Abnormal Vaginal Bleeding Policar 051611-1

Abnormal Vaginal Abnormal Vaginal BleedingBleedingAbnormal Vaginal Abnormal Vaginal BleedingBleeding

Michael S. Policar, MD, MPHMichael S. Policar, MD, MPHClinical ProfessorClinical Professor

OB,GYN, and Reproductive SciencesOB,GYN, and Reproductive SciencesUCSF School of MedicineUCSF School of [email protected]@obgyn.ucsf.edu

No commercial disclosures

Learning ObjectivesLearning ObjectivesLearning ObjectivesLearning Objectives

List 4 causes of ovulatory bleeding and 4 causes of List 4 causes of ovulatory bleeding and 4 causes of anovulatory bleedinganovulatory bleeding

List 4 indications for endometrial biopsy in each of List 4 indications for endometrial biopsy in each of post-menopausal and pre/peri-menopausal womenpost-menopausal and pre/peri-menopausal women

List 3 causes of post-coital bleeding and the List 3 causes of post-coital bleeding and the corresponding treatment of eachcorresponding treatment of each

List 4 causes of menorrhagia in a women in her forties List 4 causes of menorrhagia in a women in her forties and 2 treatments for eachand 2 treatments for each

Vaginal Bleeding…What’s Normal?Vaginal Bleeding…What’s Normal?Vaginal Bleeding…What’s Normal?Vaginal Bleeding…What’s Normal?

Onset of mensesOnset of menses– By 16 years old By 16 years old withwith 2 2oo sex characteristics sex characteristics– Start evaluation at 14 years of age if no sexual Start evaluation at 14 years of age if no sexual

developmentdevelopment Cycle length: Cycle length: 24-35 days24-35 days Menstrual days: Menstrual days: 2-7 days2-7 days Menstrual flow: Menstrual flow: 20-80 cc. per menses20-80 cc. per menses– Average flow: Average flow: 35 cc. per menses35 cc. per menses

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

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

Abnormal Abnormal amount amount of bleedingof bleeding– MenorrhagiaMenorrhagia (hypermenorrhea) (hypermenorrhea)»Prolonged duration of mensesProlonged duration of menses» Increased amount of bleeding per dayIncreased amount of bleeding per day

– HypomenorrheaHypomenorrhea »Shorter mensesShorter menses»Less flow per dayLess flow per day

Menorrhagia: Perception vs. RealityMenorrhagia: Perception vs. RealityMenorrhagia: Perception vs. RealityMenorrhagia: Perception vs. Reality

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

20-40 ml 40-60 ml 60-80 ml >80 ml

Heavy

Moderate

Light

Perception of menstrual bleeding

Actual Menstrual Blood Loss Per Cycle

Hallberg, L et al, G. Acta Obstet Gynecol Scand 1966;45:320-51.

Abnormal Vaginal Bleeding Abnormal Vaginal Bleeding Symptom DefinitionsSymptom Definitions


Abnormal Abnormal timingtiming of bleeding: of bleeding: REGULARREGULAR Cycles Cycles

– Polymenorrhea: Polymenorrhea: cycle length < 24 dayscycle length < 24 days

– Intermenstrual bleeding: (IMB)Intermenstrual bleeding: (IMB)

– Post-coital bleeding (PCB)Post-coital bleeding (PCB)

14 days14 days7 days 14 days14 days7 days 7 days

7 days21 days21 days

7 days 7 days

intercourse intercourse

7 days 7 days 7 days

Abnormal Vaginal Bleeding Abnormal Vaginal Bleeding Symptom Symptom DefinitionsDefinitions

Abnormal Vaginal Bleeding Abnormal Vaginal Bleeding Symptom Symptom DefinitionsDefinitions

Abnormal Abnormal timingtiming of bleeding: of bleeding: IRREGULAR IRREGULAR CyclesCycles– MetrorrhagiaMetrorrhagia» Light “irregularly irregular” bleedingLight “irregularly irregular” bleeding

