JUST FOR WOMEN
From the annual Family Practice Board Review Course, sponsored by the University of California, San Francisco, School
of Medicine
Michael S. Policar, MD, Associate Professor of Obstetrics, Gynecology, and Reproductive Science, University of
California, San Francisco, School of Medicine
| Vaginal trichomoniasis: recommended drugs for treating include generic metronidazole 2 g po or tinidazole (Tindamax) 2 g
po in single dose; alternative regimen (metronidazole 500 mg po bid for 7 days) not recommended
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 | Tinidazole: no generic available; associated with fewer side effects than metronidazole and has marginally higher cure
rate for trichomoniasis, but more expensive and cannot be used in patients allergic to metronidazole; generally reserved
for those who fail to respond to metronidazole or are intolerant of it
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| Points: trichomoniasis always sexually transmitted, but carrier state exists, so patient can develop infection from any previous
or current sexual partner; microscopically examine saline suspensions of organisms rapidly, utilizing fresh saline
solution (organism sensitive to heat, light, oxygen, and osmolality of solution); to make diagnosis, organisms must be
moving; single-dose metronidazole treatment of choice; both metronidazole and tinidazole pregnancy category B, ie,
safely given to pregnant women
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| Bacterial vaginosis (BV): etiology—lactobacilli that normally live in vagina lost; anaerobic bacteria increase in concentration
and release amines that further suppress lactobacilli and produce foul-smelling discharge; hypothesis that concentration
of lactobacilli decreased by adherence to sperm, allowing for overgrowth of anaerobic organisms;
transmission—sexually associated, but not sexually transmitted; no male carrier state; however, one study suggests
BV transmitted horizontally among women who have sex with women; who should be treated—pregnant women (especially
those at high risk for preterm birth), nonpregnant symptomatic women, those planning to undergo pelvic surgery,
and possibly those planning to have intrauterine device (IUD) inserted; treatment of asymptomatic BV in
nonpregnant women controversial; however, BV associated with increased risk of acquiring and transmitting HIV, pelvic
inflammatory disease (PID), and urinary tract infections (UTIs); therefore, growing belief that asymptomatic teenagers
with BV should be treated to prevent PID
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| Treatment: includes giving metronidazole 500 mg po bid for 7 days, metronidazole gel (MetroGel) or clindamycin cream
(Cleocin cream, Clindets); metronidazole 2 g po as single dose no longer approved for BV; recurrent episodes—
defined as ≥3 episodes/yr; give metronidazole vaginal gel daily for 1 to 2 wk and twice weekly thereafter; points—
patient should abstain from sexual intercourse while being treated and avoid douching; clean sex toys between uses
and/or cover with condoms; avoid following anal intercourse immediately with vaginal intercourse
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| Diagnostic points: look for clue cells microscopically (if ≥20% of epithelial cells stippled with bacteria, patient clue cell–
positive); perform amine or whiff test by adding potassium hydroxide (KOH) to discharge (development of intense
fishy odor denotes positive test); check vaginal pH (should be between 4.5 and 6); check for “homogenized milk” vaginal
discharge; culture and Papanicolaou (Pap) test have no diagnostic value
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| Therapeutic points: metronidazole for 1 wk inexpensive, but associated with many side effects; topical agents more expensive,
but associated with fewer side effects
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| Vulvovaginal candidiasis (VVC): yeast infection; uncomplicated VVC—most cases; sporadic or infrequent; mild to moderate;
usually due to Candida albicans; typically occurs in immunocompetent women; complicated VVC—recurrent
or severe cases; may be due to species other than C albicans; more likely to occur in immunocompromised women, eg,
those with diabetes
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| Treatment regimens (approved by Centers for Disease Control and Prevention [CDC]): 7-day regimen—includes use of
miconazole (Monistat-7), terconazole (Terazol-7), or clotrimazole (Gynelotrimin-7, Mycelex) as creams or vaginal
suppositories; all used once daily at bedtime; 3-day regimen—includes double-dose versions of miconazole, terconazole,
or butoconazole (Femstat-3); 1-day regimen—includes use of clotrimazole (Mycelex G-500) 500-mg suppository,
ticonazole (Vagistat-1) ointment, miconazole (Monistat-1) suppository, butoconazole (Gynazole) cream, or single
dose of fluconazole (Diflucan) po
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| Remarks: in United States 55% of all cases treated with single-dose fluconazole (quite effective); 3- and 7-day topical regimens
equally effective in nonpregnant women; however, compliance better with 3-day regimen; therefore, speaker recommends
either 1-day or 3-day regimen, and allows patient to make decision; if therapy fails—check for possible mixed
infection; switch to another drug; confirm diagnosis with candidal culture (different from fungal culture; looks only for
Candida, takes 5 days, and identifies candidal species)
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| Women with severe VVC: characterized by erythema, excoriation, and fissures; treat with topical therapy for 1 to 2 wk or
fluconazole po twice (second dose 3 days later); immunocompromised women—use either regimen for severe VVC
(described above) or topical antimycotic agent for 1 to 2 wk; pregnant women—use only topical agent for 7 days;
