■ OBGMANAGEMENT BY MICKEY KARRAM, MD, and STEVE KLEEMAN, MD

Office evaluation of : 4 easy steps Urgency, frequency, and urge incontinence can usually be diagnosed and managed without sophisticated .

66-year-old woman complains of uri- Revised terminology nary urgency, frequency, and inconti- ne of the most notable changes in the Anence, and estimates that she voids 15 Oterms used to describe lower urinary tract or more times within a typical 24-hour period. dysfunction, proposed by the International So far, she has lost only small amounts of Continence Society,3 is organization of the ter- urine—because she hurries to void at the first minology into 3 categories: symptoms, signs, sense of urgency—but she is distressed and and urodynamic observations. worried that she will have a major accident. Symptoms are now defined to more closely Sound familiar? Overactive bladder affects 17 reflect the way the patient perceives her to 33 million US women.1 Thanks to greater problem, and are set forth without specifying awareness and openness, more women today are the volume of urine required for a diagnosis of seeking medical help for their troubling symptoms, “abnormal” sensation or urgency. although only a fraction have done so up to now.2 Signs can be observed by the physician, such Ob/Gyns who are prepared to quickly evaluate the as leakage of urine when the patient coughs. problem and initiate effective management can Urodynamic observations are made dur- help restore the quality of life these patients ing urodynamic studies. enjoyed before onset of symptoms. This article: Overall, the new and revised terms are • reviews the pathophysiology of “overactive relatively vague to allow for patient-to-patient bladder”; variability. Here are a few examples: • describes a 4-step evaluation and manage- • Overactive bladder is a syndrome of ment routine that should be feasible for any symptoms that suggest dysfunction of the gynecology office setting; lower urinary tract. It is characterized by • discusses the action and the efficacy of available and forthcoming drugs; • uses newly revised terminology that reflects 4- STEP EVALUATION AND MANAGEMENT greater sensitivity to the patient. 1 Ask the right questions, get voiding diary, assess quality of life.

■ Dr. Karram is director of at Good Samaritan Hospital in Cincinnati, Ohio, and professor of obstetrics and 2 Perform ‘eyeball’ . gynecology at the University of Cincinnati. Dr. Kleeman is assistant director of the division of urogynecology and recon- 3 Conduct a thorough physical assessment. structive at Good Samaritan Hospital in Cincinnati. 4 Begin bladder retraining, pelvic floor muscle

