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A Dual 5α-Reductase Inhibitor Dutasteride Caused Reductions in Vascular Density and Area in Benign Prostatic Hyperplasia  [PDF]
Masayoshi Zaitsu,Akiko Tonooka,Koji Mikami,Mami Hattori,Yuta Takeshima,Toshimasa Uekusa,Takumi Takeuchi
ISRN Urology , 2013, DOI: 10.1155/2013/863489
Abstract: Objectives. Dutasteride, a dual 5α-reductase inhibitor, is used to treat benign prostatic hyperplasia. Nevertheless, its histopathological effects on the morphometrics of blood vessels and glands are still controversial. The aim here was to assess the histopathological effects of dutasteride in cases of benign prostatic hyperplasia in a retrospective study. Methods. Patients with benign prostatic hyperplasia more than 40?cm3 in prostatic volume were administered 0.5?mg of dutasteride daily or left untreated prior to receiving a transurethral resection of the prostate. Images of sections stained with hematoxylin/eosin and with anti-CD31 antibody were analyzed. Results. In the dutasteride-treated group, the duration of administration was weeks. Artery/arteriole density and vein/venule density in benign prostatic tissue were both lower in the dutasteride-treated group than in the control group. The vein/venule area as a percentage of the whole area was also lower in the dutasteride-treated group, while the artery/arteriole area did not show a significant difference. Glandular/CD31-expressing vessel densities as well as glandular/CD31-expressing vessel areas were comparable between the two groups. Conclusions. Dutasteride reduced the artery/arteriole and vein/venule densities and the proportion of vein/venule area in the tissue of patients with benign prostatic hyperplasia. 1. Introduction Benign prostatic hyperplasia (BPH) is a histologic diagnosis that refers to the proliferation of smooth muscle and epithelial cells within the prostatic transition zone, for which dihydrotestosterone (DHT) is the primary androgen responsible in elderly men [1]. As the initial treatment for symptomatic BPH, pharmacotherapy with -adrenergic blockers, -reductase inhibitors, antimuscarinic agents, or a combination thereof is often used [2]. Type 1 and type 2 isoenzymes of -reductase are present throughout the body [3], and dutasteride, a dual -reductase inhibitor, acts competitively and specifically on type 1 and type 2 isoenzymes to inhibit the conversion of testosterone to the more potent DHT [4–6]. In comparison with finasteride, a -reductase inhibitor selectively acting on type 2 isoenzyme [7], dutasteride is a 45-fold greater inhibitor of type 1 -reductase, and a 2.5-fold greater inhibitor of type 2 -reductase [8–10]. Patients with BPH who do not respond suitably to pharmacotherapy often undergo transurethral resection of the prostate (TUR-P), the gold standard for the surgical treatment of BPH, and microwave thermotherapy [11] in order to improve symptoms of bladder
BENIGN PROSTATIC HYPERPLASIA
Muhammad Aslam
The Professional Medical Journal , 1998,
Abstract: OBJECTIVE: This study was conducted to demonstrate the efficacy of transurethral resection of prostate(TURP) in patients of benign prostatic hyperplasia (BPH) who presented with severe prostatic symptomsor retention of urine. SETTING: Urology departments of Lahore General Hospital Lahore and MayoHospital Lahore. STUDY DESIGN: Prospective. PERIOD OF STUDY: June 1993 to April 1995.MATERIALS AND METHODS: Thirty patients of BPH who presented with severe prostatic symptomsor retention of urine were included in this study. Symptoms scoring was done according to the InternationalProstate Symptoms Score (IPSS). RESULTS: Pre-operative mean symptoms score was 34.20. The meansymptoms score reduced to 10.779, 8.03, 5.50, 4.33, 3,73 and 3.37 respectively during six months of followup after TURP. CONCLUSION: TURP is still the gold standard as a treatment modality of benign prostatichyperplasia in those patients presenting with retention of urine or severe prostatic symptoms.
Nocturia and benign prostatic hyperplasia  [PDF]
Laketi? Darko,Laketi? Vesna
Vojnosanitetski Pregled , 2008, DOI: 10.2298/vsp0810751l
Abstract: Background/Aim. Nocturia often occurs in patients with benign prostate hyperplasia (BPH). The aim of the study was to investigate the frequency of nocturia in patients with BPH. Nocturia and other factors associated with it were also investigated. Methods. Forty patients with the confirmed diagnosis of BPH were studied. Transurethral and transvesical prostatectomy were performed in all the patients. Symptoms were evaluated with the International Prostate Symptom Score before, as well as three and six months after the surgery. All the results were compared with the control group. Results. There was no statistically significant difference between the patients before and after the surgery regarding nocturia. There was, however, a statistically significant difference between the operated patients and the control group regarding nocturia, as well as a statistically significant correlation between noctruia and the age of the patients in both the investigated and the control group. A correlation also existed between nocturia and the prostatic size. Conclusion. There was no statistically significant improvement in symptoms of nocturia after the surgery. It is necessary to be very careful in decision making in patients with nonabsolute indiction for surgery and isolated bothersome symptom of nocturia. Age of a patient should also be considered in the evaluation of favorable result of the surgery because of a significant correlation between noctura and the age of a patient.
