The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia

Wurzel, Rafael; Ray, Paul S.; Major-Walker, Kim; Shannon, Jennifer B.; Rittmaster, Roger S.

doi:10.1038/sj.pcan.4500931

Cited by 64 publications

(60 citation statements)

References 20 publications

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“…After a 4-week placebo run-in period, patients were randomized to receive dutasteride or finasteride for 48 weeks, followed by an optional 24-month, open-label phase, during which patients received dutasteride 0.5 mg once daily.…”

Section: • the Enlarged Prostate Internationalmentioning

confidence: 99%

Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS)

et al. 2011

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maximum urinary flow rate (Q max ) and longterm safety in the 24-month open-label phase. RESULTS• Both dutasteride and finasteride were effective at reducing prostate volume with no significant difference between the two treatments during the study.• Similar reductions in mean AUA-SI scores and Q max were also observed for men in both treatment groups.• A similar percentage of adverse events was experienced by patients of both treatment groups, and no new adverse events were reported in the open-label phase. CONCLUSION• Dutasteride and finasteride, when administered for 12 months, were similarly effective in reducing prostate volume and improving Q max and urinary symptoms associated with BPH in men with an enlarged prostate. KEYWORDSbenign prostatic hyperplasia, finasteride, dutasteride, 5 α -reductase inhibitors What's known on the subject? and What does the study add? Both dutasteride and finasteride inhibit type 2 5 α -reductase, the dominant form of 5 α -reductase in benign prostatic tissue, making these effective treatments for BPH. In comparison with finasteride, dutasteride has a longer half-life and leads to a greater and more consistent suppression of serum and intraprostatic DHT.EPICS is currently the only prospective, randomized, double-blind study of finasteride vs dutasteride for BPH endpoints conducted for longer than a few months. Over a one-year period, treatment with dutasteride and finasteride led to similar reductions in prostate volume, and improvements in peak urine flow and urinary symptoms associated with BPH in men with an enlarged prostate. Men treated with finasteride and dutasteride also experienced similar rates of adverse events over the course of one year, which suggests that inhibition of both type 1 and type 2 5 α -reductase, resulting in greater DHT suppression than type 2 inhibition alone, does not confer an increase in adverse events. Given the long-term, progressive nature of BPH, the one-year duration of EPICS may limit the potential to observe major differences between dutasteride and finasteride treatment.Study Type -Therapy (RCT) Level of Evidence 1b OBJECTIVE• To assess the efficacy and safety of dutasteride compared with finasteride in treating men with symptomatic benign prostatic hyperplasia (BPH) for 12 months. PATIENTS AND METHODS• The Enlarged Prostate International Comparator Study was a multicentre, randomized, double-blind, 12-month, parallel-group study.• Men aged ≥ 50 years with a clinical diagnosis of BPH received once-daily treatment with dutasteride 0.5 mg ( n = 813) or finasteride 5 mg ( n = 817). After a 4-week placebo run-in period, patients were randomized to receive dutasteride or finasteride for 48 weeks, followed by an optional 24-month, open-label phase, during which patients received dutasteride 0.5 mg once daily.• The primary endpoint was change in prostate volume, and the secondary endpoints included improvement in American Urological Association Symptom Index (AUA-SI) scores, improvement in

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Section: • the Enlarged Prostate Internationalmentioning

confidence: 99%

Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS)

et al. 2011

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“…Dutasteride also blocks the type 1 5-alpha reductase enzymes which may suggest the possibility of improved outcomes with this treatment. Furthermore, dutasteride has a longer half-life compared to finasteride (approximately 4 weeks vs 6 h), which also might lead to better efficacy with dutasteride [6, 20]. …”

Section: Discussionmentioning

confidence: 99%

Rates of prostate surgery and acute urinary retention for benign prostatic hyperplasia in men treated with dutasteride or finasteride

et al. 2016

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BackgroundPrevious studies have suggested a greater benefit for various outcomes in men diagnosed with benign prostatic hyperplasia (BPH) who are treated with dutasteride than for men treated with finasteride. This study investigates whether the rates of BPH-related prostate surgery and acute urinary retention (AUR) differ between dutasteride and finasteride users in the Netherlands.MethodsFrom the PHARMO Database Network, men aged ≥50 years with a dispensing of dutasteride or finasteride with or without concomitant alpha-blocker treatment between March 1, 2003 and December 31, 2011 were selected. The incidence of BPH-related prostate surgery and AUR was determined during dutasteride or finasteride treatment and stratified by type of initial BPH-treatment (5-ARI monotherapy or combination with alpha-blocker) and prescriber (general practitioner (GP) or urologist). Comparison of the incidence of BPH-related prostate surgery and AUR between the treatment groups was done by Cox proportional hazard regression.Results11,822 dutasteride users and 5,781 finasteride users were identified. Most users started treatment in combination with an alpha-blocker. Overall, dutasteride users had a lower risk of BPH-related prostate surgery was lower among dutasteride users than finasteride users (HR: 0.75; 95 % CI: 0.56–0.99). This lower risk among dutasteride users was also seen when stratifying by monotherapy or combination therapy (HR: 0.73; 95 % CI: 0.54–0.98 for monotherapy and HR: 0.85; 95 % CI: 0.74–0.97 for combination therapy). However, the association was only present among men treated by urologists. For AUR the rates were low and no statistical significant difference was observed between dutasteride and finasteride users.ConclusionsThe risk of undergoing BPH-related prostate surgery was lower among men using dutasteride compared to men using finasteride. The association was observed for monotherapy as well as combination therapy, however, only among men who received their prescription from a urologist.

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“…Dutasteride inhibits 5a-reductase types 1 and 2, resulting in greater reductions in DHT than finasteride [22], although the clinical significance of this difference remains unclear.…”

Section: Dutasteride: the Reduce Trialmentioning

confidence: 97%

Prostate Cancer Prevention: Concepts and Clinical Trials

Hamilton

Parsons

2016

Curr Urol Rep

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Prevention is an important treatment strategy for diminishing prostate cancer morbidity and mortality and is applicable to both early- and late-stage disease. There are three basic classifications of cancer prevention: primary (prevention of incident disease), secondary (identification and treatment of preclinical disease), and tertiary (prevention of progression or recurrence). Based on level I evidence, 5-alpha reductase inhibitors (5-ARIs) should be considered in selected men to prevent incident prostate cancer. Level I evidence also supports the consideration of dutasteride, a 5-ARI, for tertiary prevention in active surveillance and biochemical recurrence patients. Vitamins and supplements, including selenium or vitamin E, have not been proven in clinical trials to prevent prostate cancer and in the case of Vitamin E has been found to increase the risk of incident prostate cancer. Ongoing and future trials may further elucidate the role of diet and immunotherapy for prevention of prostate cancer.

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The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia

Cited by 64 publications

References 20 publications

Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS)

Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS)

Rates of prostate surgery and acute urinary retention for benign prostatic hyperplasia in men treated with dutasteride or finasteride

Prostate Cancer Prevention: Concepts and Clinical Trials

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