December 2003 • OBG MANAGEMENT 17 rehabilitation, and appropriate medical therapy. urgency with or without urge incontinence, Sensory urgency is a strong, uncomfortable usually involving frequency and . need to void without fear of impending leak- • is any involuntary age; for whatever reason, the bladder has leakage of urine. become hypersensitive. Delaying voiding may • Daytime frequency. The patient feels she result in pain but rarely leads to incontinence. voids more frequently than she should during Patients with motor urgency urinate fre- the day. quently because they are afraid of experiencing • Nocturia. The patient wakes 1 or more a complete or partial involuntary void as a times at night to void. result of an involuntary bladder contraction. • Urgency. The patient feels a sudden, com- pelling desire to pass urine. How the normal bladder functions • Urge urinary incontinence is involun- he process of bladder storage and evacua- tary leakage accompanied by or immediately Ttion can be visualized as a complex of preceded by urgency. neurocircuits in the brain and spinal cord that • Bladder sensation is identified during coordinate the activity of smooth muscle in history taking: normal, increased, reduced, the bladder and (FIGURE). These cir- absent, and nonspecific. cuits act as “on/off ” switches in the lower uri- • Detrusor overactivity replaces the term nary tract, alternating between the 2 modes of “detrusor instability” or “hyperreflexia.” It is operation: storage and elimination. a urodynamic observation characterized by As the bladder gradually fills with urine, involuntary detrusor contractions during the a woman initially perceives a first sensation filling phase, and may be spontaneous or of filling between 75 and 125 cc of urine, feels provoked. It may be further qualified as the first need to void at approximately 300 cc, neurogenic (if a neurologic condition under- and reaches maximum capacity and a strong lies the problem) or as idiopathic. urge to void at 400 to 700 cc. Since the bladder is a low-pressure reser- What is abnormal bladder function? voir, intravesical bladder pressure typically ny actual incontinence should be con- rises very little despite increasing amounts of Asidered abnormal, whether diurnal urine and distention of the smooth muscle or or nocturnal. of the bladder. Pressure Frequency: More than 8 voids in 24 hours. ranges from 2 to 6 cm of water in an empty Although an ordinary voiding pattern is not state and rarely exceeds 10 cm of water at fully defined, most experts agree that a frequen- maximum capacity. cy of 8 or fewer voids in 24 hours is “normal.” At maximum capacity, a woman should be Urgency: Patient’s opinion determines. able to get to the toilet easily, initiate voluntary The sensation of urgency is more difficult to bladder contraction with complete relaxation objectively define; hence, the need to rely on of her pelvic floor, and void to completion. the patient’s perceptions. If a patient is voiding more frequently than normal because she has Urge incontinence is more an uncomfortable, sudden desire to pass urine, detrimental to quality of life she is considered to have urgency. In contrast, a f women who complain of urinary woman who voids frequently because she has Oincontinence, more than 90% have and wants to keep her blad- either loss of detrusor muscle control (urge der as empty as possible to avoid leakage has incontinence) or urethral sphincteric incom- frequency without urgency. Urgency is best petence (stress incontinence).4 In addition, classified as being sensory or motor in nature. 30% to 50% of women with stress inconti-

18 OBG MANAGEMENT • December 2003 Office evaluation of overactive bladder: 4 easy steps

FIGURE Bladder relaxation and contraction: An interplay of nerve impulses

1 Signals in the parasympathetic 3 In the sympathetic nervous system, system originate at spinal cord signals exit at spinal cord levels T1 levels S2-S4, traveling to the bladder through L2 and travel to the bladder via the pelvic nerve and binding to via the hypogastric nerve, where muscarinic receptors —specifically noradrenaline is released. Noradrenaline M2 and M3 subtypes. When M3 binds to the beta receptors, causing subtypes are set in motion, they a chain reaction that ultimately causes trigger a chain of events that leads relaxation of the bladder. to muscle contraction. M2 receptor activation ultimately inhibits T10 the relaxation caused by the 3 sympathetic system. T11 hypogastric nerve T12 alpha L2 beta L1

pelvic nerve S2 S3 S4

1 2 The striated muscle of the external pelvic urethral sphincter is innervated by plexus motor neurons that originate in Onuf’s nucleus (located within the sacral spinal cord) and travel via the 2 pudendal nerve. pudendal nerve

external urethral sphincter to perineal } muscles and striated distal external anal urogenital sphincter sphincter proximal Image: Birck Cox

nence have coexistent urge incontinence.1 only with increases in intraabdominal pres- Urge incontinence has a much more dra- sure associated with exercise, coughing, etc. matic impact on a woman’s quality of life These leakages tend to occur in small spurts than stress incontinence, because stress that are easily absorbed by protective wear. In incontinence is predictable and controllable. contrast, urge incontinence manifests as an The patient understands she will leak urine unpredictable, involuntary void in which

