Urinary Incontinence in Women: Never an Acceptable Consequence of Aging Catherine A. Matthews, MD Associate Professor Chief, Urogynecology and Pelvic Reconstructive Surgery University of North Carolina, Chapel Hill Disclosures! No conflicts of interest to report
Objectives! Review prevalence data regarding UI in women! Understand different types of UI! Review a non-specialist evaluation algorithm for UI! Describe evidence-based treatment options for SUI and OAB Prevalence of stress urinary incontinence by age and severity. Minassian et al. Obstet Gynecol 2008
Prevalence of urge urinary incontinence by age and severity Prevalence of any urinary incontinence by age and severity
7 Changing the Face of Urinary Incontinence: It Also Affects Younger Women Stereotype Reality For illustrative purposes only. Not indicative of population distribution. Case # 1! 55 yo PMP WF who complains of a 10-year history of leaking with coughing and while playing tennis. Has primarily coped by keeping my bladder empty. Cannot confidently leave the house without a pad. She also reports significant depression.
Evaluation and management! Urinalysis! Simple pelvic examination Treatment options! Incontinence pessary (ring with a knob) or tampon! Physical Therapy! Medication! Referral for surgery (minimally invasive suburethral sling)
Pelvic Muscle Rehabilitation TVT versus TOT Barber et al. Obstet Gynecol 2008.! Non-inferiority study that assessed the presence or absence of abnormal bladder function: Any UI; positive cough test; retention.! N= 171 with urodynamic stress incontinence and no detrusor overactivity
TVT versus TOT. N=170 Case # 2! 62 yo AAF with complaints of getting up at least 6 times during night to void with accompanying urgency. No enuresis. She is exhausted. Voids q 4 hours during day. Mild leakage with coughnot bothersome.
Urinary incontinence should not be considered just a disease of the bladder, but rather as a sign of an underlying problem (s). Questions?! ICS definition of OAB: Urgency with or without urge UI, usually accompanied by frequency and nocturia.! Does this patient have OAB?! OAB versus nocturnal polyuria! Evaluation and Treatment algorithm?
Nocturia versus nocturnal polyuria! Determined by simple 24 hour urine collection! Common causes: Sleep apnea (ANP), CHF, diabetes mellitus! Sleep Apnea Most under-recognized cause of nocturnal polyuria Treatment with CPAP significantly reduces nocturic frequency (Fitzgerald et al, Am J Obstet Gynecol, 2006). Nocturnal polyuria and nocturia relief in patients treated with Solifenacin Nocturia Episodes Placebo 5 mg Solifenacin 10 mg Solifenacin Mean baseline Mean actual change 1.8 2.0 1.8-0.4-0.6 (p=.025) -0.6 (p<.001) Mean % change -25% -35.5% (p=.021) -36.4% (p<.001) Brubaker et al. Int Urogynecol J, 2007
Sub-analysis! In patients with NP- no significant effect! Conclusion: Solifenacin will not provide effective treatment relief in patients whose OAB is complicated by NP Case # 3! 48 yo perimenopausal WF with urgency, frequency, and occasional urge UI. Anxious and nervous that she will embarrass herself in public. Has noticed a significant decline in sexual satisfaction and activity with onset of her bladder problems.! Medications: HCTZ and Propranolol for HTN
A Practical Approach!Medical History!Screening questions!urinalysis!physical Examination
Screening Questions must include an intake/output diary Caffeine Causes OAB by releasing intracellular Ca+ + Parasympathetic Nerve Ca+ + Sympathetic Nerve
Lower Urinary Tract Function! Bladder and urethral functions Storage Micturition! These functions are controlled by the central nervous system (CNS) through reflexes that coordinate the activity of Bladder (smooth muscle) Urethra (smooth and striated muscles) Pelvic floor muscles NeuroUrology Storage Reflex Micturition Reflex Inhibition Spinal Reflex - ß 3 Bladder Hypogastric N. Pelvic N. + M 2,3 + " 1 +N Rhabdosphincter Pudendal N. SYM Periaquaductal ON Gray Spinal Relay Neuron Pontine Micturition Center PAR
Lower Urinary Tract Innervation Pelvic Nerve (Parasympathetic) ACh Hypogastric Nerve (Sympathetic) NE +M 3 -# 3 +" 1 +N Pudendal Nerve (Somatic) ACh
Detrol LA (tolterodine tartrate extended release capsules) Receptor Selectivity Inhibition Constant Ratio (K i ) for Muscarinic Receptor Subtypes* 60 50 40 30 20 10 0 Nonselective (M 3 /M 2 ) 1.3 3.6 M 3 selective Primarily M 3 selective 12 12.3 59.2 Trospium Tolterodine Solifenacin Oxybutynin Darifenacin *Animal models. Please see full prescribing information. Heading CE. Curr Opin CPNS Investig Drugs. 2000;3:321-325. Napier C et al. Proc ICS. 2002:445. Abstract.
