criteria for repeat biopsy maintains the usefulness of prostate‐specific antigen (PSA) level for detecting high grade cancers.

PATIENTS AND METHODS

? The REDUCE study was a randomized, double‐blind, placebo‐controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy‐detectable prostate cancer in men with a previous negative biopsy. ? The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. ? The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. ? Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds.

RESULTS

? Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. ? If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8–10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8–10 cancers would have been missed in the placebo group. ? In both groups, the incidence of Gleason 7 and Gleason 8–10 cancers generally increased with greater rises in PSA. ? Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7–10 cancers in men treated with dutasteride vs placebo. ? Men with Gleason 7 and Gleason 8–10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds.

CONCLUSION

? Using treatment‐specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. ? The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8–10) or higher than (Gleason 7–10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.