Nocturia

REVIEWING THE LITERATURE News and Views from the Literature Nocturia Is Nighttime Voiding Normal or Anomalous? Margie O’Leary, MSN, RN, Michael B. Chancellor, MD University of Pittsburgh School of Medicine, Pittsburgh, PA [Rev Urol. 2001;3(2):106–107] © 2001 MedReviews, LLC N octuria, a common condition that is experienced by many people with various diseases, is particularly bothersome in the elderly. Many urologists would agree that nocturia is the single most troubling symptom of their patients with overactive bladder and benign prostatic hyperplasia (BPH). In the general medical community, nocturia is regarded as a normal part of the aging process. Consequently, many patients do not seek or receive help for this bothersome condition, and thus we are not fully aware of the scope of the problem, nor do we know its effects in the general population or on normal daily living. Significant strides can be made in the diagnosis and therapeutic treatment of this symptom only upon resolution of the fundamental question: What is nocturia? Unless there is consensus, under treatment of this disabling symptom will continue. Seventy-eight percent of men had single episodes of nocturia. Lower Urinary Tract Symptoms and Nocturia in Men and Women: Prevalence, Etiology, and Diagnosis Jackson S. BJU International 1999;84(Suppl.1);5-8. Few published studies exist defining the presence of lower urinary tract symptoms (LUTS) and nocturia in pediatric and adult populations. In Jackson’s review of the literature, studies of children were especially scarce. He presents a study by Mattson1 of 240 healthy children between the ages of 7 and 15 years old over a three-month period. Reported findings showed that 15% of children had incontinence; in addition, 35% had occasional nocturia (defined as 106 REVIEWS IN UROLOGY SPRING 2001 any micturition at night) and 4% had nocturia every night. The study found no correlation between incontinence, nocturnal micturition, and fluid intake. More data are available in reviewing the incidence of nocturia in men. According to Jackson, this may be due to studies of prostatism. Clinical findings by Garraway and colleagues2 depict the prevalence of urinary symptoms in males in a general community in Scotland. Seventy-eight percent of men had single episodes of nocturia. Using a definition of nocturia of two or more micturitions a night, 23% of men in this study had occasional episodes and 7% had frequent nocturia, thus giving an overall prevalence of 30%. In the United States, a population-based survey performed by Chute and associates3 of male urinary symptoms found that the prevalence of nocturia (more than two micturitions at night) increased with age from 16% in men aged 40 to 49 years, to 29%, 42%, and 55% in men ages 50 to 59 years, 60 to 69 years, and over 70 years, respectively. The prevalence of nocturia increased with age from 30% in men aged 45 years to 80% in those aged 80 years. Nocturia was the most prevalent symptom for all ages, with other urinary symptoms showing less increase in prevalence with increasing age. Only recently has nocturia been studied in relation to women. Swithinbank and colleagues4 published the following findings: nocturia (defined as more than 2 micturutions per night) increased with age from 9% in women aged 19 to 39 years to 51% in those over 80. These findings appear similar to results found in men. Jackson concludes that lack of a universally accepted definition of nocturia has led to wide variations in reporting of prevalence. The prevalence rate is affected by age and may occur in 10% of adults age 40 years to more than 80% in those over 80 years of age. Research has also shown that nocturia is a highly bothersome symptom with a multifactorial etiology. Self-reporting of nocturia is reliable, especially when a urinary diary is used. It is important to investigate the underlying etiology and treat it appropriately. Jackson concludes with the recommendation that nocturia requires further study in children and women. Treatment strategies must focus on etiologies. References 1. 2. 3. 4. Mattson, S. Urinary incontinence and nocturia in healthy schoolchildren. Acta Paediatr. 1994;83:950-954. Garraway WM, Collins GN, Lee RJ. High prevalence of benign prostatic hypertrophy in the community. Lancet. 1991;338:469-471. Chute CG, Panser LA, Girman CJ, et al. The prevalence of prostatism: a population-based survey of urinary symptoms. J Urol. 1993;150:85-89. Swithinbank LV, Donovan J, James MC, Yang, Q, Abrams, P. Female urinary symptoms: age prevalence in a community dwelling population using a validated questionnaire. Neurourol Urodyn. 