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Home , Atrophic vaginitis, Bacterial vaginosis, Endometrial polyp, Hypomenorrhea, Menometrorrhagia, Nugent score

UCSF Family Medicine Board Review 2013

Vaginitis and Abnormal • There are no relevant financial relationships with any commercial interests to disclose

Michael Policar, MD, MPH Professor of Ob, Gyn, and Repro Sciences UCSF School of Medicine [email protected]

Vulvovaginal Symptoms: CDC 2010: Screening and Testing

Category Condition • Screening indications – Vaginal trichomoniasis (VT) HIV positive women: annually – (BV) Consider if “at risk”: new/, history of STI, inconsistent condom use, sex work, IDU Vulvovaginal (VVC) • Newer assays Skin Conditions Fungal (candida, tinea) – Rapid antigen test:  sensitivity, specificity vs. wet mount Contact (irritant, allergic) – Aptima TMA T. vaginalis Analyte Specific Reagent (ASR) Vulvar dermatoses (LS, LP, LSC) • Other testing situations – Vulvar intraepithelial neoplasia (VIN) Suspect trich but NaCl slide neg  culture or newer assays – Psychogenic Physiologic, psychogenic Pap with trich  confirm if low risk • Consider retesting 3 months after treatment Trichomoniasis: Laboratory Tests CDC 2010: Vaginal Trichomoniasis Treatment Test Sensitivity Specificity Cost Comment Aptima TMA +4 (98%) +3 (98%) $$$ NAAT (like GC/Ct) • Recommended regimen Culture +3 (83%) +4 (100%) $$$ Not in most labs – 2 grams PO single dose Point of care – 2 grams PO single dose •Affirm VP III +3 +4 $$$ DNA probe • Alternative regimen (preferred for HIV infected women) • OSOM Rapid +3 (90%) +4 (100%) $$ CLIA waived – Metronidazole 500 mg PO BID x 7 days st NaCl suspension +2 (56%) +4 (100%) ¢¢ 1 line • Metronidazole safe at all gestational ages Pap smear +2 +3 n/a Confirm if low – Limited data on Tinidazole prevalence • Treat sex partner(s) • Accuracy data: Huppert CID 2007 Targeted screening for other STIs: GC, Ct, syphilis, HIV

BV: Pathophysiology CDC 2010 : VT Treatment Failure • • Non-inflammatory bacterial overgrowth Re-treat with either – – 100 x increase Tinidazole 2 g PO single dose – – 1000 x increase in anaerobes Metronidazole 500 mg PO BID x 7 days – More pathogen types ( , ) • If repeat failure, treat with • Suppression of H 2O2-producing crispatus and L. – Metronidazole 2 grams po x 3-5 days jensenii (L acidophilus is not present) • If repeat failure • >50% women carry G. vaginalis in their in the – Tinidazole 2-3 g po plus 1-1.5 g vaginally x14 days absence of BV – • Arrange for susceptibility testing: Call CDC!! Bacterial “C/S” of vaginal fluid doesn’t help in the – 770-488-4115 diagnosis of BV….or of any other vaginal BV: Sexually Associated or Transmitted? BV: Clinical Diagnosis

• “Sexually associated” in heterosexuals • – Amsel Criteria : 3 or more of Rare in virginal women – – Homogenous white discharge Greater risk of BV with multiple male partners – – Condom use decreases risk, Amine odor (“whiff” test) But – pH > 4.5 (most sensitive) – No BV carrier state identified in men – Clue cells > 20% (most specific) – Treatment of partner does not affect recurrences • Spiegel criteria, : Gram stain with • Women having sex with women (WSW) – – Few or no gram positive Lactobacillus spp. Infected vaginal fluid between women causes BV – – Studies of concurrence in couples suggest Excess of other gram negative morphotypes horizontal transmission

BV: Laboratory Tests Who Should Be Tested for BV?

