Showing papers in "World Journal of Urology in 2003"

Prevalence and burden of overactive bladder in the United States

Abstract: Context: the National Overactive BLadder Evaluation (NOBLE) Program was initiated to better understand the prevalence and burden of overactive bladder in a broad spectrum of the United States population. Objective: to estimate the prevalence of overactive bladder with and without urge incontinence in the US, assess variation in prevalence by sex and other factors, and measure individual burden. Design: US national telephone survey using a clinically validated interview and a follow-up nested study comparing overactive bladder cases to sex- and age-matched controls. Setting: noninstitutionalized US adult population. Participants: a sample of 5,204 adults ≥18 years of age and representative of the US population by sex, age, and geographical region. Main outcome measures: prevalence of overactive bladder with and without urge incontinence and risk factors for overactive bladder in the US. In the nested case-control study, SF-36, CES-D, and MOS sleep scores were used to assess impact. Results: the overall prevalence of overactive bladder was similar between men (16.0%) and women (16.9%), but sex-specific prevalence differed substantially by severity of symptoms. In women, prevalence of urge incontinence increased with age from 2.0% to 19% with a marked increase after 44 years of age, and in men, increased with age from 0.3% to 8.9% with a marked increase after 64 years of age. Across all age groups, overactive bladder without urge incontinence was more common in men than in women. Overactive bladder with and without urge incontinence was associated with clinically and significantly lower SF-36 quality-of-life scores, higher CES-D depression scores, and poorer quality of sleep than matched controls. Conclusions: the NOBLE studies do not support the commonly held notion that women are considerably more likely than men to have urgency-related bladder control problems. The overall prevalence of overactive bladder does not differ by sex; however, the severity and nature of symptom expression does differ. Sex-specific anatomic differences may increase the probability that overactive bladder is expressed as urge incontinence among women compared with men. Nonetheless, overactive bladder, with and without incontinence, has a clinically significant impact on quality-of-life, quality-of-sleep, and mental health, in both men and women.

Androgens and male fertility

Abstract: Androgens play a crucial role in the development of male reproductive organs such as the epididymis, vas deferens, seminal vesicle, prostate and the penis. Furthermore, androgens are needed for puberty, male fertility and male sexual function. High levels of intratesticular testosterone, secreted by the leydig cells, are necessary for spermatogenesis. Intratesticular testosterone is mainly bound to androgen binding protein and secreted into the seminiferous tubules. Inside the sertoli cells, testosterone is selectively bound to the androgen receptor and activation of the receptor will result in initiation and maintenance of the spermatogenic process and inhibition of germ cell apoptosis. The androgen receptor is found in all male reproductive organs and can be stimulated by either testosterone or its more potential metabolite dihydrotestosterone. Severe defects of the androgen receptor may result in abnormal male sexual development. More subtle modulations can be a potential cause of male infertility. Treatment of an infertile man with testosterone does improve spermatogenesis, since exogenous administrated testosterone and its metabolite estrogen will suppress both GnRH production by the hypothalamus and Luteinising hormone production by the pituitary gland and subsequently suppress testicular testosterone production. Also, high levels of testosterone are needed inside the testis and this can never be accomplished by oral or parenteral administration of androgens. Suppression of testosterone production by the leydig cells will result in a deficient spermatogenesis, as can be seen in men taking anabolic-androgenic steroids. Suppression of spermatogenesis by testosterone administration is also the basis for the development of a male contraceptive. During cytotoxic treatment or irradiation suppression of intratesticular testosterone production cells may prevent irreversible damage to the spermotogonial stem cells.

Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability

Abstract: Our objectives were to ascertain the tolerability and efficacy of trospium chloride in doses of 20 mg twice daily for long-term therapy (52 weeks) in patients with urge syndrome. The trial comprised a total of 358 patients with urge syndrome or urge incontinence. After randomisation in the ratio of 3:1, participants were treated continuously for 52 weeks with either trospium chloride (20 mg twice daily) or oxybutynin (5 mg twice daily). At intervals of 4-8 weeks, patients were physically examined with measurements of blood pressure and pulse rate, were questioned about any adverse events, checked for compliance and underwent relevant laboratory tests. As an additional safety measure, an ECG was made at 26 and 52 weeks. Urodynamic measurements were performed at the beginning, and at 26 and 52 weeks to determine the maximal cystometric bladder capacity. Among others things, the frequencies of micturition, incontinence and number of urgency events were recorded in patient diary protocols in weeks 0, 2, 26 and 52. The evaluation of vital parameters, laboratory results and ECGs did not show any relevant changes attributable to the action of the anticholinergics. Analysis of the micturition diary clearly indicated a reduction of the micturition frequency, incontinence frequency, and a reduction of the number of urgencies in both treatment groups. Mean maximum cystometric bladder capacity increased during treatment with trospium chloride by 92 ml after 26 weeks and 115 ml after 52 weeks (P=0.001). Further comparison with oxybutynin did not reveal any statistically significant differences in urodynamic variables between the drugs. Adverse events occurred in 64.8% of the patients treated with trospium chloride and 76.7% of those treated with oxybutynin. The main symptom encountered in both treatment group was dryness of the mouth. For patients on trospium chloride, the estimated risk of an unexpected adverse event was 0.027 per patient per week for all adverse events and 0.009 for dryness of the mouth, resulting in a considerably lower risk during treatment given with trospium chloride than with oxybutynin (0.045 and 0.021, respectively). An overall assessment for each of the drugs reveals a comparable efficacy level and a better benefit-risk ratio for trospium chloride than for oxybutynin due to better tolerability.

