PERPLEXING AND INSIDIOUS DISORDERS
Selections from the 5th Annual Fall Symposium, Issues in Women’s Health, sponsored by the Medical University of
South Carolina, Charleston
| CHRONIC VAGINITIS— David E. Soper, MD, Professor and Vice Chair, Clinical Affairs, Department of Obstetrics
and Gynecology, Medical University of South Carolina, Charleston
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| Vulvovaginal candidiasis: epidemiology—75% of women experience at least 1 episode, ≈45% of women have ≥2
episodes, and <5% have chronic or recurrent disease (≥4 cases/yr); predisposing factors—pregnancy, high-dose oral
contraceptives, diabetes mellitus, and use of antimicrobial agents
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 | Differential diagnosis: perform pelvic examination in symptomatic patient (eg, dysuria, vulvar pruritus, pain, swelling,
redness); perform direct microscopy if pelvic examination exhibits abnormal findings (eg, erythema, abnormal
discharge), wet mount with 10% potassium hydroxide (KOH), and pH estimation; up to 35% of patients with lower
genital tract symptoms have pH <4.5 and microscopy negative for yeast; pH >4.5 indication of bacterial vaginosis
(BV) or trichomoniasis; start antimycotic therapy in patient with normal pH, normal white blood cell (WBC) count,
and microscopy positive for yeast (ie, pseudohyphae or budding yeast); consider diagnosis of mixed infection (ie,
BV and candidiasis) if microscopy positive for yeast and pH >4.5 or if WBC elevated (occurs in 10% of patients;
check cervix to rule out concurrent mucopurulent cervicitis [MPC]); submit specimen for yeast culture and start antimycotic
therapy if direct microscopy negative for yeast and pH <4.5, with no signs of trichomoniasis or clue cells
in patient with abnormal vulvar and vaginal examination; about one third of symptomatic patients have positive
yeast culture; 23% of patients without signs of vulvar edema, fissuring, excoriation, or “cheesy” white vaginal discharge
during pelvic examination have positive yeast culture; 15% of patients positive for yeast if wet mount negative
and pelvic examination normal; obtain culture in patient with typical symptoms of candidiasis, normal pelvic
examination, and negative wet mount to prove patient does not have yeast and avoid treatment with antifungal agent
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| Treatment: high-dose inhibitory concentration of antifungal on first therapeutic day, with decreasing concentration
over time; topical therapy (eg, miconazole, terconazole, clotrimazole, fluconazole) highly effective for yeast and well
tolerated by patients; uncomplicated disease—single-dose short-term therapy; have mild-to-moderate disease (eg,
limited erythema), mild-to-moderate symptoms, infrequent or sporadic disease; pseudohyphae seen with microscopy
in normal host with normal immune system; use over-the-counter (OTC) therapy with single-dose fluconazole;
complicated disease—includes patients with moderate-to-severe disease, more severe findings on exa-
mination, recurrent disease (≥4 cases/yr), budding yeast on microscopy, and patients with compromised immunity
(eg, pregnancy, uncontrolled diabetes, HIV); recommend 2 doses of fluconazole every 3 days
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| Chronic vulvovaginal candidiasis: defined as ≥4 episodes within 12 mo; exclude other vaginal pathogens; obtain culture
if wet mount negative in patient with symptoms of candidiasis and in patient with recurrent disease to confirm
diagnosis; antifungal therapies bacteriostatic, not bactericidal; yeast not totally eradicated from vagina without intact
immune system; vaginal fungal cultures from patients with recurrent disease rapidly become positive after antibiotic
administration (within 30 days in up to 25% of women treated successfully); biotyping shows identical strains
in most recurrent disease; causal species mostly Candida albicans (sensitive to fluconazole; non-albicans Candida
not sensitive to fluconazole); consider screening for diabetes or HIV infection; identify and eliminate or control risk
factors, induce remission with initial course of therapy, and prevent relapse with suppressive therapy; long-term
maintenance—study found recurrence rate 35% with cyclic ketoconazole therapy given over 4-mo period (400 mg
daily for 5 days monthly); decrease in recurrence rate of 50% after monthly therapy with fluconazole; recurrence
rate 5% with daily low-dose administration of ketoconazole; ketoconazole associated with hepatotoxicity, but fluconazole
not associated with hepatotoxicity or resistance; treatment—initial treatment with fluconazole 150 mg
every 3 days for 4 doses; for maintenance therapy, prescribe fluconazole 150 mg weekly for 6 mo; study found 91%
of patients disease-free at 6 mo, 73% at 9 mo, and 43% at 12 mo with fluconazole
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| Bacterial vaginosis: most common vaginal infection; predisposing factors same as other sexually transmitted diseases
(STDs); semen, menses, and antibiotic therapy affect normal vaginal flora and can affect lactobacilli in normal
flora that make lactic acid (drives pH down) and hydrogen peroxide (antimicrobial); lactic acid and hydrogen peroxide
keep concentration of anaerobic bacteria down; decrease in concentration of lactobacilli increases concentration
of anaerobes, Gardnerella vaginalis, and mycoplasmas and elevates pH; clinical diagnosis—wet mount by experienced