December 2003 • OBG MANAGEMENT 19 Office evaluation of overactive bladder: 4 easy steps

urine is released in a gushing stream, often in Outlet obstruction can result in urge incon- quantities large enough to soak through tinence such as the well recognized symptoms heavy absorbent pads. of urethral obstruction in men with benign Although one might assume that subjec- prostatic hyperplasia. tive complaints would readily distinguish the Detrusor sphincter dysnergia, most common- 2 conditions, the bladder is a very poor ly secondary to or multiple “witness.” What the patient perceives often sclerosis, may affect younger men and women. fails to correlate with the true mechanism of A deficient urethral sphincter in women with incontinence. Since therapies for these 2 con- stress incontinence may induce urge inconti- ditions are completely different, the evalua- nence, as urine leaking into the urethra sec- tion of incontinence is very important. ondary to the stress incontinence stimulates In aging women, the prevalence of fre- urethral afferents that induce involuntary quency, urgency, and urge incontinence voiding reflexes.7 is much higher than that of stress inconti- Women with stress incontinence may nence. Among women 60 to 80 years of unwittingly contribute to overactive bladder age—growth-wise, the largest segment of our by voiding more and more often, hoping to population—as many as 50% experience fre- prevent any involuntary urine loss. As a result quency, urgency, and urge incontinence. of the frequent voiding, they develop frequen- High economic cost. The tremendous cy and urgency symptoms. That is, over time, expense of urinary incontinence is increas- this frequent, voluntary voiding leads to ingly recognized. In 1995, for example, the decreased bladder compliance. Thus begins a economic cost in the was $26.3 vicious cycle that ultimately leads to more fre- billion, or $3,565 per person 65 years or older quency and urgency. with the condition.5,6 Of these resources, 48%, Urogenital atrophy. Irritative symptoms of or $12.53 billion, were drawn directly from the lower urinary tract in the form of frequen- the economy to diagnose, treat, care for, and cy, urgency, and can result from lack of rehabilitate patients with incontinence. estrogen, leading to urogenital atrophy. Pelvic organ prolapse is another common Contributing factors and causes coexisting condition. Although the correla- of overactive bladder tion between anatomic descent of pelvic veractive bladder is thought to be multi- organs and lower urinary tract symptoms is Ofactorial. Symptoms often occur in the poorly understood, frequency and urgency— absence of any obvious pathology, which with or without urge incontinence—coexist makes it difficult to pinpoint a cause. with symptomatic pelvic organ prolapse in Coexisting conditions may also contribute to approximately 30% to 50% of cases. symptoms or may even be the sole cause. An enlarged uterus or adnexal mass Examples include infection or inflamma- may cause external compression of the blad- tion of the lower urinary tract, such as a simple der and lead to lower urinary tract symptoms. case of cystitis, or a foreign body in the bladder. Previous surgery of the anterior vaginal Injury or diseases of the nervous system can wall or bladder neck may sometimes trigger disrupt voluntary control of voiding in adults, de novo symptoms of frequency, urgency, and triggering the reemergence of reflex voiding, urge incontinence. In women who have which leads to bladder hyperactivity and urge undergone a previous antiincontinence pro- incontinence. At a local level, urge inconti- cedure, these symptoms may be related to nence can develop secondary to intrinsic some form of outlet obstruction. In some detrusor myogenic abnormalities. cases these patients have no increase in the