Test Sensit Specif Cost Comment • Routine screening (asymptomatic): not indicated Nugent score +4 +4 ¢¢ Labor intensive • Standard diagnostic testing Point of care tests – Check discharge, amines, vaginal pH, clue cells  Affirm VP III +4 +3 $$$ DNA probe • not available or inconclusive  OSOM BV Blue +3 +3 $$ CLIA moderate – Affirm VP III –  G vag PIP +2 +3 $$$ CLIA moderate OSOM BV Blue – G vaginalis PIP, pH+amine test cards pH + amines +2 +2 $ CLIA waived • st “Shift in vaginal flora” on cervical cytology Amsel criteria +3 +2 ¢¢ 1 line – No consensus, but poor correlation with BV…most experts Pap smear +1 +2-3 n/a Coccobacilli recommend no further follow up CDC 2010: BV Treatment CDC 2010: Recurrent BV Recommended regimens – Metronidazole 500 mg PO BID x 7 days • Consider suppression with metronidazole vaginal gel twice – Metronidazole gel 0.75% 5g per QD x 5 days weekly for 4-6 months (after full initial treatment) – 2% cream 5g per vagina QHS x 7 days • No evidence yet to support use of • Alternative regimens Don’t …with anything! – Tinidazole 2 g PO QD for 3 days • Use of condoms by male partners may reduce recurrences • – Tinidazole 1 g PO QD for 5 days Clean sex toys (or use condoms) between uses • – Clindamycin 300 mg PO BID x 7 days Avoid vaginal insertion after anal insertion of a finger or – Clindamycin ovules 100 mg per vagina QHS x 3 days

CDC 2010: VVC Classification VVC: Laboratory • • Uncomplicated VVC (80-90%) KOH suspension − – Sporadic or infrequent VVC, and C. albicans: pseudohyphae and blastospores (buds) − – Mild-to-moderate VVC, and C. glabrata: blastospores only • – Likely to be , and NaCl suspension : many WBC, normal lactobacillus • – Immunecompetant pH : 4-6 • • Complicated VVC (10-20%) Amine test : negative • – Recurrent VVC, or Confirmatory tests - – Severe VVC, or Point of care test: Affirm VP III - – Non-albicans candidiasis, or Candida culture ( not: fungus culture) - – Uncontrolled DM, immunosuppression, pregnancy Candida PCR Treatments for VVC CDC 2010: Uncomplicated VVC Treatments

• Non-pregnant women Drug OTC Prescription – 3 and 7 day topicals have equal efficacy and price Length of 7 d 3 d 1 d 7 d 3 d 1 d – Treatment Offer either : 1 or 3 day topical or oral fluconazole • Butoconazole X Topical: quickly soothing, but inconvenient • X X X Oral: convenient, but effect is not immediate • Miconazole X X X If first treatment course fails – Terconazole X X Re-confirm diagnosis (r/o dual infection) – Treat with an alternate drug X X – Perform Candida culture to confirm and speciate Fluconazole (PO) X • No role for nystatin, candicidin

CDC 2010: Complicated VVC Treatment CDC 2010: Complicated VVC Treatment

Severe VVC Recurrent VVC (RVVC) • • Advanced findings: , excoriation, fissures > 4 episodes of symptomatic VVC per year • • Topical azole therapy for 7-14 days, or Most women have no predisposing condition – Compromised host Partners are rarely source of infection • • Topical azole treatment for 7-14 days Confirm with Candidal culture before maintenance therapy; • Fluconazole 150 mg PO; repeat Q3 days 1-2 times also check for non-albicans species • Pregnancy Early treatment regimen: self- 3 days with onset of symptoms • Topical azoles for 7 days CDC 2010: Complicated VVC Treatment Vaginal Bleeding…What’s Normal?

• • Recurrent VVC: Treatment Onset of menses – o – Treat for 7-14 days of topical therapy or fluconazole 150 By 16 years old with 2 sex characteristics mg PO q 72 o x3 doses , then – Start evaluation at 14 years of age if no sexual – Maintenance therapy x 6 months development • Fluconazole 100-200 mg PO 1-2 per week • Cycle length: 24-35 days • Itraconazole 100 mg/wk or 400 mg/month • Menstrual days: 2-7 days • Clotrimazole 500 mg suppos 1 per week • Menstrual flow: 20-80 cc. per menses • Boric 600 mg suppos QD x14, then BIW – Average flow: 35 cc. per menses • Gentian violet: Q week x2, Q month X 3-6 mo

Abnormal Vaginal Bleeding (AVB) Abnormal Vaginal Bleeding (AVB) Symptom Definitions Symptom Definitions

