DISORDERS IN WOMEN
| UROGYNECOLOGIC CONCEPTS FOR THE UROLOGIST —Lesley K. Carr, MD, Assistant Professor, Division of
Urology, University of Toronto Faculty of Medicine; Sunnybrook & Women’s College Health Sciences Centre, Toronto
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| Dysuria, ie, “burning down below”: factors to consider in differential diagnosis—urologic conditions; anatomic abnormalities;
common gynecologic causes; diagnostic pointers—when obtaining history, look for associated symptoms,
ie, vaginal discharge or dryness, pruritus, dyspareunia; patient can help identify site of burning (use simple terms to help
woman locate problem, eg, “around opening of vagina or entrance of labia”); during cystoscopy, evaluate meatus and
surrounding tissue to detect erythema and atrophy; simple slide smear of discharge as useful as charcoal swab; localize
pain from vestibulitis by—touching os of vestibular glands with Q-tip; performing gentle digital examination of posterior
fourchette over meatus; palpating over pelvic floor muscles, ie, bladder base; caveat—accessory vestibular glands
entering at urethral meatus may be source of discomfort rather than more proximal problem
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| Vulvodynia: most common in white women; onset 20 to 60 yr of age; can coexist with interstitial cystitis (IC); similarities
to IC —triggers (intercourse, surgery, and vaginitis); negative biopsy; unknown etiology; types—vulvar vestibulitis
(common in premenopausal women; Q-tip test positive; entrance dyspareunia); dysesthetic or essential vulvodynia (occurs
in older, often postmenopausal, women; burning continuous, more diffuse; less dyspareunia and point tenderness);
cyclic vulvovaginitis (flares before menses or after intercourse; can be associated with yeast infection and may respond to
therapy for yeast)
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| Most common causes of vaginitis/vaginosis: bacterial vaginosis—thin, white-to-gray, malodorous, adherent discharge;
clue cells on wet mount; fishy odor on potassium hydroxide test; vaginal pH more alkaline; overgrowth of anaerobic organisms
in vagina (eg, Gardnerella) requiring treatment with metronidazole (Flagyl); Candida albicans—thick, white,
“cottage cheese” discharge with pruritus; hyphae or pseudohyphae on vaginal smear; treated with over-the-counter preparations
or single-dose fluconazole (Diflucan); Trichomonas—sexually transmitted; detected on wet mounts or culture;
discharge profuse and multicolored; cervical involvement; pointers—use history and physical examination to screen for
imbalance vaginitis; use vaginal smears to look for C albicans or bacteria; refer patients with refractory or sexually
transmitted disease to clinic
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| Postmenopausal atrophic changes: characterized by dryness, burning sensation, burning during urination, dysuria, and
dyspareunia; affected area thin, dry, and red; systemic and local estrogens treat symptoms; caveat—women on systemic
hormone replacement therapy (HRT) may require local supplementation; estrogen types—natural; oral or topical allopathic
estrogen; bioidentical; phytoestrogens (not true estrogens)
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| Vaginal estrogens: Premarin cream (short-term use recommended; long-term use common); cyclic progesterones indicated
when uterus in situ (use lowest dose that controls symptoms); estradiol hemihydrate ([Vagifem]; given daily for 2 wk,
followed by once or twice weekly administration); estradiol vaginal ring ([Estring]; safest option; maintains systemic absorption
within postmenopausal range); if uterus intact—periodic antagonism with progesterone prevents hyperplasia or
endometrial cancer; progesterone and testosterone creams may be effective
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| Estrogen therapy and stress urinary incontinence (SUI): currently, estrogen plays little role in managing SUI
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| Estrogen therapy and overactive bladder (OAB): estrogens may improve—symptomatology, ie, vaginal estrogens
may be more effective than systemic estrogens; external atrophic changes that indirectly affect bladder
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| Estrogen and recurrent urinary tract infections (UTIs): postmenopausal increase in UTIs associated with age-related
changes in vagina and vaginal pH; when compared to placebo, estrogen helped reduce incidence of UTIs (vaginal route
most effective); young women on oral contraceptives—may develop local estrogen deficiencies; vaginal estrogen administered
over 4 wk reduced infection rates
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| INTERSTITIAL CYSTITIS —Peter K. Sand, MD, Professor of Obstetrics and Gynecology, Northwestern University Feinberg
School of Medicine; Director, Division of Urogynecology and Evanston Continence Center, Evanston Northwestern
Healthcare, Chicago
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| Interstitial cystitis: continuum; symptom complex—includes urgency, frequency, and nocturia in absence of other defined
pathology; may not include pain; ranges from mild and intermittent to severe; persists average of 7 yr before diagnosis;
recurrent UTIs—problem early on; patients complain of persistent urge and discomfort after intercourse; may be
misdiagnosed as coitally-related UTI; dyspareunia—early on, problem may involve discomfort with unrelenting urgency
