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Home , Adenomyosis, Bacterial vaginosis, Endometrial hyperplasia, Vaginitis

UCSF Family Medicine Board Review March 16, 2014

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

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

Vulvovaginal Symptoms:

Category Condition Vaginal (VT) (BV) Vulvovaginal (VVC) MMWR 2010; 59 (RR-12): 1 Skin Conditions Fungal (candida, tinea) Contact (irritant, allergic) Vulvar dermatoses (LS, LP, LSC) Vulvar intraepithelial neoplasia (VIN) Psychogenic Physiologic, psychogenic Updated Guidelines to Be Published in 2015 CDC 2010: Trichomoniasis Screening and Testing Trichomoniasis: Laboratory Tests

Test Sensitivity Specificity Cost Comment • Screening indications – HIV positive women: annually Aptima TMA +4 (98%) +3 (98%) $$$ NAAT (like GC/Ct) – Consider if “at risk”: new/, history of STI, Culture +3 (83%) +4 (100%) $$$ Not in most labs inconsistent condom use, sex work, IDU Point of care • Newer assays •Affirm VP III +3 +4 $$$ DNA probe –  Rapid antigen test: sensitivity, specificity vs. wet mount •OSOM Rapid +3 (90%) +4 (100%) $$ CLIA waived – Aptima TMA T. vaginalis Analyte Specific Reagent (ASR) NaCl suspension +2 (56%) +4 (100%) ¢¢ 1st line • Other testing situations Pap smear +2 +3 n/a Confirm if low –  Suspect trich but NaCl slide neg culture or newer assays prevalence – Pap with trich  confirm if low risk • Consider retesting 3 months after treatment Accuracy data: Huppert CID 2007

CDC 2010: VT Treatment CDC 2010 : VT Treatment Failure

• • Recommended regimen Re-treat with either – – 2 grams PO single dose 2 g PO single dose – – Tinidazole 2 grams PO single dose Metronidazole 500 mg PO BID x 7 days • • Alternative regimen (preferred for HIV infected women) If repeat failure, treat with – – Metronidazole 500 mg PO BID x 7 days Metronidazole 2 grams PO x 3-5 days • Metronidazole safe at all gestational ages • If repeat failure – Limited data on Tinidazole – Tinidazole 2-3 g PO plus 1-1.5 g vaginally x14 days • Treat sex partner(s) • Arrange for susceptibility testing: Call CDC!! • Targeted screening for other STIs: GC, Ct, syphilis, HIV – 770-488-4115 BV: Pathophysiology BV: Sexually Associated or Transmitted ? • • Non-inflammatory bacterial overgrowth “Sexually associated” in heterosexuals – – 100 x increase Rare in virginal women – – 1000 x increase in anaerobes Greater risk of BV with multiple male partners – – More pathogen types ( , ) Condom use decreases risk • But Suppression of H 2O2-producing crispatus and L. – jensenii No BV carrier state identified in men – • >50% women carry G. vaginalis in their Treatment of male partner does not affect recurrences – • Women having sex with women (WSW) Bacterial “C/S” of vaginal fluid doesn’t help in the – diagnosis of BV….or of any other vaginal Infected vaginal fluid between women causes BV – BV concurrence in WSW couples suggests horizontal transmission

BV: Clinical Diagnosis Characteristic Discharge With BV

• Amsel Criteria : 3 or more of – Homogenous white discharge – Amine odor (“whiff” test) – pH > 4.5 (most sensitive) – Clue cells > 20% (most specific) • Spiegel criteria  – Gram stain with •Few or no gram positive Lactobacillus spp. •Excess of gram negative morphotypes BV: Clue Cells on Saline Suspension NOT a clue cell NaCl Slide: BV >20% of Saline: 40X epithelial objective cells are Clue cells clues

Reduced Source : Seattle STD/HIV Lactobacilli Prevention Training Center at the University of Washington Ragged cell border NOT a clue cell