• Abnormal amount of bleeding • Abnormal amount of bleeding – Menorrhagia (hypermenorrhea) – Menorrhagia (hypermenorrhea) •Prolonged duration of menses •Prolonged duration of menses •Increased amount of bleeding per day •Increased amount of bleeding per day – – Hypomenorrhea •Shorter menses •Shorter menses •Less flow per day •Less flow per day Abnormal Vaginal Bleeding Abnormal Vaginal Bleeding Symptom Definitions Symptom Definitions

• Abnormal timing of bleeding: REGULAR Cycles • Abnormal timing of bleeding: IRREGULAR Cycles – Polymenorrhea: cycle length < 24 days – Metrorrhagia • 7 days 14 days 7 days14 days 7 days Light “irregularly irregular” bleeding – – : (IMB) 21 days • Heavy “irregularly irregular” bleeding 7 days 7 days 7 days – Post-coital bleeding (PCB) 7 days 3 2 10 days 2 4

7 days 7 days 7 days – Post-menopausal: bleeding >1 year after intercourse intercourse

Abnormal Vaginal Bleeding Abnormal Vaginal Bleeding (AVB) Symptom Definitions  Is the patient pregnant?  Is it uterine? • Decreased frequency of bleeding  Is the bleeding pattern ovulatory or anovulatory? – •No bleeding 36 days- 3 months Ovulatory = Regular Anovulatory = Irregular or no – • Menorrhagia bleeding • • •No bleeding for… Hypomenorrhea Metrorrhagia/ MMR • •  3 cycle intervals or Polymenorrhea Oligomenorrhea • • Amenorrhea  6 months (in oligomenorrheic women) IMB • • PCB Post-menopausal Hx, PE, Abnormal Vaginal Preg test Bleeding (AVB) Non-Uterine Conditions:

Preg test POS Preg test NEG • Cervix : IMB, PCB, PMB – Squamous cell carcinoma Pregnant Pelvic Exam – • Location Abnl Uterine bleeding Non-uterine bleeding • Infections: IMB, PCB, menorrhagia • Viability – Mucopurulent (, , • GA Dating Cervix VaginaUrethra Anus hominis) • Benign cervical ectropion: PCB – Exposed columnar epithelial cells on ectocervix – Red appearance; bleeds to touch

Non-Uterine Conditions: Vagina Non-Uterine Conditions: Other

• Vaginal (IMB, PCB, PMB) • (post-void bleeding) – Atrophic – Urethral caruncle – Severe vaginal trichomoniasis – Squamous or transitional cell • Trauma/ • – Anus (bleeding after wiping) Vaginal wall laceration ( PCB) – – External or internal hemorrhoid Hymeneal ring tear/laceration (PCB) – – Anal fissure Vaginal foreign body (esp. pre-menarchal bleeding) – • Vaginal neoplasms Genital warts – – Squamous cell cancer, clear cell (DES) Squamous cell cancer – Childhood tumors Hx, PE, Abnormal Vaginal FIGO System for AUB, 2011 Preg test Bleeding Structural Non-Structural

Preg test POS Preg test NEG

Pregnant Pelvic Exam

•Location Abnormal Uterine Bleeding Non-uterine bleeding •Viability •GA Dating Cervix VaginaUrethra Anus

Structural Non-structural Munro MG, et al, FIGO classification system (PALM-COEIN) for causes of (PALM) (COEIN) abnormal uterine bleeding in nongravid women of reproductive age, Int J Gynecol Obstet (2011)

AUB: Structural Conditions AUB: Structural Conditions

• • P: Endometrial M: Malignancy and hyperplasia –   – IMB or PCB in 30-50 year old woman Adenomatous hyperplasia (AH) atypical AH • A: endometrial carcinoma • – , , chronic , Post-menopausal bleeding • sometimes menorrhagia Recurrent perimenopausal metrorrhagia • • L: Leiomyoma Chronic anovulator (PCOS) with metrorrhagia – – Submucous myoma Leiomyosarcoma • – Menorrhagia; rarely IMB; never metrorrhagia Post-menopausal bleeding COEIN: Coagulopathy COEIN: Coagulopathy Screen for underlying disorder of hemostasis if any of • • since Clotting factor deficiency or defect • – One of the following Liver – Post-partum hemorrhage – Congenital (Von Willebrands Disease) – Bleeding associated with surgery • Platelet deficiency (thrombocytopenia) with platelet – Bleeding associated with dental work count <20,000/mm 3 • Two or more of the following – – Idiopathic thrombocytopenic purpura (ITP) Bruising 1-2 times per month – Epistaxis 1-2 times per month – Aplastic – Frequent gum bleeding • Platelet function defects – Family history of bleeding symptoms