physician has high sensitivity and specificity; look for clue cells (20%-30% of epithelial cells); whiff test has
moderate sensitivity and specificity; KOH solution added to vaginal secretions produces “fishy” odor (caused by trimethylamine
made by anaerobic bacteria); treat with metronidazole (does not affect levels of lactobacilli; want to reestablish
normal flora and prevent relapse); recurrence— posttherapy cure rates 40% over 3 mo (may be because of
failure of lactobacilli to recolonize; yogurt and acidophilus ineffective); management—Gram stain and Nugent’s
criteria confirm diagnosis; induce remission using longer-course therapy with metronidazole or clindamycin; evaluate
patient before discontinuing therapy to confirm resolution of symptoms and signs of disease; look for substantial
decrease in anaerobic bacteria on wet mount; place patient on suppressive therapy and titrate interval dose; study—
therapy with metronidazole vaginal gel suppressive in patients who had >3 episodes of BV; asymptomatic patients
with <3 Amsel’s criteria randomized to receive gel or placebo for 2 nonconsecutive days each week; metronidazole
gel associated with few recurrences
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| Trichomonas vaginitis: protozoan infection; associated with BV in two thirds of cases; sexually transmitted; diagnosis
made with wet mount under microscopy (not very sensitive test); elevated WBC common; consider in presence
of clue cells and increased WBC; treatment—single-dose metronidazole (2 g); consider tinidazole in patients
who have metronidazole-resistant disease; recurrent disease—may be because of reinfection (treat sexual partners),
lack of compliance, or resistance; 85% of initial failures respond to another single 2-g dose of metronidazole; if second
treatment fails, increase to single 2-g dose of metronidazole daily for 3 to 5 days and address compliance or reinfection
issues; can use single-dose tinidazole (2 g) in patients who do not respond to metronidazole; for additional
failures, culture and send isolate to Centers for Disease Control and Prevention (CDC) for susceptibility studies; base
therapy on results of susceptibility studies (usually high-dose oral metronidazole or tinidazole plus vaginal metronidazole)
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| GENITAL ATROPHY AND SEXUALITY —Murray A. Freedman, MD, MS, Clinical Professor, Department of
Obstetrics and Gynecology, Medical College of Georgia, Augusta
|
| Indications for estrogen replacement: up to 50% of women >75 yr of age suffer from fractures or severe osteoporosis;
up to 80% of postmenopausal women with loss of ovarian function exhibit vasomotor symptoms (25%
have symptoms for >5 yr, 5%-10% have symptoms for >10 yr)
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| Estrogen deficiency and genitourinary changes after menopause: sexual and urinary tract function affected
by estrogen deficiency that can occur after menopause; sexual dysfunction—genital atrophy least publicized consequence
of estrogen deficiency; 97% of women show symptoms within 1 to 2 yr of menopause; high incidence of
sexual dysfunction in menopause clinics; urinary tract dysfunction—up to 40% of institutionalized women in
United States wear pads for incontinence
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| Genitourinary tract: embryology— 4- to 6-wk embryo 7 to 8 mm in size; genital tubercle and urogenital sinus
give rise to urethra, trigone, and distal vagina in adult female; these structures, containing highest concentration of
estrogen receptors, affected most by estrogen and estrogen deficiency; vaginal pH—normal pH 3.5 to 4.5; healthy
vagina maintained by well glycogenated stratified squamous epithelium, lactobacilli, and good supporting vasculature;
within 12 to 24 mo of menopause, women have atrophic epithelium with poorly vascularized dermis, resulting
in poor lubrication; changes in glycogenated stratified squamous epithelium result in decrease in concentration of
lactobacilli, and decrease in production of hydrogen peroxide and maintenance of normal acidic vaginal pH; postmenopausal
women typically have vaginal pH ≥5; study looked at 300 patients who stopped estrogen replacement
therapy (ERT); 290 (96.7%) had atrophic epithelium and vaginal pH ≥5 within 6 to 12 mo; 10 patients had normal
vaginal pH within 12 to 24 mo (7 from endogenous estrogen linked to obesity; 3 hypoestrogenic, but had high level
of sexual activity); most patients exhibited introital stenosis, resulting in dyspareunia and sexual dysfunction; collagen
content and genital atrophy—large amount of type 1 collagen in vagina (type 2 collagen found in bone);
study found some women without estrogen replacement lose 30% to 50% of type 1 collagen 3 to 5 yr after menopause;
can prevent loss of collagen with ERT and bisphosphonate
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| Urinary dysfunction: no good prospective randomized trials showing urodynamic change, but patients describe
subjective improvement with ERT; 25% of patients who complain of urinary incontinence have anatomic issue
(usually hypermotile urethrovesical angle) requiring surgical correction; patients with overactive bladders or urge
incontinence require anticholinergic therapy; 50% of women have combination of bladder dyssynergia and anatomic
defect; up to two thirds of these patients respond to ERT to correct atrophic change and to anticholinergic
therapy (or α-adrenergic agents) for dyssynergia; study of patients with recurrent urinary tract infections (UTIs)