Radical prostatectomy: a prospective comparison of oncological and functional results between open and laparoscopic approaches.

Abstract: We prospectively compared, within the same center and during the same period of time, the perioperative parameters as well as the oncological and functional results of both open retropubic (ORP) and laparoscopic radical prostatectomy (LRP). From September 1999 to September 2001, 162 patients with prostate cancer were treated with radical prostatectomy, 77 using an open retropubic technique, and 85 by the laparoscopic extraperitoneal approach. We prospectively recorded pre-, per- and postoperative parameters and complications, and evaluated the carcinological and functional results, comparing both approaches. There were no significant differences in the preoperative characteristics of the two groups. Mean operative time was statistically longer with LRP than with ORP (288 vs 168 min, P<0.0001) but median blood loss was decreased (400 vs 1,300 ml, P<0.0001). Major complications occurred in a similar number of cases (5% vs 2.4%, NS) while minor complications occurred more frequently with ORP (24.6 vs 11.8%, P=0.003). Pathological examination revealed a similar distribution of Gleason scores and stages in each group. Positive surgical margins in pT2 cases occurred in 7.8% of LRP and 7.3% of ORP. Continence rates (no pad and no leakage at all) were similar (83.9% in ORP vs 80.7% in LRP, NS). Potency rates were similar after 1 year in patients undergoing bilateral nerve sparing (55% in ORP vs 65% in LRP, NS). However, patients operated by LRP had more spontaneous erections. We conclude that this prospective, comparative study shows that LRP, when performed in specialized centers, gives oncological and functional results comparable to open surgery.

Epidemiology of prostatitis: new evidence for a world-wide problem.

Abstract: We review new data on the epidemiology of chronic prostatitis. These population-based studies used reasonable case-definitions to survey various populations from North America, Europe and Asia. Overall, 2–10% of adult men suffer from symptoms compatible with chronic prostatitis at any time and approximately 15% of men suffer from symptoms of prostatitis at some point in their lives. Other epidemiologic data suggest that chronic prostatitis may be associated with an increased risk for development of benign prostatic hyperplasia and prostate cancer. These data suggest that chronic prostatitis is an important international health care problem that merits increased priority from clinicians and researchers.

The Selenium and Vitamin E Cancer Prevention Trial

Abstract: Prostate cancer is an attractive and appropriate target for primary prevention because of its incidence, prevalence, and disease-related mortality. Despite PSA-induced stage migration, a high cure rate for localized disease, and improved understanding of prostate cancer biology, most men who develop metastatic disease are still destined to die of prostate cancer. It seems self-evident that an effective prevention strategy would spare many men from this burden of diagnosis and cure. The molecular pathogenesis of prostate cancer also lends itself to a primary prevention strategy. Clinically evident prostate cancer is rare in men \(<\) 50 years old, while the precancerous lesion PIN (prostatic intraepithelial neoplasia) is apparent at autopsy in men \(<\) 30. Furthermore, the prevalence of PIN is similar in populations at much different risks of developing clinically evident cancer, suggesting that external environmental influences are important and potentially modifiable. This chapter will review the scientific and epidemiologic evidence supporting the role of selenium and vitamin E in the prevention of prostate cancer and the design of the Selenium and Vitamin E Cancer Prevention Trial.

Overactive bladder inhibition in response to pelvic floor muscle exercises.

