Abnormal Uterine Bleeding Common in women of all agesCommon in women of all ages ~5% women of reproductive age seek ~5% women of reproductive age seek

help annuallyhelp annually Life phase determines most likely Life phase determines most likely

cause, and the likelihood of serious cause, and the likelihood of serious pathologypathology

Take your time to properly assess the Take your time to properly assess the problemproblem

Work-up and treat in a rational mannerWork-up and treat in a rational manner

Complications of pregnancy Systemic disease Intrauterine pregnancy Hepatic disease Ectopic pregnancy Renal disease Spontaneous abortion Coagulopathy Gestational trophoblastic disease Thrombocytopenia Placenta previa von Willebrand's disease

LeukemiaInfectionCervicitis Medications/iatrogenicEndometritis Intrauterine device

Hormones (oral contraceptives, Trauma estrogen, progesterone) Laceration, abrasion Foreign body Hormonal imbalance

Anovulatory cycles Malignant neoplasm Hypothyroidism Cervical Hyperprolactinemia Endometrial Cushing’s diseaseOvarian Polycystic ovarian syndrome

Adrenal dysfunction/tumorBenign pelvic lesions StressCervical polyp Excessive exerciseEndometrial polypLeiomyoma Adenomyosis

Abnormal Bleeding Cause PregnancyPregnancy Hormonal/DysfunctionalHormonal/Dysfunctional AnatomicAnatomic Coagulopathy/bleeding Coagulopathy/bleeding

disorderdisorder

History

CharacterizeCharacterize menses menses Age, parity, past pregnancies, sexual Age, parity, past pregnancies, sexual

history, contraception, past gyn history, contraception, past gyn problems, medicationsproblems, medications

Personal or family history of bleeding Personal or family history of bleeding disorderdisorder

Symptoms of thyroid diseaseSymptoms of thyroid disease History of liver diseaseHistory of liver disease

Physical Exam

Orthostatic VS if indicated by HxOrthostatic VS if indicated by Hx Pelvic exam – vagina, cervix, Pelvic exam – vagina, cervix,

uterus, adnexa, PAPuterus, adnexa, PAP Skin – ecchymoses, hirsutismSkin – ecchymoses, hirsutism Thyroid glandThyroid gland Liver and assoc. stigmataLiver and assoc. stigmata Signs of virulization Signs of virulization

Labs CBC with PltsCBC with Plts Urine ß-HCG if reproductive age Urine ß-HCG if reproductive age

Additional Tests (not routine) TSH – anovulatoryTSH – anovulatory LFTs, coagulation studies – liver dz or FHxLFTs, coagulation studies – liver dz or FHx Complete coagulation profile – consider for Complete coagulation profile – consider for

non-pregnant teensnon-pregnant teens GC, Chlamydia – if risk or exam suggestsGC, Chlamydia – if risk or exam suggests Androgen excess – free testosterone, Androgen excess – free testosterone,

DHEA-S (PCOS evaluation)DHEA-S (PCOS evaluation) FSH – suspect premature ovarian failureFSH – suspect premature ovarian failure Progesterone – confirm ovulation, draw in Progesterone – confirm ovulation, draw in

luteal phase luteal phase

Life Phase Ovulatory Status Etiology

R/O Pregnancy

Adolescent Likely anovulation

Consider bleeding disorder Pregnancy

Reproductive age

(Usually DUB)

Ovulatory(Secretory)

Anovulatory (Proliferative)

HormonalDUB

Anatomic

Coagulopathy R/O PregnancyPerimenopause Early EMB/TV Sono

Postmenopause R/O Endometrial CA

Adolescents Usually anovulation due to Usually anovulation due to

immature Hypothal-Pit axisimmature Hypothal-Pit axis Rule out pregnancyRule out pregnancy Consider bleeding disorderConsider bleeding disorder Observe or Rx with cyclic MPA or Observe or Rx with cyclic MPA or

OCsOCs

Consider Bleeding Disordervon Willebrand’s Diseasevon Willebrand’s Disease

Underdiagnosed; present in 1% of populationUnderdiagnosed; present in 1% of population Autosomal dominant; affects women and men Autosomal dominant; affects women and men

equallyequally Dx:Dx: Bleeding time, Bleeding time, Factor VIII, vW factor, Factor VIII, vW factor,

ristocetin co-factor activityristocetin co-factor activity Rx:Rx: Desmopressin (ADH) IV or intranasalDesmopressin (ADH) IV or intranasal

