madman
Super Moderator
Efficacy and safety of dutasteride compared with finasteride in treating males with benign prostatic hyperplasia: A meta‑analysis of randomized controlled trials
Abstract
The present study was an updated meta-analysis that aimed to confirm the efficacy and safety of dutasteride (0.5 mg) and finasteride (5 mg) in treating males with benign prostatic hyperplasia (BPH) over a treatment period of at least 6 months. Randomized controlled trials were retrieved using the MEDLINE, EMBASE, and the Cochrane controlled trials register databases. The references of the associated articles were also searched. A systematic review was performed using the preferred reporting items for systematic reviews and meta-analyses. The data were analyzed with RevMan v5.3.0. A total of six articles including 2,041 participants were studied. The analysis demonstrated a significantly greater decrease in international prostate symptom score [IPSS; mean difference (MD), ‑0.86; 95% CI, ‑1.62 to ‑0.11; P=0.02] and prostate‑specific antigen (PSA; MD, ‑0.13; 95% CI, ‑0.26 to ‑0.01; P=0.03) in the dutasteride group compared with that in the finasteride group, whereas no significant differences were observed in prostate volume (PV; P=0.64), maximum urine flow rate (Qmax; P=0.29), and post‑void residual volume (PVRV; P=0.14). With regard to safety assessment, including any adverse event (P=0.66), decreased libido (P=0.39), and impotence (P=0.17), there was no significant difference between dutasteride and finasteride. In conclusion, in patients with BPH, dutasteride produced a greater decrease in IPSS and PSA compared with finasteride, whereas no significant differences were identified in PV, Qmax, and PVRV. The two drugs appeared to have similar rates of adverse effects, particularly with regard to sexual dysfunction.
Introduction
Benign prostatic hyperplasia (BPH) is a primary etiology of dysplasia of the prostate that occurs mainly in the elderly and is characterized by nonmalignant hypertrophy of the prostate gland due to unrestricted proliferation of epithelial and smooth muscle cells positioned in the transition region of the prostate gland encircling the urethra (1,2). Patients with BPH may suffer from frequent micturition, interrupted urine flow, sense of incomplete bladder emptying and a high risk of acute urinary retention, which impacts the quality of life (3,4).
Changes in androgen levels are considered to be a crucial factor for the development of prostate growth with age (5). Dihydrotestosterone (DHT), an important constituent among the androgens, may be synthesized from testosterone by 5α‑reductase (5AR) in the prostate gland (6). With the reduction in testosterone levels, the excessive expression of DHT triggers the proliferation of prostate epithelial and mesenchymal cells, leading to the development of BPH (7,8). To inhibit this process, 5AR inhibitors (5ARI) are administered to lower the serum concentration of DHT, controlling the normal growth of the prostate itself and the progression of BPH (9). Two 5ARIs are available: finasteride and dutasteride. Finasteride is a selective inhibitor of type 2 5ARI, whereas dutasteride inhibits type 1 and 2 5ARI (10,11). Dutasteride, due to the additional target, induces a theoretically greater reduction in DHT and improvement in clinical presentation compared with finasteride. However, two previous meta‑analyses comparing the efficacy of the two drugs limited their search due to a lack of standard analysis of clinical data on various aspects and provided ambiguous results on whether finasteride and dutasteride exhibited any clinically significant differences (12,13).
*The present study was an updated meta-analysis aiming to compare the efficacy and safety of 0.5 mg dutasteride and 5 mg finasteride (the doses widely used in the clinic) in treating BPH during a treatment period of at least 6 months.