BV: Laboratory Tests

Test Sensit Specif Cost Comment Nugent score +4 +4 ¢¢ Labor intensive Point of care tests  Affirm VP III +4 +3 $$$ DNA probe  OSOM BV Blue +3 +3 $$ CLIA moderate  G vag PIP +2 +3 $$$ CLIA moderate pH + amines +2 +2 $ CLIA waived Amsel criteria +3 +2 ¢¢ 1st line Pap smear +1 +2-3 n/a Coccobacilli Who Should Be Tested for BV? CDC 2010: BV Treatment

• Routine screening not indicated Recommended regimens • Diagnostic testing – Metronidazole 500 mg PO BID x 7 days – Check discharge, amines, vaginal pH, clue cells – Metronidazole gel 0.75% 5g per QD x 5 days • not available or inconclusive – 2% cream 5g per vagina QHS x 7 days – Affirm VP III Alternative regimens – OSOM BV Blue – Tinidazole 2 g PO QD for 3 days – G vaginalis PIP, pH + amine test cards – Tinidazole 1 g PO QD for 5 days • “Shift in vaginal flora” on cervical cytology – Clindamycin 300 mg PO BID x 7 days – No consensus, but poor correlation with BV…most experts – Clindamycin ovules 100 mg per vagina QHS x 3 days recommend no further follow up

CDC 2010: VVC Classification CDC 2010: Recurrent BV • Uncomplicated VVC (80-90%) • Consider suppression with metronidazole vaginal gel twice – Sporadic or infrequent VVC, and weekly for 4-6 months (after full initial treatment) – Mild-to-moderate VVC, and • No evidence yet to support use of – Likely to be , and • Don’t …with anything! – Immunecompetent • • Use of condoms by male partners may reduce recurrences Complicated VVC (10-20%) – • Clean sex toys (or use condoms) between uses Recurrent VVC, or – • Avoid vaginal insertion after anal insertion of a finger or Severe VVC, or – Non-albicans candidiasis, or – Uncontrolled DM, immunosuppression, pregnancy VVC: Laboratory

• KOH suspension Candidal − C. albicans: pseudohyphae and blastospores (buds) Pseudo- − C. glabrata: blastospores only hyphae • NaCl suspension : many WBC, normal lactobacillus • pH : 4-6 10% KOH: 10X objective • Amine test : negative • Confirmatory tests Source - : Seattle STD/HIV Point of care test: Affirm VP III Prevention Training Center - Candida culture ( not: fungus culture) at the University of - Candida PCR Washington

Yeast CDC: Treatments for VVC PMNs and pseudohyphae Drug OTC Prescription Pseudohyphae Length of 7 d 3 d 1 d 7 d 3 d 1 d Treatment Saline: 40X PMNs Yeast Butoconazole X objective buds Clotrimazole X X X Miconazole X X X Source : Seattle STD/HIV Prevention Terconazole X X Training Center at the X X University of Washington Squamous epithelial cells Fluconazole (PO) X CDC 2010: Uncomplicated VVC Treatments CDC 2010: Complicated VVC Treatment

• Non-pregnant women Severe VVC – 3 and 7 day topicals have equal efficacy and price • Advanced findings: , excoriation, fissures – Offer either : 1 or 3 day topical or oral fluconazole • Topical azole therapy for 7-14 days, or • Topical: quickly soothing, but inconvenient Compromised host • Oral: convenient, but effect is not immediate • Topical azole treatment for 7-14 days • If first treatment course fails • Fluconazole 150 mg PO; repeat Q3 days 1-2 times – Re-confirm diagnosis (r/o dual infection) Pregnancy – Treat with an alternate drug • Topical azoles for 7 days – Perform Candida culture to confirm and speciate • No role for nystatin, candicidin