Abstract: A recent study by the senior author demonstrated that striated urethral sphincter contraction effected the inhibition of vesical contraction and suppression of the desire to micturate, an action suggested to be mediated through the "voluntary urinary inhibition reflex". We hypothesized that the effect of pelvic floor muscle (PFM) exercises on the overactive bladder was mediated through this reflex action. The current communication investigates this hypothesis. A total of 28 patients (mean age 44.8+/-10.2 years, 18 men, 10 women) with overactive bladder and 17 healthy volunteers (mean age 42.6+/-9.8 years, 12 men, 5 women) were enrolled in the study. The vesical and posterior urethral pressures were determined before and after vesical filling reached the volume at which urge in control subjects, and involuntary voiding in the patients, occurred. Intra-abdominal pressure was recorded to obtain detrusor pressure readings. The bladder was refilled to the above volume and the subject asked to hold PFM contractions for 10 s during which the vesical and posterior urethral pressures were recorded. In healthy volunteers, the mean detrusor and posterior urethral pressures at urge to void were 30.6+/-4.8 SD and 18.7+/-3.3 cm H(2)O, respectively. On PFM contraction, the detrusor pressure declined to 11.6+/-1.4 cm H(2)O (P<0.01) and urethral pressure increased to 139.8+/-17.4 cm H(2)O (P<0.001). In patients, the mean detrusor and posterior urethral pressure readings when the bladder was filled to the volume which induced involuntary incontinence, were 28.2+/-4.2 and 17.3+/-3.4 cm H(2)O, respectively; on PFM contractions, the detrusor pressure decreased to 10.6+/-2.1 cm H(2)O (P<0.01), while urethral pressure increased to 86.6+/-7.9 cm H(2)O (P<0.001) and voiding did not occur. In conclusion, PFM contractions led to a decline of detrusor and increase of urethral pressures and suppressed the micturition reflex. These contractions appear to induce their effect by preventing internal sphincter relaxation produced by the micturition reflex. Failure of the internal sphincter to relax seems to cause reflex detrusor relaxation, an action presumably mediated through the "voluntary urinary inhibition reflex". The results of the current study encourage the treatment of overactive bladder with PFM contractions.

Robotic-assisted laparoscopic radical prostatectomy: the Frankfurt technique

Abstract: The robotic technique, which was first introduced in laparoscopic heart surgery, has revolutionized laparoscopic surgery over the last 5 years. In May 2000, our department accomplished the first robot assisted laparoscopic radical prostatectomy. Since that time we have performed more than 118 such procedures and several other laparoscopic operations using the robotic technique. We here summarize our experience in robot assisted laparoscopic radical prostatectomy as it has been developed over the past 3 years. Between May 2000 and May 2003, 118 patients with clinically localized prostate cancer were operated using the telerobotic da Vinci Surgical System. Operations were performed with a senior surgeon at the console, assisted by an assistant and a nurse at the operating table. Bilateral pelvic lymph node dissection was undertaken as a first step in all patients. In the initial 60 cases, we investigated different laparoscopic approaches. We used transperitoneal as well as extraperitoneal approaches. For dissection of the prostate we used ascending, descending as well as combined techniques. The combined ascending and descending technique via the transperitoneal route was chosen in 30 patients, and via the extraperitoneal route in seven patients. A modification of the descending Montsouris technique was performed in 81 patients. The robot assisted laparoscopic radical prostatectomy with the da Vinci system has been well standardized. After performing more than 100 radical prostatectomies with this system, we conclude that in our hands the Mountsouris technique with only minor adoptions is the most appropriate technique for performing robot assisted radical prostatectomy.

Androgens and prostate cancer.

Abstract: Over 60 years ago Huggins and Hodges demonstrated the importance of androgens and prostate cancer. Since then, significant research has revealed that this relationship is multi-faceted and is interwoven with different signaling cascades and protein coactivators. The complex interrelationship between hormone and cancer is best exemplified by the recurrence and progression of prostate cancer after hormonal therapy to a lethally resistant phenotype despite initially encouraging therapeutic responses. If we are to significantly improve survival with novel therapies, further understanding of the emergence of this resistant phenotype is essential. The purpose of this article is to review the mechanisms of androgen action and its relation to hormonal therapy and mechanisms of hormonal resistance.

Da Vinci robot assisted Anderson-Hynes dismembered pyeloplasty: technique and 1 year follow-up

Abstract: In experienced hands, laparoscopic pyeloplasty is an effective alternative treatment for symptomatic ureteropelvic junction obstruction (UPJO). Although laparoscopic surgery can clearly benefit patients, laparoscopic pyeloplasty using conventional instrumentation is complex. The purpose of this report is to evaluate the feasibility of robot assisted laparoscopic surgery. Eleven pyeloplasties for UPJO were performed via a laparoscopic transperitoneal approach exclusively with the da Vinci Surgical System. The mean procedure time was 197 min (range 110–310 min). All operations were completed laparoscopically with no intraoperative complications and negligible blood loss. All patients recovered rapidly after surgery with excellent functional results at the 1 year follow-up. Our initial experience suggests that robot assisted Anderson-Hynes pyeloplasty is a safe and effective alternative to conventional laparoscopic surgery. In our opinion, robot assisted surgery will allow urologists to perform complex procedures with greater precision, confidence, and better results, as well as enable them to adapt the whole spectrum of laparoscopic procedures to their field.

Radiation therapy dose escalation for prostate cancer: a rationale for IMRT

Abstract: The response of prostate cancer to radiation was well-documented in the pre-PSA era. Large palpable tumors resolved within months of treatment with relatively modest radiation doses of 64-70 Gy. The use of PSA-based failure as an endpoint, however, has made it clear that cure rates were much lower than appreciated. While doses in this range are still widely used today, data from retrospective, sequential prospective and now randomized studies indicate that for patients with intermediate-to-high risk disease, doses above 70 Gy are associated with a significant reduction in biochemical failure. The use of 3D-conformal radiotherapy to escalate radiation dose has resulted in modest increases in rectal and bladder toxicity. The application of intensity modulated radiotherapy methods allows for greater sparing of the surrounding normal tissues and, hence, the potential to further escalate dose. The results of dose escalation, the ability of IMRT to reduce rectal and bladder exposure to high radiation doses and the use of new imaging methods to more accurately target the prostate are described.

