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Abstracts

Abstracts

Hyperthermia

Microwave Hyperthermia

Local deep microwave hyperthermia was evaluated. After treatment 61% were able to dispense with the catheter. The authors encourage further study to confirm their findings.

"Local Microwave Hyperthermia in The Treatment of Benign Prostatic Hypertrophy", Saranga, R., et al, British Journal of Urology, 1990;65:349-353.

Thermotherapy

Reviewed the available data on transurethral microwave thermotherapy in the treatment of patients with benign prostatic hyperplasia (BPH).

Transurethral microwave thermotherapy was designed to apply microwave energy deep within lateral prostatic lobes while simultaneously cooling the urethral mucosa, thus enabling an outpatient based anesthesia-free procedure. Lower energy protocols using the Prostraton device provide significant symptomatic improvement and improvement in maximum flow of approximately 35% over baseline.

Similar changes are being documented with other transurethral microwave thermotherapy devices. Higher energy protocols using the Prostatron device result in symptomatic improvement similar to that of lower energy protocols, while improvement in uroflowmetry is much more pronounced. However, the latter effect is achieved at the expense of increased morbidity. Second generation protocols have not yet been documented by users of the other thermotherapy devices.

Numerous studies unequivocally support the efficacy and safety of transurethral microwave thermotherapy for treatment of symptomatic BPH. Significant improvement in objective and subjective parameters has been realized with transurethral microwave thermotherapy at multiple centers in the United States and Europe.

de la Rosette JJ et al., Current status of thermotherapy of the prostate. J Urol, 1997 Feb, 157:2, 430-8.

Morphometry

Morphometry, or quantitative image analysis, offers great promise in characterizing the various histologic types of benign prostatic hyperplasia (BPH).
The prostate glands of 20 men with BPH were removed for low-volume carcinoma and subjected to a uniform, comprehensive, systematic quantification of the primary BPH tissue components using the technique of digitization and point-count morphometry.
We found the following average volumes among the 20 glands:
· epithelium, 19.9% (range 11.7% to 30.8%);
· fibromuscular stroma, 50.4% (range 32.2% to 74.4%);
· glandular lumina, 29.7% (range 11.9% to 47.5%).

Quantitative histologic differences between prostates, potentially important in clinical decision-making may be accurately diagnosed by morphometry of radially oriented biopsy specimens.

Marks LS et al., Morphometry of the prostate: I. Distribution of tissue components in hyperplastic glands. Urology, 1994 Oct, 44:4, 486-92.

Phytotherapy

Plant extracts

In Italy plant extracts represent 8.6% of all pharmacological prescriptions for Benign Prostatic Hyperplasia (data from 1991). This review evaluates all the suggested mechanisms of action for plant extracts. Recently we demonstrated an antiestrogenic effect of Serenoa Repens in BPH patients. Clinical trials with plant extracts have yielded conflicting results.

In a recent review by Dreikorn and Richter, only 5 placebo controlled studies were found. Moreover, as opposed to chemically defined drugs, it is possible that for these extracts the active ingredients are not known; consequently pharmacodynamic and pharmacokinetic data are often missing. The International Consultation of Benign Prostatic Hyperplasia (Paris, June 1991) concluded that, to date, phytotherapeutic agents must be considered as a symptomatic treatment. Now more adequate pharmacological and clinical studies, placebo controlled, should determine the exact role of these drugs in the treatment of BPH.

Di Silverio F et al., Plant extracts in BPH. Minerva Urol Nefrol. Dec 1993, 45 (4) p143-9.

Phytotherapeutic drugs

Phytotherapeutic preparations are still commonly used for the treatment of symptomatic benign prostate hyperplasia (BPH) in Germany; in recent years there has even been an increase in their use, so that sales now amount to more than DM 220 millions per year. The preparations most frequently used are extracts of Hypoxis rooperi, the roots of the stinging nettle, the fruits of the saw palmetto, pumpkin seeds and rye pollen.

Dreikorn K et al.,[Status of phytotherapeutic drugs in treatment of benign prostatic hyperplasia] Stellenwert von Phytotherapeutika bei der Behandlung der benignen Prostatahyperplasie (BPH). Urologe A. Mar 1995, 34 (2): 119-29.

Phytotherapy

Phytotherapeutic agents have enjoyed widespread use, especially in Europe, for the treatment of BPH. With the recent proliferation of nutrition and vitamin stores in the United States, use of these agents has greatly increased.

Lowe-FC & Ku-JC.: Phytotherapy in treatment of benign prostatic hyperplasia: a critical review. Urology. 1996 Jul; 48(1): 12-20.

Pharmacology

Serenoa repens (Permixon) has been available for several years for the treatment of men with benign prostatic hyperplasia (BPH). The drug is the n-hexane lipidosterolic extract of the dwarf American palm (Serenoa repens) and is a complex mixture of various compounds.

In controlled clinical trials in men with BPH, oral administration of Serenoa repens 160 mg twice daily for 1 to 3 months was generally superior to placebo in improving subjective symptoms, such as dysuria, as well as objective parameters.