and postvoid fullness after intercourse; pain syndromes—lead to neural upregulation and hyperalgesic state
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| Pathogenesis of IC: glycosaminoglycan (GAG) layer—prevents urine from contacting bladder urothelium and bacterial
pili from attaching to bladder wall; damaged layer cannot protect bladder; C-fibers—activated when damaged GAG
layer allows urinary solute and potassium to cross into bladder interstitium; once activated, carry sensations of urgency
and pain along afferent pathway and antidromally carry substance P to periphery; mast cells—release histamine and
bradykinin when activated by substance P; subsequent inflammation also damages GAG layer and bladder; inflammation
of bladder wall—eventually damages small vessels and causes endothelial leaks and glomerulation of bladder wall;
petechial hemorrhages seen with redistention of bladder
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| Tools for diagnosing IC: thorough evaluation to detect recurrent bladder infection; laparoscopic approach—
recommended; distend bladder to maximum anesthetic capacity; empty bladder after 5 to 10 min; redistend bladder and
look for damaged epithelial surface; potassium sensitivity test—highly specific; with sufficient GAG layer dysfunction,
40-mEq solution of potassium chloride can cross bladder wall to produce urgency and pain; false-positive results occur in
people with renal failure or individuals with bladders that cannot distend appropriately under anesthesia
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| Diagnosing IC: history of symptom complex including urgency, frequency, pain, and nocturia; nocturia—determined by
comparison with normal voiding pattern; can be age-dependent; other tools—voiding diary; pelvic examination; urine
culture; potassium sensitivity test; bladder cytology (microscopic hematuria absent in 58% of patients); cystoscopy; cystometrogram;
physical characteristics of IC—tenderness in suprapubic region and base of bladder; levator muscle
spasm; rectal spasm; single-digit examination underneath urethra and bladder—symptomatic examination, in absence
of hematuria or infection, indicative of IC or chronic urethral inflammation with chronic urethrotrigonitis; pain,
urgency, frequency (PUF) scoring questionnaire—can, in absence of infection or hematuria, be surrogate for potassium
sensitivity test
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| Integrated pathophysiology of IC: suggests spinal wind-up and generalized hyperalgesic state triggered by C-fiber and substance
P activity may cause neurologic activation in viscera and tissues, including peritoneal surface; may explain why patients
develop multiple areas of activation, producing pain and inflammation
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| Treatment of IC: therapeutic principles—repair or improve GAG layer; address spinal wind-up or neural hyperalgesia;
address mast cell activation or allergic or immunologic-related factors; make people feel better during treatment; bladder
diets may improve symptoms of urgency and frequency—eliminate bladder irritants, eg, caffeine, alcohol, spicy
foods; decrease acidity of urine, ie, decrease potassium content; patients should identify and eliminate foods specific to
their problem; caveat—cranberry juice or extract contraindicated; bladder retraining—timed voiding; auto-hydrodistention;
surgery—hydrodistention; bladder augmentation; urinary diversion; self-help methods—physical therapy
(useful if patient has secondary levator spasm; patient must learn to perform myofascial release); herbal therapy; pain relief
and control, eg, biofeedback, electrical stimulation, acupuncture
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| Intravesical agents: silver nitrate; hyaluronic acid (Cystistat) no more effective than placebo; sodium oxychlorosene (Clorpactin)
achieved marked improvement in 85% of patients studied; dimethyl sulfoxide (DMSO; [Rimso-50])—
approved by Food and Drug Administration (FDA) for treating IC; patients exude garlic-like odor; hydrodistend bladder
for ≈5 min; administer solution of 50 mL DMSO and 20 mg triamcinolone (Kenalog); have patient void mixture 20 min
later; combining anesthetic with heparin or pentosan polysulfate (Elmiron)—anesthetic solution relieves pain immediately;
heparin or Elmiron may improve GAG layer
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| Oral drugs: nociceptive blockers, ie, tricyclic antidepressants; gabapentin used off-label to control urgency and associated
pain; Elmiron—only oral FDA-approved drug for IC; may relieve pain; efficacy depends on duration of therapy, rather
than dose; recurrence—median time to recurrence 6 to 7 mo after DMSO therapy in newly diagnosed patients; administering
combination of DMSO and Elmiron to newly diagnosed patients may help prevent symptomatic recurrence
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| Basic management approach: attack GAG layer deficit; modulate neural upregulation and C-fiber activation; tools—
stabilize mast cells by using hydroxyzine (Atarax) to reduce sensitivity and degranulation of mast cells; Elmiron or heparin
toimprove GAG layer; tricyclic antidepressants and perhaps gabapentin to affect modulation of C-fiber activity and
nociceptive pain; antihistamines
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| PERIURETHRAL INJECTIONS FOR STRESS URINARY INCONTINENCE: NEW DEVELOPMENTS —Rodney A.
