Dutasteride significantly improves quality of life measures in patients with enlarged prostate

O’Leary, Michael P.; Roehrborn, Claus G.; Black, Libby

doi:10.1038/sj.pcan.4500990

Cited by 18 publications

(18 citation statements)

References 17 publications

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“…The current standard therapy for bothersome BPH/LUTS is ␣ 1 -adrenergic antagonist (␣-blocker) and antiandrogenic 5␣-reductase inhibitor, targeting the dynamic and static components, respectively (52,55). Although effective, these drugs may be associated with unwanted side effects, including dizziness, hypotension, and sexual dysfunction, which may be exacerbated by combination therapy (41).…”

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confidence: 99%

Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling

Zhang

Zang

Wei

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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) plays a permissive role in the development of benign prostatic hyperplasia (BPH), and phosphodiesterase 5 inhibitors (PDE5is) have been found to be effective for BPH and lower urinary tract symptoms (LUTS) in clinical trials. This study investigated the effect of T on smooth muscle (SM) contractile and regulatory signaling pathways, including PDE5 expression and functional activity in prostate in male rats (sham-operated, surgically castrated, and castrated with T supplementation). In vitro organ bath studies, real-time RT-PCR, Western blot analysis, and immunohistochemistry were performed. Castration heavily attenuated contractility, including sensitivity to phenylephrine with SM myosin immunostaining revealing a disrupted SM cell arrangement in the stroma. PDE5 was immunolocalized exclusively in the prostate stroma, and orchiectomy signficantly reduced PDE5 immunopositivity, mRNA, and protein expression, along with nNOS and ROK␤ mRNA, whereas it increased eNOS plus ␣ 1a and ␣1b adrenoreceptor expression in castrated animals. The PDE5i zaprinast significantly increased prostate strip relaxation to the nitric oxide donor sodium nitroprusside (SNP) in control but not castrated rats. But SNP alone was more effective on castrated rats, comparable with sham treated with SNP plus zaprinast. T supplementation prevented or restored all above changes, including SNP and zaprinast in vitro responsiveness. In conclusion, our data show that T positively regulates PDE5 expression and functional activities in prostate, and T ablation not only suppresses prostate size but also reduces prostatic SM contractility, with several potential SM contraction/relaxation pathways implicated. Zaprinast findings strongly suggest a major role for PDE5/cGMP in this signaling cascade. PDE5 inhibition may represent a novel mechanism for treatment of BPH. benign prostatic hyperplasia; contraction; lower urinary tract symptoms; phosphodiesterase 5; phosphodiesterase 5 inhibitors; smooth muscle myosin; nitric oxide BENIGN PROSTATIC HYPERPLASIA (BPH), a cause of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in aging men, is a common pathological process with a histological prevalence of ϳ50 -60% for men in their 60s and 80 -90% for men in their 70s and 80s (54). Although the etiology of prostatic hyperplasia is not well understood, androgens and aging are necessary for the development of BPH (55) containing two physiological components, static (increased prostate size) (40) and dynamic [increased prostatic smooth muscle (SM) tone] (11).The dynamic tone of prostatic SM is regulated mainly by the ␣ 1 -adrenoreceptor (72), with up to 50% of the total urethral pressure in BPH patients being attributed to ␣-adrenoreceptormediated muscle tone (18), and ␣ 1 -blockers are the first-line therapy for BPH. Three major subtypes of adrenoreceptors have been identified to exist in the prostate at the molecular level (␣ 1a , ␣ 1b , and ␣ 1d ) (15). Eckert et al. (14), using a patch clamp combined with the fura-2 fluorescence calcium labelin...

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confidence: 99%

Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling

Zhang

Zang

Wei

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…They reported that combination therapy significantly improved disease‐specific HRQoL when compared with each monotherapy. Two other studies assessed the effectiveness of dutasteride over 24 weeks, and both reported dutasteride to significantly improve HRQoL in patients with BPH (Desgrandchamps et al ., ; O'Leary et al ., ). It is interesting to note that the study conducted by O'Leary et al .…”

Section: Resultsmentioning

confidence: 97%

“…Seven studies evaluated the effect of medical therapy on the HRQoL of men with BPH. The study designs were RCT ( n = 3), descriptive comparative studies ( n = 4), and descriptive correlational ( n = 1) (Barkin et al ., ; Desgrandchamps, Droupy, Irani, Saussince, & Comenducci, ; Fourcade et al ., ; Höfner et al ., ; Komiya et al ., ; Montorsi et al ., ; O'Leary, Roehrborn, & Black, ; Suzuki et al ., ). All studies reported significant improvements in HRQoL following medical therapy, except one study by Fourcade et al .…”

Section: Resultsmentioning

confidence: 98%

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Health‐related quality of life and psychological well‐being in men with benign prostatic hyperplasia: An integrative review

Pinto

Chan

et al. 2016

Japan Journal Nursing Sci

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“…Androgens play a key role in prostate development, maturation, homeostasis, and pathogenesis including benign prostatic hyperplasia (BPH) and prostate cancer [1][2][3][4]. Androgen action is mediated through the androgen receptor (AR), a ligand-regulated transcription factor that regulates the expression of many androgen-responsive genes [5,6].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling Reveals Regulation of ERK Phosphorylation by Androgen-Induced Tumor Suppressor U19/EAF2 in the Mouse Prostate

Corrêa

Luo

et al. 2013

Cancer Microenvironment

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U19/EAF2 is regulated by androgens in the prostate and capable of regulating transcriptional elongation of RNA Pol II via interaction with the ELL family proteins. Inactivation of U19/EAF2 induces tumorigenesis in multiple organs; however the mechanism of U19/EAF2 tumor suppression remains unclear. To elucidate potential mechanisms of U19/EAF2 action, we performed cDNA microarray analysis and identified 164 mRNA transcripts regulated by U19/EAF2 in the mouse ventral prostate. Bioinformatics analysis indicated that U19/EAF2 knockout activates the RAS-BRAF-ERK signaling pathway, which is known to play important roles in carcinogenesis. qPCR verified increased expression of BRAF mRNA, and immunostaining and Western blot analysis demonstrated increased expression of p-ERK at the protein level suggested U19/EAF2 knockout activates this important pathway. These findings indicate that loss of EAF2 up-regulates transcription of RAS cascade genes including Grb2, PI3K, and BRAF, leading to elevated p-ERK levels, which may represent a major functional role of U19/EAF2 in the prostate. Furthermore, these observations suggest that U19/EAF2 is a key player in crosstalk between androgen receptor and the RAS-BRAF-ERK signaling pathway.

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Dutasteride significantly improves quality of life measures in patients with enlarged prostate

Cited by 18 publications

References 17 publications

Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling

Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling

Health‐related quality of life and psychological well‐being in men with benign prostatic hyperplasia: An integrative review

Gene Expression Profiling Reveals Regulation of ERK Phosphorylation by Androgen-Induced Tumor Suppressor U19/EAF2 in the Mouse Prostate

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