MENOPAUSAL MEDICINE
| URINARY INCONTINENCE: PRACTICAL EVALUATION AND TREATMENT —Jeanette S. Brown, MD, Professor
of Obstetrics, Gynecology and Reproductive Sciences, Urology and Epidemiology, University of California,
San Francisco, School of Medicine; Director, UCSF Women’s Continence Center; Co-Director, UCSF Women’s
Health Clinical Research Center, San Francisco
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| General considerations: urinary incontinence (UI) affects 25% of reproductive-age women and 40% of postmenopausal
women; risk increases 20% for every 5 yr of aging; can result in social withdrawal; increases risk for falls
and fractures and nursing home admittance; $26 billion spent annually in treating (more than all cancer care expenses
for women combined); evidence-based guidelines for evaluating UI (developed by specialists) time-consuming
and complex; recommended tests and examinations not feasible in busy practice
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| Diagnostic Aspects of Incontinence Study (DAISy): evaluated sensitivity and specificity of simple questions in
evaluating UI; 3 Incontinence Questions (3IQ) questionnaire—1) during last 3 mo, have you leaked urine, even
small amount; if yes, proceed to question 2; 2) have you leaked urine with physical activity, coughing, sneezing,
lifting, or exercise (indicates stress UI), or have you had urge, feeling need to empty but could not get to toilet fast
enough (indicates urge UI), or don’t know; 3) what occurs most often, stress incontinence or urge incontinence or
are they about same; most often patients have stress or urge incontinence rather than mixed; accuracy of 3IQ questionnaire
compared to extended evaluation—simple, inexpensive, and feasible; reproducible (≈70% for urge and
stress); acceptable accuracy (75% sensitivity, 77% specificity for urge incontinence); risk for misdiagnosis low
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| Distinguishing features: stress incontinence—associated with activity, coughing, and sneezing; small to moderate
amount of urine loss; frequency and nocturia rare; urge incontinence (overactive bladder; OAB)—patients often say,
“it just comes out”; not indicative of neurologic problem; precipitated by urge; patients try to suppress but cannot delay;
large amount of urine lost; frequency and nocturia common
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| Initial visit: clinical diagnosis using 3IQ questionnaire; obtain urine specimen; determine severity of leakage (what
provokes it, what kind of protection worn and how often changed, and severity of problem); urinary diary effective
as intervention, not necessary for diagnosis; evaluate need for bedside commode; most important tool patient education
and empowerment; patient information—self-help booklet as effective as other behavioral interventions
(eg, biofeedback); voiding diary excellent intervention for educating patient; useful in planning therapy (eg, fluid
adjustment, timing, and type of medication)
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| Falls and fractures: 20% to 40% of older women experience falls; 90% of hip fractures result of falls; at least 40%
associated with urge incontinence; urge incontinence associated with 26% greater risk for fall and 34% greater risk
for fracture; associated with frequency and nocturia; address need for bedside commode to prevent falls
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| Estrogen therapy: data show incontinence worsened with use of estrogen therapy; observational studies showed increased
urge incontinence; data show conjugated equine estrogen (CEE) plus progesterone or oral estrogen alone
(eg, Premarin) increases urge and stress incontinence 3-fold; United Kingdom study showed vaginal estrogen did
not worsen incontinence, but did not improve it either
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| Weight reduction: effective intervention and unique motivator; as effective as pharmacotherapy
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| Behavioral management: initial treatment similar for stress and urge incontinence; fluid intake modification, pelvic
floor exercises, and bladder training; provide patient with verbal and written instructions; coughing up—
recommend when patient feels cough coming on; involves tightening and bringing pelvic floor up and then coughing;
bladder training—randomized controlled trial demonstrated significant improvement; Burgio showed behavioral
interventions more effective than medications, and greater satisfaction among participants in behavioral
group; timed voids—recommended for stress UI; instruct patient to empty bladder at scheduled intervals; urge suppression
and urge distraction—involves squeezing pelvic floor muscles quickly and tightly several times to maintain
bladder control without rushing to toilet
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| Medications: none available for stress incontinence; many for OAB and urge incontinence; survey showed patients
prefer self-help measures to medications for treatment of UI; side effects—dry mouth, constipation, drowsiness,
blurred vision, and dizziness; no data on effect on cognitive function; contraindications include narrow angle glaucoma,
and hepatic or renal disease; Cochrane Review found all medications similar in effectiveness and side effects;
speaker suggests starting with oxybutynin (Ditropan); immediate-release formulations —Ditropan,
tolterodine (Detrol), and trospium (Sanctura); used as needed; extended-release formulations available for patients