The frequency of nocturia was reduced by 33 to 74%, while urinary frequency during the day decreased by 11 to 43% and peak urinary flow rate increased by 26 to 50% with Serenoa repens. Corresponding values for placebo were 13 to 39%, 1 to 29% and 2 to 35%.

The only large comparative trial conducted to date, in which > 1000 men with moderate BPH were randomised to receive Serenoa repens 160 mg twice daily or finasteride 5 mg once daily for 6 months, demonstrated similar efficacy between the two drugs.

International Prostate Symptom Score improved by 37% with Serenoa repens compared with 39% with finasteride. In much smaller comparative trials, few significant differences were demonstrated between Serenoa repens and alpha 1-receptor antagonists, and larger randomised trials of adequate duration are required to better compare the clinical efficacy of these drugs.

The most frequently reported adverse events in clinical trials with Serenoa repens have been minor gastrointestinal problems (e.g. nausea and abdominal pain). In conclusion, Serenoa repens is well tolerated and has greater efficacy than placebo and similar efficacy to finasteride in improving symptoms in men with BPH. Although there is a need for further comparative studies, particularly with alpha 2-receptor antagonists, available data indicate that Serenoa repens is a useful alternative to alpha 1-receptor antagonists and finasteride in the treatment of men with BPH.

Plosker GL et al., Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia. Drugs Aging 9 (5): 379-395 (Nov 1996)

Phytosterol

A randomized, double-blind and placebo-controlled clinical trial was conducted to assess the efficacy and safety of 130 mg free beta-sitosterol (phytosterol Azuprostat, a beta-sitosterol derived for example from species of Pinus, Picea or Hypoxis) daily, using the international prostate symptom score (IPSS) as the primary outcome variable.

There were significant improvements over placebo in those treated with beta-sitosterol.

Beta-sitosterol is an effective option in the treatment of BPH.

Klippel KF et al., A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto Study group. Br J Urol, 1997 Sep, 80:3, 427-32.

Prostate cancer

Examined the relationship between the intake of various carotenoids, retinol, fruits, and vegetables and the risk of prostate cancer.

Between 1986 and 1992, 812 new cases of prostate cancer, including 773 non-stage Al cases, were documented. Intakes of the carotenoids beta-carotene, alpha-carotene, lutein, and beta-cryptoxanthin were not associated with risk of non-stage Al prostate cancer; only Lycopene intake was related to lower risk. Of 46 vegetables and fruits or related products, four were significantly associated with lower prostate cancer risk; of the four--tomato sauce, tomatoes, and pizza, but not strawberries--were primary sources of lycopene.

Combined intake of tomatoes, tomato sauce, tomato juice, and pizza (which accounted for 82% of lycopene intake) was inversely associated with risk of prostate cancer, for consumption frequency greater than 1 0 versus less than 1. 5 servings per week.

Findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk, but other measured carotenoids are unrelated to risk.

Tomato-based foods may be especially beneficial regarding prostate cancer risk.

Giovannucci E et al: Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst, 1995 Dec 6, 87:23, 1767-76.

Clinical syndrome

The clinical syndrome of benign prostatic hyperplasia reflects a complex interplay between benign prostatic enlargement, which will affect almost all men by the age of 80, and the resulting outlet obstruction and lower urinary tract symptoms.

The disease is now known to adversely affect the quality of life of around one man in three over the age of 50.

New medical treatments and new surgical interventions are challenging the previous standard treatment of transurethral resection of prostate, which continues to have a morbidity of 17% and some mortality.

Primary care will be increasingly involved in shared care with particular emphasis on monitoring of patients on watchful waiting medical therapy- and following operative intervention.

Simpson RJ: Benign prostatic hyperplasia. Br J Gen Pract, 1997 Apr, 47:417, 235-40.

Current management

Contents:

Current Management
General practice
Management
Medical Management
Primary Care (2)

Current Management

To define the spectrum of urological care for benign prostatic hyperplasia (BPH) and clinically localized prostate cancer.

In 1995 a random sample of 394 American urologists was surveyed with a response rate of 67%.

Respondents reported seeing a median of 240 BPH patients during the preceding 12 months, and they had prescribed alpha-blockers for 70 and finasteride for 15. They had performed a median of 25 transurethral prostatectomies but few other operations for BPH.

Almost all urologists routinely used digital rectal examinations and prostate specific antigen tests for BPH diagnosis. The next most common studies were American Urological Association symptom scores and uroflowmetry.

Pressure-flow studies were rarely done. Respondents reported seeing a median of 35 new patients with prostate cancer during the last year, and performing a median of 90 prostate biopsies and 13 radical prostatectomies. Respondents had referred a median of 10 patients for external beam radiotherapy but few patients received brachytherapy or cryotherapy. Urologist staging practices varied considerably.

These data provide a picture of current practice regarding the management of BPH and prostate cancer.

Barry MJ et al., A nationwide survey of practicing urologists: current management of benign prostatic hyperplasia and clinically localized prostate cancer. J Urol, 1997 Aug, 158:2, 488-91; discussion 492.

General practice - Holland

Estimated the seriousness and inconvenience of prostatism in a general practice population and to assess the consultation with the general practitioner (GP) in relation to seriousness of prostatism.