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

Recurrent VVC (RVVC) • Recurrent VVC: Treatment • > 4 episodes of symptomatic VVC per year – Treat for 7-14 days of topical therapy or fluconazole 150 o • Most women have no predisposing condition mg PO q 72 x3 doses , then – – Screen for HIV and Type 2 DM if risk factors Maintenance therapy x 6 months • – Partners are rarely source of infection Fluconazole 100-200 mg PO 1-2 per week • Itraconazole 100 mg/wk or 400 mg/month • Confirm with Candidal culture before maintenance therapy; • also checks for non-albicans species Clotrimazole 500 mg suppos 1 per week • • Early treatment regimen: self- 3 days with onset Boric 600 mg suppos QD x14, then BIW • of symptoms Gentian violet: Q week x2, Q month X 3-6 mo …What’s Normal? Abnormal Vaginal Bleeding (AVB) Symptom Definitions • Onset of menses • – By 16 years old with 2o sex characteristics Abnormal amount of bleeding – – Start evaluation at 14 years of age if no sexual Menorrhagia (hypermenorrhea) • development Prolonged duration of menses • • Cycle length: 24-35 days Increased amount of bleeding per day – • Menstrual days: 2-7 days • • Menstrual flow: 20-80 cc. per menses Shorter menses • – Average flow: 35 cc. per menses Less flow per day

Abnormal Vaginal Bleeding Abnormal Vaginal Bleeding (AVB) Symptom Definitions Symptom Definitions • Abnormal timing of bleeding: REGULAR Cycles • Abnormal amount of bleeding – – Menorrhagia (hypermenorrhea) Polymenorrhea: cycle length < 24 days •Prolonged duration of menses 7 days 14 days 7 days14 days 7 days •Increased amount of bleeding per day – : (IMB) – 21 days Hypomenorrhea 7 days 7 days 7 days • Shorter menses – Post-coital bleeding (PCB) •Less flow per day 7 days 7 days 7 days intercourse intercourse Abnormal Vaginal Bleeding Abnormal Vaginal Bleeding Symptom Definitions Symptom Definitions

• Abnormal timing of bleeding: IRREGULAR Cycles • Decreased frequency of bleeding – Metrorrhagia – • Light “irregularly irregular” bleeding •No bleeding 36 days- 3 months – – • Heavy “irregularly irregular” bleeding •No bleeding for…  7 days 3 2 10 days 2 4 3 cycle intervals or  6 months (in oligomenorrheic women) – Post-menopausal: bleeding >1 year after

Abnormal Vaginal Bleeding (AVB) Hx, PE, Abnormal Vaginal Preg test Bleeding (AVB)  Is the patient pregnant?  Is it uterine? Preg test POS Preg test NEG  Is the bleeding pattern ovulatory or anovulatory? Pregnant Pelvic Exam Ovulatory = Regular Anovulatory = Irregular or no • Location Abnl Uterine bleeding Non-uterine bleeding • Menorrhagia bleeding • • Viability • Hypomenorrhea Metrorrhagia/ MMR • GA Dating • VaginaUrethra Anus • Polymenorrhea Oligomenorrhea • • IMB Amenorrhea • • PCB Post-menopausal Non-Uterine Conditions: Cervix Non-Uterine Conditions: Vagina

• • Vaginal (IMB, PCB, PMB) Cervix Neoplasms: IMB, PCB, PMB – – Atrophic Squamous cell carcinoma – – Severe vaginal trichomoniasis Adenocarcinoma • Trauma/ • Infections: IMB, PCB, menorrhagia – Vaginal wall laceration ( PCB) – Mucopurulent (, , – Hymeneal ring tear/laceration (PCB) ) – Vaginal foreign body (esp. pre-menarchal bleeding) • Benign cervical ectropion: PCB • Vaginal neoplasms – Exposed columnar epithelial cells on ectocervix – Squamous cell , clear cell (DES) – Red appearance; bleeds to touch – Childhood tumors

Hx, PE, Abnormal Vaginal Non-Uterine Conditions: Other Preg test Bleeding

• (post-void bleeding) Preg test POS Preg test NEG – Urethral caruncle Pelvic Exam – Squamous or transitional cell cancer Pregnant • Anus (bleeding after wiping) •Location Abnormal Uterine Bleeding Non-uterine bleeding – External or internal hemorrhoid •Viability •GA Dating – Anal fissure Cervix VaginaUrethra Anus – Genital warts – Squamous cell cancer Structural Non-structural (PALM) (COEIN) FIGO System for AUB, 2011 Structural Non-Structural AUB: Structural Conditions