Evolution of endoscopic extraperitoneal radical prostatectomy (EERPE)—technical improvements and development of a nerve-sparing, potency-preserving approach

Abstract: During the last decade, laparoscopy has become a standard technique in the armoury of the urologist due to constant technological advances and refinements. Laparoscopic radical prostatectomy (LRPE), although technically demanding and associated with a considerable learning curve, has become the surgical procedure of choice in selected and specialized urological centers around the globe for patients with clinically localized prostate cancer. However, a major drawback of LRPE is the transperitoneal route of access to the extraperitoneal prostate. The principal disadvantages of LRPE are potential intraperitoneal complications, such as bowel injury, ileus, intraperitoneal bleeding, intraperitoneal urinary leakage, intraperitoneal adhesion formation and concomitant small bowel obstruction. Endoscopic extraperitoneal radical prostatectomy (EERPE) is a further advancement of minimal invasive surgery as it overcomes the limitations of LRPE by the strictly extraperitoneal route of access combining the advantages of minimal invasive surgery with those of an extraperitoneal procedure. Based on our growing experience with this procedure, we have introduced several technical modifications, improvements and refinements including a nerve-sparing, potency-preserving approach (nEERPE) in an effort to further improve this minimally invasive procedure.

Androgen therapy with dehydroepiandrosterone

Abstract: The physiological role of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) is poorly understood. It depends in a large part on their transformation into testosterone and estradiol. The capacity of DHEA as a neurosteroid, the recent discovery of putative specific DHEA receptors on endothelial and vascular smooth muscle cells, the steady decrease of DHEA production from the 40s on, together with certain human epidemiologic data as well as various beneficial effects of DHA supplementation in rodents have suggested the possibility that this steroid is involved in cognitive and memory, metabolic and vascular, immune and sexual functions and in their aging. However, epidemiologic studies are conflicting, and no well-designed clinical trials have definitely substantiated the role of DHEA in these functions in humans, or the utility and safety of DHEA supplementation. However, beneficial effects seem plausible in women with several conditions according to the results of double-blind placebo-controlled trials: the dose of 30 to 50 mg seems beneficial to the mood, sense of well being and sexual desire and activity of women with adrenal insufficiency. The only long-term trial of supplementation devoted to women over 60 reported significant increases in bone mineral density and, in the 70-79-year-old subgroup, in sexual desire, arousal, activity and satisfaction. The dose of 200 mg also proved to decrease disease activity in systemic lupus erythematosus. Lastly, high DHEA doses have improved mood in various groups of patients of any age and gender with depressive symptoms. The use of DHEA therapy may also be discussed in women of any age when a trial of androgen supplementation seems justified because of the existence of an inhibited sexual desire or a sexual arousal disorder associated with documented androgen deficiency. The rather weak conversion of DHEA into testosterone protects from the risk of overdosing associated with testosterone preparations. However, it must be realized that DHEA is also converted into estradiol, which may be a risk factor for breast or endometrial cancer in postmenopausal women. Unlike women, no consistent beneficial effect has been found for men in the placebo-controlled trials. The present data do not exclude a role of DHEA in other conditions, but this remains to be properly established. This paper includes practical considerations on dosage to be used, contraindications and follow-up.

Electrophysiological recordings during the peripheral nerve evaluation (PNE) test in complete spinal cord injury patients.

Abstract: Up until now, the exact mechanism by which neuromodulation using sacral nerve stimulation works still remains unknown. Recent studies of pelvic floor contraction during peripheral nerve evaluation (PNE) have shown that several muscle responses are reflexly mediated. However, whether these reflexes originate from a segmental level within the sacral spinal cord or from supraspinal neuronal centers involving spino-bulbospinal pathways remains to be determined. Therefore, recordings of external anal sphincter reflexes during PNE in complete spinal cord injury (SCI) patients was performed. Three patients with complete SCI (two female and one male) suffering from neurogenic incontinence underwent the first stage of a stimulator implant (peripheral nerve evaluation). Stimulation was obtained through an electrode placed in the S3 foramen. Concomitantly, the latency of the response of the striated anal sphincter was measured using a concentric needle electrode placed in the striated part of the anal sphincter. Repeated measurements within an interval of 30 min were performed to confirm the reliability of the responses. In all subjects, reflex responses of early and late latencies could be recorded. The early response showed a mean latency of 41.2 ms (range 33.3–62 ms), which corresponds to a segmental reflex, similar to the pudendo-anal reflex. The late response appeared with a mean latency of 189.4 ms (range: 183.3–197.8 ms) and with high variability and fatigability, suggesting a reflex response organized at polysegmental spinal levels. Despite successful foramina lead placement, none of our complete SCI patients showed any improvement of neurogenic incontinence after 5 days of treatment by sacral nerve stimulation. The findings confirm that the anal contractions observed during peripheral nerve evaluation are reflex responses mediated by afferent pathways. Both the early and late reflex responses are of spinal origin, since they were obtained in complete SCI patients in whom all spino-bulbo spinal loops are supposed to be interrupted. The finding that neuromodulation is working in non-neurogenic patients but is less successful in complete SCI patients could give evidence that preserved spino-bulbo spinal loops contribute to the positive effects of neuromodulation. The role of an eventual spino-bulbo spinal loop acting during neuromodulation in non-neurogenic patients has to be assessed in further studies.