M-3 Selective Antagonists! Solifenacin! Darifenacin STAR Trial: N=1200!12-week, European, prospective, randomized, double-blind, doubledummy, 2-arm, parallel-group trial!dose titration regimen of solifenacin (5 mg or 10 mg qd) or a single dose of Tolterodine LA 4 mg qd!inclusion Criteria Average of!8 micturitions per 24 hours Average of!1 incontinence episode per 24 hours, or an average of!1 urgency episode per 24 hours!primary OBJECTIVE: Non-inferiority study!primary END-POINT: Micturition frequency!secondary end points: Incontinence episodes, urge incontinence episodes, urgency, volume voided, and tolerability Chapple CR et al. Eur Urol., 2005
STAR Trial Reported End Points End Point PRIMARY (non-inferiority) [PPS]* Solifenacin (pooled 5 mg/10 mg) (n=525) Tolterodine (4 mg qd) (n=524) P value *Per protocol set. Full analysis set. Micturition frequency/24 h 2.45 2.24 =0.004 SECONDARY (FAS) (n=578) (n=599) Urgency episodes/24 h 2.85 2.42 =0.035 Incontinence episodes/24 h 1.60 1.11 =0.006 Nocturia episodes 0.71 0.63 =0.730 Urge incontinence episodes/24 h 1.42 0.83 <0.01 Mean volume voided (ml/void) 38.00 31.00 =0.01 Patients dry (%) 59.00 49.00 =0.006 Pads/24 h 1.72 1.19 =0.0023 Perception of bladder condition 1.51 1.33 =0.0061 Please see full prescribing information. Chapple CR et al. Eur Urol, 2005. Darifenacin! Bladder selectivity (marginal) in animal studies: Not more than Tolterodine or Oxybutynin in guinea-pig! Haab et al, Eur Urol 2004: Multicenter, placebocontrolled RCT (n=561); Reduction in incontinent episodes: 67.7% Darifenacin 7.5 mg (p=0.010) 72.8% Darifenacin 15 mg (p= 0.017) 55.9% Placebo No reductions in nocturia
Darifenacin and warning time? Cardozo et al. J Urol, 2005 Difference in Medians at Week 2 = 4.3 minutes (p=.003) N=32 N=35 Non-selective muscarinic antagonists!trospium
Trospium! Quaternary amine! Used in Europe for 20 years: Many studies! Efficacy not different from standard agents! Poor bioavailability! RCT in US (phase III, Zinner et al J Urol 2004): N=523. 20 mg bid Urge UI -59% drug versus -44% placebo Nocturnal frequency decreased by week 4 Side effects: Dry mouth 21.8% CNS Considerations in the Treatment of Overactive Bladder : Passive Diffusion Across the BBB!$ Lipophilicity $ Diffusion Vasculature BBB CNS!$ Charge/polarity, hydrogen bonding % Diffusion + - - + + + - - - + - + % Molecular bulkiness $ Diffusion Pardridge WM. J Neurochem. 1998;70:1781-1792. Habgood MD et al. Cell Mol Neurobiol. 2000;231-253.
Conclusions! Urinary Incontinence is very common and has a profound negative impact on QOL! Simple questions can discriminate between basic types of UI! Look for underlying medical conditions and medications that exacerbate the problem! Initiate treatment or make a referral