Fabio Lorenzetti

Management of OAB in Those Over Age 65

The International Continence Society (ICS) defines overactive bladder (OAB) as an association of symptoms including “urgency, with or without urge incontinence, usually with increased frequency and nocturia”. This conditon has been associated with a decrease in quality of life and a higher related risk of overall health condition decrease, and is rising since its prevalence increases with age and the forecast for the world population estimates an increase of those over 65 years old. Aging alone can be considered a major risk factor for developing OAB symptoms that are considered multifactorial and due to body tissue and anatomic changes, lifestyle-associated factors, comorbidities and personal characteristics. The high prevalence of this condition and multiple etiology factors makes of its treatment a challenge—especially in the older population. A major concern over OAB treatment of elderly patients is the risk of cognitive side effects due to the pharmacologic treatment with anticholinergic drugs. First-line treatment for OAB symptoms are the use of pharmacologic therapy with antimuscarinic drugs, which has been proved to be effective in controlling urgency, urge incontinence episodes, incontinence episodes, and nocturia. The impact caused by this condition is significant regarding the economic and human costs associated bringing into attention the need of studying and reviewing this specific population. Conservative Management and Lifestyle Modifications: Behavioral therapy’s aims are to reduce urinary frequency and urgency to an accepted level and to increase bladder outlet volume. It consists of actions to teach patients to improve and learn bladder control. Lifestyle modifications are a conjunct of daily activities that can be managed to have the lowest interference on the functioning of the urinary tract. Pharmacologic Therapy: There are various medications with antimuscarinic properties available for the treatment of OAB symptoms. The most commonly used are oxybutinin, tolterodine, solifenacin, darifenacin, fesosterodine and trospium. Second-line Therapy: OAB treatment accounts for some refractory to conventional treatment patients who will require alternative therapies to achieve improvement of symptoms as the use of intradetrusor injection of botulinum A toxin by binding to receptors on the membrane of cholinergic nerves causing temporary chemodenervation and consequent muscle relaxation. Neuromodulation is also an effective therapy that aims to achieve inhibition of detrusor activity by continuous neural stimulation through peripheral nerves as the use of the tibial nerve or central as it is performed by direct spine stimulation on sacral roots through the implantation of an automated generator. In conclusion, evidence from the literature has shown that antimuscarinic treatment of OAB in the elderly population is safe and effective in improving symptoms and patient’s quality of life. Managing OAB symptoms in this population is a great challenge. An optimal therapeutic approach to treat should involve medical treatment with drug and behavioral therapy in addition to lifestyle advice.

Relation between glycemic levels and low tract urinary symptoms in elderly.

Abstract Introduction: Due the low mortality attributed to BPH, the evaluation of the impacts of LUTS on quality of life of the patients has great importance, especially on the concern of therapeutic choices, except on cases of formal surgery indication. This increase is directly related with difficulties to perform ordinary tasks and a normal living in community. Objectives: Determinate an association among Diabetes mellitus II and BPH symptoms in a group of elder men. Methodology: This is an observational clinic trial, comparative. About 62 male subjects, 60 years old or more have been active interviewed. They were divided in two similarly groups. First was composed by men without diabetes and the second with diabetic men. For the evaluation of prostatic symptoms, it was utilized the IPSS. Results: Mean age on Group I was 67.6 years old, while on Group II was 68.7 years old (p = 0.1521). After questionnaire, 51.5% of participants on Group I and 54.2% on Group II presented Systemic Arterial Hypertension (p = 0.099). IPSS was higher on group II (p < 0.0005). Discussion: Diabetes mellitus was positively associated with the increasing of the LUTS, especially NOCTÚRIA. Patients on group I had a media of 14.2 points on IPSS questionnaire, while those on group II reached the media of 7 points. This pattern was the same even after the age, corporal mass and social/economic adjustment. Conclusion: There is a statistically association between DM and LUTS on Elder men, evaluated through a specific questionnaire.

