Effects of Steroidal Antiandrogen or 5-alpha-reductase Inhibitor on Prostate Tissue Hormone Content

Shibata, Yasuhiro; Arai, Seiji; Miyazawa, Yoshiyuki; Shuto, Takahide; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Ito, Kazuto; Suzuki, Kazuhiro

doi:10.1002/pros.23315

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…Currently, dutasteride inhibits two subtypes of 5AR, and has a 45 times greater affinity for type I and a 2.5 times greater affinity for type II than finasteride. As a result of this higher affinity, dutasteride effectively inhibits DHT much more rapidly than finasteride [31, 32]. Our study found that dutasteride can also be used as an effective ingredient in combination medication, which may be even superior to past management.…”

Section: Discussionmentioning

confidence: 78%

“…Tamsulosin can selectively block α1-adrenergic receptor in the prostate to relax the smooth muscles of the prostate, expanding the prostatic part of the urethra, changing the symptoms of urinary and reducing the possibility of acute urinary retention [12]. Correspondingly, 5ARI inhibits the growth of PV by suppressing the generation of DHT and relieves pressure on the urethra from the large prostate gland [31]. Eventually, The corporate action of the two drugs results in a reduced risk of clinical progression.…”

Section: Discussionmentioning

confidence: 99%

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Meta-analysis of the efficacy and safety of combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia

Zhou

Ding

et al. 2019

BMC Urol

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BackgroundWe performed a meta-analysis to confirm the efficacy and safety of the combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia (BPH) during a treatment cycle of at least 1 year.MethodsRandomized controlled trials were searched by using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. Systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The data was evaluated and statistically analyzed by using RevMan version 5.3.0.ResultsFive studies including 4348 patients were studied. The analysis found that the combination group was significantly greater effect in international prostate symptom score (mean difference [MD], − 1.43; 95% confidence interval [CI], − 2.20 to − 0.66; P = 0.0003), prostate volume (MD, − 10.13; 95% CI, − 12.38 to − 7.88; P < 0.00001), transitional zone volume (MD, − 3.18; 95% CI, − 3.57 to − 2.79; P<0.0001), maximum urine flow rate (MD, 1.05; 95% CI, 0.82 to 1.29; P < 0.00001), prostate specific antigen (MD, − 0.54; 95% CI, − 0.80 to − 0.29; P < 0.0001) and post-void residual volume (MD, − 3.85; 95% CI, − 4.95 to − 2.76; P < 0.00001) compared with the tamsulosin group. In terms of safety, including adverse events (odds ratio [OR], 2.06; 95% CI, 1.34 to 3.17; P = 0.001), erectile dysfunction (OR, 2.24; 95% CI, 1.73 to 2.92; P < 0.00001), ejaculation disorder (OR, 3.37; 95% CI, 1.97 to 5.79; P < 0.0001), retrograde ejaculation (OR, 2.30; 95% CI, 1.08 to 4.93; P = 0.03), decreased libido (OR, 2.25; 95% CI, 1.53 to 3.31; P < 0.0001) and loss of libido (OR, 3.38; 95% CI, 1.94 to 5.88; P<0.0001), the combination group showed poor tolerance than the tamsulosin group with the exception of dizziness (OR, 1.16; 95% CI, 0.75 to 1.80; P = 0.50). The combination group significantly reduced the risk of clinical progression than the tamsulosin group especially in incidence of BPH-related symptom progression (OR, 0.56; 95% CI, 0.46 to 0.67; P < 0.00001) and acute urinary retention (OR, 0.61; 95% CI, 0.38 to 0.98; P = 0.04).ConclusionThe combination of tamsulosin plus dutasteride provides a preferable therapeutic effect for BPH with a higher incidence of sexual side effects, but combination-therapy can markedly reduce risk of BPH-related symptom progression and acute urinary retention relative to tamsulosin monotherapy.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Meta-analysis of the efficacy and safety of combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia

Zhou

Ding

et al. 2019

BMC Urol

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“…A previous study demonstrated that the normal development of the prostate and the progression of BPH are inseparable from the role of DHT, which has a high affinity for the androgen receptor and an inhibitory effect on testosterone (6). The catalytic enzyme that converts testosterone to DHT is 5AR, and 5ARIs inhibit the increase of the PV by suppressing the generation of DHT (30). A previous study found that dutasteride was 45-fold more effective in inhibiting type 1 5AR and 2.5-fold more effective in inhibiting type 2 5AR compared with finasteride (31).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of dutasteride compared with finasteride in treating males with benign prostatic hyperplasia: A meta‑analysis of randomized controlled trials

Zhou

Cui

et al. 2020

Exp Ther Med

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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 by 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.

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“…The E2 prostatic tissue concentrations were quantified using the LC-MS/MS method. Details of the LC-MS/MS procedure for tissue hormone quantification have been reported previously [ 62 ]. The estrogen content of each sample was measured by the concentrations of standard E2.…”

Section: Methodsmentioning

confidence: 99%

Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis

et al. 2022

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Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-β1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.

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Effects of Steroidal Antiandrogen or 5-alpha-reductase Inhibitor on Prostate Tissue Hormone Content

Abstract: Although treatment with AA and 5ARI show similar clinical outcomes, their effect on tissue hormone content and metabolism varied greatly. Prostate 77: 672-680, 2017. © 2017 Wiley Periodicals, Inc.

Cited by 8 publications

References 32 publications

Meta-analysis of the efficacy and safety of combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia

Meta-analysis of the efficacy and safety of combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia

Efficacy and safety of dutasteride compared with finasteride in treating males with benign prostatic hyperplasia: A meta‑analysis of randomized controlled trials

Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis

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