The prevalence of prostatism with moderate to severe symptoms was 20%. The majority (60%) of the men with prostatism did not consult their GP with these symptoms, and one fifth (19%) felt "mostly dissatisfied" to "terrible" due to their symptoms.

Of this last group, a few (1.4% of the total population) nevertheless did not consult their GP.

Prostatism is a symptom complex caused not only by benign prostate hyperplasia. Prostatism is under-reported in general practice. Men with micturition problems should be encouraged to consult their practitioner.

Wille-Gussenhoven MJ et al., Prostate symptoms in general practice: seriousness and inconvenience. Scand J Prim Health Care, 1997 Mar, 15:1, 39-42.

Management

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.

Barry M & Roehrborn C: Management of benign prostatic hyperplasia. Annu Rev Med, 1997, 48:, 177-89.

Medical management

The ageing population is presenting an increasing demand on future healthcare services. In males, prostatic disease is one of the commonest disorders contributing to this.

Alternatives to surgical intervention have to be considered as the preferred option for individuals and whether this be a therapeutic or a financial option to be taken.

Two major medical alternatives are alpha-blockers and 5-alpha reductase inhibitors. The results of such treatment can be very beneficial in selected groups of patients. Side-effects with improved drugs electivity are reducing.

Overall, while surgery still holds the gold standard, medical therapy has a significant role in the treatment of benign prostatic hypertrophy. Cost analysis may be a factor in deciding which treatment to have.

McDermott T: Optimising the medical management of benign prostatic hyperplasia. Br J Clin Pract, 1997 Mar, 51:2, 116-8.

Primary Care

Although patients with prostate disorders are frequently referred to urologists for diagnosis and management, primary care physicians (PCPs) are beginning to take a more active role. However, there is concern that PCPs are not optimally educated in the diagnosis and management of these disorders.

A 10-question survey determined PCP practice patterns in evaluating and treating benign prostatic hyperplasia (BPH) and screening for prostate cancer.

Most PCPs (89%) indicated that up to 30% of their patients have symptomatic BPH, and a significant proportion of these are treated initially by the PCP. Although 61% of PCPs are aware of the American Urological Association (AUA) symptom score and its recommended role in clinical practice guidelines, only 38% currently use it.

The most popular BPH therapies are long-acting alpha blockers and watchful waiting. DRE is performed routinely by 84% of PCPs in men > 50 years, and annual serum prostate-specific antigen is routinely requested by 69% of PCPs.

Although PCPs play an increasing role in the diagnosis and management of prostate disorders, they are not taking full advantage of published clinical practice guidelines.

Fawzy A Practice patterns among primary care physicians in benign prostatic hyperplasia and prostate cancer. Fam Med, 1997 May, 29:5, 321-5.

Primary care (2)

Defined primary care physicians' (PCPs) practices in managing patients with benign prostatic hyperplasia [BPH], and to compare these practices to portions of the Agency for Health Care Policy and Research BPH guideline and urologists' practices. (A Mail survey.)

Primary care physicians (n = 444, response = 51%) reported seeing a median of 35 patients with BPH over the preceding year, in contrast to 240 for urologists (n = 394, response = 68%).

Regarding tests recommended by the guideline, two thirds of PCPs reported rarely or never using the American Urological Association (AUA) symptom index, nearly all reported routinely performing digital rectal examinations, and many (66%) reported routinely ordering tests to determine the serum creatinine level.

Although considered "optional" by the guideline, more than 90% of PCPs reported routinely ordering a prostate-specific antigen test, while infrequently using other optional tests. Regarding "not recommended" studies, a substantial minority reported selectively or routinely ordering intravenous pyelography (34%) and renal ultrasound (33%), while two thirds reported rarely or never ordering these tests. 86% of PCPs reported prescribing medications for BPH over the preceding year; alpha blockers to a median of 12 patients, and finasteride to a median of 2. Variation in urology referral thresholds was suggested in responses to two patient scenarios.

Primary care physicians are actively managing patients with BPH. Some of their diagnostic evaluations vary from the recommendations of a national guideline and urologists' practices. Referral thresholds appear to vary considerably.

Collins MM et al., Diagnosis and treatment of benign prostatic hyperplasia. Practice patterns of primary care physicians. J Gen Intern Med, 1997 Apr, 12:4, 224-9.

Treatment guidelines

Contents:

Adherence to AHCPR guidelines
Guideline
Non-instrumental treatment
Treatment guidelines (Pharmacology)
Treatment options

Adherence to AHCPR guidelines

Determined adherence rates to guideline recommendations for the diagnosis and treatment of benign prostatic hyperplasia published and distributed by the Agency for Health Care Policy and Research in 1994.

Assessed reliability and validity and determined results for each of the following measures of care:
1) documentation of indications for a transurethral resection of the prostate;
2) documentation of appropriate preoperative assessment;
3) documentation of indications for an inpatient excretory urogram (IVP) and/or sonogram when the procedures were performed and
4) documentation of surgical time and grams of tissue removed. Adherence rates for all measures of care were determined.

Adherence to selected Agency for Health Care Policy and Research guideline recommendations is documented infrequently in the medical record.

Hood HM et al., Adherence to Agency for Health Care Policy and Research guidelines for benign prostatic hyperplasia. J Urol, 1997 Oct, 158:4, 1417-21.

