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PubMed2000

The clinical role of alpha-blockers in the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a highly prevalent condition that represents a significant health problem, which is likely to worsen as the population continues to age. alpha-1 adrenoceptor antagonists have been used in the treatment of this condition for well over 20 years and much is now known about their effects on the urinary tract. As these drugs have improved, their use as a first line treatment option in patients with lower urinary tract symptoms (LUTS), secondary to BPH, has continued to increase. This review details some of the background and rationale for the use of these drugs and, using the available information, compares their efficacy and tolerability profiles.

Adrenergic alpha-Antagonists↗

PubMed2002

Does the prostatic vascular system contribute to the development of benign prostatic hyperplasia?

Benign prostatic hyperplasia (BPH) is a disease condition characterized by abnormal prostate growth in conjunction with distinct lower urinary tract symptoms. This paper considers the extent to which the prostatic vascular system contributes to normal prostate growth control as well as whether abnormal blood flow patterns in the aging prostate gland might lead to hypoxia-stimulated prostate growth. This relationship is posited from accumulated research that suggests the prostatic vascular system is a primary androgen action target and other research demonstrating the diverse effects of hypoxia in eliciting cell death or cell growth responses. This hypothesis is further supported by the coincidental clinical finding that the presence of cardiovascular disease conditions are among the general risk factors for the development of BPH, and that cardiovascular-active drugs can be used for the treatment of BPH symptoms. This hypothesis has major implications for our understanding of the etiology of BPH, as well as for the development of new and better treatments for this extremely common condition.

Adrenergic alpha-Antagonists↗

PubMed2006

Turbulent urinary flow in the urethra could be a causal factor for benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common form of prostate disease in middle-aged and elderly men, and leads to severe impairment later in life. Despite its significant impact on public health, the underlying cause of BPH is yet to be determined. This hypothesis proposes a new causal factor for BPH. Applying concepts of dynamics of fluids to the process of urination it could be stated that a turbulent urinary flow through the passage of the urethra. The turbulent urinary flow in the urethra applies pressure and stretch forces to the surrounding tissue. This stimulus repeated over time and coupled with age-related changes of the urethral tissue could contribute to the development of BPH. In support of this hypothesis, several mechanotransduction studies have shown that vibration and pressure forces applied to different cell tissues can provoke cellular and molecular changes. Another supportive data is the presence of the hyperplasic reaction surrounding the urethra specifically located in the transition zone, the only zone where BPH develops. It is crucial to identify causal factors to understanding the disease and to determine effective primary prevention strategies. Future studies of the dynamics of fluids in the urethra are warranted. The finding of significant forces transmitted to the periurethral tissue from a turbulent urinary flow could give us the clue to the underlying cause of BPH. If this hypothesis proves to be valid there are several primary prevention measures that could be implemented to impede the development of BPH. Educational intervention measures in younger populations to avoid frequent urinary retention and active urination (process of forcing the urine through the urethra at a high velocity) could be considered. Studies of the impact of turbulence in the standing vs. sitting position during urination in men should also be considered.

Aged↗

PubMed2004

[Dutasteride: main results in the treatment of benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is a progressive disease characterized by an increase in prostatic volume. The resulting urinary irritative and/or obstructive symptoms, when present, often reduce the patient's quality of life. Prostatic dihydrotestosterone, the androgen produced following transformation of testosterone by the enzyme 5-alpha-reductase, is responsible for these changes. Among various products used for drug therapy, 5-alpha-reductase inhibitors play a specific role in the long-term management of BPH. Between the two currently available products, dutasteride is the only dual 5-alpha-reductase inhibitor (types 1 and 2). The efficacy of dutasteride was tested in several scientific studies and the cumulative results of three controlled, double-blind pivotal studies, showed at 2-year a clear improvement in all parameters modified during this disorder. A significant decrease in the severity and frequency of the urinary symptoms, in prostate volume, the risk of urine retention, the necessity to resort to surgery and an increase in peak urinary flow were observed with dutasteride. These results were confirmed in the 4-year-open label extension of these pivot studies both for tolerability of the product and the maintenance of its efficacy over time.