Increases vW factor, factor VIII,Increases vW factor, factor VIII,plasminogen activatorplasminogen activator

Reproductive Age H&PH&P Check urine ß-HCGCheck urine ß-HCG Genital tract lesion—Bx or referGenital tract lesion—Bx or refer Enlarged uterusEnlarged uterus

r/o pregnancyr/o pregnancy sono for anatomic causesono for anatomic cause

(e.g., fibroids)(e.g., fibroids)

Reproductive Age If not pregnant and normal exam:If not pregnant and normal exam:

Usually DUB Usually DUB (i.e.,(i.e., hormonal) hormonal) Determine ovulatory status Determine ovulatory status key!key! Treatment: Usually hormonalTreatment: Usually hormonal

Ovulatory Cycles Regular cycle lengthRegular cycle length Presence of premenstrual symptoms Presence of premenstrual symptoms Breast tenderness, dysmenorrhea Breast tenderness, dysmenorrhea MittleschmertzMittleschmertz Biphasic temperature curve Biphasic temperature curve

Anovulatory Cycles Unpredictable cycle length Unpredictable cycle length Unpredictable bleeding pattern Unpredictable bleeding pattern Frequent spotting Frequent spotting Infrequent heavy bleeding Infrequent heavy bleeding Monophasic temperature curveMonophasic temperature curve

Anovulatory Bleeding 90-95% of reproductive age 90-95% of reproductive age Cause: Cause: systemicsystemic hormonal hormonal

imbalance imbalance Always a relative progestin-Always a relative progestin-

deficient statedeficient state

Anovulatory Bleeding Assess for secondary hypothalamic Assess for secondary hypothalamic

disorderdisorder stress, eating disorder, excessive stress, eating disorder, excessive

exercise, wt loss, chronic illness exercise, wt loss, chronic illness Check TSH Check TSH Test for PCOS if indicatedTest for PCOS if indicated

obesity, hirsutism, insulin resistanceobesity, hirsutism, insulin resistance Consider chronic anovulationConsider chronic anovulation

Anovulatory DUB Treatment Address underlying disorderAddress underlying disorder Treat with monthly OCs or Treat with monthly OCs or

progesterone withdrawal every 3 progesterone withdrawal every 3 months (MPA or DMPA)months (MPA or DMPA) Regulate cycles, protect againstRegulate cycles, protect against

endometrial CAendometrial CA Clomiphene for ovulation induction Clomiphene for ovulation induction

in select casesin select cases

Ovulatory Bleeding Usually underlying prostaglandin Usually underlying prostaglandin

imbalance (DUB)imbalance (DUB) Defects in Defects in locallocal endometrial hormonal endometrial hormonal

hemostasishemostasis Structural lesionsStructural lesions

Leiomyoma, adenomyosis, polypsLeiomyoma, adenomyosis, polyps Systemic diseaseSystemic disease

Liver dz, renal failure, bleeding Liver dz, renal failure, bleeding disorderdisorder

Ovulatory Bleeding Much less common—5-10%Much less common—5-10% Consider empiric treatment Consider empiric treatment

without further w/u without further w/u (normal exam)(normal exam) NSAIDs, OCs, progesterone IUDNSAIDs, OCs, progesterone IUD

If Rx fails, proceed with work up If Rx fails, proceed with work up Metabolic labsMetabolic labs Imaging, EMBImaging, EMB

Ovulatory DUB Treatment NSAIDs (prostaglandin synthetase NSAIDs (prostaglandin synthetase

inhibitors) e.g., Ibuprofen, Naproxen, inhibitors) e.g., Ibuprofen, Naproxen, Mefenamic acidMefenamic acidFirst 5d of mensesFirst 5d of menses

Cyclic OCs x 3-6 mosCyclic OCs x 3-6 mos Progesterone IUD – most effective Progesterone IUD – most effective

[Tranexamic acid – anti-fibrinolytic][Tranexamic acid – anti-fibrinolytic]

Evaluating endometrial cavityConsider EMB:Consider EMB:

Higher risk womenHigher risk women Prolonged exposure to unopposed Prolonged exposure to unopposed

estrogenestrogen Age > 40Age > 40 Failure to respond to initial Failure to respond to initial

managementmanagement

Evaluating endometrial cavityEndometrial Biopsy (EMB)Endometrial Biopsy (EMB)