Benign prostatic hyperplasia: An overview of existing treatment  [cached]
Dhingra Neelima,Bhagwat Deepak
Indian Journal of Pharmacology , 2011,
Abstract: Benign prostatic hyperplasia (BPH) is the most common condition in aging men, associated with lower urinary tract symptoms (LUTS). A better understanding of the prostate physiology, function, and pathogenesis has led to the development of promising agents, useful in the management of LUTS in men. The specific approach used to treat BPH depends upon number of factors like age, prostrate size, weight, prostate-specific antigen level, and severity of the symptoms. 5α-reductase inhibitors decrease the production of dihydrotestosterone within the prostate, which results in decreased prostate volume, increased peak urinary flow rate, improvement of symptoms, decreased risk of acute urinary retention, and need for surgical intervention. α1 -adrenergic receptor (α1 -AR) 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. Clinical efficacy of either 5α-reductase inhibitor or α1 -AR antagonist has been further improved by using combination therapy; however, long-term outcomes are still awaited. Many more potential new therapies are under development that may improve the treatment of BPH. This article gives a brief account of rationale and efficacy of different treatment options presently available in the management of BPH.
Silodosin in the treatment of benign prostatic hyperplasia  [cached]
Maxime Rossi,Thierry Roumeguère
Drug Design, Development and Therapy , 2010,
Abstract: Maxime Rossi, Thierry RoumeguèreDepartment of Urology, Erasme Hospital, University Clinics of Brussels, ULB, Brussels, BelgiumAbstract: Benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS due to BPH. Alpha-adrenergic receptor blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit early onset of efficacy with regard to both symptoms and flow rate improvement, and this is clearly demonstrated in placebo-controlled trials with extensions out to five years. These agents have been shown to prevent symptomatic progression of the disease. The aim of this article is to offer a critical review of the current literature on silodosin, formerly known as KMD-3213, a novel alpha-blocker with unprecedented selectivity for a1A-adrenergic receptors, as compared with both a1B- and a1D -adrenoceptors, exceeding the selectivity of all currently used a1-blockers, and with clinically promising effects.Keywords: silodosin, a1A- blockers, lower urinary tract symptoms, benign prostatic hyperplasia, uroselectivity
Management of benign prostatic hyperplasia with silodosin
Tomonori Yamanishi,Tomoya Mizuno Takao Kamai,et al
Open Access Journal of Urology , 2009,
Abstract: Tomonori Yamanishi1, Tomoya Mizuno1, Takao Kamai1, Ken-ichiro Yoshida1, Ryuji Sakakibara2, Tomoyuki Uchiyama31Department of Urology, Dokkyo Medical University, Tochigi, Japan; 2Department of Neurology, Sakura Hospital, Toho University, Toho, Japan; 3Department of Neurology, Chiba University, Chiba, JapanAbstract: It has been reported that blockade of α1A-adrenoceptor (AR) relieves bladder outlet obstruction, while blockade of α1D-AR is believed to alleviate storage symptoms due to detrusor overactivity. Silodosin, (-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy) phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7- carboxamide, is a new α1A-AR selective antagonist. Silodosin is highly selective for the α1A-AR subtype, showing an affinity for the α1A-AR that is 583- and 55.5-fold higher than its affinity for the α1B- and α1D-ARs, respectively. In randomized, double-blind, placebo-controlled phase III studies performed in Japan and the United States, silodosin has been shown to be effective for both storage and voiding symptoms associated with benign prostatic hyperplasia. Early effects of silodosin (after 2–6 hours or day 1) on lower urinary tract symptoms have also been reported. In urodynamic studies, detrusor overactivity disappeared in 40% and improved in 35% of patients after administration. In pressure flow studies, the grade of obstruction on the International Continence Society nomogram showed improvement in 56% of patients. The rate of adverse events in the silodosin, tamsulosin and placebo groups was 88.6%, 82.3%, and 71.6%, respectively. The most common adverse event was (mostly mild) abnormal ejaculation (28.1%). However, few patients (2.8%) discontinued silodosin because of abnormal ejaculation. Orthostatic hypotension showed a similar incidence in the silodosin (2.6%) and placebo (1.5%) groups. In conclusion, silodosin improves detrusor overactivity and obstruction and thus may be effective for both storage and voiding symptoms in patients with benign prostatic hyperplasia.Keywords: alpha-blocker, silodosin, benign prostatic hyperplasia, lower urinary tract symptoms
Silodosin in the treatment of benign prostatic hyperplasia
Maxime Rossi, Thierry Roumeguère
Drug Design, Development and Therapy , 2010, DOI: http://dx.doi.org/10.2147/DDDT.S10428
Abstract: dosin in the treatment of benign prostatic hyperplasia Review (6524) Total Article Views Authors: Maxime Rossi, Thierry Roumeguère Published Date October 2010 Volume 2010:4 Pages 291 - 297 DOI: http://dx.doi.org/10.2147/DDDT.S10428 Maxime Rossi, Thierry Roumeguère Department of Urology, Erasme Hospital, University Clinics of Brussels, ULB, Brussels, Belgium Abstract: Benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS due to BPH. Alpha-adrenergic receptor blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit early onset of efficacy with regard to both symptoms and flow rate improvement, and this is clearly demonstrated in placebo-controlled trials with extensions out to five years. These agents have been shown to prevent symptomatic progression of the disease. The aim of this article is to offer a critical review of the current literature on silodosin, formerly known as KMD-3213, a novel alpha-blocker with unprecedented selectivity for a1A-adrenergic receptors, as compared with both a1B- and a1D -adrenoceptors, exceeding the selectivity of all currently used a1-blockers, and with clinically promising effects.