Azasteroids↗

PubMed1995

Benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a pathologic disorder that develops in response to the action of dihydrotestosterone on the aging prostate and to changes in stromal and epithelial cells in this exocrine gland. The current therapies for this disorder are chosen after other causes for irritative and obstructive symptoms have been excluded and the status of the urinary tract has been assessed. This evaluation includes a detailed medical history, a thorough genitourinary and neurological examination, assessment of serum prostate specific antigen and creatinine levels, as well as a urinalysis. A urodynamic evaluation consisting of a combined pressure-flow study is required if the diagnosis of obstruction is to be made. Patients with minimal symptoms and normal test results require no therapy. Mild to moderate symptoms can be controlled, at least temporarily, with alpha-adrenergic blockers such as terazosin or doxazosin. A subset of BPH patients with obstructive symptoms respond to the 5 alpha-reductase inhibitor finasteride. Early results with minimally invasive treatments such as laser prostatectomies, hyperthermia, and ultrasonic and radiofrequency ablation appear encouraging for those with moderate symptoms of prostatism. Severe symptoms, urinary retention, gross hematuria, recurrent urinary tract infections, bladder calculi, and hydronephrosis or renal insufficiency warrant transurethral incision, resection, vaporization, or open prostatectomy (for very large neoplasms). Although the morbidities of these latter surgical therapies are not insignificant, these treatments offer the best and most durable results for relief of obstruction and amelioration of symptoms.

Adrenergic alpha-Antagonists↗

PubMed2001

Evaluation of symptoms and quality of life in men with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common histologic condition among older men, which conveys its morbidity through lower urinary tract symptoms and complications, such as acute urinary retention, obstructive uropathy, and urinary tract infections. The mechanisms linking the histologic process and lower urinary tract symptoms remain uncertain; prostatic enlargement and bladder outlet obstruction are involved. However, measurements of prostate size and the severity of bladder outlet obstruction correlate poorly with the severity of lower urinary tract symptoms. The severity of lower urinary tract symptoms associated with BPH can be measured reliably, from the patient's perspective, with a number of validated questionnaires, including the International Prostate Symptom Score, the Danish Prostate Symptom Score, and the International Continence Society (ICS)male questionnaire. In the clinical setting, these questionnaires can be used (1) to assess the severity of symptoms in men with lower urinary tract symptoms that may be attributable to BPH, based on their age and clinical characteristics; and (2) to follow changes in symptoms over time and with treatment. None of these questionnaires can accurately determine whether a symptomatic patient has underlying bladder outlet obstruction. Additional questionnaires are available to measure the impact of lower urinary tract symptoms on men's lives, as well as associated phenomena, such as continence and sexual function, which may be affected by BPH and its treatments. Men with a severe burden of lower urinary tract symptoms often have measurable decrements in overall health-related quality of life, which can be ameliorated by treatment.

Aged↗

PubMed1995

Worldwide patterns of prevalence and mortality from benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) can be found in 88% of autopsies in men > or = 80 years, with compatible symptomatology reported in nearly 50% of men aged > or = 50 years in the general population. Despite such a common occurrence, little is known with any certainty about the epidemiology of BPH (for which "prostatism" is a commonly, and wrongly, used synonym). Knowledge of risk factors is sparse: analytic epidemiologic studies of BPH are difficult to conduct. It is essential to establish an epidemiologic definition of BPH for these reasons. Both BPH and prostatism are the problems that seem set to increase in absolute terms. They are clearly identified as priority areas for research into their causes and treatment. However, it is clear that there is a great need for more epidemiologic information, particularly regarding prostatism, whose occurrence is unknown in many parts of the world.

