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Benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common condition, which increases with increasing age. Although not a life-threatening condition, BPH can significantly affect quality of life. BPH manifests clinically with lower urinary tract symptoms (LUTS) and may be associated with sexual dysfunction. As many as 60% of men aged 60 years have some degree of clinical BPH. With the projected increases in the distribution of people over the age of 60, BPH isset to become an even greater problem in men's health.

Age Factors↗

Insulin-like growth factor axis abnormalities in prostatic stromal cells from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. To assess whether patients with BPH have alterations in their prostatic IGF axis, we measured the expression (by Northern blotting) and the production (by Western ligand blotting and RIA) of insulin-like growth factor-II (IGF-II) and IGF-binding proteins (IGFBPs) in prostatic epithelial and stromal cell strains grown from normal (n = 7), hyperplastic (n = 7), and malignant (n = 5) surgical specimens. Levels of IGF-II messenger ribonucleic acid (mRNA; normalized for actin expression) were 10-fold higher in BPH stromal cell strains compared to those in normal stromal cell strains (P < 0.0001). Western ligand blotting of conditioned medium (CM) from normal stromal cells demonstrated the presence of IGFBP-2, -3, and -4. In the CM of BPH stromal cells, IGFBP-2 levels were dramatically reduced to less than 20% of normal (P < 0.001). Additionally, IGFBP-5, which was not observed in significant amounts in normal stromal cell-CM, was found in large quantities in BPH stromal cell-CM. Northern blot analysis of mRNA from normal and BPH stromal cells demonstrated a 5-fold decrease in IGFBP-2 mRNA (P < 0.001) and a 4-fold increase in IGFBP-5 mRNA (P < 0.01) in BPH compared to normal cells. In prostate stromal cells from cancer specimens, no abnormalities were found. No abnormalities were observed in the IGF axis parameters evaluated in prostate epithelial cells from BPH or cancer strains. We conclude that prostatic stromal cell strains isolated from patients with BPH hyperexpress the mRNA for IGF-II and IGFBP-5 while expressing reduced amounts of IGFBP-2 mRNA. IGFBP, but not IGF-II, peptide levels in CM correspond to the mRNA differences. This is the first documentation of altered gene and protein expression in this common disease. We speculate that these abnormalities in the IGF axis may be important in the pathogenesis of BPH.

Blotting, Northern↗

Decreased expression of Wilms' tumor gene WT-1 and elevated expression of insulin growth factor-II (IGF-II) and type 1 IGF receptor genes in prostatic stromal cells from patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. We have previously documented that the insulin-like growth factor (IGF) axis is critical for prostate cell growth and is abnormal in BPH. The type 1 IGF receptor (IGF-1R) is constitutively expressed by most body tissues and plays a significant role in regulating cell proliferation, consistent with the role of its ligands (IGF-I and IGF-II) as important mitogenic factors. The Wilms' tumor gene product (WT-1) is a tumor suppressor that has been shown to be altered in rare kidney tumors and is known to regulate IGF-II and IGF-1R. We investigated the possibility that the expression of prostatic WT-1, IGF-1R, and IGF-II genes is altered in patients with BPH. We utilized primary cultures of prostatic stromal cells grown from normal (n = 9) and hyperplastic (n = 9) surgical specimens and analyzed WT-1, IGF-1R, and IGF-II messenger RNA levels. In all of the BPH cell strains, WT-1 expression (measured by RT-PCR and RNase protection assays) was strikingly lower than that found in normal strains (0-20% of normal, mean 14% of normal, P < 0.01). The expression of both the IGF-1R (300% of normal, P < 0.05) and IGF-II (1000% of normal, P < 0.01) messenger RNAs was higher in BPH strains as compared with normal strains. No changes were seen in stromal cell strains derived from prostatic adenocarcinoma. Thus, in cultured human prostatic stromal cell strains from patients with BPH, decreased WT-1 gene expression is associated with increases in the expression of the IGF-1R and IGF-II genes that are known transcriptional targets of WT-1. These findings indicate that reduced expression of the WT-1 tumor suppressor gene and elevated IGF-1R and IGF-II gene expression may be involved in the pathophysiology of prostatic hyperplasia, implying a new role for the Wilms' tumor gene in nonmalignant states.