• P: – IMB or PCB in 30-50 year old woman • A: – , , chronic , sometimes menorrhagia • L: Leiomyoma – Submucous myoma – Munro MG, et al, FIGO classification system (PALM-COEIN) for causes of Menorrhagia; rarely IMB; never metrorrhagia abnormal uterine bleeding in nongravid women of reproductive age, Int J Gynecol Obstet (2011)

AUB: Structural Conditions COEIN: Coagulopathy

• M: Malignancy and • Clotting factor deficiency or defect – Adenomatous hyperplasia (AH) atypical AH  – Liver endometrial carcinoma – Congenital (Von Willebrands Disease) •Post-menopausal bleeding • Platelet deficiency (thrombocytopenia) with platelet •Recurrent perimenopausal metrorrhagia count <20,000/mm 3 •Chronic anovulator (PCOS) with metrorrhagia – Idiopathic thrombocytopenic purpura (ITP) – Leiomyosarcoma – Aplastic •Post-menopausal bleeding • Platelet function defects COEIN: Ovulatory COEIN: Ovulatory • Mainly due to anovulatory bleeding • – Age-related : peri-menarche, perimenopause • Hypothyroidism – Estrogenic : unopposed exogenous or endogenous • Luteal phase defects – Androgenic : PCOS; CAH, acute stress – Systemic : Renal disease, liver disease • Diagnosis of exclusion – Menometrorrhagia not due to by anatomic lesion, , pregnancy

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 AVB: History

• Is bleeding ovulatory or anovulatory? • Is the patient pregnant? – Bleeding pattern: regular, irregular, none – Pregnancy symptoms, esp. breast tenderness – Molimenal symptoms: only in ovulatory cycles – Intercourse pattern – Previous history of menstrual disorders – Contraceptive use – Recent onset weight gain or hirsuitism • Is it uterine? – Menopausal symptoms – Coincidence with bowel movement and wiping, during or – History of excess bleeding; coagulation disorders after urination – – Current and past medications; street drugs Pain or of vagina, introitus, , perinuem, or – anal skin Chronic medical illnesses or conditions – Nipple discharge from breasts

AVB: Physical Exam AVB: Laboratory

• • General: BMI > 30 Urine highly sensitive pregnancy test – • Skin: acne, hirsutism, acanthosis nigricans; bruising Quantitative B-hCG is unnecessary • • Breasts: galactorrhea CBC • Abdomen: uterine enlargement, abdominal pain – Find severe anemia; baseline value for observation • Pelvic exam – Platelet estimation (detect thrombocytopenia) – Vulva and • TSH, Prolactin – Anal and peri-anal skin – Amenorrhea or recurrent anovulatory bleeds only – Speculum: vaginal walls and cervix • FSH, LH levels are unnecessary – Bimanual: uterine enlargement, softness, masses Who Needs an EMB? Who Needs an EMB?

• Purpose: detect or cancer • Menopausal woman • Premenopausal women – Any postmenopausal bleeding, if not using HT – Prolonged metro rrhagia – Unscheduled bleeding on continuous-sequential – Unexplained post-coital or intermenstrual bleeding hormone therapy – Endometrial cells on Pap smear in anovulatory – Bleeding > 3 mo after start of continuous-combined premenopausal woman hormone therapy – Abnormal glandular cells (AGC) Pap – Endometrial stripe > 5 mm (applies to postmenopausal • Abnormal endometrial cells woman only) • Older than 35 years old – Pap smear: any endometrial cells or AGC Pap • < 35 years old with abnormal bleeding

Tips for Internal Os Stenosis

• Pain relief – Use para-cervical or intra-cervical block – Intrauterine instillation of lidocaine • Cervical dilation – Grasp sampler with sponge forceps 3-4 cm from tip – Freeze endometrial sampler to increase rigidity – Use cervical “os finder” device – Use small size Pratt or Hegar dilators – No studies to support misoprostol; not helpful for IUCs AVB: Imaging Studies AVB: Presentation-based Management