Appell, MD, Professor and Chief, Division of Voiding Dysfunction and Female Urology, Baylor College of Medicine,
Houston
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| Injectable therapy for SUI: safe; effective; can be performed in office under local anesthesia; factors undermining use as
first-line therapy—inability to quantify amount of material needed for specific patient; questionable durability in relation
to cost; safety; injectables work by—mucosal coaptation (increased urethral closure pressure and resistance to passive
outflow of urine; especially beneficial for patients with severe intrinsic sphincteric dysfunction); cephalad
elongation of functional urethral length (increased efficiency of pressure transmission to proximal portion of urethra);
points—most candidates for injection therapy have fixed outlet obstruction and severe intrinsic sphincteric deficiency
(ISD); patients with certain amount of hypermobility achieve good results; ideal candidates for injection therapy—
have poor urethral function; lack detrusor instability; have adequate bladder capacity and anatomic support; injection
techniques—transurethral; periurethral; fear, uncertainty, and doubt (FUD) factor—determines quantity and duration
of injection therapy
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| Factors determining degree of correction: etiology of defect; status of tissue at injection site; plane of placement of
agent—injections designed to be placed intraurethrally; injectables should enter superficial layers of urethral muscle and
push mucosa out
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| Glutaraldehyde cross-linked (GAX) bovine collagen: biocompatible; biodegradable, ie, begins to degrade 12 wk postinjection;
persists histologically for 18 mo; goals—achieve neovascularization and invasion of host fibroblasts; lay down
new endogenous collagen to replace dissipating injectable bovine collagen; most patients require additional treatment
to achieve and maintain dryness—12% to 40% of patients who achieve initial success must be reinjected at ≤2 yr; 40%
of individuals reinjected achieve results similar to those achieved with initial injection; complications—rare; include de
novo urgency and short-lived urinary retention; no reports of migration; collagen as injectable material—favorable
characteristics include safety, ease of administration, minimal tissue reactivity, and lack of migration; unfavorable characteristics
include poor durability and cost
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| Pyrolytic carbon-coated zirconium oxide beads: “off the shelf” synthetic; injection procedure identical to that used with
collagen; carbon coating facilitates passage of beads through needle and prevents mucosal damage after injection; large-
bore (18-gauge) injection needle necessary to inject large-diameter beads; advantages—in some respects, safer than
collagen, ie, lack of antigenicity precludes need to perform skin test first; nonbiodegradable; problems—intraneedle resistance;
large-bore needle puncture can cause material to extrude during withdrawal; smaller beads—used in new formulation;
prevent migration; facilitate injection by avoiding need to hydrodistend tissue initially; permit use of standard
transurethral injection technique
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| Advances in technology: ethylene vinyl alcohol combined with DMSO (Uryx)—with fluid contact, DMSO diffuses and
solid polymer expands to consistency of moist Styrofoam; approved by FDA for intrinsic sphincteric deficiency and
stress urinary incontinence; safe; ease of injection favors transurethral technique; biocompatible and nonmigratory; minimal
foreign body reaction disappears over time; use small needle to inject 1 mL of material on each side of urethra (to
avoid extrusion or escape from mucosa, inject material over 1 min; leave needle in place for additional 1 min before extraction);
calcium hydroxyapatite spheres suspended in sodium carboxymethylcellulose aqueous gel—retains putty-like
consistency postinjection; acts as “new washer” at bladder neck; nonantigenic and noninflammatory; uniform particulate
size precludes migration; particles become enmeshed in soft tissue matrix which retains volume; resists other forms of
calcification; visualized radiographically; reduces daily pad usage by 45% among study subjects; achieved good cure rate
with single injection; dextranomer microspheres suspended in viscous sodium hyaluronic acid—large particle size
precludes migration; biodegradable; previously approved for managing vesicoureteral reflux in children; safe; ≈25% of
adults receiving injection retained continence for 5 yr; injected with “implacer” device into midurethra; tissue
engineering—bioimplants produce functional nonimmunogenic tissue that survives in vivo; satisfies criteria for ideal
injectables
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Educational Objectives
| The goal of this program is to educate the listener about urogynecologic disease. After hearing and assimilating this program,
the clinician will be better able to:
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 | 1. Evaluate and treat gynecologic causes of dysuria.