Aged↗

Activation of caspases-3, -6, and -9 during finasteride treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) results from an increase in both epithelial and stromal compartments of the human prostate. Although inhibitors of 5alpha-reductase such as finasteride have been shown to reduce the size of BPH tissues by inducing apoptosis, their mechanisms of action still remain unknown. The present study supports that such a process triggered by finasteride is caspase dependent with a possible involvement of two effector caspases (caspase-3 and 6) and two initiator caspases (caspase-8 and 9). Indeed, by using tissues from patients affected by BPH and treated by finasteride (5 mg/d) for 2-3, 6-8, or 27-32 d, we observed that the 5alpha-reductase inhibitor induced apoptosis in epithelial cells (evaluated through cell number positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) as early as 2-3 d of treatment, with a maximal activity (250-fold increase, P < 0.0001) at 6-8 d of treatment. However, after 27-32 d of treatment, the number of apoptotic cells was reduced and was close to control. Caspases-3, -6, -8, and -9 were immunolocalized to (basal and secretory) epithelial cells and to a lesser extent to stromal cells. Activated caspase-3 immunoexpression was restricted to epithelial secretory cells, and its immunostaining intensity appeared to be higher in BPH tissues from patients treated for 2-3 or 6-8 d. Consistently, in Western blotting analyses, activated caspases-3 and -6 were detected as early as 2-3 d of treatment in BPH tissues, and their levels were increased after 6-8 d of treatment. In real time quantitative PCR experiments, caspase-3 and -6 mRNA levels were found to be unchanged after finasteride treatment. Activated caspase-8 was not detected in the different conditions tested, whereas activated caspase-9 protein levels were maximally enhanced after 2-3 d of finasteride treatment. In conclusion, we report here that finasteride treatment of BPH tissues induced a caspase-dependent apoptotic process restricted to epithelial cells by activating effector caspases-3 and -6 and exhibited a transient action because the apoptotic process was no longer observed after 27-32 d of treatment.

Aged↗

Subtype selective alpha1-adrenoceptor antagonists for the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is highly prevalent in the male population beyond the age of 60. Impairment of urinary flow due to prostate enlargement gives rise to symptoms of 'prostatism' that have a detrimental impact on the quality of life. The current trend in the management of symptomatic BPH favours pharmacotherapy as a first line option, while the number of surgical procedures being performed has experienced a steady decline during the last ten years. Among the pharmacological treatments, the use of alpha1-adrenoceptor blockers has demonstrated to be an effective treatment option for BPH. These agents reduce the adrenergic tone to the prostate and increase urinary flow, with a concomitant reduction of lower urinary tract symptoms. The alpha1-blockers currently approved include compounds such as alfuzosin, terazosin and doxazosin, originally developed for the treatment of hypertension, and more recently tamsulosin, an alpha1-subtype selective drug. The blockade of alpha1-adrenoceptors present in vascular smooth muscle is largely responsible for the most prominent side effects of current drugs, which can be severe and require patients dose titration. The limitation imposed by side effects naturally raises the possibility that complete blockade of prostatic alpha1 receptors is not attained at the maximum tolerated dose. The extensive efforts by the pharmaceutical industry towards the development of uroselective alpha1-blockers, is the subject of this review. Advances in the molecular cloning of genes encoding three alpha1-adrenoceptors led to the identification of the alpha1A-subtype as the predominant receptor responsible for the contraction of prostate smooth muscle. In preclinical animal models, selective alpha1A-antagonists have consistently been found to have minimal cardiovascular effects, thus providing a pharmacological rationale for uroselectivity. It has also become apparent, however, that uroselectivity can emerge in a poorly understood manner from the pharmacodynamic properties of compounds without alpha1A-subtype selectivity. Clinical experience with tamsulosin, an alpha1A/alpha1D selective drug, has failed to demonstrate a significant improvement in efficacy beyond that demonstrated for non-subtype selective alpha1-blockers, and gives support to the notion that alpha1A-selective antagonists might achieve greater efficacy for the treatment of BPH. Given the demonstrated uroselectivity of alpha1A-selective antagonists in preclinical models, it is anticipated that third generation alpha1-blockers will exhibit improved urinary flow efficacy and be better tolerated than tamsulosin. The extent to which the improvement in urinary flow will translate to the relief of symptoms of prostatism, however, remains to be demonstrated in randomised placebo-controlled clinical trials of alpha1A-selective antagonists.

