[Antiandrogen therapy of prostate carcinoma]. / Gezielte Testosteronblockade statt Kastration.

Thanks to improved examination techniques, many cases of prostate cancer are now being diagnosed in younger patients. It is therefore of ever greater importance that treatment should have no great impact on the patient's quality of life. Nonsteroidal antiandrogens have a more favorable side effect profile than surgical or pharmacological castration, since the serum concentration of testosterone remains within the normal range. Depending on the stage of the illness, they can be employed in the form of monotherapy as an adjuvant to prostatectomy or radiotherapy in local advanced prostate cancer, and as components of maximum androgens blockade.

Biphosphonates in advanced prostate and renal cell cancer--current status and potential applications.

OBJECTIVE: This review summarizes recent findings on the therapeutic benefits of biphosphonates in patients with advanced prostate or renal cell carcinoma (RCC). The role of biphosphonates in ADT-induced osteoporosis and delay of skeletal-related events (SREs) in metastatic bone disease is discussed. A brief overview on the proposed modes of action is given. METHODS: Literature search of PubMed documented publications and abstracts from meetings. RESULTS: Among the biphosphonates currently available, zoledronic acid is the only one known to be capable of delaying SREs in RCC and prostate cancer patients. Zoledronic acid counteracts cancer treatment-induced osteoporosis in men with prostate malignancies. The antitumor activity of biphosphonates found in vitro and in vivo is intriguing and has to be further assessed in clinical studies. CONCLUSION: Due to its unique properties, zoledronic acid is a breakthrough in the management of metastatic bone disease in patients with advanced prostate cancer and RCC. It significantly improves the patients' quality of life, drastically prolongs time to first SRE, and showed a positive but not significant effect on survival.

Alpha-adrenoceptors are a common denominator in the pathophysiology of erectile function and BPH/LUTS--implications for clinical practice.

A literature search of PubMed documented publications and abstracts from proceedings of scientific meetings was made to review the available data on benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) and erectile dysfunction (ED) with a special focus on the role of alpha-adrenoceptors as critical mediators of pathophysiology. The reader is introduced to clinical results on the therapeutic potential of alpha-blockers alone and in combination with phosphodiesterase type 5 (PDE-5) inhibitors in the treatment of ED associated with LUTS/BPH. Epidemiological studies clearly show that an association exists between ED and LUTS/BPH. The severity of LUTS is correlated with the risk for ED. A significant number of LUTS/BPH patients are nonresponsive to the common ED treatment with PDE-5 inhibitors. As smooth muscle contractility is regulated by adrenoceptors in the corpus cavernosum, prostate and detrusor, the alpha-adrenoceptor system may be considered a common pathophysiological mediator in the development of ED and LUTS/BPH. Blockade of alpha-adrenoceptors for the treatment of BPH/LUTS may have the potential of improving sexual function. Conversely, PDE-5 inhibitors may exhibit positive effects in LUTS patients. Pilot studies on combination regimens of alpha-adrenoceptor antagonists and PDE-5 inhibitors have yielded encouraging results in LUTS patients with persistent ED. On the basis of pharmacological and clinical evidence, it is established that the alpha-adrenoceptor system plays an important role in the pathophysiology of ED and LUTS secondary to BPH. Larger trials on the combination of alpha-adrenoceptor antagonists with PDE-5 inhibitors are necessary to develop an integrated treatment approach for BPH/LUTS patients with comorbid ED.

Reversible, non-barrier male contraception: status and prospects.

OBJECTIVE: Male, non-barrier, contraceptive options are limited to vasectomy and inadequate methods such as withdrawal and periodic abstinence. Herein we give an overview of current research on male contraception by pharmacological means. METHODS: Literature search of PubMed documented publications and abstracts from meetings. RESULTS: Cross-cultural surveys show men's willingness to carry contraceptive responsibility. Clinical trials substantiate that hormonal contraception involving suppression of gonadotropins holds the best promise to provide a male pharmacological contraceptive. Androgens have been demonstrated to induce reversible infertility particularly in combination with certain progestins and GnRH antagonists. Advances in non-endocrine contraception include intervention with triptolide derivatives, alkylated imino sugars, and immunization by eppin. CONCLUSION: The prospect of a pharmacological, male contraceptive has been considerably advanced in recent years. Long-term studies involving a greater number of subjects may result in a safe, reversible and effective means. Asia is likely to be the first market for male, hormonal contraceptive methods. The clinical evaluation of non-endocrine approaches may ultimately lead to an alternative to hormone-based male contraception.

Dehydroepiandrosterone treatment in the aging male--what should the urologist know?

OBJECTIVE: Dehydroepiandrosterone (DHEA) has attracted considerable attention as a means against the decrements of aging. This review will summarize clinical studies evaluating DHEA as a treatment option for age-related conditions and diseases. METHODS: Literature search of PubMed documented publications and abstracts from meetings. RESULTS: The collected data indicate that DHEA supplementation to counteract its gradual decrease over age is beneficiary. Positive effects on the cardiovascular system, body composition, BMD, the skin, the CNS, and the immune system have been reported. Improvement of sexual function by DHEA has been demonstrated. CONCLUSION: Although long-term clinical trials (applying the standards of evidence-based methods) are not available at present, the consistency of the data and the extensive practical experience may justify the use of DHEA in aging men given the rules of classical endocrinology are thoroughly followed including diagnosis based on clinical picture and biochemical evidence, compliance to periodic evaluations, and individual dose adjustment to maintain serum concentrations in the physiological range of young males. Being one among other important hormonal factors, DHEA can delay and correct age-related disorders only to a certain degree.