1998;16:432-434. Nocturia Nocturia: A Disease or Normal Aging? Fonda D. BJU International 1999;84(Suppl.1):13-15. Nocturia increases with advancing age; more than 80% of people over the age of 80 rise at least once a night to void. According to Fonda, the normal range of nighttime awakenings to void must be standardized in order to assess effectively for any changes from the norm. Variations in age, sex, and cultural differences must also be considered. Another factor to consider is that nocturia is often underreported, especially among older people who tend to consider it untreatable and a normal part of aging. There must be a greater understanding of whether nocturia is a result of a person voiding “more urine” and/or voiding “more often,” and whether sleep disturbances may contribute to the problem. There are many factors associated with nocturia that can cause polyuria and/or nocturnal frequency: aging, psychological or behavioral changes, alterations in sleep patterns or amount of time spent in bed, polyuria syndromes, bladder problems, and neurological changes. They can occur alone or in combination with each other. With advancing age, more time is spent in bed. Nocturia should be considered both as a disease and as part of Nocturia is generally regarded as a normal part of the aging process. normal aging. In managing the older person, Fonda posits that nocturia must be assumed to be a disease upon initial assessment. It should be fully evaluated so that appropriate treatment, if available, can be given. The results of nocturia in older people are lack of sufficient rest, daytime sleepiness, a risk of falling and fracturing a limb, and nocturnal enuresis. Fonda concludes with a plea for prospective studies of older people with nocturia. The relative importance of various etiological factors must be considered to assist the targeting of clinical trials to the most responsive groups. Reference 1. Stewart RB, Moore MT, May FE, Marks RG, Hale WE. Nocturia: a risk factor for falls in the elderly. J Am Gen Soc. 1992;40:1217-1220. Prostate Cancer Cyclooxygenase-2 as a Marker for Prostate Cancer Reviewed by Alan W. Partin, MD, PhD The Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, MD [Rev Urol. 2001;3(2):107] © 2001 MedReviews, LLC A great deal of basic and clinical evidence is emerging that indicates that cyclooxygenase-2 (COX-2) may be a useful marker and a potential target for prostate cancer detection and treatment. It is known that COX-2 is an essential enzyme in the very early phases of prostaglandin synthesis from arachidonic acid. Nonsteroidal anti-inflammatory drugs (NSAIDs) act through inhibition of the cyclooxygenase enzymes. Populationbased, case-control studies have suggested a reduced risk of prostate cancer with regular use of NSAIDs. The recent discovery by several pharmaceutical groups of specific inhibitors of the COX-2 protein has ignited great interest in the use of these agents for chemoprevention and/or treatment of prostate cancer. In a recent paper in the British Journal of Urology International, Madaan and colleagues demonstrated overexpression of the COX-2 enzyme in human prostate cancer. Cytoplasmic Induction and Over-expression of Cyclooxygenase-2 in Human Prostate Cancer: Implications for Prevention and Treatment Madaan S, Abel PD, Chaudhary KS, et al. BJU Int. 2000;86:736-741. The authors assess the level and morphologic distribution of both cyclooxygenase-1 (COX-1) and COX-2 in human prostates and investigated whether or not there was a relationship between the concentrations of these enzymes and the Gleason histologic grading of prostate cancer tissue. In this retrospective study, they analyzed prostate tissue from 30 patients with histologically confirmed benign prostatic hyperplasia (BPH) in 82 prostate cancer tumors. The authors used immunohistochemistry to assess the expression of both COX-1 and COX-2. In addition, they used Western blot techniques to study 13 samples (6 BPH and 7 cancer) for the presence of these enzymes. Although COX-1 expression was in fact found in the stromal SPRING 2001 REVIEWS IN UROLOGY 107 Nocturia continued component of both BPH and prostate cancer tissue, it demonstrated weak cytoplasmic expression in both normal and neoplastic epithelial cells. The authors demonstrated significant (P = .008) increases in COX-2 expression in the epithelial component