needing daily dosing; combination treatment—data show added benefit; starting with behavioral therapy and
switching to medication decreased UI by 84%; starting with medication and switching to behavioral therapy decreased
UI by 89%
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| Summary: be creative in treating problem; patient should have reasonable expectations; ask patients what they
want from treatment; start with simple treatments and be flexible in approach; combine treatments; educate and
empower patients
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| Questions: reason for UI in aging—multifactorial; 90% of OAB idiopathic; surgery—appropriate only for stress
incontinence; no surgery for urge incontinence; Burch procedure and transvaginal tape (TVT) reasonable options
for stress incontinence; new receptor blockers—Cochrane Review and other data show similarity among all receptor
blockers; bladder irritants—no good evidence linking diet to UI; alcohol and caffeine reported empirically;
prolapse and incontinence—3% to 4% of women have symptomatic prolapse; treatment should start with
simple interventions; 30% failure with surgery; incontinence and prolapse associated with hysterectomy—meta-
analysis showed hysterectomy increases risk for UI by 60% and prolapse by 30%; surgery should be based on
quality-of-life issues
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| BRAIN FUNCTION IN THE AGING: BALANCE, REFLEXES, AND COGNITION —Stanley J. Birge, MD, Associate
Professor of Medicine, Division of Geriatrics, Washington University School of Medicine, St. Louis, MO
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| Effects of estrogen on brain function: multiple effects on central nervous system (CNS); stimulates axonal
growth; neuroprotective (increases variety of neurotransmitters); stimulates tropic factors (eg, brain-derived neurotropic
factor), and increases blood flow to hippocampus
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| Effects of estrogen on memory: ≈62% of women report cognitive changes at perimenopause (eg, concentration,
memory); Baltimore Longitudinal Study of Aging—showed women using hormone therapy (HT) performed better
across variety of cognitive function domains than women not using HT (however, uncontrolled for baseline cognitive
function); Cache County Study on Memory in Aging—studied effect of HT in reducing cognitive decline in
older women; average age at baseline 75 yr, with 3-yr follow-up; little difference in first decade, but greater separation
between women exposed to HT and never users in later decades; cognitive decline and serum estradiol
levels—data show women with highest concentration of estradiol less likely to develop cognitive impairment than
women with low concentrations; suggests relatively low level of hormone (20-30 pg/mL) protects CNS from age-
related declines in cognitive function; data also show loss of hip bone mineral density (BMD) associated with cognitive
decline; cognitive function in past users and current users of HT vs never users—current users did not differ
significantly from never users, but past users showed significant slowing in rate of cognitive decline; past users
more likely initiated HT at time of menopause for management of menopausal symptoms, whereas current users
may have initiated HT for prevention of osteoporosis; effect of surgical menopause on short-term verbal
memory—data show greater reduction in cognitive function (measured by number of words recalled); surgical
menopause shown to increase other neurodegenerative diseases (eg, Parkinson’s disease, Alzheimer’s disease)
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| Alzheimer’s disease: women have ≈30% chance of developing in lifetime; 1.5- to 3-fold higher in women than in
men in same age group, even after accounting for longer life span; men at ≈50 yr of age have 3 times circulating
level of estradiol as women at same age (men convert testosterone and dehydroepiandrosterone [DHEA] to estradiol);
6 times level of estradiol seen on autopsy in brains of women who did not have Alzheimer’s disease, compared
to those who did (aromatase enzyme may be key); Columbia Longitudinal Study of Health and Aging—
compared current users of estrogen (average length of use >15 yr) to never users; at 85 yr of age, ≈40% of never
users developed Alzheimer’s disease, compared to 5% of current users; almost 40% reduction in incidence among
women taking estrogen for ≤1 yr but initiating use at time of menopause; Cache County study (additional results)
—looked at incidence of Alzheimer’s disease in men and women (average age 74 yr) over 3-yr interval; ≈60%
lower incidence in men, compared to women who never used HT; 20% to 30% lower incidence in women using
HT for <3 yr; ≈50% lower incidence in women using HT for 3 to 10 yr; 83% lower incidence in women using HT
for 10 yr; incidence 2-fold greater among women who used HT <3 yr or those using HT <10 yr, starting after age
64 yr; Women’s Health Initiative (WHI) results comparable with results from Cache County study; pathogenesis of
Alzheimer’s type dementia—cerebrovascular disease major risk factor; damage to CNS triggers cascade of events
leading to amyloid deposition and neuronal loss; inflammatory process ultimately results in symptoms of dementia
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| Coronary heart disease (CHD): no evidence of coronary artery events (as seen in Heart and Estrogen/progestin
Replacement Study [HERS] trial or later years of WHI) when estrogen initiated at time of menopause or within 10
yr of menopause; increased incidence may be related to preexisting cardiovascular disease; initiating HT early may