ISA, ISSAM and EAU recommendations for the investigation, treatment and monitoring of late-onset hypogonadism in males: scientific background and rationale.

Prescription sales for testosterone products have substantially increased over the last several years reflecting the growing awareness of physicians for the potential benefits of testosterone replacement therapy in men with hypogonadism. Indiscriminate administration of testosterone poses a risk and has to be deprecated. Testosterone supplementation to treat late-onset hypogonadism (LOH), a term for androgen deficiency in elderly men, is still controversially discussed mainly due to a lack of large, controlled clinical trials on efficacy and safety. To provide guidance for physicians primarily dealing with aging men, ISSAM is periodically updating and publishing its recommendations as new data become available [Morales A, Lunenfeld B. International Society for the Study of the Aging Male. Investigation, treatment and monitoring of late-onset hypogonadism in males. Official recommendations of ISSAM. International Society for the Study of the Aging Male. Aging Male 2002;5:74-86 and Morales A, Lunenfeld B. Androgen replacement therapy in aging men with secondary hypogonadism. Draft recommendations for endorsement by ISSAM. Aging Male 2001;4:1]. Following a panel discussion at the 4th ISSAM Congress in Prague in February 2004, the International Society of Andrology (ISA), the International Society for the Study of the Aging Male (ISSAM) and the European Association of Urology (EAU) revised existing recommendations on the definition, diagnosis and management of LOH. The recommendations are based on the currently available scientific data on androgen supplementation therapy and should be regarded as provisional until larger-scale, long-term studies are available. While certainly not intending to be exhaustive, this review will highlight some relevant background information and provide the underlying scientific rationale for the ISA, ISSAM and EAU recommendations on LOH published in this issue.

[Early detection of cancer of the prostate. Pros and cons]. / Leitlinien fordern zur Vorsorge beim Prostatakarzinom: Bestimmen Sie auch den PSA-Wert.

Since the introduction of PSA determination for the detection of cancer of the prostate, there have been discussions of the pros and cons of PSA screening for early detection of this cancer. The PSA test used in combination with digital rectal examination has proven to be a superior diagnostic instrument for the diagnosis of malignant prostate disease at an early stage. The German Guideline Catalog for the early detection of carcinoma of the prostate recommends measurement of the PSA from the age of 45 onwards in patients who have first been comprehensively informed about the further proceedings in the event of a positive result. To date, PSA screening has not been shown to lower the disease-specific mortality rate. Two ongoing randomized, multicentre studies (ERSPC and PLCO) are expected to throw more light on the matter.

Erectile dysfunction (ED) is prevalent, bothersome and underdiagnosed in patients consulting urologists for benign prostatic syndrome (BPS).

OBJECTIVES: The aim of the present study was to determine the prevalence of erectile dysfunction (ED) in patients visiting office-based urologists in Germany because of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and to evaluate the impact of ED on quality of life (QoL) in these patients. METHODS: 500 office-based urologists in Germany were invited to evaluate 20 consecutive patients for erectile dysfunction, who presented because of BPH-related LUTS. Physicians provided information on demographic factors, duration and treatment history of BPH, severity of LUTS, ED risk factors, and assessed the patient for the clinical diagnosis of ED. Patients were asked to complete the German version of the IPSS to measure LUTS severity. ED-patients quantified erectile dysfunction and impact on quality of life with validated German questionnaires (Cologne assessment of male erectile dysfunction KEED, and Qol-Med). RESULTS: Office-based urologists were aware of ED in 37.3% of 8768 patients presenting for LUTS before the study, 14.7% of patients were treated for ED. After the study-related assessment, physicians diagnosed ED in 62.1% of these patients and planned treatment in 46.9%. Severity of LUTS and ED prevalence correlated significantly after age-stratification. The incidence of ED was increased in patients with established ED risk factors. Mean QoL-Med score (best QoL: 100, worst QoL: 0) was 53.8 in patients with ED and 50.1 in ED-patients considering treatment. CONCLUSION: ED is highly prevalent in LUTS patients visiting an office-based urologist and is accompanied by a profound impact on the quality of life. Apparently, even during an urological consultation many ED-patients are hesitant to actively ask for treatment. Sexual issues should become key considerations for physicians managing patients with LUTS, especially since effective and well established oral treatment for ED is available.

The probiotic approach: an alternative treatment option in urology.

OBJECTIVE: The prophylactic and therapeutic use of probiotic microorganisms is a wide and still controversial field. The review paper is aimed to summarize recent findings on the health-benefiting effects of probiotics in urological diseases. The use of certain beneficial strains against urogenital infections, bladder cancer recurrence and renal stone formation is discussed. METHODS: Literature search of PubMed documented publications and abstracts from meetings. RESULTS: Various clinical trials have now been performed which substantiate the beneficial effects of the probiotic strains L. rhamnosus GR-1, L. fermentum RC-14 and L. crispatus CTV-05 against urogenital infections, such as urinary tract infections and bacterial vaginosis. The potential of L. casei Shirota to reduce the recurrence rate of bladder cancer is one of the most intriguing examples for the use of probiotics in medical practice. The use of O. formigenes in the prevention of calcium oxalate stone disease was only recently suggested and needs to be further investigated. CONCLUSION: Clinical trials increasingly provide a profound scientific basis for the use of probiotics in medicinal practice including urology. Efforts to make probiotic products available which are validated according to the guidelines recommended by the WHO and FAO and produced according to Good Manufacturing Practice will contribute to the acceptance of probiotic therapy by both the physicians and the patients.