showed that up to 10% of postmenopausal women >70 yr of age not taking ERT suffer from recurrent UTI; study
looking at intravaginal estradiol found marked reduction in recurrent infection rate in women treated with estrogen
within 8 mo
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| Sexual dysfunction: 50% of postmenopausal women list sexual dysfunction as 1 of top 3 complaints; lack of available
partner most common reason for lack of sexual activity; premenopausal sexuality best predictor of postmenopausal
sexuality; sexual response cycle—positive central erotic stimulation (ie, desire) leads to peripheral
vasocongestion in pelvis, producing erection in men or lubrication and clitoral enlargement in women, leading to
orgasm; typical physiologic cycle requires <3 min in men and 12 to 13 min in women; difference in cycle length result
of learned behavior; men learn autoeroticism and have low rate of anorgasmia; 10% to 15% of women anorgasmic
after 1 yr of marriage; study looking at men and women with virtual reality simulation found both took 15
to 30 sec to reach orgasm; during orgasm, in both men and women, 8 to 12 pelvic levator muscle contractions occur
at 0.08-sec intervals; sexual response in men orgasm-oriented, while sexual response in women satisfaction-oriented;
young men typically have 3 to 5 orgasms per week, while women have 1 to 2 orgasms per week; estrogen
levels—study looking at hormone levels at menopause found drop in estradiol levels corresponded to decline in
sexual activity that occurs in early perimenopause transition through first or second year after menopause, while increased
gonadotropin secretion stimulates ovarian stroma, resulting in maintenance of testosterone levels (most
women almost hyperandrogenic during this period); study looked at estradiol levels and physical complaints about
sexuality during menopause (eg, pain, burning, vaginal dryness, dyspareunia); compared women with low (<50 pg/
mL) to normal (>50 pg/mL) estradiol levels; complaints occurred more frequently in women with low estradiol
levels than in those with normal levels; 60% of study participants aware of and bothered by complaints
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Educational Objectives
| The goal of this program is to educate the listener about chronic vaginitis and the effect of genital atrophy on sexuality
in postmenopausal women. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Describe the differential diagnosis of vulvovaginal candidiasis, bacterial vaginosis, and trichomonas vaginitis.
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| 2. Select treatment for a patient with recurrent vaginitis.
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| 3. List the indications for estrogen replacement in postmenopausal women.
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| 4. Explain how estrogen deficiency affects the genitourinary tract in postmenopausal women.
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| 5. Evaluate the effect of estrogen deficiency on sexuality in postmenopausal women.
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Discussed on This Program
| Miconazole nitrate (several trade names)
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Terconazole [Terazol 3, Terazol 7]
Clotrimazole (several trade names)
Fluconazole [Diflucan]
Ketoconazole [Nizoral, Nizoral A-D, Nizoral Cream Shampoo]
Metronidazole [Flagyl, Flagyl 375, Flagyl ER, Flagyl IV, Flagyl IV RTU, Metric 21, MetroCream, MetroGel,
MetroGel-Vaginal, MetroLotion, Noritate, Protostat]
Clindamycin [Cleocin, Cleocin Pediatric, Cleocin Phosphate, Cleocin T, Clindagel, ClindaMax, ClindaMax Lotion,
Clindesse, Clindets]
Tinidazole [Tindamax]
Suggested Reading
Castelo-Branco C et al: Management of post-menopausal vaginal atrophy and atrophic vaginitis. Maturitas.
52:S46, 2005; Dan M et al: High rate of vaginal infections caused by non-C. albicans Candida species among asymptomatic
women. Med Mycol. 40:383, 2002; Freedman MA: Female sexual dysfunction. Int J Fertil Womens
Med. 47:18, 2002; Goldstein I et al: Practical aspects in the management of vaginal atrophy and sexual dysfunction
in perimenopausal and postmenopausal women. J Sex Med. 2:154, 2005; MacNeill C et al: Clinical resistance of
recurrent Candida albicans vulvovaginitis to fluconazole in the presence and absence of in vitro resistance. J Reprod
Med. 48:63, 2003; Moller LA et al: The outcome of pelvic examinations in women 40-60 years of age with lower
urinary tract symptoms. J Obstet Gynaecol. 20:414, 2000; Sobel JD et al: Treatment of complicated Candida
vaginitis: comparison of single and sequential doses of fluconazole. Am J Obstet Gynecol. 185:363, 2001; Sobel JD
et al: Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. N Engl J Med. 351:876, 2004; Sobel
JD et al: Single oral dose fluconazole compared with conventional clotrimazole topical therapy of Candida vaginitis.
Fluconazole Vaginitis Study Group. Am J Obstet Gynecol. 172:1263, 1995.
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. For this issue,
the faculty reported nothing to disclose.
Drs. Soper and Freedman were recorded October 28-30, 2005, in Charleston, SC, at the Fifth Annual Fall Symposium:
Issues in Women’s Health, sponsored by the Medical University of South Carolina College of Medicine,
Charleston. The Audio-Digest Foundation thanks the speakers and the sponsor for their cooperation in the production
of this program.
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