Testosterone supplementation's effects on age-related bladder remodeling - experimental study in rats.

Abstract Objective: This study was designed to evaluate the effect of testosterone replacement on the fibrotic process of the detrusor bladder muscle during the normal aging process. Methods: 15 Wistar senile rats, aged between 18 and 20 months were divided into two groups: testosterone group – 11 animals submitted to the administration of testosterone undecanoate (50 mg/kg intramuscular), once per month; and, Control group – four animals underwent a sham procedure. At the end of eight weeks, animals from both groups were sacrificed; bladders were removed and subsequently stereologically evaluated to determine the volumetric density of collagen fibers. The success of testosterone administration was confirmed by the measurement of serum testosterone at the beginning and end of the experiment. Results: In the replacement group, testosterone average was 3.2 ng/ml, whereas in the control group, the mean testosterone at the end of the experiment was 0.64 ng/ml (p < 0.05). Analysis of stereological collagenous fiber showed higher density in the control group compared to the testosterone group I (56% versus 37.02%, respectively). The difference of volume concentration of collagen between both groups was statistically significant (p < 0.000). Conclusion: Bladder wall fibrosis was reduced in senile rats subjected to testosterone replacement.

Elderly men's quality of life and lower urinary tract symptoms: an intricate relationship

PURPOSE To evaluate the impact of lower urinary tract symptoms (LUTS) on the quality of life (QoL) in a group of elderly men. MATERIALS AND METHODS Observational clinical study contained 200 men recruited between March-September 2008 in the community and Urology and Geriatrics ambulatories. The data collected included health and sociodemographic conditions; the International Prostate Symptom Score (IPSS); an anxiety/depression inventory; the World Health Organization Quality of Life -Bref and -Old questionnaires (WHOQoL). Participants were classified according to IPSS: Group I (moderate/severe symptoms) and Group II (absence/mild symptoms) and 100 men were included in each group. RESULTS The groups were statistically similar in sociodemographic, morbidity, and anxiety/depression scores. Both QoL scales showed significant lower median scores in group I in all parameters, except the global subjective self-evaluation of QoL. The domains social and environmental relations presented the most significative differences (p < 0.0005) in both questionnaires, and final mean WHOQoL-OLD score was lower in group I (p < 0.0005). CONCLUSIONS For elderly men, moderate to severe LUTS do significantly impact almost all parameters of QoL proposed by the WHO, especially social and environmental relations.

Inhibitory activity of α-tocoferol on apoptosis in the rat bladder wall subjected to androgen deprivation†‡

Alpha‐tocopherol (2,5,7,8‐tetramethyl‐2‐(4,8,12‐trimethyltridecyl)‐chromon‐8‐ol) is used in many previous urological studies. Thus to add to this knowledge in this study we studied the potential inhibitory activity on oxidative stress and process apoptosis on bladder wall in male rats subjected to androgen deprivation. A causal relationship between lower testosterone levels and apoptosis, as a component of castration‐induced muscle atrophy, has been shown. Male Wistar rats (250–300 g) were used in this experiment, divided into four groups: control (sham operation; n = 10); castration (n = 10); castration, with alpha‐tocopherol supplementation over preceding four weeks (n = 10); and castration, with alpha‐tocopherol supplementation over preceding four weeks and subsequent eight weeks (n = 10). Activated caspase‐3 was detected using a previously described technique, with analysis using stereological methodology. Nonparametric methods were used to test statistical significance, taking a significance level of P < 0.005. This study was approved by the ethics committee of the university where the project was developed. The serum testosterone concentrations before castration were less than 20 pg/ml. Analysis of 8‐isoprostane showed statistical significance (P < 0.0003). The volumetric density of caspase‐3 showed significant differences between the groups. There was no statistical significance regarding caspase‐3 between sham and alpha‐tocopherol plus castration or between the groups that received alpha‐tocopherol supplementation. The observations showed that there was greater apoptosis in the group with castration alone than in the groups with alpha‐tocopherol supplementation. This finding, together with the induced androgen deprivation and higher 8‐isoprostane levels, corroborates the hypothesis that alpha‐tocopherol supplementation has an important protective effect under conditions of oxidative stress, thereby avoiding the apoptotic process, especially regarding aging. Neurourol. Urodyn. 30:194–198, 2011.