Guideline

To critique the US Department of Health and Human Services Public Health Service, Agency for Health Care Policy and Research, Clinical Practice Guideline on Benign Prostatic Hyperplasia: Diagnosis and Treatment; and to provide an update on management and treatment of benign prostatic hyperplasia (BPH) since the Guideline was published.

Management of BPH is directed at ameliorating voiding symptoms. For moderate or severe BPH, medical or surgical therapy should be offered to the majority of patients. Medical therapy options include alpha-adrenergic antagonists and finasteride. The former offer the advantage of a more prompt onset of action (within weeks) when compared with finasteride. Finasteride produces a lower response rate and smaller improvement in voiding symptoms. Combination therapy of terazosin and finasteride has not been proven to be more effective than terazosin monotherapy.

When medical therapy is indicated for moderate or severe BPH, alpha-adrenergic antagonists exhibit a faster onset of action and produce greater improvement of voiding symptoms than does finasteride.

Lee M & Sharifi R: Benign prostatic hyperplasia: diagnosis and treatment guideline. Ann Pharmacother, 1997 Apr, 31:4, 481-6.

Non-instrumental treatment

Review the clinical effects in benign prostatic hyperplasia (BPH) patients that can be achieved with the presently available medical treatment options.

Classes of drugs include: 5-alpha-reductase inhibitors, alpha-blockers, cholesterol-lowering agents and phytotherapeutic drugs.

Taking into account that the symptomatic and the flow rate improvements achieved are below the level of perception in most of these trials, there seems to be no convincing evidence that medical treatment of BPH with the presently available drugs is also clinically more effective than placebo.

Ruud Bosch JL: Conservative non-instrumental treatment of benign prostatic hyperplasia. Urol Res, 1997, 25 Suppl 2:, S107-14.

Treatment guidelines (Pharmacology)

Symptomatic benign prostatic hyperplasia (BPH) is a common condition in older men and has a significant impact on their daily lives. Transurethral resection of the prostate (TURP) or open prostatectomy are currently the most effective therapies for BPH. TURP is, however, associated with clinically significant adverse events in 20% of patients. Therefore, patients who need treatment for BPH based on the presence of symptoms should also be offered other therapy options.

Transurethral incision of the prostate is an effective therapy with minimal adverse effects in patients with a prostate not larger than 30 g. Minimally invasive procedures, such as electrovaporisation, laser prostatectomy, transurethral needle ablation, high intensity focused ultrasound, transurethral microwave therapy and insertion of prostatic stents, can be performed instead of the standard surgical procedures. They are either performed as outpatient procedures or are associated with shorter durations of hospitalisation than TURP; in addition, they can also be performed in high risk patients.

The efficacy of these procedures lies between that of TURP and medical therapy. Medical therapy is becoming increasingly important in the treatment of patients with moderate symptoms of BPH. Both androgen-suppressing therapy and alpha-adrenoceptor blockade are well tolerated and effective modalities. Compared with placebo, both types of therapy produce improvements in maximum urinary flat rate and reductions in symptom scores of 15 to 20%.

Finasteride, a potent 5 alpha-reductase inhibitor, must be given for 6 months before it effectiveness in a given patient can be assessed, and for at least 12 months to achieve maximum prostate shrinkage and the full extent of its other beneficial effects. This may be perceived as a disadvantage when compared with the rapid relief afforded by surgery or alpha-blockade. The efficacy of finasteride is also dependent on prostate size; it should not be tried in patients with a prostate volume of < 40 ml. On the other hand, finasteride may reverse the progression of the disease process.

Of the alpha 1-adrenoceptor antagonists, terazosin, doxazosin and tamsulosin can be administered once daily. In contrast, prazosin, alfuzosin and indoramin must be administered twice daily, which may have a negative impact on patient compliance. Because of its specificity for alpha 1A-receptors, no dosage titration is needed when tamsulosin is used; in addition, in contrast with the other alpha-blockers used in BPH, tamsulosin lacks significant effects on blood pressure. On the other hand, nonselective alpha-blockers are preferable in hypertensive patients with BPH.

The final decision about the best treatment for a particular patient must take into account the patient's preference after he has been informed of the different options.

Tammela T: Benign prostatic hyperplasia. Practical treatment guidelines. Drugs Aging, 1997 May, 10:5, 349-66.

Treatment options

To examine current treatment options for benign prostatic hyperplasia with emphasis on randomized, clinical trials and our current management approach.

Benign prostatic hyperplasia remains difficult to define clinically or measure objectively. As a result, research has been fairly weak. With newer treatments, however, more definitive studies have been reported.

Transurethral resection of the prostate remains the criterion standard for severe disease. Watchful waiting, medical management, or early surgical intervention are all valid options for moderate disease and should be tailored to the characteristics and desires of individual patients. Recent minimally invasive surgical techniques, such as microwave and laser surgery, have not yet achieved the quality of evidence to be generally recommended.

Management of benign prostatic hyperplasia should be individualized to patients' circumstances and personal choices.

Portis AJ & Mador DR: Treatment options for benign prostatic hyperplasia. Can Fam Physician, 1997 Aug, 43:, 1395-404.

