Gonadal function in adult male patients with congenital adrenal hyperplasia.

CONTEXT: Current knowledge on gonadal function in congenital adrenal hyperplasia (CAH) is mostly limited to single-center/country studies enrolling small patient numbers. Overall data indicate that gonadal function can be compromised in men with CAH. OBJECTIVE: To determine gonadal function in men with CAH within the European 'dsd-LIFE' cohort. DESIGN: Cross-sectional clinical outcome study, including retrospective data from medical records. METHODS: Fourteen academic hospitals included 121 men with CAH aged 16-68 years. Main outcome measures were serum hormone concentrations, semen parameters and imaging data of the testes. RESULTS: At the time of assessment, 14/69 patients had a serum testosterone concentration below the reference range; 7 of those were hypogonadotropic, 6 normogonadotropic and 1 hypergonadotropic. In contrast, among the patients with normal serum testosterone (55/69), 4 were hypogonadotropic, 44 normogonadotropic and 7 hypergonadotropic. The association of decreased testosterone with reduced gonadotropin concentrations (odds ratio (OR) = 12.8 (2.9-57.3)) was weaker than the association between serum androstenedione/testosterone ratio ≥1 and reduced gonadotropin concentrations (OR = 39.3 (2.1-732.4)). Evaluation of sperm quality revealed decreased sperm concentrations (15/39), motility (13/37) and abnormal morphology (4/28). Testicular adrenal rest tumor (TART)s were present in 39/80 patients, with a higher prevalence in patients with the most severe genotype (14/18) and in patients with increased current 17-hydroxyprogesterone 20/35) or androstenedione (12/18) serum concentrations. Forty-three children were fathered by 26/113 patients. CONCLUSIONS: Men with CAH have a high risk of developing hypothalamic-pituitary-gonadal disturbances and spermatogenic abnormalities. Regular assessment of endocrine gonadal function and imaging for TART development are recommended, in addition to measures for fertility protection.

Needs of children with a chronic bladder in preparation for transfer to adult care.

OBJECTIVE: Transfers to adult care can be problematic, resulting in postponement due to the protective nature of pediatric care and patient dependency. It is unknown whether these findings apply specifically to urology patients. Our department is taking part in a national general transition project. In this light, our aim was to investigate the specific needs of adolescent urologic patients, regarding their independence and transition. PATIENTS AND METHODS: 80 patients, born in 1975-1998, with a chronic bladder condition received a questionnaire. They were divided into pre- and post-transfer groups. Parents (n = 7) of post-transfer patients formed a third group. Questionnaires were based on those used in the national transition study, supplemented with urological questions. Pre-transfer patients were asked about their level of independence, what subjects were discussed during consultations, and their expectations and wishes regarding transfer. Post-transfer patients and parents were asked for their opinions on the transfer process. RESULTS: 73% (n = 58) responded (55 pre-transfer and 3 post-transfer patients plus parents). It appeared that the confidence built-up with the pediatric urologist impeded the transfer. An adequate level of disease-related knowledge was reported. Relationships, sexuality and fertility were hardly talked about (respectively n = 17, 16 and 18). Parents played an important role, which patients appreciated, confirming their dependency. Despite the 49% (n = 27) who stated they can arrange their urological care themselves, 44% (n = 24) felt ill-prepared for transfer. CONCLUSION: Although overall self-perceived knowledge is sufficient, the trust in and personal relationship with the pediatric urologist formed the greatest obstruction to successful transition. These findings have been used to improve support during transition by creating a transition protocol.

Urotherapy in children: quantitative measurements of daytime urinary incontinence before and after treatment according to the new definitions of the International Children's Continence Society.

OBJECTIVE: To assess the effectiveness of urotherapy in children with lower urinary tract dysfunction, according to the new definitions of the International Children's Continence Society. MATERIAL AND METHODS: We performed a retrospective review of 122 children (aged 8.8 ± 2.0 years) treated in an outpatient program for lower urinary tract dysfunction. Exclusion criteria included all neurologic abnormalities. In 98 children (80%) daytime urinary incontinence was a predominant symptom. Therapy consisted of an individually adapted drinking and voiding schedule, pelvic floor relaxation, instructions on toilet behavior, biofeedback uroflowmetry and if necessary recommendations for regulation of defecation. Before and at the end of training, patients were evaluated for number and severity of daytime wet accidents per week, using a scoring system to grade the severity of incontinence. Secondary measurements of accompanying voiding symptoms were performed. RESULTS: Of the 90 children with daytime urinary incontinence for whom sufficient objective data were collected, 42% became completely dry during the daytime and 36% showed a 50% or greater level of response. Secondary measurements showed a significant reduction in daily voiding frequency (mean 7.0 ± .3, P<0.0001) and mean post-void residual (P<0.003), and an improvement in flow pattern (P<0.05). CONCLUSIONS: Urotherapy is successful for the treatment of daytime urinary incontinence in children. Additional benefit was evident in improvement of accompanying voiding symptoms. A combination of the definitions of the International Children's Continence Society and a scoring system to grade severity improved the evaluation method. Further research into long-term efficacy will be performed.