– MenometrorrhagiaMenometrorrhagia» Heavy “irregularly irregular” bleedingHeavy “irregularly irregular” bleeding

– Post-menopausal: Post-menopausal: bleeding bleeding >>1 year after menopause1 year after menopause

7 days 3 2 10 days 2 4



Decreased Decreased frequencyfrequency of bleeding of bleeding– OligomenorrheaOligomenorrhea»No bleeding 36 days- 3 monthsNo bleeding 36 days- 3 months

– AmenorrheaAmenorrhea»No bleeding for…No bleeding for…

3 cycle intervals 3 cycle intervals oror 6 months (in oligomenorrheic women)6 months (in oligomenorrheic women)

Frasier I, Fertility and Sterility 2007; 87:466-76

The “New Normal”: Proposed Terms for Vaginal Bleeding The “New Normal”: Proposed Terms for Vaginal Bleeding

Abnormal Vaginal BleedingAbnormal Vaginal BleedingAbnormal Vaginal BleedingAbnormal Vaginal Bleeding

Ovulatory = RegularOvulatory = Regular MenorrhagiaMenorrhagia HypomenorrheaHypomenorrhea PolymenorrheaPolymenorrhea IMBIMB PCBPCB

Anovulatory = Irregular Anovulatory = Irregular or no bleedingor no bleedingMetrorrhagia/ MMRMetrorrhagia/ MMROligomenorrheaOligomenorrheaAmenorrheaAmenorrheaPost-menopausal Post-menopausal

Is the patient pregnant?Is the patient pregnant? Is it uterine?Is it uterine? Is the bleeding pattern ovulatory or anovulatory?Is the bleeding pattern ovulatory or anovulatory?

Hx, PE,Hx, PE,Preg testPreg test

Preg test POSPreg test POS Preg test NEGPreg test NEG

Pregnant

• LocationLocation• ViabilityViability• GA DatingGA Dating

Abnormal VaginalAbnormal Vaginal BleedingBleeding



Pregnant

• LocationLocation• ViabilityViability• GA DatingGA Dating

Non-uterine bleeding Non-uterine bleeding

Pelvic ExamPelvic Exam

Uterine bleedingUterine bleeding

CervixCervix VaginaVagina AnusAnusUrethraUrethra

Abnormal VaginalAbnormal VaginalBleedingBleeding

Non-Uterine Conditions: Non-Uterine Conditions: CervixCervixNon-Uterine Conditions: Non-Uterine Conditions: CervixCervix

Cervix Neoplasms: Cervix Neoplasms: IMB, PCB, PMBIMB, PCB, PMB– Squamous cell carcinomaSquamous cell carcinoma– AdenocarcinomaAdenocarcinoma

Infections: Infections: IMB, PCB,IMB, PCB, menorrhagiamenorrhagia– Mucopurulent cervicitis (chlamydia, gonorrhea, Mucopurulent cervicitis (chlamydia, gonorrhea,

mycoplasma hominis)mycoplasma hominis) Benign cervical ectropion: Benign cervical ectropion: PCBPCB– Exposed columnar epithelial cells on ectocervixExposed columnar epithelial cells on ectocervix– Red appearance; bleeds to touchRed appearance; bleeds to touch

Non-Uterine Conditions: Non-Uterine Conditions: VaginaVaginaNon-Uterine Conditions: Non-Uterine Conditions: VaginaVagina

Vaginal inflammation Vaginal inflammation ((IMB, PCB, PMB)IMB, PCB, PMB)– Atrophic vaginitisAtrophic vaginitis– Severe vaginal trichomoniasisSevere vaginal trichomoniasis

Trauma/ foreign bodyTrauma/ foreign body– Vaginal wall laceration (Vaginal wall laceration (PCB)PCB)– Hymeneal ring tear/laceration Hymeneal ring tear/laceration (PCB)(PCB)– Vaginal foreign body (esp. pre-menarchal bleeding)Vaginal foreign body (esp. pre-menarchal bleeding)