Munro M, Int J Gynecol Obstet (2011)

COEIN: Ovulatory Normal Ovarian Hormone Cycle Precipitous drop of E+P • Synchronous • • Universal – Age: peri-menarche and perimenopuse Withdrawal Bleed – PCOS – Stress • Hypothyroidism • defects

menses Abnormal Ovarian Hormone Cycles COEIN: Ovulatory

• Mainly due to anovulatory bleeding Estrogen – Age-related : peri-menarche, perimenopause Amenorrhea – Estrogenic : unopposed exogenous or endogenous estrogen – Androgenic : PCOS; CAH, acute stress E withdrawal bleed – Systemic : Renal disease, liver disease Progesterone • Diagnosis of exclusion – Menometrorrhagia not due to by anatomic lesion, anovulation Menometrorrhagia: , pregnancy heavy, irregular bleeding

COEIN: Ovulatory COEIN: Ovulatory • Hyperthyroidism or hypothyroidism • Luteal Phase Defect (LPD) – Bleeding can be excessive, light, or irregular – Luteal phase lasts 7-10 days (vs. 14 days) or inadequate – Only severe, uncorrected thyroid disease causes peak luteal phase progesterone (P) abnormal bleeding patterns • Diagnosis – Normal pattern when corrected to euthyroid – Polymenorrhea (“periods every 2 weeks”) – o o 1 hypothyroidism assoc. with 2 amenorrhea – Mid-luteal phase P level between 4-8 ng/ml    Low T 4 high TRH high TSH normal T 4 – >2 days out of phase • Management high PRL amenorrhea + galactorrhea – Unexplained : clomiphene, P supplement – Pregnancy not desired: observation or OCs to cycle CO EIN: Endometrial COE IN: Iatrogenic Conditions • Idiopathic • Anticoagulants – Unexplained menorrhagia – Over-anticoagulation: menorrhagia • – Therapeutic levels will not cause bleeding problems – Post-partum • Chronic steroids, opiates – Post-abortal endometritis • Progestin-containing contraceptives – Endometritis component of PID • Intrauterine Contraception (IUC) • In teens, PID commonly presents with abnormal bleeding – "Normal" side effect menorrhagia (menorrhagia, IMB), not pelvic pain – PID, pregnancy (IUP or ectopic), perforation, expulsion – Any teen with abnormal bleeding + pelvic pain requires bimanual exam to evaluate for PID

AVB: History COEI N: Not Classified • • Is the patient pregnant? Chronic endometritis – Pregnancy symptoms, esp. breast tenderness • AVM – Intercourse pattern • Myometrial hypertrophy – Contraceptive use • Is it uterine? – Coincidence with bowel movement and wiping, during or after – Pain or of vagina, introitus, , perinuem, or anal skin AVB: History AVB: Physical Exam

• Is bleeding ovulatory or anovulatory? • General: BMI > 30 – Bleeding pattern: regular, irregular, none • Skin: acne, hirsutism, acanthosis nigricans; bruising – Molimenal symptoms: only in ovulatory cycles • Breasts: galactorrhea – Previous history of menstrual disorders • Abdomen: uterine enlargement, abdominal pain – Recent onset weight gain or hirsuitism • Pelvic exam – Menopausal symptoms – Vulva and – History of excess bleeding; coagulation disorders – Anal and peri-anal skin – Current and past medications; street drugs – Speculum: vaginal walls and cervix – Chronic medical illnesses or conditions – Bimanual: uterine enlargement, softness, masses – Nipple discharge from breasts

AVB: Laboratory AVB: Imaging Studies

• Urine highly sensitive • Mainly for evaluation of ovulatory AUB if no response – Quantitative B-hCG is unnecessary to treatment or suspect anatomic defect • CBC • Not useful for demonstrating or excluding hyperplasia in – Find severe anemia; baseline value for observation – premenopausal women Platelet estimation (detect thrombocytopenia) • • Saline infusion sonogram (SIS) helpful for polyps, sub- TSH, mucus myomata – Amenorrhea or recurrent anovulatory bleeds only – • 80% sensitivity, 69% specificity compared to FSH, LH levels are unnecessary AVB: Presentation-based Management Management of Acute DUB