Inflammation

Identified morphological parameters of benign prostatic hyperplastic inflammation that correlate with pre-biopsy prostate specific antigen (PSA) concentrations.

A total of 66 patients with exclusively benign prostatic tissue on prostate biopsies was analyzed. Difference between inflammation graded groups was not significant when considering serum or urinary PSA. There was a significant correlation between aggressiveness grading and serum PSA, whereas aggressiveness grading and urinary PSA did not correlate.

Prostatic subclinical inflammation is not associated with high urinary PSA. Unless associated with glandular epithelial disruption, density of prostatic interstitial inflammatory cell infiltrate is not significantly correlated with serum PSA concentration.

This issue should be considered when interpreting a prostate biopsy.

Irani J et al., Inflammation in benign prostatic hyperplasia: correlation with prostate specific antigen value. J Urol, 1997 Apr, 157:4, 1301-3.

International

Contents:

International
Latin America

International

Investigated the international differences in the reporting of lower urinary tract symptoms and related bother in patients with symptoms suggestive of bladder outlet obstruction.

Country of origin was significantly associated with the prevalence of a large number of lower urinary tract symptoms (10 of 20), even after adjusting for potentially confounding variables, including physical and socio-demographic factors. Country of origin was also significantly associated with the reporting of bother but for a much smaller number of symptoms.

In different countries lower urinary tract symptoms may be reported to different extents. Therefore, the results of studies in particular countries may not be generally applicable to other countries. It is likely that symptom scores will conceal this variation, necessitating consideration of individual symptoms (as in the International Continence Society "benign prostatic hyperplasia" study) or the development of country specific scoring systems.

An alternative would be to focus on bother, which appeared to be much less sensitive to international differences.

Witjes WP et al., The International Continence Society "Benign Prostatic Hyperplasia" Study: international differences in lower urinary tract symptoms and related bother. J Urol, 1997 Apr, 157:4, 1295-300.


Latin America

OBJECTIVES: To determine the acceptance of the self-administered International Prostate Symptom Score (IPSS) by people of differing educational levels in two different countries.

The questionnaire adopted by the World Health Organization and known as the IPSS attempts to measure the severity of lower urinary tract symptoms in men with benign prostatic hyperplasia.

An international study was performed in Brazil and Argentina and included 768 patients. The IPSS was self-administered and used to evaluate and quantify the clinical symptoms resulting from benign prostatic hyperplasia.

A total of 40 (12.9%) men filled out the questionnaire incompletely, 31 (77.5%) in the lower-education subgroup and 9 (22.5%) in the higher-education subgroup. An incomplete questionnaire was more frequent among the patients with lower education.

In spite of the cultural variations, there was no significant difference in the number of patients unable to answer the questionnaire in the two countries.

Rodrigues Netto N Jr et al., Latin American study on patient acceptance of the International Prostate Symptom Score (IPSS) in the evaluation of symptomatic benign prostatic hyperplasia. Urology, 1997 Jan, 49:1, 46-9.

Urodynamics

The International Continence Society Benign Prostatic Hyperplasia Study (ICS-BPH) was devised in response to the perceived underutilization of urodynamics in the diagnosis of benign prostatic obstruction (BPO), together with the apparent reliance on symptoms alone when selecting patients for invasive therapies, despite evidence that lower urinary tract symptoms (LUTS) had poor diagnostic specificity for BPO.

The ICS-BPH Study is an international multicenter study employing a wide-ranging patient-completed questionnaire, with questions on symptoms, bothersomeness, quality of life, and sexual function.

In addition, each patient underwent multiple urine flow studies and standardized urodynamic investigations (phase I). Phase II was an observational assessment of outcome following a range of treatments: conservative, medical, and surgical. Phase III included data from randomized controlled trials involving a wide range of therapies.

Patients (# 1,271mean age, 66 years) were included in phase I from 12 countries: 18% of patients were unobstructed, 22% mildly obstructed, and 60% obstructed on pressure flow studies; 83% of patients performed at least two flow studies.

The ICS-BPH Study will allow definitive statements to be made concerning the diagnostic potential of a wide range of LUTS, and will define the place of urine flow studies, describe patients who will need pressure flow studies prior to invasive treatment, and identify those likely to experience an adverse outcome. Although an aim of the study is to produce a diagnostic symptom score, there is considerable doubt as to whether this can be achieved where aging and a variety of lower urinary tract dysfunctions often coexist.

Witjes WP et al., The International Continence Society "Benign Prostatic Hyperplasia" Study: international differences in lower urinary tract symptoms and related bother. J Urol, 1997 Apr, 157:4, 1295-300.

Elderly

Elderly men

BPH is an age-related condition that can give rise to urinary symptoms.

A range of effective treatments is available, and although there are certain absolute indications for surgery, patients with moderate or severe symptoms require counseling to reach a decision on the treatment modality most appropriate for them.

Concomitant age-related disease and use of multiple medications add to the complexity of treating elderly men for BPH.

In every case of BPH, the risks of each treatment option should be weighted against the potential benefits and a joint decision reached by physician and patient.