women with recurrent VVC (≥ 4 symptomatic episodes/yr)—confirm diagnosis with candidal culture; have patient do
early self-treatment, ie, treat for 3 days with antifungal cream or single oral dose of fluconazole; consider suppressive
regimens (topical agent for 1-2 wk or fluconazole q72h for total of 3 doses; wash-in therapy); maintenance therapy—
fluconazole 150 mg po once or twice weekly; how speaker manages recurrent cases—topical therapy or oral fluconazole
for 1 to 2 wk, followed by oral fluconazole twice weekly for 1 mo, then weekly fluconazole
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| Observations: two-thirds of women who think they have chronic or recurrent VVC do not; suspect causation by other
species of Candida for women who are not improving; yogurt consumption or topical yogurt does not prevent or treat
yeast infections because Lactobacillus crispatus species found in vagina not present in any yougurt
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| CERVICAL CANCER SCREENING
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| Introduction: Pap test most successful cancer screening program in United States; since 1945, women have been told they
needed this test every year; however, new screening guidelines approved by various medical organizations, including
United States Preventive Services Task Force (USPSTF), now in effect
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| New guidelines: do first Pap test 3 yr after first intercourse or at 21 yr of age; discontinue test in women who have had total
hysterectomy for benign disease; USPSTF suggests upper limit for doing test 65 yr of age for “well screened women,”
whereas American Cancer Society (ACS) places upper limit at 70 yr of age in these women; remark—“well screened”
means 3 negative Pap tests over past 10 yr
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| Rationale for not screening older women: metabolically active squamous metaplasia required in transformation zone of
cervix for human papillomavirus (HPV) to “plant seeds” for dysplasia and cervical cancer; 65-yr-old women lack metabolically
active metaplasia
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| Frequency of doing Pap test: annual screening indicated for women <30 yr of age unless liquid-based cytology (LBC; less
specific) used (once every 2 yr with LBC); screening indicated every 2 to 3 yr for well screened women >30 yr of age
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| Pap test after hysterectomy: reserved for 2 circumstances, ie, history of invasive cervical cancer; presence of high-grade
squamous intraepithelial lesion (HSIL) at time of procedure (screen until 3 negative vaginal cuff Pap tests, then discontinue);
women who have had hysterectomies for benign disease never need another Pap test
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| Reasons for not doing Pap test on teenagers until they have been sexually active for 3 yr: high-grade lesions take years
to develop; minimum of 3 yr after sexual debut required for HSILs to develop and 5 yr for invasive cancers to emerge;
high-grade lesions rare in teenagers (3 cases per 1000 women 15-19 yr of age); low-grade lesions, eg, cervical intraepithelial
neoplasia 1 (CIN 1) often resolve spontaneously (91%), while 6% remain stable, and only 3% progress to high-grade
dysplasia; in teenagers, biopsy-proven CIN 2 lesions often act like CIN 1 lesions, ie, regress; guidelines recommend observation,
with treatment only if lesions remain for ≥1 yr
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| American College of Obstetricians and Gynecologists (ACOG) committee opinion: doing Pap test in teens <3 yr from
sexual debut does more harm than good; if woman <21 yr of age has atypical squamous cells of undetermined significance
(ASC-US) or low-grade squamous epithelial lesion (LSIL) on Pap test, repeat it at 6 and 12 mo or do HPV test at
1 yr; reflex HPV test not recommended; do not refer for colposcopy
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| Combined HPV and Pap test: used in women ≥30 yr of age who are immunocompetent and have cervix; caveats—
always tell women they are being screened for HPV; if Pap test negative but HPV test positive, repeat combination test in
1 yr; if both Pap and HPV negative (92% of women tested), patient must wait 3 yr before having another combination test
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| Adherence to new Pap test guidelines: not very good; study involving questionnaire sent to 355 obstetrician/gynecologists
(60% return rate)—75% of them still screening virginal women at 18 yr of age; two-thirds still doing annual Pap test in
women >35 yr of age; 80% still doing Pap tests in women who had undergone hysterectomy for benign disease; study involving
3000 physicians and nurse practitioners—≈33% doing combination Pap and HPV test routinely in women >30 yr
of age; ≈25% doing combination test in women <30 yr of age (not recommended in this age group); most explained to patient
that HPV test being done, but ≈25% of time no disclosure; 91% used HPV test after abnormal Pap test, 90% after ASC-
US (correct); 72% had done reflex HPV test after finding of atypical squamous cells:cannot exclude HSIL (ASC-H), 36%
after LSIL, and 21% after HSIL Pap tests (wrong; HPV testing of no value after ASC-H, LSIL, or HSIL); tests being overused
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| Clinical implications of new Pap test guidelines: far fewer Pap tests in women <21 yr of age and in those >65 yr of age;
half as many Pap tests if LBC used; one-third as many Pap tests if combined Pap and HPV test used and patient negative
for both; no Pap tests for women who underwent total hysterectomy for benign disease; no need for both antepartum and
postpartum Pap tests (do only one)