of prostate cancer tissue compared to normal or BPH tissue. They also noted marked differences in the immunohistochemical staining patterns as well. A strong correlation between COX-2 expression (P < .001) and Gleason histologic grading was found. Similar results were demonstrated by Western blotting. The authors demonstrated significant (P = .008) increases in COX-2 expression in the epithelial component of prostate cancer tissue compared to normal or BPH tissue. This study investigated the overexpression of COX-2 in human prostate cancer tissue and demonstrated a marked and significant difference between prostate cancer and BPH. This important study and others like it have prompted both the National Cancer Institute and several pharmaceutical companies to initiate prospective, randomized, double-blind, placebo-controlled studies investigating the use of COX-2 inhibitors for both chemoprevention and treatment of prostate cancer. These randomized, controlled trials will address the issue of efficacy of these medications for these purposes and should provide useful clinical information within the next few years. This new class of medication may ultimately hold great promise as a weapon in our armamentarium in the fight against prostate cancer. the hormone levels in males with unilateral undescended testis as it correlates to pretreatment testicular location. It has been shown that bilateral cryptorchidism dramatically compromises fertility, while unilateral cryptorchidism decreases fertility to a level that is almost similar to controls. Infertility has been defined as a “lack of conception after more than 12 months of attempts to initiate a pregnancy." Therefore, unilateral cryptorchidism results in infertility in 10.5% of patients as compared with 5.4% in controls. In this select group of previously unilateral cryptorchid patients, there were significantly higher follicle-stimulating hormone (FSH) levels and lower sperm counts relative to controls. A risk for unsuccessful paternity includes increased FSH, decreased sperm density, varicocele, partner fertility problems, and a parenchymal suture placed through the testis at orchiopexy. These investigators have not identified an association between patient age at orchidopexy and successful paternity, although they did observe that inhibin-B levels were higher and FSH was lower when orchidopexy was performed before 2 years of age. It has been shown that bilateral cryptorchidism dramatically compromises fertility, while unilateral cryptorchidism decreases fertility to a level that is almost similar to controls. Paternity and Hormone Levels after Unilateral Cryptorchidism: Association with Pretreatment Testicular Location Lee PA, Bellinger MT J Urol. 2000;164:1697-1701 Pediatric Urology Paternity and Hormone Levels Reviewed by Ellen Shapiro, MD New York University School of Medicine, New York, NY [Rev Urol. 2001;3(2):107–108] © 2001 MedReviews, LLC O ver the past 5 years, we have gained a better understanding of fertility in cryptorchid patients as a result of the male fertility studies at the Children’s Hospital of Pittsburgh. This report examines paternity and 108 REVIEWS IN UROLOGY SPRING 2001 In study participants, the location of the testis was intraabdominal in 11.3%, at the internal inguinal ring in 10%, intracanalicular in 41%, and at the external ring in 23.4%. The testis was ectopic or in the superficial pouch in 11.6%, and just above the scrotum in 2.8%. Paternity was achieved in 90% (288/320), while the remaining 32 were unsuccessful after at least 12 months. Paternity was somewhat lower for subjects whose testes were intra-abdominal (83.3%) versus those located at the internal inguinal ring (100%); however, this difference was not statistically significant. There was also no statistical difference between fertility rates in relation to the age at orchidopexy and pretreatment position. Although the previously unilateral cryptorchid patients had a 90% fertility rate, 24.9% needed more than 12 months to achieve conception, and testicular Pediatric Urology location was not a factor. There was also no difference when a testis was atrophic at the time of surgery. Interestingly, on physical examination in adulthood, the combined testicular volumes in these patients were within the normal adult range. In his editorial comment, Dr. Douglas Husmann theorized that testicular compensatory growth occurs in adolescence and normalizes total testicular size and fertility rates. There were also no differences