Overactive Bladder

Reviewing the Literature

RIU0263_04-20.qxd 26/4/06 3:59 Page 92 Urinary Incontinence continued progestin), the ability to generalize these findings to women taking other MHT formulations is limited. However, the findings are consistent with those from an observational study that reported on the use of several different formulations of estrogen plus progestin and estrogen alone and suggested an increased risk of UI associated with MHT. What then is the biologic background of these findings? On the basis of a recent study of estrogen’s effect on connective tissues, the investigators suggested that estrogen might actually alter collagen metabolism, which would result in damage to the periurethral connective tissues essential for effective urethral closure. The take home messages from this study are these: first, long-term oral conjugated equine estrogens can no longer be regarded as an effective treatment option for UI in postmenopausal women. Second, we should remember that this trial dealt only with oral administration, and whether topical estrogens might prove beneficial remains unknown. Finally, more investigation in basic science is needed to discover the functional role of estrogen in normal and aging urinary tract and pelvic floor composition. As for the initial question of whether estrogen for urinary incontinence is good or bad, thus far the balance seems to lean toward the negative. However, the information we have is still far from complete. We definitely need more clinical trials with various formulations, including topical estrogens, more systematic characterization of UI by objective and subjective measures, and comprehensive outcomes assessment. Only with such information will we be able to reach a final answer to this question. Overactive Bladder What is the Effect of Overactive Bladder Medication on Sleep? Reviewed by Dae Kyung Kim, MD,* Michael B. Chancellor, MD† *Department of Urology, Eulji University School of Medicine, Daejeon Korea; †Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA [Rev Urol. 2006;8(2):92] © 2006 MedReviews, LLC T 92 he incidence and intensity of central nervous system (CNS) side effects from anticholinergics depend on the pharmacokinetic and pharmacodynamic proper- VOL. 8 NO. 2 2006 REVIEWS IN UROLOGY ties of the specific agents. CNS side effects are especially worrisome and often exaggerated in the elderly. Effects on Sleep of Anticholinergics Used for Overactive Bladder Treatment in Healthy Volunteers Aged
50 Years Diefenbach K, Arold G, Wollny A, et al. BJU Int. 2005;95:346-349. In a randomized, double-blind, placebo-controlled study with a crossover design, Diefenbach and colleagues assessed the influence of oxybutynin, tolterodine, or trospium chloride, anticholinergics used to treat bladder overactivity, on sleep and the cognitive skills of healthy volunteers at least 50 years old. According to previous reports, changes in sleep structure are mainly related to rapid-eye-movement (REM) sleep and manifest themselves in an increased REM latency and a reduced REM duration. Twenty-four healthy sleepers (12 men and 12 women, aged 51–65 years) underwent polysomnographic recordings and cognitive tests in a sleep laboratory. The crossover design was chosen to minimize the influence of interindividual variance of sleep variables. Study medications were given as a single dose containing the total recommended daily dose (oxybutynin 3  5 mg, tolterodine 2  2 mg, trospium chloride 3  15 mg) to shorten the treatment period. The duration of REM sleep, as a percentage of total sleep time, was used as the primary target variable to compare tested drugs. Potential impairment of cognitive function was also assessed with appropriate questionnaires. The key finding of this study was that there was a significant reduction in REM sleep (approximately 15%) and a slightly (but not significantly) greater REM latency with oxybutynin and tolterodine than with placebo. REM duration and latency with trospium chloride were comparable to those with placebo. There was no effect of the tested anticholinergics on cognitive and subjective sleep variables. Subjects aged 50 years or more had a more distinct impairment of REM sleep after oxybutynin and tolterodine than had young subjects, but the reduction in REM sleep did not reach a pathologic degree in this study. There was no apparent impairment of concentration or cognitive function, but impairment of cognitive function and neuropsychological side effects cannot be excluded, especially in elderly patients with impaired REM sleep from various psychiatric diseases (eg, depression) and/or other sleep disturbances. The effect of long-term anticholinergic therapy should not be extrapolated from this single-dose study.