Vaginal neoplasmsVaginal neoplasms– Squamous cell cancer, clear cell (DES)Squamous cell cancer, clear cell (DES)– Childhood tumorsChildhood tumors

Non-Uterine Conditions: Non-Uterine Conditions: OtherOtherNon-Uterine Conditions: Non-Uterine Conditions: OtherOther

Urethra Urethra (post-void bleeding)(post-void bleeding)– Urethral caruncleUrethral caruncle– Squamous or transitional cell cancer Squamous or transitional cell cancer

Anus Anus (bleeding after wiping)(bleeding after wiping)– External or internal hemorrhoidExternal or internal hemorrhoid– Anal fissureAnal fissure– Genital wartsGenital warts– Squamous cell cancer Squamous cell cancer



Pregnant

•LocationLocation•ViabilityViability•GA DatingGA Dating

(Oligo) Anovulation(Oligo) AnovulationIatrogenicIatrogenicOvulatoryOvulatory

Non-uterine bleeding Non-uterine bleeding

Pelvic ExamPelvic Exam

Uterine bleedingUterine bleeding

CervixCervix VaginaVagina AnusAnusUrethraUrethra

Abnormal Vaginal Abnormal Vaginal Bleeding: Bleeding: Standard DefinitionsStandard Definitions

Uterine Uterine BleedingBleeding

• Polyp• Adenomyosis• Leiomyoma• Malignancy

• Coagulopathy• Infections• Thyroid dz• LPD

StructuralStructural Non-StructuralNon-StructuralIdiopathic

OvulatoryOvulatory IatrogenicIatrogenic AnovulatoryAnovulatory


Estrogenic (DUB)Estrogenic (DUB) Hypo-EstrogenicHypo-Estrogenic

OvulatoryOvulatory IatrogenicIatrogenic AnovulatoryAnovulatory

PhysiologicPhysiologic

•Menarche•Peri-menopause

AnatomicAnatomic

AndrogenicAndrogenic Systemic DzSystemic Dz

•Hypothalamic•Pituitary•Ovarian

• Hyperplasia• EM Cancer

• PCOS• CAH• Cushings

• Renal• Liver

Uterine Uterine BleedingBleeding


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

StructuralStructuralStructuralStructural Non-StructuralNon-StructuralNon-StructuralNon-Structural

FIGO System for AUB, 2011FIGO System for AUB, 2011FIGO System for AUB, 2011FIGO System for AUB, 2011

AUB: AUB: Structural ConditionsStructural ConditionsAUB: AUB: Structural ConditionsStructural Conditions

PP: Endometrial polyp: Endometrial polyp– IMB or PCB in 30-50 year old womanIMB or PCB in 30-50 year old woman

AA: Adenomyosis: Adenomyosis– Dysmenorrhea, dyspareunia, chronic pelvic pain, Dysmenorrhea, dyspareunia, chronic pelvic pain,

sometimes menorrhagiasometimes menorrhagia LL: Leiomyoma: Leiomyoma– Submucous myomaSubmucous myoma– Menorrhagia; rarely IMB; never metrorrhagiaMenorrhagia; rarely IMB; never metrorrhagia

AUB: AUB: Structural ConditionsStructural ConditionsAUB: AUB: Structural ConditionsStructural Conditions

MM: Malignancy and hyperplasia: Malignancy and hyperplasia– Adenomatous hyperplasia (AH) Adenomatous hyperplasia (AH) atypical AH atypical AH

endometrial carcinomaendometrial carcinoma»Post-menopausal bleedingPost-menopausal bleeding»Recurrent perimenopausal metrorrhagiaRecurrent perimenopausal metrorrhagia»Chronic anovulator (PCOS) with metrorrhagia Chronic anovulator (PCOS) with metrorrhagia

– LeiomyosarcomaLeiomyosarcoma»Post-menopausal bleedingPost-menopausal bleeding

CCOEIN: CoagulopathyOEIN: CoagulopathyCCOEIN: CoagulopathyOEIN: Coagulopathy

Clotting factor deficiency or defectClotting factor deficiency or defect– Liver diseaseLiver disease– Congenital (Von Willebrands Disease)Congenital (Von Willebrands Disease)