Bladder function in obstructed men – does age matter?

Abstract Aim: The high prevalence of diseases and disabilities in the elderly will therefore impose major future challenges for governments, particularly in social security, health system and social care. Methods: Nine hundred and seventy-one men, 40 years or older referred for low urinary tract symptoms (LUTS) evaluation who underwent full urodynamic investigation, were reviewed. Urodynamic parameters were obtained, such as Uroflowmetry, those of Filling Cystometry and those of pressure flow study (PFS). Results: Mean age was of 66.1 years old. Most the patients included in the analysis were categorized as Schafer score 2–4. Correlation analysis of uroflowmetry parameters revealed statistically significant decrease in voided volume (p = 0.013), Qmax (p = 0.023) with aging. Cystometric parameters revealed significant age-related decrease in bladder capacity (p < 0.001) and bladder compliance (p = 0.004). PFS revealed significant decrease in voiding efficiency (p = 0.029), voided volume (p < 0.001), Qave (p = 0.008) and Qmax (p = 0.048) with progressing age. Age subgroup analyses showed significant differences in voiding efficiency (KW, p = 0.032), voided volume (KW, p < 0.001) and Qave (KW, p = 0.036). Conclusions: Age-related changes in voiding function might not be a result of impaired detrusor contractility or increased outflow obstruction, intrinsic causes must be suspected. Changes in the storage function of the bladder represent specific pathophysiological mechanisms influenced by aging.

Impact of castration with or without alpha-tocopherol supplementation on the urethral sphincter of rats

OBJECTIVE To analyze the impact of low levels of testosterone induced by orchiectomy and the effect of alpha-tocopherol supplementation on oxidative stress in the urethral sphincter. MATERIALS AND METHODS Forty male Wistar rats weighing 250-300 g were divided into four groups with 10 each: Sham group; Orchiectomy group: bilateral orchiectomy; Orchiectomy-pre-Tocopherol group: bilateral orchiectomy preceded by alpha-tocopherol supplementation for four weeks; Orchiectomy-full-Tocopherol group: bilateral orchiectomy with alpha-tocopherol supplementation for four weeks preceding the procedure and for eight weeks afterwards. At the protocol end, animals were euthanized and had the sphincter analyzed stereologically focusing on collagen and muscle fibers percentage. Oxidative stress levels were determined using 8-epi-PGF2. RESULTS The 8-epi-PGF2 levels were statistically higher (p < 0.0003) in the Orchiectomy group compared to others groups while Sham and Orchiectomy-full-Tocopherol groups presented statistically similar values (p = 0.52). Collagen volumetric densities were significantly lower in Sham and Orchiectomy-full-Tocopherol groups (p < 0.022). Sham group presented statistically greater muscle fiber percent. CONCLUSION Castration caused oxidative stress in the urethral sphincter complex, with increased collagen deposition. Alpha-tocopherol had a protective effect and its supplementation for twelve weeks provided the greatest protection.

Antioxidant supplementation decreases the cell death rate in the prostatic stromal tissue of long-term castrated rats