Management of benign prostatic hyperplasia with silodosin
Tomonori Yamanishi, Tomoya Mizuno Takao Kamai, et al
Research and Reports in Urology , 2009, DOI: http://dx.doi.org/10.2147/RRU.S5004
Abstract: nagement of benign prostatic hyperplasia with silodosin Review (6331) Total Article Views Authors: Tomonori Yamanishi, Tomoya Mizuno Takao Kamai, et al Published Date August 2009 Volume 2009:1 Pages 1 - 7 DOI: http://dx.doi.org/10.2147/RRU.S5004 Tomonori Yamanishi1, Tomoya Mizuno1, Takao Kamai1, Ken-ichiro Yoshida1, Ryuji Sakakibara2, Tomoyuki Uchiyama3 1Department of Urology, Dokkyo Medical University, Tochigi, Japan; 2Department of Neurology, Sakura Hospital, Toho University, Toho, Japan; 3Department of Neurology, Chiba University, Chiba, Japan Abstract: It has been reported that blockade of α1A-adrenoceptor (AR) relieves bladder outlet obstruction, while blockade of α1D-AR is believed to alleviate storage symptoms due to detrusor overactivity. Silodosin, (-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy) phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7- carboxamide, is a new α1A-AR selective antagonist. Silodosin is highly selective for the α1A-AR subtype, showing an affinity for the α1A-AR that is 583- and 55.5-fold higher than its affinity for the α1B- and α1D-ARs, respectively. In randomized, double-blind, placebo-controlled phase III studies performed in Japan and the United States, silodosin has been shown to be effective for both storage and voiding symptoms associated with benign prostatic hyperplasia. Early effects of silodosin (after 2–6 hours or day 1) on lower urinary tract symptoms have also been reported. In urodynamic studies, detrusor overactivity disappeared in 40% and improved in 35% of patients after administration. In pressure flow studies, the grade of obstruction on the International Continence Society nomogram showed improvement in 56% of patients. The rate of adverse events in the silodosin, tamsulosin and placebo groups was 88.6%, 82.3%, and 71.6%, respectively. The most common adverse event was (mostly mild) abnormal ejaculation (28.1%). However, few patients (2.8%) discontinued silodosin because of abnormal ejaculation. Orthostatic hypotension showed a similar incidence in the silodosin (2.6%) and placebo (1.5%) groups. In conclusion, silodosin improves detrusor overactivity and obstruction and thus may be effective for both storage and voiding symptoms in patients with benign prostatic hyperplasia.
Current status of 5α-reductase inhibitors in the treatment of benign hyperplasia of prostate  [cached]
Kumar Vijay,Wahane Vishal
Indian Journal of Medical Sciences , 2008,
Abstract: Benign prostatic hyperplasia (BPH) is a common problem in aging men, which is associated with lower urinary tract symptoms. This condition is dependent on the presence of androgens for its progression, and medical therapy is the first-line treatment for BPH patients with moderate-to-severe symptoms and includes the use of either alpha 1-adrenergic blockers or 5α-reductase inhibitors. Adrenergic blocking drugs reduce the dynamic component while the 5α-reductase inhibitors reduce the static component of bladder outlet obstruction in BPH. By inhibiting the generation of active form of testosterone, viz., dihydrotestosterone, the 5α-reductase inhibitors not only reduce the symptoms of BPH but also decrease the need for surgery and further progression of BPH. Besides, prolonged use of combination of 5α-reductase inhibitors and alpha 1-adrenergic blockers has been found to be more beneficial than either of the two drugs given alone. This review gives a brief account of rationale and efficacy of treatment by 5α-reductase inhibitors in the management of BPH.
NEW TRENDS IN THE MANAGEMENT OF BENIGN PROSTATIC HYPERPLASIA
Safdar H. Javed Sial
The Professional Medical Journal , 1995,
Abstract: Benign prostate hyperplasia (BPH) is the most common urological disease of the old age. If the patient presentswith early prostatic symptoms without urinary obstruction, medical treatment should be advised. If there aresignificant obstructive prostatic symptoms, transurethral resection of prostate (TURP) is the answer providedthe patient is fit for anaesthesia. If the patient is unfit, prostatic stents can be advised.
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