20 OBG MANAGEMENT • December 2003 Office evaluation of overactive bladder: 4 easy steps

postvoid residual, and only subtle urodynam- voiding diary to fill out 48 hours prior to her ic testing elicits evidence of obstruction. office visit. The reason: The diary often reveals more information than can be elicited from the Step 1 patient’s history. For example, it may highlight Ask the right questions, get voiding daily activities associated with voiding, such as diary, assess quality of life excessive consumption of liquids, high ost women can be thoroughly evaluated intake, high-impact exercise, and so on. Mwithin the clinical practice setting of any Quality-of-life assessment. An objective gynecologist. The first and most important means of quantifying the effects of inconti- aspect of this assessment is understanding and nence on the woman’s quality of life is recom- appreciating the severity of a patient’s lower mended. We use the short form of the urinary tract symptoms. This can be done by Incontinence Impact Questionnaire and the asking pointed questions, in the following Urinary Distress Inventory. approximate sequence: 1. Do you have problems with accidental loss Step 2 of urine? Perform ‘eyeball’ cystometry, 2. How many months or years have you had a simple and revealing office test leakage? sk the patient to go to the restroom and 3. Do you have to wear pads or protective Acomfortably empty her bladder into a clothing to prevent or help with urinary loss? urine-collection device to determine the If so, how many pads do you wear a day? amount voided. Have a nurse measure the 4. How many trips do you make to the bath- postvoid residual using a soft red rubber room during the day? At night? . A sample can be taken for urinalysis 5. Do you ever wet the bed while sleeping? and, if necessary, sent for culture. 6. Are you bothered by a strong sense of Next, perform a simple filling or “eyeball” urgency to void? Can you overcome it? cystometry. Connect a Toomey syringe to the 7. Do you sometimes fail to reach the bath- end of the red rubber catheter and pour sterile room in time? water into it. Ask the patient to tell you when 8. Does the sound, sight, or feel of running she feels the first sensation of filling, first desire water cause you to lose urine? to void, strong urge to void, and maximum 9. Do you lose urine when you cough, capacity, recording the levels at which each sneeze, run, or lift heavy objects? occurs. During filling, any evidence of bladder 10. Do you lose urine with posture changes, contraction will be revealed by a rise in the col- standing, or walking? umn of water. Record any significant discom- 11. Do you feel as though you are constantly wet? fort or other observations during the filling 12. Do you feel as though your bladder is com- portion of the study. When maximum capacity pletely empty after passing urine? is reached, remove the catheter. 13. Do you have difficulty starting a stream of urine? Step 3 Also ask about pelvic organ prolapse, defe- Conduct a thorough physical assessment catory dysfunction, and sexual dysfunction. ith the patient in the supine position, Take a thorough medical history, as well as a Wseparate the labia and ask her to cough surgical history with emphasis on previous blad- forcefully and perform the Valsalva maneuver der or gynecologic procedures. 3 times, recording any evidence of water or Also review all prescription medications. urine loss through the urethral meatus. (If the 48-hour voiding diary. Give the patient a patient has advanced pelvic organ prolapse, try

December 2003 • OBG MANAGEMENT 23 Treating overactive bladder: An expanding ‘pharmacopeia’

ntimuscarinic medications have been the mainstay A transdermal version of was recently Aof pharmacologic therapy for overactive bladder. In released. In theory, transdermal treatment offers poten- fact, the 2 most commonly prescribed drugs for overac- tial advantages such as more stable plasma concentra- tive bladder are antimuscarinics: oxybutynin and toltero- tions and lower presystemic metabolism, which may dine. Other medications also are available that affect dif- decrease the primary active metabolite of N-Desethyl- ferent aspects of the neurophysiology of micturition. oxybutynin. In a randomized, placebo-controlled trial of 3 Oxybutynin. The bladder contains 5 subtypes of mus- doses of transdermal oxybutynin (1.3, 2.6, and 3.9 mg carinic receptors, with a predominance of M2 and M3 daily), only the highest dose out-performed placebo for subtypes. Oxybutynin has some selectivity for M3 recep- median changes in incontinence episodes, frequency, tors. It has been shown to inhibit bladder contractions, and normal void volume.13 Quality of life also was signifi- but because of muscarinic blockade in other parts of the cantly improved with the 3.9-mg dose. body, it can have bothersome side effects. For example, side effects were comparable between active and place- oxybutynin has shown a higher affinity for muscarinic bo groups. receptors in the parotid gland than the bladder, leading to is a potent muscarinic-receptor antagonist dry mouth. In addition, the active metabolite of oxybu- without selectivity for particular subtypes. It is marketed tynin, N-Desethyl-oxybutynin, can reach concentrations in both immediate- and extended-release (tolterodine LA) that are 6 times the parent compound after oral adminis- formulations. A recent series compared both forms of tration.9 Other side effects include , gastroin- the drug with placebo in 1,529 adults with overactive testinal upset, and blurry vision. bladder.14 The primary measure of efficacy was change in Alternate routes of administration have been devel- the mean number of incontinent episodes weekly. Both oped to improve tolerability, including extended-release medications showed a significantly better response than oral formulations, rectal administration, and a transdermal placebo. Dry mouth was significantly lower with toltero- patch. Oxybutynin XL is the extended-release form, dine LA. When the authors used median values instead which incorporates a push-pull osmotic system. In paral- of mean values (because of non-normal distributed data), lel randomized, controlled clinical trials comparing imme- tolterodine LA showed improved efficacy over the imme- diate- and extended-release oxybutynin, oxybutynin XL diate-release formulation. This study was sponsored by was just as effective as the immediate-release formula- the drug’s manufacturer. tion but had fewer side effects.10-12 Absorption of oxybu- Comparisons of oxybutynin and tolterodine. In a tynin XL may occur to a larger degree in the colon than in prospective, double-blind, head-to-head study of the 2 the stomach and proximal small intestine, thereby drugs sponsored by the manufacturer of oxybutynin XL, decreasing conversion to N-Desethyl-oxybutynin. 378 men and women were randomized to receive oxy- Oxybutynin XL comes in 3 doses (5, 10, and 15 mg) and butynin XL (10 mg daily) or tolterodine immediate-release offers the advantage of dose titration, a very important (2 mg twice daily).15 Inclusion criteria included 7 or more aspect of management. episodes of urge incontinence per week and at least 10