Global Health↗

PubMed1999

High intensity focused ultrasound in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is an extremely common condition and represents a major health issue in terms of patient numbers and treatment cost. Traditionally, the choice of treatment has been between watchful waiting and surgery, however, the side effects of surgery lead to reluctance for treatment in many men, other than those with severe symptoms and complications. In the last 2 decades there has been a rapid expansion in the number of treatments being offered and the number of patients submitting to novel therapies. Medical management has evolved to achieve a central role in the management of BPH. Heat based treatments are also being investigated with considerable interest. Transrectal high intensity focused ultrasound (HIFU) is one such treatment, which allows radiation-free treatment, without the need for intra-urethral manipulation. Imaging can be performed during treatment and treatment results in symptomatic improvement, which is retained with medium-term follow-up. It involves a brief hospital stay and post-operative complications are few. The use of HIFU has also been extended to the treatment of renal, prostatic and bladder tumours and the results in these areas suggest further expansion of its role in urological practice.

Follow-Up Studies↗

PubMed2006

Drug Insight: 5alpha-reductase inhibitors for the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common problem among older men, which is characterized by an enlarged prostate, lower urinary tract symptoms, and decreased flow of urine. It is a progressive disease that can lead to complications such as acute urinary retention (AUR) or a need for BPH-related surgery in some men. Dihydrotestosterone is the primary androgen involved in both normal and abnormal prostate growth and 5alpha-reductase inhibitors (5ARIs) inhibit the conversion of testosterone to dihydrotestosterone. There are two 5ARIs licensed for the treatment of BPH; dutasteride, which inhibits both type 1 and type 2 isoenzymes of 5alpha reductase, and finasteride, which inhibits the type 2 isoenzyme. Both 5ARIs have been shown to decrease prostate volume, improve urinary flow and lower urinary tract symptoms and reduce the risk of AUR and BPH-related surgery. The prevention of disease progression, by treating the underlying cause, and the alleviation of symptoms are important aims of BPH therapy. 5ARIs are the only currently available medical therapy that can reduce the risk of AUR and BPH-related surgery while providing long-term symptom control. This provides a mandate for their use in men with enlarged prostates (volume >or=30 ml), who are at increased risk of disease progression.

5-alpha Reductase Inhibitors↗

PubMed2000

Models for studying benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most common diseases affecting aging man. Attempts have been made to clarify the etiology and pathogenesis and, to that end, experimental models have been developed. To date, in vitro and in vivo models have been used, depending on the concept of the study. Spontaneous animal models are limited to the chimpanzee and the dog. Ethical and financial factors restrict the applicability of these models. The hormonal-induced canine BPH model is a good alternative that closely resembles human BPH in many aspects. The experimental models currently used for studying BPH are reviewed. Prostate Cancer and Prostatic Diseases (2000) 3, 28-33

Journal Article↗

PubMed2006

Evidence of a novel biomarker, alphas1-Casein, a milk protein, in benign prostate hyperplasia.

Benign prostate hyperplasia (BPH) is a common disease in elderly men. Although it is a non-malignant disease, it has a significant detrimental impact on the quality of life in patients with late-stage disease. Owing to the lack of specific markers, diagnosis of early-stage BPH has been proven unsuccessful. Recently, using two-dimensional electrophoresis, we identified a group of prostatic secretory proteins that are specifically produced by BPH cells (Xu et al., Electrophoresis 2003; 24: 1311). In this study, we investigated the potential diagnostic value of one of the secretory proteins, alphas1-Casein, in BPH by inmmunohistological staining of normal, BPH and prostate cancer tissues. We found that 90% (20 out of 22) of BPH tissues showed moderate to strong alphas1-Casein protein expression whereas none of the normal tissues (0 out of 10) and less than 10% of the prostate cancer tissues (3 out of 30) showed similar staining intensity. Our results suggest that alphas1-Casein may be a potential biomarker for early identification of BPH patients.