A total of five RCTs containing PSA data demonstrated that dutasteride was more effective compared with finasteride in reducing the serum level of PSA. 5ARI may induce the degradation of prostate tissue, which is a source of serum PSA, and the inhibition of DHT may indirectly decrease the level of serum PSA (32). PSA is a commonly used screening indicator for the diagnosis of prostate cancer (PC) (33). Long‑term use of 5ARI may lead to low PSA levels, which may reduce the detection rate of PC and increase the rate of misdiagnosis (34). The results of the present study indicated that compared with finasteride, dutasteride may reduce the diagnostic efficacy of PSA in PC to a greater extent. If PSA changes in patients being screened for PC during treatment with dutasteride, further examination may be required for patients being screened for PC. Andriole et al (35) reported that patients exhibited a >40% decrease of PSA after 6-month treatment with dutasteride, which may indicate a low risk for PC, and re‑biopsy may be required.
The safety assessment of the studies included in the present analysis suggested that dutasteride and finasteride were well-tolerated. Regarding the adverse reactions assessed, including any AE, decreased libido, and impotence, the dutasteride group exhibited no significant differences compared with the finasteride group. Traish et al (36) suggested that long-term dutasteride therapy led to a deterioration of erectile dysfunction, reduced testosterone levels and increased glucose and glycated hemoglobin and changed lipid profiles, suggesting an imbalance of metabolic function and deterioration of gonadal function. It is strongly recommended that the physician explains the potential serious side effects of long‑term 5ARI treatment to the patient prior to adopting this treatment.
The limitations of the present meta‑analysis require to be acknowledged. The quality of the selected studies was flawed, primarily in terms of study design, patient selection, blinding, and outcome data. Therefore, the results of the present meta‑analysis should be interpreted with caution. However, the publications included in the present study were all RCTs, which reinforced the results. Bias regarding the selection and subjective factors may also affect the final results of the present study. More high‑quality RCTs with sufficient sample sizes and statistics are required to confirm the efficacy of dutasteride and finasteride in treating BPH.
The present meta-analysis demonstrated that dutasteride exhibited a greater decrease in IPSS and PSA in the treatment of BPH compared with finasteride, whereas no significant differences were observed in PV, Qmax, and PVRV. The two drugs appeared to exhibit similar rates of adverse reactions. In contrast to finasteride, dutasteride offered a significant improvement in patients with LUTS; however, long‑term use of dutasteride may result in low PSA levels, which may lead to a significant reduction in the relevance ratio of PSA regarding PC.
Abstract
The present study was an updated meta-analysis that aimed to confirm the efficacy and safety of dutasteride (0.5 mg) and finasteride (5 mg) in treating males with benign prostatic hyperplasia (BPH) over a treatment period of at least 6 months. Randomized controlled trials were retrieved using the MEDLINE, EMBASE, and the Cochrane controlled trials register databases. The references of the associated articles were also searched. A systematic review was performed using the preferred reporting items for systematic reviews and meta-analyses. The data were analyzed with RevMan v5.3.0. A total of six articles including 2,041 participants were studied. The analysis demonstrated a significantly greater decrease in international prostate symptom score [IPSS; mean difference (MD), ‑0.86; 95% CI, ‑1.62 to ‑0.11; P=0.02] and prostate‑specific antigen (PSA; MD, ‑0.13; 95% CI, ‑0.26 to ‑0.01; P=0.03) in the dutasteride group compared with that in the finasteride group, whereas no significant differences were observed in prostate volume (PV; P=0.64), maximum urine flow rate (Qmax; P=0.29), and post‑void residual volume (PVRV; P=0.14). With regard to safety assessment, including any adverse event (P=0.66), decreased libido (P=0.39), and impotence (P=0.17), there was no significant difference between dutasteride and finasteride. In conclusion, in patients with BPH, dutasteride produced a greater decrease in IPSS and PSA compared with finasteride, whereas no significant differences were identified in PV, Qmax, and PVRV. The two drugs appeared to have similar rates of adverse effects, particularly with regard to sexual dysfunction.
Introduction
Benign prostatic hyperplasia (BPH) is a primary etiology of dysplasia of the prostate that occurs mainly in the elderly and is characterized by nonmalignant hypertrophy of the prostate gland due to unrestricted proliferation of epithelial and smooth muscle cells positioned in the transition region of the prostate gland encircling the urethra (1,2). Patients with BPH may suffer from frequent micturition, interrupted urine flow, sense of incomplete bladder emptying and a high risk of acute urinary retention, which impacts the quality of life (3,4).