to reduce the prolapse to eliminate any again record the amount voided. anatomic distortion of the urethra.) After the patient has emptied her bladder, Then ask the patient to stand with a full again ask her to cough forcefully 3 times in the bladder and to squat, again having her cough supine position, noting any evidence of leakage forcefully 3 times. Record any additional uri- from the urethra (empty supine stress test). nary loss. Finally, ask the patient to void and Perform an overall inspection of the per-

24 OBG MANAGEMENT • December 2003 Office evaluation of overactive bladder: 4 easy steps

... continued voids per 24 hours. The Overactive Bladder: Judging tolterodine LA (2 mg) was similar to both doses of oxybu- Effective Control and Treatment (OBJECT) trial demon- tynin XL. This study was hampered by the fact that no data strated greater efficacy with extended-release oxybu- were supplied on the number of patients with isolated fre- tynin than with tolterodine, although both medications quency and urgency versus those who had urge inconti- decreased weekly episodes of urge incontinence. nence. Also, no objective parameters such as a voiding Oxybutynin XL also showed a small but significant advan- diary were utilized. tage for mixed incontinence and urinary frequency. Dry Three antimuscarinic drugs in the pipeline. Other mouth and central nervous system side effects were antimuscarinic agents include trospium, a quaternary similar for the 2 drugs. amine with some antimuscarinic activity. Because of its A second head-to-head study also was sponsored by structure, it does not cross the brain barrier well and may the manufacturer of oxybutynin—this one a randomized, thus have fewer central side effects. double-blind comparison of the extended-release versions Two new drugs awaiting approval from the US Food of both drugs. The Overactive Bladder: Performance of and Drug Administration are , which has high Extended Release Agents (OPERA) trial randomized 790 selectivity for M3 receptors, and , an M3 women to oxybutynin XL (10 mg daily) or tolterodine LA (4 antagonist with greater selectivity for the bladder than mg daily).16 Inclusion criteria included at least 21 to 60 the salivary glands in animal models. incontinent episodes per week and urgency and frequen- All 3 drugs should be available in the United States cy exceeding 10 episodes per 24 hours. The drugs were some time in 2004. similar in both measures, as well as in side effects, Antiadrenergic medications. Because the bladder also although dry mouth, usually mild, was more common contains alpha- and beta-adrenergic receptors, antiadren- among oxybutynin users. However, oxybutynin was signif- ergic medications have been developed. Currently avail- icantly more effective in reducing micturition frequency, able alpha-adrenergic agonists include ephedrine, phenyl- and 23% of women taking oxybutynin reported no propanolamine, and pseudoephedrine. Beta-adrenergic episodes of incontinence, compared with 16.8% of agonists include isoproterenol and terbutaline. women taking tolterodine. This finding was significant. Serotonergic agents. Both sympathetic and parasym- A third head-to-head study involved 2 separate trials pathetic autonomic nuclei—as well as urethral sphincter conducted in parallel, with individual centers evaluating motor nuclei—receive serotonergic input from the Raphe only 1 drug. In it, 1,289 patients were randomized to open- nuclei in the caudal brain stem. Serotonergic pathways label treatment with either 2 mg or 4 mg of tolterodine LA generally enhance urine storage by activating sympathet- in 1 trial and with 5 mg or 10 mg of oxybutynin XL in the ic pathways and inhibiting parasympathetic pathways. other.17 Inclusion criteria included 18 years of age or greater Duloxetine is a selective serotonin and norepinephrine and symptoms of and frequency. After 8 reuptake inhibitor that may be effective against both urge weeks, tolterodine LA (4 mg) was found to be significant- and stress incontinence. It is currently awaiting approval ly more effective than either dose of oxybutynin XL, while by the US Food and Drug Administration.