Guthrie R: Benign prostatic hyperplasia in elderly men. What are the special issues in treatment? Postgrad Med, 1997 May, 101:5, 141-3, 148, 151-4 passim.

Older men

Medical therapy with alpha 1-adrenergic blockers or 5 alpha-reductase inhibitors offers an alternative to the traditional choices of watchful waiting and surgery.

Patients with obstructive symptoms and a small prostate appear to respond to treatment with an alpha 1-adrenergic blocker, while a 5 alpha-reductase inhibitor may be the preferred agent for a large gland.

Albertsen PC: Prostate disease in older men: 1. Benign hyperplasia. Hosp Pract (Off Ed), 1997 May 15, 32:5, 61-4, 67-8, 77 passim.

Pharmacoeconomics

Men with moderate symptoms of benign prostatic hyperplasia (BPH) are the best candidates for medical treatment, while surgery is usually indicated for patients with severe symptoms. Men with mild symptoms do not usually need treatment, but they might be re-evaluated annually if desirable.

Finasteride, which produces selective hormonal deprivation, is now established as a well tolerated drug for the long term medical therapy of BPH. Recent studies suggest that finasteride is most effective in men with large prostates (> 40 ml), and the drug should probably be reserved for these patients.

alpha-Blockers work in men with small or large prostates, and their rapid onset of action facilitates the identification of responders. alpha-Blockers are more effective than finasteride during the first year of treatment, but only finasteride induces regression of the prostate and offers increased efficacy over time.

Even if drug therapy reduces the need for prostate surgery, the total economic cost of BPH treatment is likely to rise because of the increasing application of medical treatment. The magnitude of this increase depends largely on what percentage of the male population embark on long term therapy, at what age treatment is started, and how successful it is. At present, the answers to these questions are largely unknown. The personal economic expenses for men who begin long term medical therapy will probably be an important factor in deciding how common drug treatment for BPH will become in the future.

For many men, the main benefit of drug treatment will be the relief of urinary symptoms, but whether this improvement is substantial enough to improve their overall quality of life has not yet been clearly demonstrated in controlled studies.

Eri LM & Tveter KJ: Treatment of benign prostatic hyperplasia. A pharmacoeconomic perspective. Drugs Aging, 1997 Feb, 10:2, 107-18.

Radiation

Prostate cancer is one of the commonest tumours of adult males. It shows a range of biological behaviour: many tumours are discovered incidentally; others will kill by producing widespread metastatic disease.

Despite the fact that radiation is frequently used in the treatment of a range of pelvic lesions, including adenocarcinoma of the prostate itself, studies on the morphological changes in the normal prostate gland after irradiation are limited.

Patients often suffer from lower urinary tract symptoms such as frequency and dysuria and it is possible that these may be related to prostatic and/or periprostatic injury pelvic following irradiation.

Investigated the prostate glands removed at cystoprostatectomy for transitional cell carcinomas of the bladder which had received radiotherapy pre-operatively. The changes were compared to control prostatic tissue from transurethral resection specimens for benign myoadenomatous hyperplasia.

A range of inflammatory, fibrotic and reactive cytological features, including many of the changes seen in benign hyperplasia, but these were significantly more exaggerated in the post-radiation group. In addition intraprostatic vascular and neural changes were prominent.

Sheaff MT & Baithun SI: Effects of radiation on the normal prostate gland. Histopathology, 1997 Apr, 30:4, 341-8.

Sex steroids

Contents:

Melatonin
Sex steroids
Smoking

Melatonin

Human benign prostatic epithelial cells contain functional melatonin receptors that can suppress cell growth and viability. The development of benign prostatic hyperplasia in men is assumed to result from androgen-estrogen imbalance. Investigated the impact of sex steroids on melatonin receptors in human benign prostate epithelial cells.

Data indicate that:
1) DHT and E2 enhance prostate epithelial cells growth, but reduce cell growth when combined;
2) DHT extenuates the inhibitory effects of melatonin on epithelial cell growth; and
3) E2 acts to inactivate melatonin receptors and consequently responses in human epithelial benign prostatic hyperplasia cells.

This process is probably mediated by protein kinase C. Together, these results show an interplay between melatonin and sex steroids in the regulation of benign prostatic epithelial cell growth.

Gilad E et al., Interplay between sex steroids and melatonin in regulation of human benign prostate epithelial cell growth. J Clin Endocrinol Metab, 1997 Aug, 82:8, 2535-41.

Sex steroids

It has long been suspected that sex steroids play a key role in the pathogenesis of benign prostatic hyperplasia (BPH).

Prostatic diseases do not occur in males castrated before puberty or in males with heritable disorders of androgen production or action. Both estrogens and androgens have been shown to induce BPH in experimental animals.

Both the GnRH agonists and finasteride result in prostatic size reduction and alleviate symptoms in some patients. Both therapies are more effective in men with larger prostates (> 40 cc). Finasteride is less efficacious in terms of size reduction than the GnRH agonists but also has fewer side effects.

To date, clinical trials with aromatase inhibitors have not yielded dramatic positive results in the treatment of BPH.

Levine AC et al., The role of sex steroids in the pathogenesis and maintenance of benign prostatic hyperplasia. Mt Sinai J Med, 1997 Jan, 64:1, 20-5.

