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Importance of the Field: Benign prostatic hyperplasia (BPH) is the fourth most commonly diagnosed medical condition in the elderly. Selective α-blockers (tamsulosin) and dual 5α-reductase inhibitors (dutasteride) have an important role in the medical treatment of symptomatic BPH. Safety and efficacy of combination therapy with dutasteride and tamsulosin as well as long-term benefit on prevention of disease progression have been widely studied in recent trials., Areas Covered in This Review: The present article summarizes the pharmacologic properties of both dutasteride and tamsulosin. Clinical efficacy of combination therapy in different trials has also been reported. Major randomized trials on this concept published between 2000 and 2010 have been covered in this article., What the Reader Will Gain: Long-term efficacy and safety of combination therapy and its beneficial effect on quality of life and risk reduction of need for BPH-related surgeries have been discussed., Take Home Message: Combination therapy with dutasteride and tamsulosin is a highly efficacious medical treatment in patients with moderate-to-severe lower urinary tract symptoms due to benign prostatic enlargement, which could be safely tolerated and administrated for ≥ 4 years.

Dutasteride (Avodart), an oral synthetic 4-azasteroid, is a potent, selective, irreversible inhibitor of type 1 and type 2 5alpha-reductase (5AR), the enzyme that converts testosterone to dihydrotestosterone (DHT) intracellularly. Although type 2 5AR predominates, both isoenzymes are overexpressed in prostate tissue in benign prostatic hyperplasia (BPH) and at all stages in some prostate cancers. Oral dutasteride 0.5 mg once daily is approved for the treatment of moderate to severe symptomatic BPH in men with an enlarged prostate to improve symptoms, and to reduce the risk of acute urinary retention (AUR) and the need for BPH-related surgery.In pivotal 2-year phase III trials, oral dutasteride 0.5 mg once daily improved urinary symptoms, decreased total prostate volume (TPV), and reduced the risk of AUR and BPH-related surgery in men with moderate to severe symptoms of BPH and prostate enlargement. The good efficacy and tolerability of dutasteride was maintained for up to 4 years in open-label extension studies. Results of the pre-planned, 2-year interim analysis of the CombAT trial showed that the combination of dutasteride and tamsulosin was superior to either drug as monotherapy in improving BPH-related symptoms, peak urinary flow and BPH-related health status. The overall adverse event profile for combination therapy was consistent with those reported for both monotherapies. Although drug-related adverse events were more frequent with combination therapy versus both monotherapies, most did not result in treatment cessation. Dutasteride is being investigated for its efficacy in reducing the risk of prostate cancer in at-risk men in the 4-year REDUCE study and as treatment to extend the time to progression in men with low-risk localized prostate cancer who would otherwise undergo watchful waiting in the 3-year REDEEM study. Thus, dutasteride is an effective treatment option in patients with moderate to severe symptomatic BPH and demonstrable prostatic enlargement, and may have potential to reduce the risk of developing biopsy-detectable prostate cancer in at-risk individuals or extending the time to progression in low-risk localized prostate cancer.

Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary symptoms, with a prevalence of 50% by the sixth decade of life. Hyperplasia of stromal and epithelial prostatic elements that surround the urethra cause lower urinary tract symptoms (LUTS), urinary tract infection, and acute urinary retention. Medical treatments of symptomatic BPH include; 1) the 5alpha-reductase inhibitors, 2) the alpha1-adrenergic antagonists, and 3) the combination of a 5alpha-reductase inhibitor and a alpha1-adrenergic antagonist. Selective alpha1-adrenergic antagonists relax the smooth muscle of the prostate and bladder neck without affecting the detrussor muscle of the bladder wall, thus decreasing the resistance to urine flow without compromising bladder contractility. Clinical trials have shown that alpha1-adrenergic antagonists decrease LUTS and increase urinary flow rates in men with symptomatic BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. Inhibitors of 5alpha-reductase decrease production of dihydrotestosterone within the prostate resulting in decreased prostate volumes, increased peak urinary flow rates, improvement of symptoms, and decreased risk of acute urinary retention and need for surgical intervention. The combination of a 5alpha-reductase inhibitor and a alpha1-adrenergic antagonist reduces the clinical progression of BPH over either class of drug alone.