in sperm count, testosterone level, free testosterone level, and FSH level for testes in various locations. The mean sperm count was lower in infertile men. This study provides important information for physicians caring for children with undescended testes because parents often have many concerns about future fertility in the cryptorchid child. Comparative Assessment of Pediatric Testicular Volume: Orchidometer Versus Ultrasound Diamond DA, Paltiel HJ, DiCanzio J, Zurakowski D, Bauer SB, Atala A, Ephraim PL, Grant R, Retik AB. J Urol. 164:1111-1114, 2000 The indication for varicocelectomy is based upon a 20%-25% testicular volume differential.1 Therefore, it is imperative to be able to accurately compare initial and subsequent testicular volume differential in a patient with a varicocele. Diamond et al studied 65 males, ages 7-24 years, using two types of orchidometers and scrotal ultrasound. Almost all of the patients studied had a varicocele. The objective of their study was to determine the correlation of orchidometer measurements with ultrasound and the sensitivity and specificity of orchidometer and ultrasound in determining defined volume differentials between testes of 10%, 15%, 20% and 25%. The Prader orchidometer consists of 12 solid ellipses of various sizes (1-25 cc) while the Rochester orchidometer is a series of flat cut out elliptical rings (1-30 cc) which can be placed directly over the testis to its midportion. Scrotal ultrasound has also been very useful in assessing testicular measurements and volume.2 Ultrasound was performed by scanning in an axial and longitudinal plane. The largest measurements for each dimension were recorded and the testicular volume was calculated using the formula for a prolate ellipsoid (lengthwidththickness 0.52). The absolute testicular volume asymmetry was determined using the left testis volume minus the right testis volume. The relative volume differential was calculated using the formula unaffected testicular volume—affected testicular volume/unaffected testicular volume. The sensitivity (percent of true positives) and the specificity (percent of true negatives) of the orchidometers to detect volume differentials accurately between testes of 10%, 20%, and 25% was examined. They utilized ultrasound measurements as the gold standard. There was a linear relationship between the measurements of absolute testicular volume using either the Prader and Rochester orchidometers versus ultrasound. Although the measurements correlated well with ultrasound, the orchidometric measurements overestimated testicular volume by a mean of 6 ccs. When a comparison was made between the capability of the orchidometers and ultrasound to distinguish a volume differential, they found that for each of the volume differentials studied, the sensitivity of the Prader and Rochester orchidometers was <50%. This would mean that if a volume differential of 10%, 15%, 20% and 25% existed, this differential would not be detected by orchidometry. Therefore, ultrasound is recommended for detecting testicular volume differentials, especially in patients with varicoceles. Although the orchidometers are not useful for this purpose, they are a valuable tool in serial examinations of an individual testis. The authors conclude that annual ultrasound of testicular volume should be assessed in patients who are being followed for a varicocele. Scrotal ultrasound has also been very useful in assessing testicular measurements and volume. Comment: This is an important study by Diamond and his colleagues since there have been no studies comparing orchidometer to ultrasound in the assessment of volume differentials. This paper was presented at the American Academy of Pediatrics Section on Urology, October, 1999. In the discussion that followed the presentation of the paper, the authors note that they are performing an animal study to assess whether ultrasound is indeed the gold standard.3 References 1. Sayfan J, Siplovich L, Koltun L, et al. Varicocele treatment in pubertal boys prevents testicular growth arrest. J Urol. 1997;157;1456-1457. 2. Rivkees SA, Hall DA, Boepple PA, et al. Accuracy and reproducibility of clinical measures of testicular volume. J Pediatr. 1987;110:914-917. 3. Paltiel H J, Atala A, DiCanzio J, et al. Assessment of testicular volume: comparison of orchidometer and ultrasound measurements in dogs. May 2000; Presented at Conference of European Society of Pediatric Radiology, Lisbon, Portugal. SPRING 2001 REVIEWS IN UROLOGY 109