ineum and external genitalia and record a ask the patient to forcefully squeeze around it. description in the patient’s chart. Record the forcefulness of the squeeze on a scale Attempt to elicit an anal wink, and perform of 0 to 5, with 0 being no appreciable movement a brief neurological examination to ensure that and 5 being the most forceful squeeze possible. spinal cord segments S2, S3, and S4 are intact. During this portion of the exam, instruct the Next, gently insert a finger into the vagina and patient on how to perform a

December 2003 • OBG MANAGEMENT 25 without recruiting the muscles of the buttocks retraining. The following week, we increase and the abdominal wall. the interval to an hour and 15 minutes, the Next, use a finger to gently massage the third week to 1.5 hours, and so on, with an urethra, looking for any possible discharge from ultimate goal of 3 hours between voids. the urethral meatus that would be consistent We also give instructions on pelvic floor with . Also note any ten- rehabilitation or Kegel exercises. If the patient derness or pain elicited during the exam. is able to voluntarily contract her pelvic floor Inserting a half-speculum into the vagina, muscles adequately, we recommend an exer- displace the rectum away from the bladder. As cise regimen that involves contracting her the patient performs a Valsalva maneuver or muscles numerous times a day for at least 10 coughs forcefully, evaluate the support of the seconds each time. If she is unable to contract anterior vaginal wall. Then turn the speculum her muscles or has a “dead” pelvic floor, she is 180 degrees and displace the bladder anteriorly, referred to a physical therapist for biofeedback examining the posterior pelvic wall for any signs and possibly electrical stimulation. of prolapse. Also note any urogenital atrophy. We also instruct the patient to avoid racing Finally, use a full speculum to evaluate the to the bathroom when she feels an urge to void. vaginal apex and cervix (if the patient has not Instead, have her stop, contract her pelvic floor had a hysterectomy). Bimanual and abdominal muscles, and allow the urge to pass. She can examinations also are important to rule out any then walk comfortably to the bathroom. abdominal or pelvic mass that could be irritat- As mentioned earlier, the voiding diary ing or causing pressure on the bladder. may highlight problems such as excessive Reexamine the patient for evidence of pro- intake of fluids. lapse when she is standing. Some cases are dif- Local estrogen therapy can be added if ficult to detect when the patient is supine. there are signs of urogenital atrophy. Medical therapy. In addition to education, Step 4 timed voids, pelvic floor rehabilitation, and Begin multipronged therapy estrogen therapy, we usually start the extend- Bladder retraining. Review the patient’s ed-release form of tolterodine (4 mg) or history, voiding diary, and findings from the oxybutynin (10 mg), which are antimuscarinic physical exam to identify an appropriate agents. (See “Treating overactive bladder: An treatment. After sharing all findings with the expanding ‘pharmacopeia’” on page 24). patient, instruct the patient on bladder We ask her to return for a follow-up visit in retraining, which has 3 main components: 4 to 6 weeks to inquire about her symptoms and education, scheduled voiding, and positive any significant side effects. We ask the patient to reinforcement. (Bladder retraining can be an prepare another voiding diary for that visit so extremely successful modality.) we can objectively measure decreases in fre- Education consists of explaining the patho- quency, urgency, and urge incontinence. physiology of overactive bladder and answering Dose adjustment is very important in any questions the patient may have, so she patients with overactive bladder. If the woman understands why she is having the problem. is experiencing minimal effect with no side For scheduled voiding—also known as effects, titrate the dosage upward. If she is hav- bladder retraining—examine the voiding ing good effect with significant side effects, diary to determine the approximate length of decrease the dosage or consider switching to time between voids in a day. For instance, if the transdermal form of oxybutynin. the patient voids every hour, we generally ask When all these conditions are met and the her to continue doing so for the first week of patient remains severely affected, we perform