Role of positive urethrovesical feedback in vesical evacuation. The concept of a second micturition reflex: the urethrovesical reflex.

Abstract: Upon feeling the urge to urinate, the urinary bladder contracts, the urethral sphincters relax and urine flows through the urethra. These actions are mediated by the micturition reflex. We investigated the hypothesis that vesical contraction is maintained by positive feedback through continuous flow of urine through the urethra, and that the cessation of urine flow aborts detrusor contraction. Normal saline was infused into the urinary bladders of 17 healthy volunteers (age 35.2 years±4.2(SD); ten women and seven men) at a rate of 100 ml/min. On urge, which occurred at a mean volume of 408.6 ml±28.7of saline, the subject micturated while the vesical and urethral pressures during voiding were being recorded; residual urine was measured. The test was repeated after anesthetizing the urethra with xylocaine gel or, on another occasion, after applying a bland gel . On micturition, the urine was evacuated as a continuous stream without straining; no residual fluid was collected. After urethral anesthetization, the fluid came out of the urethra in multiple intermittent spurts and only with excessive straining. There was a large amount of residual fluid (184.6 ml±28.4). The results of bland gel application showed no significant difference (P>0.05) from those without gel. Detrusor contraction during micturition is suggested to be maintained by positive urethrovesical feedback elicited by the continued passage of urine through the urethra. This feedback seems to be effected through the urethrovesical reflex, which produces vesical contraction on stimulation of the urethral stretch receptors. Abortion of this reflex by urethral anesthetization resulted in failure of detrusor contraction and excessive straining was needed to achieve bladder evacuation in multiple spurts. The urethrovesical reflex is thus assumed to constitute a second micturition reflex responsible for the continuation of detrusor contraction and urination. The role of this reflex in the pathogenesis of micturition disorders needs to be studied.

Antiestrogens and selective estrogen receptor modulators reduce prostate cancer risk

Abstract: The development of chemoprevention strategies against prostate cancer would have the greatest overall impact both medically and economically against prostate cancer. Estrogens are required for prostate carcinogenesis. Estrogenic stimulation through estrogen receptor alpha in a milieu of decreasing androgens contributes significantly to the genesis of benign prostatic hyperplasia, prostate dysplasia, and prostate cancer. The ability of antiestrogens and selective estrogen receptor modulators (SERMs) to delay and to suppress prostate carcinogenesis is supported by preclinical, clinical, and epidemiological studies. SERMs have many features that make them attractive candidates for prostate cancer chemoprevention including their favorable safety profile and efficacy in preclinical prostate cancer models. The true clinical benefits of SERMs for chemoprevention to prevent prostate cancer, however, should continue to be investigated through human clinical trials. A phase IIb/III human clinical trial is currently evaluating safety and efficacy of toremifene, a SERM, in men who have high-grade prostatic intraepithelial neoplasia.

Androgen and estrogen receptors in the human corpus cavernosum penis: immunohistochemical and cell culture results.

Abstract: Despite the central and peripheral effects of androgens on the nervous system, the local effects of androgens in the corpus cavernosum penis and their importance for erectile function is still unclear. In this study corpus cavernosum biopsies of eight adult potent patients, aged 19-63 years, undergoing penile deviation surgery (group A) and 12 patients undergoing male-to-female transsexual surgery (group B) were immunostained for nuclear androgen and estrogen-alpha receptors. Additionally, primary corpus cavernosum endothelial cell cultures were obtained from six transsexual patients and exposed to testosterone, dihydrotestosterone, estradiol and progesterone likewise for 7 days. Total cell count was performed and cell metabolic activity was measured by a tetrazolium salt-based assay. Androgen and estrogen-alpha receptors were detected in stromal as well as in endothelial cells. Of all cell nuclei, 74.9% (SD 16.4) in group A and 63.5% (SD 17.1) in group B were positively stained for androgen receptors. The respective percentage of estrogen receptors was 11% (SD 9.5) and 21.2% (SD 12.6). An age-dependent difference in receptor distribution was not observed in either group. In the cell culture system only cultures exposed to testosterone and dihydrotestosterone showed a dose-dependent increase of cell metabolic activity compared to the cultures supplemented with estradiol and progesterone. The significant and age-independent high androgen and low estrogen-alpha receptor distribution found in both groups suggests a possible peripheral effect of androgens at the level of the corpus cavernosum penis in adult humans. This is supported by the observed effect of testosterone and dihydrotestosterone on cell count and endothelial cell metabolism in our cell culture system. The role of estrogens remains unclear.