Journal Article↗

Emerging drug therapies for benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is the nonmalignant enlargement of the prostate gland caused by increases in number of both epithelial and stromal cells. Clinically, BPH leads to voiding dysfunction, which is most often referred to as lower urinary tract symptoms (LUTS). Historically, the only treatments for LUTS due to BPH were watchful waiting or surgery (transurethral or open prostatectomy). However, over the last 20 years medical therapy has taken a prominent role in the management of BPH. Current medical treatments for BPH include alpha-adrenergic receptor antagonists, inhibitors of the 5-alpha reductase enzyme and various phytotherapies. These agents are generally effective and safe; however, many patients are unable to tolerate the side effects or are refractory to medical management and require surgery. In light of this, many potential new therapies for the treatment of BPH are under development. Some represent a variation of current treatments, whereas others target novel molecular pathways within the prostate. The aim of this review is to examine current pharmacotherapies as well as to highlight emerging drugs that may improve our treatment of patients with LUTS secondary to BPH.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Terazosin. A pharmacoeconomic evaluation of its use in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disorder in elderly men which carries a substantial economic burden. Urinary symptoms associated with moderate to severe disease can significantly interfere with daily activities and reduce quality of life. Obstruction of urine flow in men with BPH can result from nonmalignant enlargement of the prostate gland (static component of BPH) and from alpha 1 receptor-mediated increased smooth muscle tone of the bladder neck and prostate (dynamic component of BPH). Transurethral resection of the prostate (TURP) is generally very effective and has traditionally been the standard treatment for men with moderate to severe BPH. However, response to therapy with TURP is not universal and the procedure is associated with a number of potential complications. Moreover, many men prefer to avoid or are not suitable candidates for this invasive procedure. Thus, there is an increasing role for less invasive treatment, including drug therapy, in men with moderate to severe BPH. Terazosin is an alpha 1 receptor antagonist which has been shown in placebo-controlled trials to significantly improve American Urology Association (AUA) symptom and quality-of-life scores and symptom problem index ('bother' score), as well as increase peak urinary flow rate, in men with BPH. In a recent large randomised US trial, treatment for 1 year with terazosin titrated to 10 mg/day improved mean AUA symptom score and peak urinary flow rate to a significantly greater extent than finasteride 5 mg/day in men with moderate to severe BPH. The most frequently reported adverse events associated with terazosin include dizziness, asthenia, postural hypotension, somnolence, headache, peripheral oedema, nasal congestion/rhinitis and syncope. Approximately 5% of men with BPH discontinue terazosin because of adverse events. Results of an economic evaluation of terazosin, in which both clinical and economic data were collected prospectively in a randomised placebo-controlled study design, showed similar total direct treatment costs per 1000 patients associated with 1 year of therapy with terazosin ($US3.57 million) and placebo ($US3.78 million) in men with moderate to severe BPH (1992 dollars). The analysis, which was conducted from the perspective of a managed care organisation in the US, demonstrated that the lower medication costs in the placebo group relative to the terazosin group were offset by increased inpatient care costs. Thus, terazosin (titrated to response up to a maximum of 10 mg/day) was significantly more effective than placebo in improving disease-specific symptoms and quality of life, but at a similar overall cost to placebo. Another economic analysis, also conducted from a third-party payer perspective in the US, modelled direct treatment costs associated with terazosin, finasteride and TURP during the first 2 years after initiating therapy in men with moderate to severe BPH. Results of the study favoured terazosin; the private insurance cost per patient undergoing primary treatment with TURP was $US6411, compared with $US2860 with finasteride (45% of the cost of TURP) and $US2422 with terazosin (38% of the cost of TURP). Medicare costs were lower for all 3 treatment groups but the relative comparisons were similar; corresponding costs per patient were $US3874, $US2161 and $US1820 (1992 dollars). A companion break-even cost analysis used a hypothetical cohort of men with BPH starting treatment at age 67 years. Private insurance costs associated with terazosin remained lower then those associated with TURP for approximately 15 years (the corresponding break-even point was 10 years for finasteride vs TRUP). Medicare costs associated with terazosin would not exceed those of TURP for approximately 7 years (5.5 years for finasteride vs TURP). In conclusion, a limited number of detailed pharmacoeconomic analysis of terazosin have been conducted to date, although it has not been compared with other a1 receptor antagonists.

