abnormal uterine bleeding
DESCRIPTION
Diffferent Causes of Abnormal Uterine BleedingTRANSCRIPT
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Abnormal Uterine Bleeding
Todd May, M.D.Todd May, M.D.
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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
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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
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Abnormal Bleeding Cause PregnancyPregnancy Hormonal/DysfunctionalHormonal/Dysfunctional AnatomicAnatomic Coagulopathy/bleeding Coagulopathy/bleeding
disorderdisorder
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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
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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
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Labs CBC with PltsCBC with Plts Urine ß-HCG if reproductive age Urine ß-HCG if reproductive age
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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
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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
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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
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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]
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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
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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 bleedingProliferative: confirms anovulationProliferative: confirms anovulationSecretory: confirms ovulationSecretory: confirms ovulationHyperplasia: chronic unopposed estrogenHyperplasia: chronic unopposed estrogenAtrophy: menopause or continous OCs, HRT, Atrophy: menopause or continous OCs, HRT,
DMPA DMPA
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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
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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
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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
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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)
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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!
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Cervical Cancer Screening
Todd May, MDTodd May, MD
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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
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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
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Risk Factors for Neoplasia Multiple sexual partnersMultiple sexual partners HPVHPV SmokingSmoking HIVHIV
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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
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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
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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)
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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
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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
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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
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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
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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
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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
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ASC–H / LSIL
Colposcopy
CIN 2 or 3, CIS Neg or CIN 1
PAP q6 mos x 2 RX
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HSIL
Colposcopy + ECC
Satisfactory Unsatisfactory
No CIN or CIN 2, 3 Diagnostic CINI Excision
Diagnostic Excision Rx
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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