Intra-prostatic vasculature studies: can they predict the outcome of transurethral microwave thermotherapy for the management of bladder outflow obstruction?

BACKGROUND: Blood perfusion regulates intraprostatic temperatures during transurethral microwave thermotherapy (TUMT). We evaluated baseline intraprostatic vasculature, as a predictor of efficacy of TUMT. METHODS: Twenty-two patients, with lower urinary tract symptoms (LUTS) suggestive of bladder outflow obstruction, were treated with TUMT (Prostatron). At baseline, three-dimensional contrast-enhanced power-flow-Doppler prostate ultrasonography (3D-CE-PFD) was performed. Assuming that the percentage of perfused area (PPA) is a realistic measure of blood flow, it was used to quantify intraprostatic vasculature. RESULTS: The median (range) age, prostate size, and energy delivered were 66 years (48-80), 47 cm(3) (30-121), 110 kJ (29-136), respectively. The response was 77% (5 failures). The median (range) PPA was 2.76% (0.7-11.3). No difference in PPA among good and poor responders was detected nor was any correlation between PPA and baseline parameters. CONCLUSIONS: The baseline intraprostatic vascularization, documented by CE-PFD studies, has no predictive value for the efficacy of TUMT. It seems that "static" baseline blood flow does not reflect the "dynamic" thermoregulatory role of blood flow during treatment.

alpha-Blockade improves symptoms suggestive of bladder outlet obstruction but fails to relieve it.

PURPOSE: We investigated the effect of the alpha-blockers alfuzosin, terazosin and tamsulosin on urodynamic parameters after 6 months of therapy. MATERIALS AND METHODS: Between February 1992 and June 1998, 163 patients with lower urinary tract symptoms suggestive of bladder outlet obstruction were treated with alfuzosin (60), terazosin (66) and tamsulosin (37). Patients were evaluated with urodynamic studies, including pressure flow analysis, before treatment and after 6 months of therapy. Initially, all patients were also assessed by the International Prostate Symptom Score questionnaire and measurement of urinary flow rate. RESULTS: The majority of patients had no clear improvement in obstructive parameters, regardless of the alpha-blocker used, as urethral resistance factor and detrusor pressure maximum flow rate decreased by only 4 cm. H2O. There was a clear subjective and statistically significant decrease in International Prostate Symptom Score and quality of life scores of 6 and 2 points, respectively. No relevant statistical difference was noted among the effects of the 3 alpha-blockers on relieving symptoms or improving urodynamic parameters of obstruction. CONCLUSIONS: The alpha-blockers are effective for treating symptoms suggestive of bladder outlet obstruction in patients presenting with lower urinary tract symptoms but not for treating the obstruction.

Efficacy and safety of the new high-energy 30-minute transurethral microwave thermotherapy: results of 1-year follow-up in a multicenter study.

PURPOSE: To assess the efficacy and durability of a new 30-minute algorithm for high-energy transurethral microwave thermotherapy (TUMT, Prostasoft 3.5) in the treatment of men with lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 167 men (mean age 67 years) with bothersome LUTS were treated with the new TUMT protocol. Evaluation included assessment of the short- and long-term objective and subjective outcome measures of this treatment. RESULTS: The treatment is well tolerated. The International Prostate Symptom Score improved from a mean of 19.2 at baseline to 7.9 at 12 months after treatment. Maximum urinary flow improved from 8.9 to 16.4 mL/s at 12 months. Mean duration of catheterization was 16.1 days. Urodynamic evaluation showed a change from the obstructed to the nonminimally obstructed zone. There were no serious complications. CONCLUSION: High-energy TUMT using the new high-dose Prostasoft 3.5 protocol appears to be a safe, effective, and durable treatment. The faster procedure improves tolerance of the treatment. Subjective and objective improvements were significant and the treatment-related morbidity low.