Smoking

Investigated the association between cigarette smoking and sex hormone concentrations in men with benign prostatic hyperplasia (BPH) and thus provide some understanding of the underlying mechanism of the effects of cigarette smoking on prostatic enlargement.

The mean prostate volume was greater in non-smokers than smokers. Current cigarette smokers had significantly higher mean serum oestradiol levels than did the non-smokers (33.8 and 26.7 pg/mL, respectively).

Cigarette smoking was inversely but not significantly related to testosterone level.

These differences persisted after adjusting for body mass index. There was no significant difference in serum DHEA and DHEA-S levels between smokers and non-smokers.

There was a weak correlation between the degree of prostatic enlargement, the presence of obstructive symptoms and urinary flow rates.

These results indicate that cigarette smoking may affect the size of the enlarging prostate, but through indirect effects of smoking on factors provoking the development of BPH.

K?peli B et al., The role of cigarette smoking in prostatic enlargement. Br J Urol, 1997 Aug, 80:2, 201-4.

Cigarette Smoking

Investigated the association between cigarette smoking and sex hormone concentrations in men with benign prostatic hyperplasia (BPH) and thus provide some understanding of the underlying mechanism of the effects of cigarette smoking on prostatic enlargement.

The mean prostate volume was greater in non-smokers than smokers. Current cigarette smokers had significantly higher mean serum oestradiol levels than did the non-smokers (33.8 and 26.7 pg/mL, respectively).

Cigarette smoking was inversely but not significantly related to testosterone level.

These differences persisted after adjusting for body mass index. There was no significant difference in serum DHEA and DHEA-S levels between smokers and non-smokers.

There was a weak correlation between the degree of prostatic enlargement, the presence of obstructive symptoms and urinary flow rates.

These results indicate that cigarette smoking may affect the size of the enlarging prostate, but through indirect effects of smoking on factors provoking the development of BPH.

K?peli B et al., The role of cigarette smoking in prostatic enlargement. Br J Urol, 1997 Aug, 80:2, 201-4.

Symptom Index

To quantify the relative effects of age and ultrasonic appearance of benign prostatic hyperplasia (BPH) on urinary symptoms as evaluated by the American Urological Association (AUA) symptom index score.

Among 7 symptoms included in the AUA symptom index weak stream and hesitancy scores were not influenced by age, prostatic volume or presumed circle area ratio.

As a parameter representing the degree of BPH in terms of the severity of urinary symptoms, presumed circle area ratio was preferable to prostatic volume. Regression analyses confirmed again that the AUA symptom index was influenced considerably by age and was not specific to BPH.

Kojima M et al., The American Urological Association symptom index for benign prostatic hyperplasia as a function of age, volume and ultrasonic appearance of the prostate. J Urol, 1997 Jun, 157:6, 2160-5.

Quality of Lifestyle

Contents:

Quality of life
Sexuality

Quality of life

Studies in disease specific populations have emphasized disease specific quality of life with little study of general quality of life.

To model the emotional component of general quality of life in patients with prostate disease.

Neural networks created reasonably good models of the emotional component of general quality of life.

All models of general quality of life relied primarily on disease nonspecific inputs, including social support, activities of daily living and coping.

Efforts to optimize general quality of life in patients with prostate disease must integrate disease nonspecific variables.

Krongrad A et al., Predictors of general quality of life in patients with benign prostate hyperplasia or prostate cancer. J Urol, 1997 Feb, 157:2, 534-8.

Sexuality

Benign prostatic hyperplasia (BPH) and its treatment can impair the quality of life (QoL) of patients with the condition. Among the BPH-specific instruments (89-item questionnaire) available for assessing QoL, no consensus has emerged on the concepts that should be measured, particularly for aspects of sexual life.

To determine which aspects of QoL were most affected by prostatic symptoms and which patients considered the most important.

Aspects reported to be most affected and to be the most important were: sleep, anxiety and worry about the disease, mobility, leisure, daily activities, sexual activities and satisfaction with sexual relationships. French patients considered all sexual aspects of life more important than English patients.

Assessment of sexual functioning and behavior must be included in any further evaluations of BPH treatments effects on QoL.

Calais Da Silva F et al., Relative importance of sexuality and quality of life in patients with prostatic symptoms. Results of an international study. Eur Urol, 1997, 31:3, 272-80.

Natural history

Defined outcomes for men with a clinical diagnosis of benign prostatic hyperplasia.

Candidates (#500 ) were followed over 4 years for elective prostatectomy treated nonoperatively in 5 North American urology practices.

There were 371 survivors with complete data at 4 years.

Of 60 men with mild, 245 with moderate and 66 with severe baseline symptoms 10, 24 and 39%, respectively, had undergone surgery; 27, 31 and 27%, respectively, were on pharmacological therapy, and 63, 45 and 33%, respectively, were off active treatment at 4 years. Mild or moderate symptoms were noted at 4 years in 83, 59 and 23% of the patients, respectively, while 17, 41 and 77%, respectively, had severe symptoms or had undergone surgery.

Outcomes for men with a clinical diagnosis of benign prostatic hyperplasia depend on initial symptom severity. However, the course of symptoms also varies among patients even with the same initial symptom severity.