Safe, simple office procedureSafe, simple office procedure Rule out endometrial CARule out endometrial CA Confirm ovulatory statusConfirm ovulatory status

EMB best done while bleedingEMB best done while bleeding Proliferative: confirms anovulationProliferative: confirms anovulation Secretory: confirms ovulationSecretory: confirms ovulation Hyperplasia: chronic unopposed estrogenHyperplasia: chronic unopposed estrogen Atrophy: menopause or continous OCs, HRT, Atrophy: menopause or continous OCs, HRT,

DMPA DMPA

Evaluating endometrial cavityDilation and Curettage (D&C)Dilation and Curettage (D&C)

OR procedure, less commonly usedOR procedure, less commonly used

Rule out endometrial carcinoma or Rule out endometrial carcinoma or hyperplasiahyperplasia

Yield slightly higher than EMB, but still Yield slightly higher than EMB, but still “blind” sampling technique“blind” sampling technique

Evaluating endometrial cavityTransvaginal UltrasonographyTransvaginal Ultrasonography

(TVSono)(TVSono) Alternative to EMB to assess endometrium, Alternative to EMB to assess endometrium,

comparable accuracycomparable accuracy Endometrial stripe >5mm Endometrial stripe >5mm EMB for tissue EMB for tissue

diagnosisdiagnosis Often can detect atrophic endometrium, Often can detect atrophic endometrium,

leiomyomas, and endometrial polypsleiomyomas, and endometrial polyps

Evaluating endometrial cavitySonohysterography Sonohysterography (“water sono”)(“water sono”)

TVSono with saline infusion into endometrial TVSono with saline infusion into endometrial cavitycavity Enhances detection of submucosal fibroids Enhances detection of submucosal fibroids

and polypsand polyps

Evaluating endometrial cavityHysteroscopyHysteroscopy

““Gold standard” for endometrial assessmentGold standard” for endometrial assessment Office procedureOffice procedure Thorough, direct inspection of endometrial Thorough, direct inspection of endometrial

cavitycavity Directed biopsy or treatment possible (e.g., Directed biopsy or treatment possible (e.g.,

polyp excision) polyp excision)

Perimenopause H&PH&P Check urine ß-HCGCheck urine ß-HCG Genital tract lesion—Bx or referGenital tract lesion—Bx or refer Enlarged uterusEnlarged uterus

r/o pregnancyr/o pregnancy TV Sono for anatomic evaluation TV Sono for anatomic evaluation

(e.g., fibroids)(e.g., fibroids)

Perimenopause If not pregnant and normal exam:If not pregnant and normal exam: Consider early EMB or TV SonoConsider early EMB or TV Sono

r/o edometrial hyperplasia, CAr/o edometrial hyperplasia, CA If negative, Rx with low dose OCs If negative, Rx with low dose OCs

or monthly Medroxyprogesteroneor monthly Medroxyprogesterone Sonohysterography or Sonohysterography or

hysteroscopy if Rx failshysteroscopy if Rx fails r/o anatomic causesr/o anatomic causes

Postmenopause 5-10% endometrial carcinoma5-10% endometrial carcinoma Proceed directly to EMB or TV SonoProceed directly to EMB or TV Sono DDx: DDx: endometrial hyperplasia,endometrial hyperplasia, cervical cervical

cancer, cervicitis, atrophic vaginitis, cancer, cervicitis, atrophic vaginitis, endometrial atrophy, submucosal endometrial atrophy, submucosal fibroids, endometrial polypsfibroids, endometrial polyps

Rx specific to causeRx specific to cause

Treatment: Acute Bleeding Conj. Eq. Estrogens x 21d Conj. Eq. Estrogens x 21d

+ MPA last 7–10d+ MPA last 7–10d Use Estrogen IV for severe bleeding; hospitalizedUse Estrogen IV for severe bleeding; hospitalized

High dose OC: 1 QID x 7d; High dose OC: 1 QID x 7d; then OC daily x 3 months then OC daily x 3 months or MPA x 10d q month x 2-3 more cyclesor MPA x 10d q month x 2-3 more cycles

Surgical TreatmentTherapeutic D+CTherapeutic D+C

fastest method to stop bleeding in unstable fastest method to stop bleeding in unstable patientspatients

must follow with hormones to prevent must follow with hormones to prevent recurrencerecurrence