• Mainly for evaluation of ovulatory AUB if no response • Acute dysfunctional (anovulatory) bleeding to treatment or suspect anatomic defect • • Recurrent dysfunctional bleeding Not useful for demonstrating or excluding hyperplasia in • premenopausal women Post-coital bleeding • • Saline infusion sonogram (SIS) helpful for polyps, sub- Recurrent (ovulatory) menorrhagia • mucus myomata Postmenopausal bleeding (PMB) – 80% sensitivity, 69% specificity compared to Note: a menstrual calendar will help to differentiate these conditions

Management of Acute DUB Oral MPA and COCs for Acute Uterine Bleeding Munro MG, et al Obstet Gynecol 2006;108:924-9 • Substitute a pharmacologic luteal phase for missed • physiologic luteal phase 40 women with non-anatomic AUB randomized to – • If minimal bleeding for a few days MPA 20 mg TID, then QD for 3 weeks vs – Rx MPA 10-20 mg QD (or microP, 200 BID) x10d – COC (1 mg nor + 35 mcg EE) TID x1 week, QD x3 wks – Bleeding stops < 3 d; menses after progestin ended • Results • Moderate or heavy bleeding > 3 days – Median time to bleeding cessation was 3 days – Monophasic OC taken BID-TID x 7 days, then daily OC for 3 – Cessation in 88% OC group, 76% in MPA group weeks (or longer) – Surgery avoided in 100% MPA, 95% COC subjects – Using “OC taper” and then stopping is illogical – Compliance similar in both groups • Torrential bleed : surgical curettage (MUA) – “Would use again”…81% MPA, 69% COC Management of Recurrent DUB Recurrent Menorrhagia • Pregnancy: cycle with clomiphene or metformin • Differential diagnosis • Contraception: cycle with OC – Endometrial polyp • Not interested in pregnancy or contraception – Submucus myoma – MPA or microP first 10-14 days each month or every other – Coagulpathy: vWD, ITP, liver disease month if pt prefers fewer menses – – Place LNG-IUS (Mirena) Idiopathic • Diagnostic – Consider endometrial if childbearing completed – Coag panel: consult with hematologist • Perimenopausal bleeding – Saline Infusion Sonography (SIS) – Once hyperplasia excluded, the goal is cycle control – Hysteroscopy • Low estrogen dose OC – NOT or pelvic US alone • Cyclic sequential EPT

Recurrent Menorrhagia Recurrent Menorrhagia

• Submucous myoma (fibroids) • Idiopathic menorrhagia – Medical: OCs, progestins, tranexamic acid – Oral contraceptives (extended regimen or cycle) – LNG-IUS (Mirena) – NSAIDS (before and during menses) – Myomectomy • (400 mg tid), Na (275 mg every 6 • , hysteroscopy, or laparotomy hours after a loading dose of 550 mg) – Uterine artery embolization (UAE) – LNG intrauterine system (Mirena) – (VH, LAVH, LASH) – Tranexamic acid (Lysteda) – GnRH-a (Lupron) is given for 1-3 months only – • To facilitate surgery by reducing myoma volume – Hysterectomy (VH, LAVH, LASH) • To induce amenorrhea to treat severe anemia Tranexamic Acid (Lysteda) for HMB Global Endometrial Ablation • FDA: treatment of cyclic • Mechanism of action is antifibrinolytic • Bipolar Dessication (NovaSure ™) • Use: 1,300 mg (two 650 mg tablets) TID for up to 5 days • • (Her Option™) Contraindications • – Thermal Balloon (Thermachoice ™, Caviturm®) Active thromboembolic disease • – History or intrinsic risk of DVT Microwave Endometrial Ablation (Microsulis) • • Cautions Hydrothermal Ablation (Hydro ThermAblator ™) – Concomitant therapy with OCs may further increase the • Radiofrequency Thermal Balloon risk of blood clots, stroke, or MI – Women using CHC should use only if a strong medical need and benefit outweighs risk of TE event