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| 2. Assess the role of vaginal estrogen in the management of various urologic disorders in postmenopausal women.
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| 3. Diagnose patients presenting with interstitial cystitis (IC).
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| 4. Review dietary, intravesical, and oral alternatives for managing IC.
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| 5. Review the clinical merits of current and future injectable therapies for stress urinary incontinence.
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Discussed on This Program
Amitriptyline HCl [Elavil]
Dimethyl sulfoxide (DMSO) [Rimso-50]
Doxepin HCl [Sinequan, Sinequan Concentrate, Zonalon]
Estradiol hemihydrate [Vagifem, Estrasorb]
Estradiol, vaginal ring [Estring]
Estrogen, vaginal [Premarin Vaginal Cream, others]
Estrogens, conjugated [Premarin, Premarin Intravenous]
Fluconazole [Diflucan]
Gabapentin [Neurontin]
Heparin sodium injection
Hyaluronic acid [Cystistat] (not available in United States)
Hydroxyzine [Atarax, Atarax 100, Vistaril0]
Metronidazole [Flagyl, others]
Oxychlorosene sodium [Clorpactin WCS-90]
Pentosan polysulfate sodium [Elmiron]
Progesterone [Crinone, Prochieve, Progesterone In Oil, Prometrium]
Raloxifene [Evista]
Silver nitrate
Triamcinolone acetonide (Kenalog; others]
Suggested Reading
Castelo-Branco C et al: Management of post-menopausal vaginal atrophy and atrophic vaginitis. Maturitas 52 Suppl
1:S46, 2005; Goldstein SR et al: Incidence of urinary incontinence in postmenopausal women treated with raloxifene or
estrogen. Menopause 12:160, 2005; Hendrix SL et al: Effects of estrogen with and without progestin on urinary incontinence.
JAMA 293:935, 2005; Kallestrup EB et al: Treatment for interstitial cystitis with Cystistat: a hyaluronic acid product.
Scand J Urol Nephrol 39:143, 2005; Kershen RT et al: Beyond collagen: injectable therapies for the treatment of
female stress urinary incontinence in the new millennium. Urol Clin North Am 29:559, 2002; McCrery RJ, Appell RA:
Safety of carbon bead injection for incontinence in patients taking warfarin. Urology 67:97, 2006; Muthusamy A et al:
Enhanced binding of modified pentosan polysulfate and heparin to bladder—a strategy for improved treatment of intersitial
cystitis. Urology 67:209, 2006; Parsons M, Toozs-Hobson P: The investigation and management of interstitial cystitis.
J Br Menopause Soc 11:132, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed:
Dr. Appell is affiliated with Astellas Pharma Inc., American Medical Systems, Boston Scientific, Novartis, Ortho-
McNeil Inc., Pfizer Inc., and Watson Pharmaceuticals; Dr. Carr is affiliated with Allergan, Bioniche Life Sciences, Inc.,
Cook, Gynecare, Mentor, and Pfizer Inc.; Dr. Sand is affiliated with American Medical Systems, Astellas Pharma, Inc.,
Boston Scientific, GlaxoSmithKline, Indevus Pharmaceuticals Inc., Ortho Urology, and Watson Pharmaceuticals Inc.
Dr. Carr gave her scientific presentation at Urology Update 2005, New Ideas, Approaches and Techniques, presented
October 21 to 22, 2005, in Toronto, Canada, by the University of Toronto Faculty of Medicine; Drs. Appell and Sand
gave their scientific presentations at Advances in Urogynecology and Reconstructive Pelvic Surgery, presented June
9 to 11, 2005, in Chicago, by the Northwestern University Feinberg School of Medicine and the Evanston Continence
Center Division of Urogynecology, Evanston Northwestern Healthcare. The Audio-Digest Foundation thanks the
speakers and the sponsors for their cooperation in the production of this program.
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