Platelet deficiency Platelet deficiency (thrombocytopenia) with platelet (thrombocytopenia) with platelet count <20,000/mmcount <20,000/mm33

– Idiopathic thrombocytopenic purpura (ITP)Idiopathic thrombocytopenic purpura (ITP)– Aplastic anemiaAplastic anemia

Platelet function defectsPlatelet function defects

CCOEIN: CoagulopathyOEIN: CoagulopathyCCOEIN: CoagulopathyOEIN: CoagulopathyScreen for underlying disorder of hemostasis if any of Screen for underlying disorder of hemostasis if any of Heavy menstrual bleeding since menarcheHeavy menstrual bleeding since menarche One of the followingOne of the following– Post-partum hemorrhagePost-partum hemorrhage– Bleeding associated with surgeryBleeding associated with surgery– Bleeding associated with dental workBleeding associated with dental work

Two or more of the followingTwo or more of the following– Bruising 1-2 times per monthBruising 1-2 times per month– Epistaxis 1-2 times per monthEpistaxis 1-2 times per month– Frequent gum bleedingFrequent gum bleeding– Family history of bleeding symptomsFamily history of bleeding symptoms

Munro M, Int J Gynecol Obstet (2011)

CCOOEIN: EIN: OvulatoryOvulatoryCCOOEIN: EIN: OvulatoryOvulatory

AnovulationAnovulation– Age: peri-menarche and perimenopuseAge: peri-menarche and perimenopuse– PCOSPCOS– StressStress

HypothyroidismHypothyroidism Luteal phase defectsLuteal phase defects

Normal Ovarian Hormone CycleNormal Ovarian Hormone CycleNormal Ovarian Hormone CycleNormal Ovarian Hormone Cycle

Estrogen

Progesterone

mensesovulation

Precipitous drop of E+P• Synchronous• Universal Withdrawal Bleed

Precipitous drop of E+P• Synchronous• Universal Withdrawal Bleed

Abnormal Ovarian Hormone CyclesAbnormal Ovarian Hormone CyclesAbnormal Ovarian Hormone CyclesAbnormal Ovarian Hormone Cycles

EstrogenEstrogen

ProgesteroneProgesterone

anovulation

AmenorrheaAmenorrhea

E withdrawal bleedE withdrawal bleed

Menometrorrhagia:Menometrorrhagia:heavy, irregular bleedingheavy, irregular bleeding

CCOOEIN: EIN: OvulatoryOvulatoryCCOOEIN: EIN: OvulatoryOvulatory

Mainly due to anovulatory bleedingMainly due to anovulatory bleeding– Age-relatedAge-related: peri-menarche, perimenopause: peri-menarche, perimenopause– EstrogenicEstrogenic: unopposed exogenous or endogenous : unopposed exogenous or endogenous

estrogenestrogen– AndrogenicAndrogenic: PCOS; CAH, acute stress: PCOS; CAH, acute stress– SystemicSystemic: Renal disease, liver disease: Renal disease, liver disease

Diagnosis of exclusionDiagnosis of exclusion– Menometrorrhagia Menometrorrhagia notnot due to by anatomic lesion, due to by anatomic lesion,

medications, pregnancymedications, pregnancy

CCOOEIN: EIN: OvulatoryOvulatoryCCOOEIN: EIN: OvulatoryOvulatory Hyperthyroidism or hypothyroidismHyperthyroidism or hypothyroidism– Bleeding can be excessive, light, or irregularBleeding can be excessive, light, or irregular– Only severe, uncorrected thyroid disease causes Only severe, uncorrected thyroid disease causes

abnormal bleeding patternsabnormal bleeding patterns– Normal pattern when corrected to euthyroidNormal pattern when corrected to euthyroid– 11oo hypothyroidism assoc. with 2 hypothyroidism assoc. with 2oo amenorrhea amenorrhea