Adenocarcinoma↗

PubMedDate not supplied

Infrared microspectroscopic detection of epithelial and stromal growth in the human benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men. It describes an overgrowth of the epithelial and fibromuscular tissues in the human prostate, in which both epithelium and stroma continue to proliferate at different rates. There is lack of suitable techniques for direct evaluation of the biophysical structure of molecular constituents and the proliferative changes in the structure of both compartments at the microscopic level. Reflectance Fourier transform infrared (FT-IR) microspectroscopy was used to pathologically image and examine the structural changes in the proliferation of epithelial and stromal tissues of human BPH. Two successive thin tissue slices were obtained by cutting the tissue with a microtome: one unstained slice was used for FT-IR spectroscopic analysis and the other stained slice was used for position referencing. The result indicates that the amide I maximum for BPH epithelial tissue was near 1,638 cm(-1) and showed its protein secondary structure by a combination of unordered and beta-sheet structures. However, an intense absorption band of amide I was at 1,630 cm(-1) for stromal BPH tissue due to the predominant beta-sheet structure. The higher peak intensity of several IR bands at 1,337, 1,281, 1,238, 1,206, 1,055, and 1,034 cm(-1), assigned to the C-O stretching mode of collagen, was observed in BPH stromal tissue. This suggests that the obvious collagen will be more enriched in the stroma of BPH tissue.

Aged↗

PubMed1995

Defective functional response to membrane stimuli in lymphocytes from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a local disturbance in the prostate that may involve an inflammatory infiltrate predominantly composed of activated lymphocytes and macrophages. The activation and proliferative response of T lymphocytes to different mitogenic signals has been analysed in peripheral blood mononuclear cells (PBMC) from 45 patients with BPH and 55 healthy controls. The PBMC obtained from the patients showed a significant specific impairment in proliferation, CD25 expression and IL-2 production in response to stimulation with lectins (phytohaemagglutinin (PHA), concanavalin A (Con A)), that was not corrected by the addition of IL-2 or of phorbol esters (phorbol myristate acetate (PMA)). Also, the CD28 response was defective in patient PBMC. Activation with anti-CD3 or anti-CD2 MoAbs was normal, but the addition of PMA to these stimuli provoked a significant defective response. Only the use of transmembrane stimuli (PMA and ionomycin) elicited responses similar to those found in the control group. The results indicate that peripheral T lymphocytes from BPH patients show a functional impairment that is mainly explained by an alteration of membrane signals (PHA, CD28) and is distal to protein kinase C (PKC) activation.

Aged↗

PubMed2006

Efficacy and safety of alfuzosin 10 mg once daily in the treatment of symptomatic benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disorder in ageing men. Patients with BPH often present with bothersome irritative and obstructive lower urinary tract symptoms -- urgency, frequency, nocturia, feeling of insufficient bladder emptying and weak or intermittent flow. alpha(1)-Blockers are the most frequently prescribed oral medications for the first-line treatment of the symptoms associated with BPH. Alfuzosin is a uroselective alpha(1)-blocker that relaxes the smooth muscle of the bladder neck and prostate gland to alleviate BPH symptoms. A pooled analysis of three phase III trials confirmed that treatment with alfuzosin 10 mg q.d. significantly improves the peak urinary flow rate and symptom severity compared with placebo treatment. Unlike some other alpha(1)-blockers, alfuzosin 10 mg q.d. is associated with a low incidence of sexual and vasodilatory side effects. Based on the clinical trials reviewed, alfuzosin 10 mg q.d. is an effective and well-tolerated treatment for the urinary symptoms associated with BPH.

Adrenergic alpha-Antagonists↗

PubMed2004

Saw palmetto and benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common health issue that affects 8% of all men at the age of 40, 60% of men in their 70s, and 90% of those greater than 80 years of age. One-fourth of these men will develop moderate to severe lower urinary tract symptoms that greatly affect their quality of life. Recent evidence suggests that the use of saw palmetto leads to improvements in urinary function for those suffering from BPH. The favorable comparison of saw palmetto with tamsulosin, a well-known first line agent in the treatment of urinary tract symptoms, demonstrates promise towards a beneficial effect of this herbal agent, with very few, if any, adverse effects. However, what degree of this beneficial activity is due to placebo effects is yet to be determined. In addition, the precise mechanism of action of saw palmetto in men with BPH remains unclear.