A new oral testosterone undecanoate formulation

Abstract: Testosterone undecanoate has been available on the market for more than 20 years. This testosterone ester is used worldwide for oral treatment of male hypogonadism. So far, testosterone undecanoate has been dissolved in oleic acid, leading to inconvenient storage conditions. It will now be available in a new formulation with castor oil and propylene glycol laurate instead of oleic acid, thus improving storage conditions markedly (stable at room temperature for approximately 3 years). Pharmacokinetic and pharmacodynamic studies have demonstrated bioequivalence of the old and the new formulation of testosterone undecanoate. Therefore, the results of studies that were performed with the old formulation can be transferred to the clinical use of the new formulation. Controlled studies have shown its efficacy in the treatment of symptoms associated with reduced serum testosterone levels. In these cases testosterone undecanoate improves bone mineral density, quality of life, muscle mass, libido and mood. Further studies will help evaluate the efficacy and safety of the new formulation in the treatment of elderly men with late-onset hypogonadism.

Recommendations for the evaluation of patients with prostatitis

Abstract: Prostatitis is a prevalent, confusing and frustrating clinical presentation for urologists. Three recent international and North American consensus meetings have drafted suggestions for the evaluation of a man presenting with prostatitis. Published consensus statements from the 2000 Washington meeting of the International Prostatitis Collaborative Network, the 2002 Virginia meeting of the National Institutes of Health Chronic Prostatitis Collaborative Research Network and the 2002 Giessen meeting of the International Consensus Conference on Advances in the Diagnosis and Treatment of Prostatitis were examined to develop suggestions for evaluation of the prostatitis patient by urologists. Clinical, laboratory and imaging evaluations for the patient presenting with prostatitis and chronic prostatitis/chronic pelvic pain syndrome can be categorized as basic or mandatory evaluations (which would include a complete history, focused physical examination, and urinalysis/urine culture), further or recommended evaluations (those that are recommended but not mandatory) and optional evaluations in selected patients. As more evidence and data are accumulated and published, these recommendations may eventually evolve into practice guidelines for the evaluation of men presenting with prostatitis symptoms.

The role of cytokines in prostatitis.

Abstract: There is substantiating evidence to support the role of the immune system in the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Inflammation of the prostate is mediated through the cytokine-induced expression of several factors such as chemokines, inducible nitric oxide synthase, and cyclooxygenase-2. The balance between the effects of proinflammatory and anti-inflammatory cytokines determines the outcome of the inflammatory process. Several proinflammatory and anti-inflammatory cytokines have been identified in CPPS patients, their roles characterized, and their inter-relationships defined. Study of this system will provide further insights into the etiology of CP/CPPS, and lead the way for the development of novel therapeutic approaches for this morbid condition.

Prostatitis: ancient history and new horizons.

Abstract: Prostatitis has a prominent role in the history of urology. Since antiquity, prostatitis and related conditions have had a large role in establishing the need for a separate guild of practitioners devoted to the medical and surgical treatment of genitourinary tract diseases. Lower urinary tract infection and inflammation, often associated with obstruction, resulted in the need to develop new treatments. Bacterial urinary tract infection, sexually transmitted diseases, urethral stricture and prostatic inflammation were treated by practitioners who developed skills in urethral catheterization, instillations, dilation, lithotomy and related procedures. These basic human needs have changed little during the last 5,000 years.

Androgen therapy in the aging male

Abstract: The world population is expanding rapidly; at the same time, life expectancy is increasing, and fertility rates are decreasing. Due to these facts, it is expected that the biggest increases of population growth will occur in the aging population. In the aging male, endocrine changes and a decline in endocrine function involve tissue responsiveness as well as reduced secretory output from peripheral glands and alterations in the central mechanism controlling the temporal organization of hormonal release. The latter are likely to be responsible for the dampened circadian hormonal and non-hormonal rhythms. These are in part responsible for the age-dependent decrease of the peripheral levels of testosterone, dehydroepiandrosterone (DHEA), the thyroid hormones, growth hormone (GH), IGF1 and melatonin. These hormonal changes, which develop in most men at about the age of 50, are in part responsible for endocrine deficiencies of some older men. One of the best-studied endocrine deficiencies is late-onset hypogonadism. This is a syndrome characterized by adverse effects on multiple organ systems and decreased quality of life, associated with advancing age and characterized by signs and symptoms of hypogonadism and a deficiency in serum androgen levels with or without a decreased genomic sensitivity to androgens. In cases of endocrine deficiencies, traditional endocrinology aims to replace the missing hormone or hormones with substitutes. It has been demonstrated that interventions such as hormone therapies may favorably influence some of the pathological conditions in aging men by preventing the preventable and delaying the inevitable. A comprehensive medical, psycho-social and life-style history, a physical examination and laboratory testing are essential for the diagnosis and management of late-onset hypogonadism. Acute, chronic or inter-current diseases must be taken into consideration prior to initiating any hormonal substitution therapy. In the era of evidence-based medicine, we have to acknowledge that data on testosterone therapy (HT) in the aging male is mostly circumstantial, based on experience in the treatment of transitional or chronic hypogonadism in young men resulting from disease or experiments of nature. However, over the past several years prospective studies on testosterone therapy in the aging male were performed and shown to be beneficial for certain older men in preventing or delaying some aspects of aging. Recommendations for algorithms for the diagnosis of late-onset hypogonadism and monitoring therapy for safety and efficacy are the subject of this paper.