Endometrial Ablation/ResectionEndometrial Ablation/Resection laser or electrocautery laser or electrocautery good option if fertility not desiredgood option if fertility not desired

Surgical TreatmentHysterectomyHysterectomy if all else fails or patient prefersif all else fails or patient prefers subtotal hysterectomy is an option to preserve subtotal hysterectomy is an option to preserve

optimal sexual and bladder functionoptimal sexual and bladder function hysterectomy now is rarely necessary solely hysterectomy now is rarely necessary solely

for uterine bleedingfor uterine bleeding

Life Phase Ovulatory Status Etiology

R/O Pregnancy

Adolescent Likely anovulation

Consider bleeding disorder Pregnancy

Reproductive age

(Usually DUB)

Ovulatory(Secretory)

Anovulatory (Proliferative)

HormonalDUB

Anatomic

Coagulopathy R/O PregnancyPerimenopause Early EMB/TV Sono

Postmenopause R/O Endometrial CA

Adolescents Most likely anovulatory due to Most likely anovulatory due to

immature Hypothal-Pit axisimmature Hypothal-Pit axis Rule out pregnancyRule out pregnancy Consider bleeding disorderConsider bleeding disorder Observe or Rx with cyclic MPA or Observe or Rx with cyclic MPA or

OCsOCs

Anovulatory Adults Identify secondary causes of Identify secondary causes of

Hypothal-Pit dysfunction, thyroid Hypothal-Pit dysfunction, thyroid disease, PCOSdisease, PCOS

Address underlying causeAddress underlying cause Manage bleeding with cyclic MPA, Manage bleeding with cyclic MPA,

DMPA, or OCsDMPA, or OCs

Ovulatory Adults Causes: endometrial modeling defect, Causes: endometrial modeling defect,

structural lesions, systemic diseasestructural lesions, systemic disease Consider empiric Rx without further w/u Consider empiric Rx without further w/u

if history and exam are normalif history and exam are normal NSAIDs, OCs, Progesterone IUDNSAIDs, OCs, Progesterone IUD

If Rx fails, w/u with metabolic labs, If Rx fails, w/u with metabolic labs, imaging, and EMB if indicatedimaging, and EMB if indicated

Perimenopause Progressive anovulation due to Progressive anovulation due to

declining ovarian functiondeclining ovarian function Rule out pregnancyRule out pregnancy Consider early EMB or TVSono Consider early EMB or TVSono

(esp. with endometrial CA risk factors)(esp. with endometrial CA risk factors) Rx withRx with OCs or monthly MPAOCs or monthly MPA

Postmenopause Rule out endometrial CA (5-10%)Rule out endometrial CA (5-10%)

Proceed directly to EMB or TVSonoProceed directly to EMB or TVSono Evaluate for other causesEvaluate for other causes

endometrial hyperplasia,endometrial hyperplasia, cervical cervical cancer, cervicitis, atrophic vaginitis, cancer, cervicitis, atrophic vaginitis, endometrial atrophy, submucosal endometrial atrophy, submucosal fibroids, endometrial polypsfibroids, endometrial polyps

Rx specific to underlying cause Rx specific to underlying cause

Summary Abnormal uterine bleeding is Abnormal uterine bleeding is veryvery

commoncommon Life phase and detailed menstrual Life phase and detailed menstrual

history are keyhistory are key Employ rational evaluation and Employ rational evaluation and

treatment strategytreatment strategy You can manage it!You can manage it!

Cervical Cancer Screening

Todd May, MDTodd May, MD

Cervical Cancer 12,800 cases/yr12,800 cases/yr 50% never screened50% never screened Death rate Death rate 70% since 1940s 70% since 1940s

Pap introducedPap introduced

Natural History HPV acquired in teens, 20sHPV acquired in teens, 20s Prolonged pre-malignant phaseProlonged pre-malignant phase Spontaneous HPV clearing Spontaneous HPV clearing

commoncommon CIN peaks 20s-30sCIN peaks 20s-30s Small number progress to Small number progress to

invasive cancerinvasive cancer

Risk Factors for Neoplasia Multiple sexual partnersMultiple sexual partners HPVHPV SmokingSmoking HIVHIV

Routine Screening Recs Start:Start:

3yrs after first vaginal intercourse3yrs after first vaginal intercourse Age 21 (unless virginal?)Age 21 (unless virginal?)