Low TLow T44 high TRH high TRH high TSH high TSH normal T normal T44

high PRL high PRL amenorrhea + amenorrhea + galactorrheagalactorrhea

CCOOEIN: EIN: OvulatoryOvulatoryCCOOEIN: EIN: OvulatoryOvulatory Luteal Phase Defect (LPD)Luteal Phase Defect (LPD)– Luteal phase lasts 7-10 days (vs. 14 days) or inadequate Luteal phase lasts 7-10 days (vs. 14 days) or inadequate

peak luteal phase progesterone (P)peak luteal phase progesterone (P) DiagnosisDiagnosis– Polymenorrhea (“periods every 2 weeks”)Polymenorrhea (“periods every 2 weeks”)– Mid-luteal phase P level between 4-8 ng/mlMid-luteal phase P level between 4-8 ng/ml– Endometrial biopsy >2 days out of phaseEndometrial biopsy >2 days out of phase

ManagementManagement– Unexplained infertility: clomiphene, P supplementUnexplained infertility: clomiphene, P supplement– Pregnancy not desired: observation or OCs to cyclePregnancy not desired: observation or OCs to cycle

COCOEEIN: IN: EndometrialEndometrialCOCOEEIN: IN: EndometrialEndometrial IdiopathicIdiopathic– Unexplained menorrhagiaUnexplained menorrhagia

EndometritisEndometritis– Post-partumPost-partum– Post-abortal endometritisPost-abortal endometritis– Endometritis component of PIDEndometritis component of PID

In teens, PID commonly presents with abnormal In teens, PID commonly presents with abnormal bleeding (menorrhagia, IMB), not pelvic painbleeding (menorrhagia, IMB), not pelvic pain– Any teen with abnormal bleeding + pelvic pain Any teen with abnormal bleeding + pelvic pain

requires bimanual exam to evaluate for PIDrequires bimanual exam to evaluate for PID

COECOEIIN: N: Iatrogenic ConditionsIatrogenic ConditionsCOECOEIIN: N: Iatrogenic ConditionsIatrogenic Conditions

AnticoagulantsAnticoagulants– Over-anticoagulation: menorrhagiaOver-anticoagulation: menorrhagia– Therapeutic levels will not cause bleeding problemsTherapeutic levels will not cause bleeding problems

Chronic steroids, opiates Chronic steroids, opiates Progestin-containing contraceptivesProgestin-containing contraceptives Intrauterine Contraception (IUC)Intrauterine Contraception (IUC)– "Normal" side effect menorrhagia"Normal" side effect menorrhagia– PID, pregnancy (IUP or ectopic), perforation, PID, pregnancy (IUP or ectopic), perforation,

expulsionexpulsion

COEICOEINN: : Not ClassifiedNot ClassifiedCOEICOEINN: : Not ClassifiedNot Classified

Chronic endometritisChronic endometritis AVMAVM Myometrial hypertrophyMyometrial hypertrophy

AVB: HistoryAVB: HistoryAVB: HistoryAVB: History

Is the patient pregnant?Is the patient pregnant?– Pregnancy symptoms, esp. breast tenderness Pregnancy symptoms, esp. breast tenderness – Intercourse patternIntercourse pattern– Contraceptive useContraceptive use

Is it uterine?Is it uterine?– Coincidence with bowel movement and wiping, Coincidence with bowel movement and wiping,

during or after urinationduring or after urination– Pain or irritation of vagina, introitus, vulva, Pain or irritation of vagina, introitus, vulva,

perinuem, or anal skinperinuem, or anal skin

AVB: HistoryAVB: HistoryAVB: HistoryAVB: History

Is bleeding ovulatory or anovulatory?Is bleeding ovulatory or anovulatory?– Bleeding pattern: regular, irregular, noneBleeding pattern: regular, irregular, none– Molimenal symptoms: Molimenal symptoms: only in ovulatory cyclesonly in ovulatory cycles– Previous history of menstrual disordersPrevious history of menstrual disorders– Recent onset weight gain or hirsuitismRecent onset weight gain or hirsuitism– Menopausal symptomsMenopausal symptoms– History of excess bleeding; coagulation disordersHistory of excess bleeding; coagulation disorders– Current and past medications; street drugsCurrent and past medications; street drugs– Chronic medical illnesses or conditionsChronic medical illnesses or conditions– Nipple discharge from breastsNipple discharge from breasts