Chronic prostatitis/chronic pelvic pain pyndrome): seminal markers of inflammation

Abstract: The new prostatitis classification proposes the inclusion of seminal leukocytes in the diagnosis of inflammatory chronic pelvic pain syndrome (CPPS). The present study has been performed to clarify the role of seminal leukocytes and inflammatory seminal plasma parameters in order to contribute to the differential diagnosis between inflammatory (category IIIA) and non-inflammatory (category IIIB) CPPS. A total of 112 consecutive symptomatic patients (mean age 37.3 years; range 21-64) attending our prostatitis outpatient clinic were investigated. Men with evidence for bacterial infection were excluded by prior standardized lower urinary tract localization studies. Men were categorized into inflammatory and non-inflammatory CPPS according to the leukocyte analysis in expressed prostatic secretions (EPS) and urine after prostatic massage (VB 3). Ejaculate analysis was performed after lower urinary tract localization studies. Inflammatory markers included peroxidase positive leukocytes (PPL) and PMN-elastase. Receiver operating characteristic curves were constructed to analyze cutpoints provided that the differences were significant. Increased leukocyte counts in EPS/VB 3 were found in 64 men, while in 48 this was not the case. No differences could be detected in relation to patients' age ( P>0.05). In men with category IIIA prostatitis, PPL and elastase in the seminal fluid were significantly increased ( P 0.113 x 10(6)/ml) and elastase (>280 ng/ml) in the seminal fluid indicate inflammatory disease provided that the ejaculate analysis is performed on the same day after lower urinary tract localization studies.

Chronic pelvic pain syndrome: a non-prostatocentric perspective.

Abstract: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological diagnosis affecting young and middle aged men. Symptoms of genital or pelvic pain associated with voiding or sexual dysfunction were historically attributed to an inflamed prostate gland. A review of urological and non-urological literature pertaining to CPPS was conducted in order to devise a plausible alternative description of this syndrome. Due to publisher's criteria, only select articles are included and cited for this purpose. Evidence of a bacterial etiology is non-existent, while evidence of prostatic inflammation is conflicting and non-specific. More plausible causes of prostatitis-like symptoms include musculoskeletal pain, pelvic floor muscular dysfunction, myofascial pain syndromes or functional somatic syndromes. Thorough evaluation and appropriate therapy for patients has been seriously hindered by decades of a prostatocentric approach to CP/CPPS. The following article introduces an alternative perspective.

Herbal and complementary medicine in chronic prostatitis

Abstract: Chronic prostatitis is a very common and poorly understood condition with significant impact on quality of life. The etiology of prostatitis can be multifactorial and can present with a variety of symptoms. Given the lack of proven efficacy of conventional therapies such as antibiotics, many patients have turned to phytotherapy and other alternative treatments. This review will cover the alternative therapies commonly used in prostatitis with an emphasis on those with published data. These treatments include phytotherapy (quercetin, bee pollen) and physical therapy. Complementary therapies have shown the potential to help men with prostatitis, particularly when allopathic therapies have failed.

Transdermal testosterone delivery: testosterone patch and gel.

Abstract: Testosterone replacement treatment is usually life-long. Fortunately, testosterone administration is relatively safe and until the age of 50 years few side effects are noted with normal doses of testosterone. After the age of 50 years when prostate disease becomes more prevalent, shorter-acting testosterone preparations, allowing a fast reduction of circulating testosterone levels, may be an advantage. Testosterone has an impact on sexual and non-sexual behaviour and short-acting testosterone preparations may be better suited for the initiation of long-term administration allowing the monitoring of behavioural effects. Testosterone can be delivered to the circulation through the intact skin, both genital and non-genital. Transdermal administration delivers testosterone at a controlled rate into the systemic circulation, avoiding hepatic first pass and reproducing the diurnal rhythm of testosterone secretion and without the peak and trough levels observed with the use of the traditional long-acting testosterone injections. In conclusion, both the testosterone patch and testosterone gel are valuable contributions to androgen replacement treatment meeting the requirements specified for testosterone replacement treatment.

Oxytocin plasma levels in the systemic and cavernous blood of healthy males during different penile conditions.