Changes in androgen levels are considered to be a crucial factor for the development of prostate growth with age (5). Dihydrotestosterone (DHT), an important constituent among the androgens, may be synthesized from testosterone by 5α‑reductase (5AR) in the prostate gland (6). With the reduction in testosterone levels, the excessive expression of DHT triggers the proliferation of prostate epithelial and mesenchymal cells, leading to the development of BPH (7,8). To inhibit this process, 5AR inhibitors (5ARI) are administered to lower the serum concentration of DHT, controlling the normal growth of the prostate itself and the progression of BPH (9). Two 5ARIs are available: finasteride and dutasteride. Finasteride is a selective inhibitor of type 2 5ARI, whereas dutasteride inhibits type 1 and 2 5ARI (10,11). Dutasteride, due to the additional target, induces a theoretically greater reduction in DHT and improvement in clinical presentation compared with finasteride. However, two previous meta‑analyses comparing the efficacy of the two drugs limited their search due to a lack of standard analysis of clinical data on various aspects and provided ambiguous results on whether finasteride and dutasteride exhibited any clinically significant differences (12,13).
*The present study was an updated meta-analysis aiming to compare the efficacy and safety of 0.5 mg dutasteride and 5 mg finasteride (the doses widely used in the clinic) in treating BPH during a treatment period of at least 6 months.
A total of five RCTs containing PSA data demonstrated that dutasteride was more effective compared with finasteride in reducing the serum level of PSA. 5ARI may induce the degradation of prostate tissue, which is a source of serum PSA, and the inhibition of DHT may indirectly decrease the level of serum PSA (32). PSA is a commonly used screening indicator for the diagnosis of prostate cancer (PC) (33). Long‑term use of 5ARI may lead to low PSA levels, which may reduce the detection rate of PC and increase the rate of misdiagnosis (34). The results of the present study indicated that compared with finasteride, dutasteride may reduce the diagnostic efficacy of PSA in PC to a greater extent. If PSA changes in patients being screened for PC during treatment with dutasteride, further examination may be required for patients being screened for PC. Andriole et al (35) reported that patients exhibited a >40% decrease of PSA after 6-month treatment with dutasteride, which may indicate a low risk for PC, and re‑biopsy may be required.
The safety assessment of the studies included in the present analysis suggested that dutasteride and finasteride were well-tolerated. Regarding the adverse reactions assessed, including any AE, decreased libido, and impotence, the dutasteride group exhibited no significant differences compared with the finasteride group. Traish et al (36) suggested that long-term dutasteride therapy led to a deterioration of erectile dysfunction, reduced testosterone levels and increased glucose and glycated hemoglobin and changed lipid profiles, suggesting an imbalance of metabolic function and deterioration of gonadal function. It is strongly recommended that the physician explains the potential serious side effects of long‑term 5ARI treatment to the patient prior to adopting this treatment.
The limitations of the present meta‑analysis require to be acknowledged. The quality of the selected studies was flawed, primarily in terms of study design, patient selection, blinding, and outcome data. Therefore, the results of the present meta‑analysis should be interpreted with caution. However, the publications included in the present study were all RCTs, which reinforced the results. Bias regarding the selection and subjective factors may also affect the final results of the present study. More high‑quality RCTs with sufficient sample sizes and statistics are required to confirm the efficacy of dutasteride and finasteride in treating BPH.
The present meta-analysis demonstrated that dutasteride exhibited a greater decrease in IPSS and PSA in the treatment of BPH compared with finasteride, whereas no significant differences were observed in PV, Qmax, and PVRV. The two drugs appeared to exhibit similar rates of adverse reactions. In contrast to finasteride, dutasteride offered a significant improvement in patients with LUTS; however, long‑term use of dutasteride may result in low PSA levels, which may lead to a significant reduction in the relevance ratio of PSA regarding PC.