Variability of pressure-flow studies in men with lower urinary tract symptoms.

The objective of this study was to assess the short-term test-retest variability of pressure-flow studies (PFS) in men with lower urinary tract symptoms (LUTS). By choosing a short interval between two consecutive PFS, but notably not performing two tests within a single session, both tests represent the same routine testing procedure. Eighty-nine patients with LUTS suggestive of bladder outlet obstruction or detrusor underactivity, who received PFS, were asked to undergo a second urodynamic evaluation within 4 weeks after the initial test. At both visits, specialized physicians performed the PFS. Obstruction was quantified using the Abrams-Griffiths number (AG number). Each patient was classified as obstructed, unobstructed, or equivocally obstructed according to the International Continence Society nomogram. As expected, no systematic difference was observed in AG number between the first and the second visit at the group level. There was, however, considerable variation at the individual level. The average within-patient standard deviation was 14 cm H(2)O. This finding shows that if a patient's AG number is 30 at the first visit, his true AG number can be any value between 30 +/- 1.96 * 14 = 3 to 57, owing to random variability alone. The average within-patient standard deviation did not differ significantly between sub-groups of obstruction and other variables such as patient age, symptom score, prostate volume, or residual volume. The variability appeared to increase slightly with an increased interval between visits. Of all patients, 39% changed at least one category of obstruction at the second visit and 3% changed from definitely obstructed to definitely unobstructed or vice versa. We conclude that PFS cannot stand the test of serving as a gold standard to identify bladder outlet obstruction in patients with LUTS.

Long-term followup of randomized transurethral microwave thermotherapy versus transurethral prostatic resection study.

PURPOSE: We evaluate the durable effect of high-energy transurethral microwave thermotherapy and transurethral prostatic resection for treatment of patients with lower urinary tract symptoms suggestive of bladder outflow obstruction. MATERIALS AND METHODS: Between January 1996 and March 1997, 155 patients with lower urinary tract symptoms suggestive of bladder outflow obstruction were randomized to receive transurethral microwave thermotherapy (Prostatron*; device and commercial software) (82) or undergo transurethral prostatic resection (73). Initial patient evaluation was performed according to international standards. Patients were followed annually with the International Prostate Symptom Score (I-PSS) and uroflowmetry (maximum flow rate). The Kaplan-Meier survival analysis was used to calculate the cumulative risk of re-treatment, adjusted for loss to followup. RESULTS: A total of 78 patients received transurethral microwave thermotherapy and 66 underwent transurethral prostatic resection. Median followup was 33 months. In the thermotherapy group mean maximum urinary flow rate improved from 9.2 ml. per second at baseline to 15.1, 14.5 and 11.9 ml. per second at 1, 2 and 3 years, and mean I-PSS decreased from 20 to 8, 9, and 12, respectively. In the resection group the corresponding numbers for maximum urinary flow rate were 7.8, 24.5, 23.0 and 24.7 ml. per second at 1, 2 and 3 years, and for I-PSS were 20, 3, 4 and 3, respectively. At 36 months, 14 patients in the thermotherapy and 8 from the resection groups underwent re-treatment, and the cumulative risk was 19.8% (95% confidence interval 10.4% to 29.3%) and 12.9% (4.5% to 21.3%), respectively (p = 0.28). CONCLUSIONS: Transurethral microwave thermotherapy and transurethral prostatic resection achieve durable improvement in patients with lower urinary tract symptoms suggestive of bladder outflow obstruction, while the magnitude of improvement is higher with resection. The repeat thermotherapy is based on failure of therapy whereas repeat resection is based on complications of therapy.

Tolerability of 3.5 versus 2.5 high-energy transurethral microwave thermotherapy.