• • Substitute a pharmacologic luteal phase for missed Acute dysfunctional (anovulatory) bleeding physiologic luteal phase • Recurrent dysfunctional bleeding • If minimal bleeding for a few days • Post-coital bleeding – Rx MPA 10-20 mg QD (or microP, 200 BID) x10d • Recurrent (ovulatory) menorrhagia – Bleeding stops < 3 d; menses after progestin ended • • Postmenopausal bleeding (PMB) Moderate or heavy bleeding > 3 days – Monophasic OC taken BID-TID x 7 days, then daily OC for 3 weeks (or longer) – Using “OC taper” and then stopping is illogical Note: a menstrual calendar will help to differentiate • Torrential bleed : surgical curettage (MUA) these conditions

Oral MPA and COCs for Acute Uterine Bleeding Management of Recurrent DUB Munro MG, et al Obstet Gynecol 2006;108:924-9 • Pregnancy: cycle with clomiphene or metformin • Contraception: cycle with OC • 40 women with non-anatomic AUB randomized to • – Not interested in pregnancy or contraception MPA 20 mg TID, then QD for 3 weeks vs – MPA or microP first 10-14 days each month or every other – COC (1 mg nor + 35 mcg EE) TID x1 week, QD x3 wks month if pt prefers fewer menses • Results – Place LNG-IUS (Mirena) – Median time to bleeding cessation was 3 days – Consider endometrial ablation if childbearing completed – Cessation in 88% OC group, 76% in MPA group • Perimenopausal bleeding – Surgery avoided in 100% MPA, 95% COC subjects – Once hyperplasia excluded, the goal is cycle control – Compliance similar in both groups • Low estrogen dose OC – “Would use again”…81% MPA, 69% COC • Cyclic sequential EPT Recurrent Menorrhagia Recurrent Menorrhagia • • Differential diagnosis Submucous myoma (fibroids) – – Medical: OCs, progestins, tranexamic acid – – Submucus myoma LNG-IUS (Mirena) – – Coagulpathy: vWD, ITP, liver disease Myomectomy • – Idiopathic Laparoscopy, hysteroscopy, or laparotomy – • Diagnostic Uterine artery embolization (UAE) – – Coag panel: consult with hematologist (VH, LAVH, LASH) – – Saline Infusion Sonography (SIS) GnRH-a (Lupron) is given for 1-3 months only • – Hysteroscopy To facilitate surgery by reducing myoma volume • – NOT endometrial biopsy or pelvic US alone To induce amenorrhea to treat severe anemia

Recurrent Menorrhagia Tranexamic Acid (Lysteda) for HMB

• Idiopathic menorrhagia • FDA: treatment of cyclic heavy menstrual bleeding – Oral contraceptives (extended regimen or cycle) • Mechanism of action is antifibrinolytic • – NSAIDS (before and during menses) Use: 1,300 mg (two 650 mg tablets) TID for up to 5 days • • Ibuprofen (400 mg tid), naproxen Na (275 mg every 6 Contraindications hours after a loading dose of 550 mg) – Active thromboembolic disease – – LNG intrauterine system (Mirena) History or intrinsic risk of DVT • – Tranexamic acid (Lysteda) Cautions – – Endometrial ablation Concomitant therapy with OCs may further increase the risk of blood clots, stroke, or MI – Hysterectomy (VH, LAVH, LASH) – Women using CHC should use only if a strong medical need and benefit outweighs risk of TE event Endometrial Ablation vs Hysterectomy Global Endometrial Ablation • Advantages • Bipolar Dessication (NovaSure ™) – Office procedure or outpatient surgery – • Cryoablation (Her Option™) Very low rate of major complications • – Rapid post operative recovery period Thermal Balloon (Thermachoice ™, Caviturm®) – • Less time consuming and costly vs hysterectomy Microwave Endometrial Ablation (Microsulis) • • Disadvantages Hydrothermal Ablation (Hydro ThermAblator ™) – Amenorrhea in 50-70%, but >95% have less bleeding • Radiofrequency Thermal Balloon – May fail over time; 2nd ablation required in 5-10% – Reduces fertility, but not highly effective contraception – Cervical, may occur