Barry MJ et al., The natural history of patients with benign prostatic hyperplasia as diagnosed by North American urologists. J Urol, 1997 Jan, 157:1, 10-4; discussion 14-5.

DHEA activation

An androgen receptor (AR) gene mutation identified in the androgen-dependent human prostate cancer xenograft, CWR22 an epithelial cell tumor, expresses a 9.6-kb AR mRNA similar in size to the AR mRNA in human benign prostatic hyperplasia.

With dihydrotestosterone at a near physiological concentration (0.01 nM), H874Y and wild type androgen receptor (AR) induced 2-fold greater luciferase activity than did the LNCaP mutant AR T877A. The adrenal androgen, dehydroepiandrosterone (10 and 100 nM) with H874Y stimulated a 3- to 8-fold greater response than with wild type AR and at 100 nM the response was similar with the LNCaP mutant

AR mutations that alter ligand specificity may influence tumor progression subsequent to androgen withdrawal by making the AR more responsive to adrenal androgens or antiandrogens.

Tan J et al., Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells. Mol Endocrinol, 1997 Apr, 11:4, 450-9.

Zinc & BPH

Zinc and magnesium

Studied serum levels of zinc and magnesium (before and after prazosin therapy [Minipress-Pfizer] 4 mg daily) in patients (#32 ) with benign prostatic hyperplasia (BPH).

Following cessation of therapy a slight increase in Zn levels was observed, i.e. from 100 to 103 micrograms/dl, whereas Mg levels did not change significantly (1.95 and 1.94 mg/dl, respectively).

In comparison with other organs, the human prostate is characterized by high Zn and Mg content. In BPH the Zn levels are increased. They are markedly decreased in carcinoma of the prostate and in prostatitis.

Zn and Mg play an important role as catalysts in various enzymatic reactions. It has been postulated that changes in concentrations of these two elements are parallel.

Zinc ions inhibit androgen metabolism in the prostate. Physiologic Zn serum levels are equal to or above 90 micrograms/dl.

Magnesium, unlike zinc, is uniformly distributed within different areas of the gland. In BPH, both normal and increased Mg levels in the prostate have been reported. Mg plays an important role as an activator of enzymes (phosphatases) involved in ATP metabolism, thus affecting both katabolic and anabolic processes.

Dutkiewicz S: Zinc and magnesium serum levels in patients with benign prostatic hyperplasia (BPH) before and after prazosin therapy. Mater Med Pol, 1995 Jan-Mar, 27:1, 15-7.

Diets

Diets

Diets high in butter, margarine or zinc may increase the risk of benign prostatic hyperplasia whereas diets high in fruit may reduce that risk. Over 400 patients with or without the prostate condition had lowered risk of benign prostatic hyperplasia among those who ate plenty of fruit. Diets high in butter, margarine and zinc had increased the risk. Thus, diets high in fruit consumption may prevent benign prostatic hyperplasia among men.

Lagiou P, Wuu J, Trichopoulou A, Hsieh CC, Adami HO, Trichopoulos D. Diet and benign prostatic hyperplasia: a study in Greece. Urology 1999 Aug;54(2):284-90.

Saw Palmetto and Stinging Nettle

Saw Palmetto and Stinging Nettle

Saw palmetto and stinging nettle are possible herbal remedies for benign prostatic hyperplasia, according to this study. Extracts of these plants have been subject to an increasing amount of studies that evaluate their mode of action and explicate their success in clinical trials. The most current studies tout the efficacy of these and other phytotherapeutics in the treatment of benign prostatic hyperplasia as well as advertise their favorable safety profile. Adding these medicinal herbs to the current therapeutic options of watchful waiting, changes of lifestyle, medical treatments, and invasive therapies may be helpful.

Koch E: Extracts from fruits of saw palmetto (Sabal serrulata) and roots of stinging nettle (Urtica dioica): viable alternatives in the medical treatment of benign prostatic hyperplasia and associated lower urinary tracts symptoms, Planta Med 2001 Aug;67(6):489-500

Pygeum Extract

Pygeum extract

Pygeum africanum extract may help relieve the irritating symptoms of benign prostatic hyperplasia (BPH), according to this study. The authors reviewed studies from the Medline, EMBASE, Cochrane Library, and Phytodok databases that were randomized, included men with BPH, compared pygeum to placebo or other BPH medications, and included specific outcomes like urologic symptom scales, symptoms, or urodynamic measurements. Analysis of 18 studies involving a total of 1562 men found that many of the studies reported improvement in urologic symptoms and flow measures in men taking pygeum compared to those taking placebo. Those who took pygeum were more than twice as likely to report that their symptoms had been suppressed than those on placebo. Among the symptoms reduced were: nocturia (19%), residual urine volume (24%), and peak urine flow (23%). Overall, any adverse effects experienced by men taking pygeum were relatively mild and comparable to placebo. Larger and longer studies on the effectiveness of pygeum for BPH are needed.

Wilt T, Ishani A, MacDonald R, Rutks I, Stark G: Pygeum africanum for benign prostatic hyperplasia (Cochrane Review), Cochrane Database Syst Rev 2002;(1):CD001044