PURPOSE: To evaluate the tolerability of high-energy microwave thermotherapy in patients with benign prostatic hyperplasia (BPH) using two different treatment protocols (Prostasoft 2.5 and Prostasoft 3.5). MATERIALS AND METHODS: Pain and discomfort during treatment was evaluated using a visual analog scale in 39 patients undergoing 60-min Prostasoft 2.5 treatment and 41 patients undergoing 30-min Prostasoft 3.5 treatment. The duration of transurethral microwave thermotherapy (TUMT) 3.5 treatment is significantly shorter than TUMT 2.5 treatment. RESULTS: The pain level is significantly higher at the beginning of the Prostasoft 3.5 treatment compared to the Prostasoft 2.5 treatment. The reported pain level becomes similar 10 min into treatment, and remains similar to the end of the 3.5 treatment (at 30 min), when the pain level returns to baseline. The 2.5 protocol patients experience continuously increasing pain until the end of the treatment at 60 min. One minute following termination of treatment, the pain level drops back to the baseline level. No correlation between the level of pain and the baseline subjective or objective voiding parameters was observed. A correlation is also absent between the pain level, age and catheterization time. There only seems to be a weak correlation between the pain level and TUMT energy in the Prostasoft 2.5 treatment group. CONCLUSIONS: Both TUMT 2.5 and TUMT 3.5 are well tolerated. Even though patients undergoing TUMT 3.5 treatment experience more discomfort initially, the ultimate discomfort is similar to the TUMT 2.5 treatment, during the first 30 min. Shortening of treatment time significantly reduces the pain and discomfort experienced by the patient. Pretreatment parameters are not predictors of the pain level experienced.

Clinical efficacy of a new 30-min algorithm for transurethral microwave thermotherapy: initial results.

OBJECTIVE: To assess the efficacy of a new 30-min algorithm for high-energy transurethral microwave thermotherapy (TUMT, Prostasoft 3.5) in the treatment of men with lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia. PATIENTS AND METHODS: A total of 108 men (mean age 66 years) with bothersome LUTS were treated with the new TUMT protocol. All patients were evaluated using a standard assessment at baseline, 6, 12, 26 and 52 weeks after TUMT. The evaluation included the assessment of objective and subjective outcome measures, with a urodynamic evaluation using pressure-flow analysis, and the occurrence of adverse events. RESULTS: The treatment was well tolerated. In general, the International Prostate Symptom Score improved from a mean of 20.0 at baseline to a mean of 9.3 at 6 months after treatment. The maximum urinary flow improved from 9.4 mL/s to 14.6 mL/s at 6 months. The mean duration of catheterization was 17.9 days. The urodynamic evaluation showed a change from the obstructed to the equivocal zone on the Abrams-Griffith nomogram. There were no serious complications. Urgency and frequency were the most frequent side-effects after treatment; these all resolved within 3 months. CONCLUSION: High-energy TUMT using the new high-dose Prostasoft 3.5 protocol appears to be a safe and effective treatment. The faster procedure improves the tolerance of the treatment. The subjective and objective improvements were significant and the treatment-related morbidity low. A longer follow-up is needed to assess the durability of this new treatment protocol.

High energy transurethral microwave thermotherapy for the treatment of patients in urinary retention.

PURPOSE: We evaluated the efficacy of high energy transurethral microwave thermotherapy for treating urinary retention due to benign prostatic hyperplasia. MATERIALS AND METHODS: Between October 1993 and March 1999, 41 patients with urinary retention were treated with high energy transurethral microwave thermotherapy. Initial evaluation consisted of a history, clinical examination, urethrocystoscopy, transrectal prostate ultrasonography and urodynamic investigation with a pressure flow study. Followup visits at 12, 26 and 52 weeks included International Prostate Symptom Score (I-PSS), uroflowmetry and post-void residual urine volume determination. At 26 weeks the urodynamic study was repeated. Kaplan-Meier plots were constructed to evaluate the risk of re-treatment adjusted for patients lost to followup. RESULTS: At baseline median patient age was 74 years and median prostate size was 67 ml. Median 133 kJ. were administered. Nine patients underwent re-treatment and 11 were lost to followup. The re-treatment rate after 1 year was 25% (95% confidence interval 11 to 40). In good responders at 12, 26 and 52 weeks median maximal urine free flow was 15, 11 and 15 ml. per second, post-void residual urine volume was 61, 8 and 35 ml., and I-PSS was 7, 5 and 2, respectively. Quality of life (I-PSS question 8) was 1 at all visits. CONCLUSIONS: In patients with severe co-morbidity transurethral microwave thermotherapy is often the only alternative to an indwelling catheter with obvious quality of life advantages. High energy transurethral microwave thermotherapy appears to be effective in these patients.

Intra- and inter-investigator variation in the analysis of pressure-flow studies in men with lower urinary tract symptoms.