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| Pregnant women <21 yr of age: no Pap test needed because likelihood of invasive cervical cancer <1 in 1 million; obtain
it at postpartum visit
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| DYSFUNCTIONAL UTERINE BLEEDING AND MENOPAUSE
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| Abnormal vaginal bleeding (AVB): first suspect pregnancy in all women of reproductive age; if pregnancy not present, consider
ovulatory and anovulatory causes and medications (iatrogenic)
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| Diagnostic work-up: includes history, physical examination, and pregnancy test; if pregnancy test positive, determine if
pregnancy intrauterine or ectopic and its exact location and gestational age; if pregnancy test negative, determine if
bleeding ovulatory or anovulatory
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| Ovulatory bleeding: structural causes—include fibroids, polyps, foreign bodies in vagina, and invasive cervical cancer;
≈50% of cases of menorrhagia idiopathic; treatment modalities include endometrial ablation; nonstructural causes—
include PID, cervicitis, atrophic vaginitis, coagulopathies, luteal phase defects, and thyroid disease; iatrogenic causes—
include oral contraceptives (OCs) and overuse of anticoagulants
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| Dysfunctional uterine bleeding (DUB): anovulatory bleeding; causes—too much androgen, eg, polycystic ovary syndrome
(PCOS); acute stress; too much unopposed exogenous or endogenous estrogen (eg, estrogen-secreting ovarian tumor);
excess prolactin eg, pituitary prolactinoma; perimenarchal and perimenopausal phases of life
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| What happens in women with anovulatory bleeding: estrogen levels go up and stay up, progesterone levels stay down,
and eventually, estrogen levels start bouncing up and down; bleeding occurs when estrogen level hits trough
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| Management of DUB: involves substituting pharmacologic luteal phase for missing physiologic luteal phase; minimal
bleeding—give medroxyprogesterone (eg, Provera) or micronized progesterone (eg, Prometrium) for 10 days; moderate to
heavy bleeding >3 days—give estrogen to stabilize endometrium and progestin to cause endometrial maturation from proliferative
to secretory phase, usually with monophasic OC; give one high-dose estrogen pill (eg, Desogen) bid for 7 days,
then stop abruptly (patient will bleed); then give progesterone-only pill, tid for 7 days (taper regimen not indicated)
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| Recurrent DUB: PCOS—if pregnancy desired, give clomiphene or metformin or both; if pregnancy not sought, give OC
(regulates cycles, prevents hyperplasia, and provides contraception); 41-yr-old woman who has undergone tubal ligation
and does not desire pregnancy—give progestin-only pill 10 mg/day or micronized progesterone from days 1 to 10 of
each calendar month
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| Postmenopausal bleeding: etiologies to consider—excess of exogenous or endogenous estrogen; causes—acute stress
(adrenal androgens converted to estrogen stimulate endometrium); estrogen-secreting tumors; atrophic vaginitis; endometrial
hyperplasia or cancer; endometrial hypoplasia
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| Management: patient not on hormone therapy (HT)— evaluate endometrium with endometrial biopsy or endovaginal ultrasonography
(US) to check for hyperplasia or cancer (normal stripe <5 mm on US rules out these problems; stripe >5
mm indication for endometrial biopsy); patient on HT—do endometrial biopsy to evaluate unscheduled bleeding; if
bleeding continues 3 mo after start of HT, suspect relationship to HT
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| Indications for endometrial biopsy: postmenopausal women—suspected endometrial hyperplasia or cancer main reasons;
women likely to have hyperplasia or cancer include those with postmenopausal bleeding, women on HT with unscheduled
bleeding, women with thick stripes, and those whose Pap tests show endometrial cells or atypical glandular cells
(AGC); premenopausal women—prolonged metrorrhagia (“irregularly irregular” DUB); unexplained bleeding after intercourse;
bleeding between menstrual periods; endometrial cells on Pap test in anovulatory women; presence of endometrial
cells on AGC Pap test; myth—any woman ≥35 yr age who has abnormal bleeding should have endometrial biopsy
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| Menopause: retrospective diagnosis; defined as 1 yr of amenorrhea; surgical menopause assumed if ovaries removed or irradiated;
biomarker for menopause in women >45 yr of age is follicle-stimulating hormone (FSH) level >30 mIU/mL;
both FSH and luteinizing hormone (LH) levels required to make diagnosis in women ≤45 yr of age; newer evidence
suggests single random levels of FSH, LH, or estradiol not good indicators of menopause
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| Controversy over HT: involves results of 2 studies (eg, Women’s Health Initiative [WHI] and Estrogen/Progestin Replacement
Study [HERS]; WHI—concluded that postmenopausal women taking both estrogen and progestin have
30% increased risk for myocardial infarctions, 40% increased risk for strokes, 26% increased risk for breast cancer,
and doubling of risk for thromboembolic events; also found these women have fewer hip fractures and lower rate of
colorectal cancer; among those using estrogen alone, no difference in rates of heart disease and breast cancer, but
slightly increased risk for stroke, along with lower rate of hip fractures
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Suggested Reading
Anderson MR et al: Evaluation of vaginal complaints. JAMA 291:1368, 2004; Apgar BS et al: Treatment of menorrhagia.