The dual 5alpha-reductase inhibitor, dutasteride has been shown to suppress serum dihydrotestosterone (DHT) by >90%. In the present study, the effect of dutasteride 0.5 mg/day on intraprostatic DHT levels was investigated. In this multicenter, double-blind trial, 43 men with benign prostatic hyperplasia (BPH) scheduled to undergo transurethral resection of the prostate (TURP) were randomized to receive dutasteride, 0.5 mg/day or placebo for 3 months before surgery. Intraprostatic DHT, testosterone and dutasteride levels were determined at the time of TURP. Changes in serum DHT and testosterone from baseline, and both serum and intraprostatic dutasteride levels at the time of TURP were also assessed. Dutasteride reduced intraprostatic DHT by 94% relative to placebo (P<0.001); the adjusted mean intraprostatic DHT concentration was 3.23 and 0.209 ng/g in the placebo and dutasteride groups, respectively. In the dutasteride group, serum DHT was reduced from baseline by 93% at month 3, a significantly greater reduction (P<0.001) than the 15% decrease observed in the placebo group. There was a reciprocal increase in intraprostatic testosterone but the level of intraprostatic testosterone in the dutasteride group tended to be lower than the intraprostatic DHT level in the placebo group (P=0.06). Significant intraprostatic DHT suppression was achieved in all subjects who received dutasteride, regardless of the level of intraprostatic dutasteride. There was a strong positive correlation between serum and intraprostatic dutasteride concentrations (R(2)=0.73). After 3 months of treatment, dutasteride 0.5 mg/day provided near-complete suppression of both intraprostatic and serum DHT in men with BPH.

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, drug interactions, and dosing recommendations of dutasteride, a 5-alpha reductase inhibitor for benign prostatic hyperplasia (BPH)., Data Sources: A MEDLINE search (1966-February 2006) was conducted to extract human research data in the English language on dutasteride. Search terms included benign prostatic hyperplasia, dutasteride, and finasteride. The reference lists of articles identified through this search process, the manufacturer's Web site, and dutasteride prescribing information were also examined., Study Selection and Data Extraction: All published studies and clinical data from the manufacturer were included, with emphasis placed on randomized, controlled trials., Data Synthesis: Dutasteride is approved for the treatment of symptomatic BPH in men with an enlarged prostate to improve urinary symptoms, reduce the risk of acute urinary retention, and reduce the need for BPH-related surgical interventions. Compared with placebo, dutasteride has been shown to significantly improve BPH symptoms, reduce the incidence of acute urinary retention and BPH-related surgery, and improve BPH-related quality of life. Few published data exist comparing dutasteride with finasteride. The most common adverse effects of dutasteride include ear, nose, and throat infection; malaise; headache; dizziness; and musculoskeletal pain., Conclusions: Clinical trials, sponsored primarily by the manufacturer, have shown dutasteride to be an effective treatment of BPH compared with placebo and to likely possess efficacy similar to that of finasteride. Further studies are needed to gain a more clear understanding of any clinically significant differences between dutasteride and finasteride.

Dutasteride is a new 5-alpha reductase inhibitor for the treatment of men with moderate to severe lower urinary tract symptoms secondary to benign prostatic hyperplasia. It has been available in the UK since March 2003. It is a competitive inhibitor of both type I and type II isoforms of the 5-alpha reductase enzyme that converts testosterone to the more potent androgen, dihydrotestosterone. Randomised controlled studies have shown dutasteride to be statistically more effective than placebo in reducing lower urinary tract symptoms and increasing maximum urinary flow rates. This is a consequence of a reduction in serum dihydrotestosterone and hormone dependent prostate volume. Dutasteride has also been shown to decrease the absolute risk of urinary retention and the need for prostate-related surgery when compared to placebo taken over a 24-month period. In this review article we discuss the pharmacology and clinical effects of dutasteride, a new dual-acting 5-alpha reductase inhibitor.

Dutasteride, a potent inhibitor of type 1 and 2 5alpha-reductase, reduced dihydrotestosterone levels by >90% in 85% of patients following 1 years' administration of oral dutasteride 0.5 mg/day. A combined analysis of three placebo-controlled clinical studies conducted in patients with benign prostatic hyperplasia (BPH) found sustained improvements in American Urological Association- Symptom Index scores and urinary flow rate and a 57% decrease in the risk of acute urinary retention throughout the 2-year treatment period (all p < 0.001 vs placebo). Total prostate and transition zone volume were also reduced (both p < 0.001), as was the risk of BPH-related surgery (by 48%). A nonblind extension study found that dutasteride maintains efficacy for up to 4 years. Dutasteride monotherapy maintained symptom relief following combination treatment with dutasteride and tamsulosin in all patients but those with severe symptoms. Dutasteride was generally well tolerated. Impotence, reduced libido, gynaecomastia and ejaculation disorder occurred significantly more often in dutasteride than placebo recipients, but incidence was generally low. With the exception of gynaecomastia, incidence consistently decreased over time.