Adrenergic alpha-Antagonists↗

PubMed1997

Management of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common cause of morbidity among older men. Primary care physicians need to develop expertise in its management. The causes of BPH are unknown; aging and the presence of male androgens are the dominant risk factors. Obtaining a medical history is a key step in assessing whether lower urinary tract symptoms are due to BPH or to some other process. A reliable and valid seven-item questionnaire has been developed to objectively assess symptom severity. A focused physical examination including a digital rectal exam should be performed, as well as a urinalysis and serum creatinine. Optional tests include uroflowmetry, post-void residual urine, and prostate-specific antigen measurements. BPH is treated primarily to improve the quality, rather than increase the quantity, of life. Optimal decisions about treatment are best made by a clinician and an informed patient working together.

Humans↗

PubMed2002

alpha-Adrenoceptor antagonists in the treatment of benign prostate hyperplasia.

Benign prostate hyperplasia (BPH) is a common malady affecting elderly men throughout the world, and it is the most common cause of voiding dysfunctions in man. The disease becomes prevalent, as the mean age of the population increases. In BPH the glandular cells and myofibroblasts of periurethral and transition zones proliferate excessively. This excessive growth of tissue mass physically compresses the urethra, leading to urinary obstruction and lower urinary tract symptoms (LUTS). Another major factor that contributes to LUTS in BPH is the increase in smooth muscle tone, a dynamic component. Contraction of the prostate gland is mainly under the control of the autonomic system and is mediated through alpha-adrenoceptors. In addition to alpha1-adrenoceptors, there are many other components that influence growth and contraction of the prostate gland, resulting in the development of BPH and LUTS. The prostate gland is contracted on stimulating 5-HT, endothelin, tachykinin, and muscarinic cholinergic receptors. Growth of the prostate gland is under the control of androgens, endothelin growth factor, vasoactive intestinal peptide, nerve growth factor, and growth hormone. The combination of excessive growth and the tone produced by different components results in LUTS and BPH. alpha1-Adrenoceptor antagonists were successfully used in the treatment of BPH to relieve the LUTS. The high selectivity of alpha1A-adrenoceptor antagonists reflects the uroselectivity. The uroselective compounds like terazosin, doxazosin, tamsulosin, and alfuzosin are in clinical use. Other new potent uroselective compounds, which are analogs of nigulidipine, 5-methyl-urapidil, or naftopidil, are in clinical trials. In addition to alpha-antagonists, antiandrogens (5alpha-reductase inhibitors) and polyherbal formulations are used to treat BPH. The success of BPH treatment lies in the development of new chemical entities which are efficacious as well as more uroselective and hence have least side effects.

Adrenergic alpha-Antagonists↗

PubMed1994

Future implications for the management of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a growing medical problem in terms of morbidity, mortality, and health care costs. Renewed research has highlighted the lack of standardized parameters available with which to define and evaluate BPH and its treatment. The many treatments available, ranging from surgery to watchful waiting, point to the complex pathophysiology of BPH and the subjectivity of the treatment decisions. Workup of patients with micturition disorders, coupled with use of the International Prostate Symptom Score evaluation, permits the development of criteria for evaluating treatment efficacy and acceptable treatment options. Based on double-blind, placebo-controlled trials, a-blockers and finasteride have been accepted as treatment options. The former produce relaxation of the smooth muscle by inhibiting adrenergically induced increases in intracellular calcium. The latter blocks the 5a-reductase system, which effectively stops the conversion of testosterone to dihydrotestosterone. a-Blockers improve symptoms and flow immediately while finasteride diminishes the prostate volume, specifically of glandular tissue, leading to improved symptoms and flow. All other medical and nonmedical treatments require further evaluation by randomized, prospective trials to determine their safety profile and efficacy.

Humans↗