Abstract: It is well established that transmitters of the nonadrenergic-noncholinergic (NANC) system are involved in the control of sexual arousal and penile erection in healthy males The proerectile activity of dopamine D1/D2 receptor agonist apomorphine-HCl (IXENSE, UPRIMA) involves oxytocinergic pathways descending from the hypothalamus to the brain stem and spinal autonomic centers Although it has been demonstrated that injection of oxytocin into the paraventricular nucleus and the hippocampus produces penile erection in rats, the significance of the peptide in the control of sexual arousal and penile erection in man has been, up until now, only poorly evaluated The present study was undertaken to determine whether oxytocin (OT) plasma levels alter in the systemic and cavernous blood of healthy males under different penile conditions (flaccidity, tumescence, rigidity, detumescence) Twenty-five healthy adult males were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and rigid erection Blood was taken from the corpus cavernosum (CC) and the cubital vein (CV) during penile flaccidity, tumescence, rigidity and detumescence Following extraction from plasma aliqouts, oxytocin was measured by means of a radioimmunoassay An increase was observed in the mean OT plasma levels in the systemic and cavernous blood when the flaccid penis became tumescent (CC: from 667±34 to 75±44 pg/ml; CV: from 71±41 to 79±495 pg/ml) From tumescence to rigidity, OT further rose in the cavernous blood (to 81±58 pg/ml), whereas it remained unaltered in the systemic circulation During detumescence, oxytocin plasma levels dropped in the cavernous but again increased in the systemic blood (to 94±49 pg/ml) Our results support the hypothesis of a pivotal role of OT in the mechanism of male sexual arousal and penile erection and provide a rationale for the use of apomorphine in the treatment of erectile dysfunction

High dose rate brachytherapy in the treatment of prostate cancer

Abstract: The optimal treatment of patients with localized prostate cancer remains controversial. Significant clinical data are available, however, demonstrating that patients treated with radiation therapy (RT) have a significantly better outcome as the dose to the gland is increased. What remains debatable, however, is how to best deliver these higher doses of RT without significantly increasing normal tissue toxicities. Conformal high dose rate brachytherapy (C-HDR BT) represents an alternative means of precise dose delivery that offers similar tumoricidal effects as three-dimensional (3D) conformal external beam radiotherapy (EBRT) or permanent interstitial prostate seed implants with potential additional advantages. Since C-HDR BT consists of temporarily placing afterloading needles or catheters directly into the prostate gland under real-time ultrasound guidance, a steep dose gradient between the prostate and adjacent normal tissues can be generated that is minimally affected by organ motion and edema or treatment setup uncertainties. The ability to control the amount of time the single HDR radioactive source "dwells" at each position along the length of each brachytherapy catheter further enhances the conformity of the dose. In addition, recent radiobiological data on prostate cancer treatment suggest that C-HDR BT should produce tumor control and late normal tissue side effects that are at least as good as achieved with conventional fractionation, with the additional possibility that acute side effects might be reduced. Published data from several groups performing C-HDR BT as boosts in patients with locally advanced disease have supported these assumptions. Combined with the physical advantages discussed above, C-HDR BT should provide similar tumor control as 3D conformal EBRT with the added advantages of reduced treatment times, less acute toxicity, and no additional technological requirements to account and correct for treatment setup uncertainties and organ motion. Due to the success of C-HDR BT as boost treatment in locally advanced disease, this form of radiation treatment has recently been applied to low-risk prostate cancer patients as an alternative brachytherapy technique to permanent interstitial seed implantation. Advantages in this setting include an improved ability to define and deliver the prescribed dose, a significantly shortened treatment schedule compared to 3D conformal EBRT, and the fact that patients are not radioactive after implantation.

Tomatoes, lycopene and prostate cancer: a clinician's guide for counseling those at risk for prostate cancer.

Abstract: Prostate cancer has become a major public health issue and the search for etiologic risk factors and the development of chemopreventive agents has gained momentum over the last decade. An important epidemiologic finding has been the association between the consumption of tomato products and a lower risk of prostate cancer. Several investigators have proposed that lycopene, a carotenoid consumed largely from tomato products, may be the component responsible for lowering the risk of prostate cancer. Laboratory and clinical studies have been initiated with the goal of assessing the ability of pure lycopene to serve as a chemopreventive agent for prostate cancer. The focus on lycopene should continue, and an improved understanding of lycopene absorption, distribution, role in antioxidant reactions, and metabolism is critical in the quest to elucidate mechanisms whereby this compound may possibly reduce prostate cancer risk.

Etiology: where does prostatitis stop and interstitial cystitis begin?

Abstract: Male chronic pelvic pain syndrome (MCPPS) and interstitial cystitis (IC) patients show striking similarities in clinical presentation, diagnostic evaluation, purported pathogenesis, and even response to therapy. This makes the distinction between them very difficult. This review aims to show just how easy it is for the clinician to miss the features of IC in the MCPPS patient (and conversely). Misdiagnosis can result in the rejection of various potentially helpful therapies while accurate early diagnosis will lead to appropriate therapies and a better quality of life for the patient.