provide window of opportunity to affect CHD
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| Cerebrovascular accident (CVA): WHI showed increase in stroke, which increases with greater duration of exposure
to HT (in contrast, WHI showed increase in incidence of CHD only in first 6 mo of use); mechanism for cause
likely different from that for cardiovascular events; effect of estradiol dose on C-reactive protein (CRP)—WHI
and Nurse’s Health study showed 35% increase in risk for stroke with higher levels of HT (CRP significantly increased
with 0.625-mg dose of estrogen); 46% reduction in incidence of stroke observed with lower dose of HT
(0.3 mg); lower-dose HT decreases CRP, thereby decreasing risk for thromboembolic events
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| Postural balance: women 3 times more likely to fall than men of same age; progressive deterioration in postural
stability after ≈60 yr of age due to multiple factors (eg, changes in vision, vestibular system, muscle weakness,
joint stiffness); most important determinant of postural stability is speed at which person processes sensory input
and generates appropriate postural response to loss of balance; deteriorates with advancing age; study by
Naessen et al—showed no significant difference in postural balance in women who received estrogen from onset
of menopause to ≈68 yr of age, compared to young controls; also demonstrated significant improvement in
postural stability with HT use; effect of time of initiation of HT—improvement in symptoms related to when HT
initiated in relation to menopause; appears there is limited window of opportunity when woman transitioning
from estrogen depleted state to estrogen deficiency state; intervening at particular point in time may maintain
or restore postural stability and prevent age-related changes in cognitive function; older adults who lose balance
likely to fall to floor before brain transmits message they have lost balance; wrist fractures increase after
menopause; exponential increase in hip fractures after age ≈70 yr, leading investigators to believe hip fracture
more likely function of brain disease than bone disease; risedronate shown to have no effect on reduction of hip
fracture in subjects >80 yr of age; WHI showed estrogen effective in preventing hip fracture (only 8% of WHI
subjects had osteoporosis)
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| Summary: data suggest low doses of estrogen effective in maintenance of CNS and delayed expression of Alzheimer’s
disease; low-dose estrogen can reduce exposure to progestin in women with uterus
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Patient Resources
Women’s Continence Center: www.ucsf.edu/wcc
Suggested Reading
Brown JS et al: The sensitivity and specificity of a simple test to distinguish between urge and stress urinary incontinence.
Ann Intern Med 144:715, 2006; Burgio KL: Influence of behavior modification on overactive bladder.
Urology 60(5 Suppl 1):72, 2002; Burgio KL et al: Combined behavioral and drug therapy for urge incontinence in
older women. J Am Geriatr Soc 48:370, 2000; Carlson MC et al: Hormone replacement therapy and reduced cognitive
decline in older women: the Cache County Study. Neurology 57:2210, 2001; Naessen T et al: Bone loss in elderly
women prevented by ultralow doses of parenteral 17beta-estradiol. Am J Obstet Gynecol 177:115, 1997; Tang
MX et al: Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 343:429,
1996; Yaffe K et al: Cognitive decline in women in relation to non-protein-bound oestradiol concentrations. Lancet
356:708, 2000; Yue X et al: Brain estrogen deficiency accelerates Abeta plaque formation in an Alzheimer’s disease
animal model. Proc Natl Acad Sci U S A 102:19198, 2005.
Educational Objectives
| The goals of this program are to improve the management of urinary incontinence (UI) and to provide evidence supporting
the role of hormone therapy (HT) in reducing cognitive decline in older women. After hearing and assimilating
this program, the clinician will be better able to:
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 | 1. Evaluate the feasibility of the 3 Incontinence Questions (3IQ) questionnaire for diagnosing UI.
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| 2. Utilize estrogen therapy, weight reduction strategies, and behavioral therapies for UI.
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| 3. Assimilate study data about the effect of HT on cognitive function in menopausal women.
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| 4. Discuss the effect of estrogen in reducing coronary heart disease and how it affects cognitive functioning.
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| 5. Counsel patients about the role of estrogen in preserving cognitive function.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any
identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the following has been disclosed: Dr. Brown has received
research support from Pfizer. Dr. Birge is on the Speaker’s Bureau of Wyeth Pharmaceuticals.
Acknowledgements
Dr. Brown was recorded at Controversies in Women’s Health, sponsored by the University of California, San Francisco,
School of Medicine, and held on December 7-8, 2006, in San Francisco, CA. Dr. Birge was recorded at
Menopausal Medicine, Care for the Mature Female, sponsored by the Mayo Clinic, and held March 1-3, 2007, in
San Diego, CA. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the
production of this program.
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