Interval:Interval: Annually age <30Annually age <30 Age >30 q2-3yrs if normal x 3 annualsAge >30 q2-3yrs if normal x 3 annuals

Stop:Stop: Age 65-70 if consistently normalAge 65-70 if consistently normal After hysterectomy for benign conditionAfter hysterectomy for benign condition

High-Risk Screening RecsPap every 6 months x 2, then annually Pap every 6 months x 2, then annually

for:for: HIV positiveHIV positive Immunocompromised by organ Immunocompromised by organ

transplant, chemoRx, chronic steroid transplant, chemoRx, chronic steroid useuse

Prior Rx for CINII/III or cancerPrior Rx for CINII/III or cancerRationale: Progression to HSIL and CA Rationale: Progression to HSIL and CA

more common and more rapidmore common and more rapid

Essentials of Pap Sampling Collect cells before bimanual examCollect cells before bimanual exam Gently remove cervical mucus/dcGently remove cervical mucus/dc Visualize entire portio of cervixVisualize entire portio of cervix Use scraper for ectocervix; brush Use scraper for ectocervix; brush

for endocervical specimenfor endocervical specimen Fix slide immediately (<3-4sec)Fix slide immediately (<3-4sec)

Cytologic Interpretation Adequacy of specimenAdequacy of specimen

““Satisfactory” or “unsatisfactory”Satisfactory” or “unsatisfactory” Descriptive diagnosisDescriptive diagnosis

Bethesda 2001Bethesda 2001 Presence/absence of Presence/absence of

endocervical cellsendocervical cells

Negative for IEL or Malig.Benign cellular changesBenign cellular changes TrichomonasTrichomonas Fungus c/w Fungus c/w candida sppcandida spp—No action—No action Floral shift/BV—No actionFloral shift/BV—No action Suspect Suspect ChlamydiaChlamydia—call back to test—call back to test HSV—notify patientHSV—notify patient HPV/koilcytosis—manage as LSILHPV/koilcytosis—manage as LSIL ActinomycesActinomyces (IUD)—Rx with Amox (IUD)—Rx with Amox

Negative for IEL or Malig.Reactive changesReactive changes Inflammation—No action Inflammation—No action Atrophy w/ inflam. (“atrophic vaginitis”)Atrophy w/ inflam. (“atrophic vaginitis”)

—Rx w/ topical estrogen, repeat if no —Rx w/ topical estrogen, repeat if no ECCECC

Radiation—No actionRadiation—No action Reactive/reparative Atypia—No actionReactive/reparative Atypia—No action Squamous metaplasia—No actionSquamous metaplasia—No action

Squamous Cell Abnormalities ASCUS—undetermined significanceASCUS—undetermined significance ACS-H—cannot exclude HSILACS-H—cannot exclude HSIL LSIL—low grade—includes HPV, LSIL—low grade—includes HPV,

mild dysplasia/CINImild dysplasia/CINI HSIL—high grade—includes mod-HSIL—high grade—includes mod-

severe dysplasia, CINII/III, CISsevere dysplasia, CINII/III, CIS Invasive SCCaInvasive SCCa

Glandular Cells Endometrial cells—consider EMB if Endometrial cells—consider EMB if

age>40 or abnormal bleedingage>40 or abnormal bleeding Atypical Endocervical cells—colpo, Atypical Endocervical cells—colpo,

Bx, ECCBx, ECC Atypical Endometrial cells—EMB, Atypical Endometrial cells—EMB,

D&C, or hysteroscopyD&C, or hysteroscopy Endocervical, Endometrial, or Endocervical, Endometrial, or

Extrauterine Ca—definitive RxExtrauterine Ca—definitive Rx

ASC – US

HPV DNA Testing Repeat 4-6 months HIV

Negative > ASC – US (for high risk types) HPV Positive HPV Negative

Colposcopy

Routine Screening Repeat PAP 12 months

ASC–H / LSIL

Colposcopy

CIN 2 or 3, CIS Neg or CIN 1

PAP q6 mos x 2 RX

HSIL

Colposcopy + ECC

Satisfactory Unsatisfactory

No CIN or CIN 2, 3 Diagnostic CINI Excision

Diagnostic Excision Rx

Bottom LineWhen to refer for colposcopy:When to refer for colposcopy:

ASC-US x 2 (x1 if HIV+)ASC-US x 2 (x1 if HIV+) ASC-HASC-H LSILLSIL HSILHSIL