Adrenergic alpha-Antagonists↗

Trends in the development of new drugs for treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common condition in aging men that is characterized by nonmalignant enlargement of the prostate gland, and is frequently accompanied by urinary obstruction, and lower urinary tract symptoms (LUST). Currently pharmacotherapy of BPH is based on two classes of drugs: alpha(1)-adrenoceptor (alpha(1)-AR) antagonists and 5alpha-reductase inhibitors. It has been shown that alpha(1)-AR antagonists reduce symptom scores and increase peak urinary flow rates in BPH. Of particular importance for BPH therapy are uroselective alpha(1)-AR antagonists for which the hypotensive related side-effect caused by alpha(1)-AR blockade is reduced. 5alpha-Reductase inhibitors reduce prostate volume and symptom scores, while increasing peak urinary flow rates. This review describes new alpha(1)-AR antagonists and 5alpha-reductase inhibitors in the treatment of BPH. The new alpha(1)-AR antagonists represent various structures such as quinazolines, phenylethylamines, piperidines, and arylpiperazines. 5alpha-Reductase inhibitors are classified into two groups: steroidal and non-steroidal. The newer non-steroidal inhibitors include derivatives of benzo[c]quinolizinones, benzo[f]quinolonones, piperidones and carboxylic acids. Besides the development of new compounds belonging to the above mentioned groups, new agents for BPH treatment are sought among combined 5alpha-reductase/alpha(1)-AR inhibitors, endothelins, androgen receptors antagonists, growth factors, estrogens and phosphodiesterase isoenzymes as well as several phytomedicines, used for prevention and treatment of prostate disorders. These new agents can be used for the design of future targets and development of new drugs in the treatment of BPH. The discovery of a number of active leads may also ultimately help in developing new safe and effective drugs.

5-alpha Reductase Inhibitors↗

Medical therapy for benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common clinical entity in elderly men. We review the epidemiology of BPH and the mechanisms by which it causes bladder outlet obstruction. The currently available medical therapies are examined with respect to mechanism of action, effectiveness, side effects, and cost. They are briefly compared with the more traditional treatment options of watchful waiting and transurethral prostatectomy. A logical approach to the treatment of symptomatic BPH is discussed.

Adrenergic alpha-Antagonists↗

Evaluation and medical management of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is common among aging men. Untreated BPH may lead to complications including urinary tract infection, acute urinary retention, and obstructive nephropathy. Diagnosing BPH can be challenging because lower urinary tract symptoms are found in conditions other than BPH, and prostate size correlates poorly with symptoms of obstruction. Nonetheless, a careful medical history and physical examination, along with prudent use of diagnostic tests, can yield an accurate diagnosis. We review the evaluation of men with suspected BPH and indications for referral to a urologist for invasive therapy. We also review supporting evidence and treatment considerations for saw palmetto and the 2 major classes of prescription medications, alpha1-adrenergic antagonists and 5alpha-reductase inhibitors.

Adrenergic alpha-Antagonists↗

[Epidemiology and natural course of benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is a frequent condition in men over 50 years of age. At autopsy the histological characteristics of BPH are seen in 80% of all men older than 80 years. Although BPH is so frequent, its precise etiology is still unknown. Each of the various sources from which epidemiological data on BPH can be obtained has its own specific problems in terms of potential errors and biases, which have to be taken into account in interpretation of the data from these sources. There are clear differences in the incidence of BPH in various races. In negroids BPH is more frequent than in Caucasians, while in Asiatic races BPH is less frequent. However, in Asiatics BPH occurs more frequently in men who have immigrated into western countries. Age and hormonal status are well known to be involved in the development of BPH. Other factors, such as marital status, socioeconomic class, smoking, diet, diabetes, hypertension, and liver cir-rhosis have been implicated, but their relation with the risk of developing BPH has never been proven. The natural history of BPH is characterized by an age-dependent increase in histological changes and an increase in prostate size. The histological changes compatible with BPH are found in men below the age of 30 with an incidence of less than 10%. During the 6th decade, 42% of prostatic specimens have histological signs of BPH and during the 8th decade of life more than 80% of prostatic specimens. The histological changes of BPH precede prostatic enlargement by roughly 1 decade. There is an initial spurt of prostate growth during the period of maturation and puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A current review of medical therapy for benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most common diseases of aging men. It is estimated that by age 60 years, greater than 50% of men will have histologically documented evidence of the disease. Therapy for this disease has evolved considerably from its inception. Recent data from long-term population-based studies have shed new light on the treatment of this common problem in aging men. The authors review the current state of diagnosis of BPH and medical therapy for this condition in the primary care setting.