OBJECTIVE The purpose of this study was to compare the effects of castration on cell death rate of the adult rat prostates and to evaluate the benefic action of alpha tocopherol supplementation to avoid apoptosis post-orchiectomy. MATERIAL AND METHODS Thirty male Wistar rats weighing 250-300g were divided into three groups: group I - they were subjected to bilateral orchiectomy and sacrificed eight weeks after the procedure; group II - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure; and group III - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure and for eight weeks afterwards. At the end of the experiment, the prostatectomy was performed in all rats. The presence of oxidative stress was determined by assaying the blood level of 8-isoprostane and the occurrence of apoptosis was evaluated by identification of active caspase-3 through immunohistochemical analysis. RESULTS The statistic analysis of active caspase-3 showed that in the long-term castrated group the detection was higher than in groups were the alpha-tocopherol was supplemented (p=0.007). Analysis of 8-isoprostane levels showed higher concentrations of reactive oxygen species in group I compared to other groups (p < 0.05). Groups II and III presented active caspase-3 lower than in group I (p < 0.05). CONCLUSION Our exploratory analyses demonstrate a method to study the aging process and its influence on oxidative stress of prostatic tissue and cells death rate. Based on our results we can suggest that alpha tocopherol supplementation can decrease the apoptotic process as well as the oxidative stress levels induced by androgen deprivation of the prostate gland.

The use of Hypochlorous Acid as a Model for Investigating Bladder Overactivity

UNLABELLED Involuntary detrusor contractions play an important role in the development of urge incontinence. Also in an in-vitro situation contractions which develop spontaneously can be seen; a parallel with the in vivo observations is likely. In order to study this muscle overactivity we investigated the possibility to induce this phenomenon with oxidative stress using hypochlorous acid (HOCl). MATERIALS AND METHODS Urinary bladder muscle strips from pigs were mounted in a custom made organ bath and incubated for 20 minutes in Krebs solution. Next HOCl (10 µM) was added to the organ bath and the onset of overactive contractions was closely followed. Overactivity was defined as a development of more than 5 phasic detrusor contractions per minute without any other provocation in the 30 minutes following addition of HOCl to the organ bath. RESULTS Of the 50 strips which were used 36 (72%) became overactive after exposure to HOCl during 30 minutes recording. In 76% of the overactive strips overactivity occurred within 5 minutes, in 19% between 5 and 15 minutes, and in 5% it took longer than 15 minutes. The overactivity could be stopped by washing out HOCl for 10 minutes after which still a significant contraction after EFS and ACh stimulation was seen. CONCLUSIONS It can be concluded that an oxidative stressor, like HOCl, is capable of inducing smooth muscle overactivity. This model can be used for the development and testing of new treatment modalities for the overactive detrusor. Furthermore, this study provides evidence for a causal relationship between oxidative stress and detrusor overactivity.

α-Tocopherol supplementation avoids apoptosis in the anal sphincter.

Purpose: To analyze the influence of α-tocopherol supplementation on the levels of oxidative stress and apoptosis rates in the anal sphincter induced by orchiectomy in rats. Methods: Forty male Wistar rats weighing 250–300 g, were divided into four groups and sacrificed 8 weeks after: I– Control: sham; II– Orchiectomy: bilateral orchiectomy; III– Pre Orchiectomy Tocopherol: α-tocopherol supplementation for 4 weeks preceding bilateral orchiectomy; IV– Orchiectomy Full Tocopherol: α-tocopherol supplementation for 4 weeks before and 8 weeks after bilateral orchiectomy. The anal sphincter was analyzed stereologically to evaluate the density of collagen and the muscle fibers. The oxidative stress and the apoptosis were determined with 8-isprostane and caspase-3, respectively. Results: The collagen fibers concentration was statistically greater in Orchiectomy group than the others. The muscle fibers concentration was higher in Control and Orchiectomy Full Tocopherol than Orchiectomy and Pre Orchiectomy Tocopherol groups. Orchiectomy group showed higher 8-isoprostane concentrations compared to the other groups (p < 0.0003). Pre Orchiectomy Tocopherol and Orchiectomy Full Tocopherol groups presented caspase-3 levels lower than the Orchiectomy group (0.0072). Conclusion: Vitamin supplementation with α-tocopherol for 12 weeks had the highest protection against bilateral orchiectomy generation of reactive oxygen species as well as apoptosis in the muscle fibers of the anal sphincter of rats.