The objective of this study was to assess the intra- and inter-investigator variation in the analysis of pressure-flow studies that were performed in men with lower urinary tract symptoms. Two hospitals were involved in this study. In each hospital 100 PFS were selected. Photocopies of printouts of all PFS were analyzed manually by six experienced investigators, including determination of P(detQmax) and Q(max). Afterward, all 200 PFS were analyzed again in a different order. For each P(detQmax) and accompanying Q(max) the AG-number was calculated. With these AG numbers, the intra-investigator SD, the inter-investigator SD and the intra- and inter-investigator SD combined were calculated. The intra- and inter-investigator SD combined was 10.7. This implies that if one investigator analyzes a PFS once and determines an AG number of 40, another investigator may determine an AG number between 40 +/- 2. 77*10.7 = 10-70, using a 95% confidence interval. The inter-investigator SD was 10.0 and the intra-investigator SD was 3.7. The reproducibility of the manual analysis of urodynamic studies is moderate owing to a considerable intra- and inter- investigator variation. This is mostly caused by the substantial intra-investigator variation.

Low reproducibility of maximum urinary flow rate determined by portable flowmetry.

To evaluate the reproducibility in maximum urinary flow rate (Qmax) in men with lower urinary tract symptoms (LUTSs) and to determine the number of flows needed to obtain a specified reliability in mean Qmax, 212 patients with LUTSs (mean age, 62 years) referred to the University Hospital Nijmegen, with various degrees of obstruction on pressure-flow studies, used a portable home-based uroflowmeter with 12 disposable beakers. Voided volume and maximum flow rate were recorded continuously during micturition. Flows with voided volumes of at least 100 ml and without possible artifacts were included. All analyses were repeated while excluding flows with voided volumes <150 ml. A coefficient of variation (CV) was calculated for each patient. The CV represents the standard deviation relative to the mean. All individual CVs were subsequently pooled into a population mean CV. This parameter was used to estimate the number of flows required to obtain a mean Qmax with specified reliability for an individual patient. All analyses were repeated, while successively excluding the first, the first two, and the first three flows, to assess a possible learning curve. A total of 1,854 flows was available for analyses, yielding an average of nine flows per patient. Mean Qmax was 13.2 ml/sec; the mean CV was 24%. To allow, for instance, a 10% deviation from the true mean Qmax (e.g., 15 ml/s +/- 1.5 ml/s), approximately 25 flows are necessary. The actual number of flows needed is in fact even higher due to the presence of small and artifactual flows. Using a 150 ml volume cutoff point, somewhat fewer flows are required, but the total number of flows needed (that is, valid, small, and artifactual flows) increases. There was no evidence of a learning curve. The boundaries of a confidence interval around a single Qmax measurement that is likely to contain the true mean Qmax, lie approximately 50% below or above that single Qmax measurement. To reduce this proportion down to 10%, approximately 25 flows are needed. Thus, to obtain reliable mean Qmax values, considerably more flows are required than are normally performed in urologic practice.

The tolerability of urodynamic studies and flexible cysto-urethroscopy used in the assessment of men with lower urinary tract symptoms.

OBJECTIVE: To determine the overall tolerability of urodynamic studies used in the assessment of men with lower urinary tract symptoms (LUTS), by assessing the objective and subjective morbidity experienced during and after urodynamic studies, and to assess the voiding complaints caused by the combination of urodynamic studies with flexible cysto-urethroscopy. PATIENTS AND METHODS: A total of 103 men with LUTS, who underwent a urodynamic study combined with flexible cysto-urethroscopy, completed a questionnaire designed to assess objective and subjective symptoms and degree of bother, with emphasis on the urodynamic study. In addition, a urine specimen was analysed and cultured. In all, 78 patients who underwent a second urodynamic study completed the questionnaire twice. RESULTS: The results of the first questionnaire showed that more than half of the patients experienced some urge after the urodynamic study and cysto-urethroscopy (56%); 35% of the patients experienced little and 19% experienced severe voiding discomfort after the combined investigations, compared with 24% and 5%, respectively, after a urodynamic study alone. Three patients (3%) had a symptomatic urinary tract infection. Haematuria, increased voiding frequency and increased nocturia occurred occasionally. Most of the patients found the urodynamic study less bothersome than they had expected (64%) and only 9% found it worse than expected. The overall degree of discomfort, experienced during and after the urodynamic study combined with cysto-urethroscopy, was low, and after a second urodynamic study was even lower. CONCLUSION: In contrast with earlier results, this clinic-based urodynamic investigation was associated with a low proportion of urinary tract infection, and low objective and subjective morbidity. The combination of a urodynamic study with a flexible cysto-urethroscopy does not cause significant additional voiding complaints. Most patients find urodynamic studies tolerable and not very bothersome.