Adrenergic alpha-Antagonists↗

Lower urinary tract symptoms and benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is an important cause of lower urinary tract symptoms (LUTS). However, many other causes, including smooth muscle dysfunction and neurological factors may contribute to these symptoms, and accurate diagnosis is imperative before invasive treatments are chosen. Careful recording of symptoms, giving emphasis on how they interfere with the patient's quality of life, as well as the use of properly selected tests, constitutes the mainstay of making a correct diagnosis. Men with mild or moderate symptoms not experiencing complications are ideal candidates for medical treatment. For the rest with persistent symptoms or complications such as infection, bleeding, chronic retention or renal impairment further investigation and more invasive forms of treatment need to be considered. We review the patho-physiology of the disease, and current approaches and management of this common problem.

Acute Disease↗

[Progress in the studies of alpha1-receptor blocker for benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is a common senile disease, and its main clinical manifestation is lower urinary tract symptom (LUTS), which has long been afflicting old male patients. Previous study showed that alpha1-receptor in the prostate was involved in the development of LUTS. At present, alpha1-receptor blocker is generally accepted as a choice drug for treating BPH and relieving LUTS. The article reviews the tissue distribution of alpha1-receptor and clinical application of alpha1-receptor blocker.

Adrenergic alpha-1 Receptor Antagonists↗

Laser irradiation for the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is one of the most common medical problems encountered in the United States. For many years, transurethral resection of the prostate (TURP) has been the mainstay of treatment for symptomatic BPH. In recent times, newer modalities of treatment in the form of drugs (a- blockers, LHRH-agonist, anti-androgens, 5 a-reductase inhibitors), microwave hyperthermia, prostatic stents, balloon urethroplasty, laser prostatectomy, and most recently High Intensity Focal Ultrasound (HIFU) and Trans Urethral Needle Ablation (TUNA) are challenging TURP as the gold standard therapy for BPH. Today, laser prostatectomy holds a special place in therapy of BPH, as it is easy to perform, safe to apply with a vastly improved patient compliance, and is the first choice in certain special circumstances, e.g., patients on anticoagulants. In this chapter we discuss the present status of laser prostatectomy for BPH.

Journal Article↗

[Transurethral ablation (Precision Plus) in the treatment of patients with benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is a common condition among elderly men. Transurethral needle ablation of the prostate (TUNA) is a minimally invasive procedure for treatment of BPH. With TUNA, the inner region of the prostate is selectively ablated with temperatures approaching 90-100 degrees C while prostatic urothelium is preserved. The TUNA (Precision Plus) was used in 9 patients with BPH: 1 patient had acute urinary retention, 6 ones had suprapubic catheter and 2 patients had lateral and median lobes. The patient with acute urinary retention and 4 patients with suprapubic catheter resumed voiding after TUNA. Two patients with lateral and median lobes showed improvement of subjective and objective parameters. The size of the prostate did not change one month after TUNA. Thus, TUNA is a safe and effective therapy for treatment of BPH that can be performed with local anaesthesia.

Humans↗

[Advances in the studies of morphological histology and imaging of benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is a familiar usually involves senile males. In recent 50 years, the incidence of BPH in China has been increasing. The morphological histology of hyperplastic prostate showed the volume enlarged and weight increase, and the hyperplastic part was mainly located in transitional zone. Researchers at home and abroad studied the tissue characteristics of hyperplastic prostate by routine and special staining coupled with computer-assisted quantitative image analysis system, and found that the proliferation was mainly occurred in interstitial tissue of prostate. The imaging examination is an important assistant method to diagnose BPH. Especially, Transrectal ultrasound and magnetic resonance imaging can displayed hyperplastic prostate more clearly.

Humans↗

Epidemiology and natural history of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) afflicts the majority of elderly men, and if current rates of surgery persist, the average 40-year-old man in the United States will have a 30 to 40 per cent chance of undergoing a prostatectomy if he survives to age 80. Age is by the far the most important determinant of BPH occurrence. Symptomatic BPH has a waxing and waning course, and a few men may have long-term remission. Surprisingly, the natural history of BPH is poorly defined, particularly with regard to the magnitude of the risks of its complications.

Aging↗