26 OBG MANAGEMENT • December 2003 Office evaluation of overactive bladder: 4 easy steps

multichannel urodynamic testing along with 9. Gupta SK, Sathyan G. Pharmacokinetics of an oral once-a-day controlled-release oxybutynin formulation compared with immediate release oxybutynin. J Clin . If the testing supports the diagno- Pharmacol. 1999;39:289. sis of overactive bladder, and all other mecha- 10. Anderson RU, Mobley D, Blank B, Saltzstein D, Susset J, Brown JS. Once daily controlled versus immediate release oxybutynin chloride for urge urinary nisms for improvement have been exhausted, incontinence. J Urol. 1999;161:1809. 11. Birns J, Lukkari E, Malone-Lee JG. A randomized controlled trial comparing the we counsel the patient about intravesical efficacy of controlled-release oxybutynin tablets (10 mg once daily) with conven- administration of botulism toxin, which relax- tional oxybutynin tablets (5 mg twice daily) in patients whose symptoms were sta- bilized on 5-mg twice daily of oxybutynin. BJU Int. 2000;85:793. es skeletal and smooth muscle by preventing 12. Versi E, Appell R, Mobley D, Patton W, Saltzstein D. Dry mouth with conven- release of acetocholine from nerve terminal tional and controlled-released oxybutynin in urinary incontinence. The Ditropan XL Study Group. Obstet Gynecol. 2000;95:718. endings. Another option is sacroneuromodu- 13. Dmochowski RR, Davila GW, Zinner NR, et al. Efficacy and safety of transder- lation (InterStim therapy). mal oxybutynin in patients with urge and mixed urinary incontinence. J Urol. 2002;168:580-586. 14. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A. Tolterodine once-daily: Implications of the placebo effect superior efficacy and tolerability in the treatment of the overactive bladder. . 2001;57:414. e lack a complete understanding of 15. Appell RA, Sand P, Dmochowski R, et al, for the OBJECT Study Group. Prospective randomized controlled trial of extended-release oxybutynin chloride Whow all the parts of this process interact and tolterodine tartrate in the treatment of overactive bladder: results of the and why. Most of the medications in use affect OBJECT Study. Mayo Clin Proc. 2001;76:358-363. 16. Diokno AC, Appell RA, Sand PK, et al, for the OPERA Study Group. Prospective, only 1 part of the complex process that governs randomized, double-blind study of the efficacy and tolerability of the extended- urine storage and elimination. release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Mayo Clin Proc. 2003;78:687-695. In controlled trials, patients on placebo 17. Sussman D, Garely A. Treatment of overactive bladder with once-daily extended- have experienced 30% improvement—or release tolterodine or oxybutynin: the Antimuscarinic Clinical Effectiveness Trial (ACET). Curr Hosp Res Opin. 2002;18:177-184. greater—in their symptoms. This would seem Dr. Karram serves on the speakers bureau for Ortho-McNeil and the to suggest that education, behavioral retrain- advisory boards of Ortho-McNeil and Watson. Dr. Kleeman serves on ing, and attention from physicians are respon- the speakers bureau for . sible for some of the improvement. Indeed, in a recent systematic review of 32 trials involv- ing 6,800 participants, Herbison et al8 found ADVERTISERS’ INDEX significant but relatively small differences 3M Pharmaceuticals (www.3M.com) between anticholinergic medications and Aldara (www.3M.com/ALDARA)...... ………….