Am Fam Physician 75:1813, 2007; Flynn CA et al: Bacterial vaginosis in pregnancy and the risk of prematurity: a metaanalysis.
J Fam Prac 48:885, 1999; Gabriel SR et al: Hormone replacement therapy for preventing cardiovascular disease in
postmenopausal women. Cochrane Database Syst Rev (2):CD002229, 2005; Hickey M et al: Progestogens versus estrogens
and progestogens for irregular uterine bleeding associated with anovulation. Cochrane Database Syst Rev (4):CD001895,
2007; Jeavons HS: Prevention and treatment of vulvovaginal candidiasis using exogenous Lactobacillus. J Obstet Gynecol
Neonatal Nurs 32:287, 2003; Joesoef MR, Schmid GP: Bacterial vaginosis: review of treatment options and potential clinical
indications for therapy. Clin Infect Dis 20(Suppl 1):S72, 1995; Juneja A et al: A survey of risk factors associated with
cervical cancer. Indian J Cancer 40:15, 2003; Karnon J et al: Liquid-based cytology in cervical screening: an updated rapid
and systematic review and economic analysis. Health Technol Assess 8:1, 2004; McCormack S: Vaginal microbicides. Curr
Opin Infect Dis 15:57, 2002; McFadden SE, Schumann L: The role of human papillomavirus screening for cervical cancer.
J Am Acad Nurs Pract 13:116, 2001; McLachlin CM et al: Ontario cervical cancer screening clinical practice guidelines. J
Obstet Gynaecol Can 29:344, 2007; Schlicht JR: Treatment of bacterial vaginosis. Ann Pharmacother 28:483, 1994;
Sharma A, Menton U: Screening for gynecological cancers. Eur J Surg Oncol 32:818, 2006; Sharma S: Hormone replacement
therapy in menopause: concerns and considerations. Kathmandu Univ Med J 1:228, 2003; Spinelli A: Preinvasive diseases
of cervix, vulva, and vagina. Semin Oncol Nurs 18:184, 2002; Strickland J et al: Dysfunctional uterine bleeding in
adolescents. J Pediatr Adolesc Gynecol 19:49, 2006; Walden MS: Primary care management of dysfunctional uterine bleeding.
JAAPA 19:32, 2006; Zhang ZF, Begg CB: Is Trichomonas vaginalis a cause of cervical neoplasia? Results form a combined
analysis of 24 studies. Int J Epidemiol 23:682, 1994.
Educational Objectives
| The goal of this program is to provide an update on vaginal infections, cervical cytology, dysfunctional uterine bleeding
(DUB), and the menopause. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Diagnose and treat vaginal trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis.
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| 2. Screen women for cervical cancer, utilizing the new national guidelines for the Papanicolaou test.
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| 3. Recognize the various causes of ovulatory and anovulatory DUB.
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| 4. Manage patients with dysfunctional uterine bleeding.
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| 5. Advise postmenopausal women about the benefits and drawbacks of hormonal therapy.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee 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 speaker and planning committee reported nothing to disclose.
Acknowledgements
Dr. Policar was recorded July 10, 2007, at the annual Family Medicine Board Review Course, sponsored by the University
of California, San Francisco, School of Medicine. The Audio-Digest Foundation thanks Dr. Policar and UCSF for making
this program possible.
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