….…...... ………34-36 Metrogel (www.3M.com/mgv)...... ….….…….….……….…………..51-52 placebo for many of the outcomes studied. Aloka Obviously, we have more to learn about the ProSound SSD-3500…………….…….….…….…..…..…………..…….5 Aventis Pharmaceuticals intricacies of this condition before we can Actonel (www.actonel.com)…...…..…..…….…..…..……..…..…...….21-22 ■ eliminate it completely. Braintree Laboratories MiraLax (www.MiraLax.com)…….….….…….…..…….…...... …...…....59 REFERENCES Cook (www.cookobgyn.com) 1. Stewart W, Herzog R, Wein A, et al. Prevalence of overactive bladder in the US: Stratasis……………………………….….….….….…..…...….…...….... 67 results from the Noble Program. Poster presented at the Second International CooperSurgical (www.coopersurgical.com) Consultation on Incontinence, July 2001, Paris, France. H/S Elliptosphere…………………….….….….…...….…..……...…...... 13 2. Voelker R. International group seeks to dispel incontinence ‘taboo.’ JAMA. Lumax…………………….….….….…...….…..…..…..…...... ……...... 15 1998;280:951. Duramed Pharmaceuticals, subsidiary of Barr Labs Inc 3. Abrams P, Cardozo L, Fall M, et al. The standardization of terminology of lower Seasonale (www.seasonale.com)….….….…...….…….….....….…...... 9-12 urinary tract function: report from the standardization sub-committee of the Glaxo Smithkline International Continence Society. Neurol Urodynamics. 2002;21:167-178. Paxil....………….……………..….…….…...... …….…..…...... …..…63-64 4. Walters MD, Diaz K. Q-tip test: a study of continent and incontinent women. King Pharmaceuticals Obstet Gynecol. 1987;70:208-211. Prefest (www.prefest.com)………………..….…….….…..…...... …....54-56 5. Wagner TH, Hu TW. Economic costs of urinary incontinence in 1995. Urology. Ortho-McNeil Pharmaceutical 1998;51:355. Ortho Tri-Cyclen Lo (www.orthotri-cyclenlo.com)…….……...... ….31-32 6. Wagner TH, Hu TW. Economic costs of urinary incontinence. Int Urogynecol J Pfizer Pelvic Floor Dysfunct. 1998;9:127. Zoloft………….……….……..….…….…...... …...... …….………....C3,C4 7. Jung SY, Fraser MO, Ozawa H, et al. Urethral afferent nerve activity affects the United States Surgical micturition reflex; implication for the relationship between stress incontinence Syneture………….………...... …..…..…….…..…..….....…….…...……...7 and detrusor instability. J Urol. 1999;162:204. Warner Chilcott 8. Herbison P, Hay-Smith J, Ellis G, Moore K. Effectiveness of anticholinergic drugs Femring………….………...………...... …..…..….….…….…...….…41-42 compared with placebo in the treatment of overactive bladder: systematic review. Wyeth Pharmaceuticals BMJ. 2003;326:841-844. Prempro (www.prempro.com)..………...... …...... ….....….….C2,1-3

December 2003 • OBG MANAGEMENT 27