AVB: Physical ExamAVB: Physical ExamAVB: Physical ExamAVB: Physical Exam

General: BMI General: BMI >> 30 30 Skin: acne, hirsutism, acanthosis nigricans; bruisingSkin: acne, hirsutism, acanthosis nigricans; bruising Breasts: galactorrheaBreasts: galactorrhea Abdomen: uterine enlargement, abdominal painAbdomen: uterine enlargement, abdominal pain Pelvic examPelvic exam– Vulva and perineumVulva and perineum– Anal and peri-anal skinAnal and peri-anal skin– Speculum: vaginal walls and cervixSpeculum: vaginal walls and cervix– Bimanual: uterine enlargement, softness, massesBimanual: uterine enlargement, softness, masses

AVB: LaboratoryAVB: LaboratoryAVB: LaboratoryAVB: Laboratory

Urine highly sensitive pregnancy test Urine highly sensitive pregnancy test – Quantitative B-hCG is unnecessaryQuantitative B-hCG is unnecessary

CBCCBC– Find severe anemia; baseline value for observationFind severe anemia; baseline value for observation– Platelet estimation (detect thrombocytopenia) Platelet estimation (detect thrombocytopenia)

TSH, ProlactinTSH, Prolactin– Amenorrhea or recurrent anovulatory bleeds Amenorrhea or recurrent anovulatory bleeds onlyonly

FSH, LHFSH, LH levels are levels are unnecessaryunnecessary

Kouides PAHemostasis and menstruation: appropriateinvestigation for underlying disorders of hemostasisin women with excessive menstrual bleedingFertil Sterility 2005;84:1345–51.

Kouides PAHemostasis and menstruation: appropriateinvestigation for underlying disorders of hemostasisin women with excessive menstrual bleedingFertil Sterility 2005;84:1345–51.

Hemostasis evaluation: consult with a Hemostasis evaluation: consult with a hematologist before ordering coag tests!!hematologist before ordering coag tests!!

AVB: Imaging StudiesAVB: Imaging StudiesAVB: Imaging StudiesAVB: Imaging Studies

Mainly for evaluation of ovulatory AUB if no response Mainly for evaluation of ovulatory AUB if no response to treatment or suspect anatomic defectto treatment or suspect anatomic defect

Not useful for demonstrating or excluding hyperplasia Not useful for demonstrating or excluding hyperplasia in premenopausal womenin premenopausal women

Saline infusion sonogram (SIS) helpful for polyps, Saline infusion sonogram (SIS) helpful for polyps, sub-mucus myomatasub-mucus myomata– 80% sensitivity, 69% specificity compared to 80% sensitivity, 69% specificity compared to

hysteroscopyhysteroscopy

Who Needs an EMB?Who Needs an EMB?Who Needs an EMB?Who Needs an EMB?

Purpose: detect endometrial hyperplasia or cancerPurpose: detect endometrial hyperplasia or cancer Menopausal womanMenopausal woman– Any postmenopausal bleeding, if not using HTAny postmenopausal bleeding, if not using HT– Unscheduled bleeding on continuous-sequential Unscheduled bleeding on continuous-sequential

hormone therapyhormone therapy– Bleeding > 3 mo after start of continuous-combined Bleeding > 3 mo after start of continuous-combined

hormone therapyhormone therapy– Endometrial stripe Endometrial stripe >> 5 mm (applies to 5 mm (applies to

postmenopausal woman only)postmenopausal woman only)– Pap smear: Pap smear: anyany endometrial cells or AGC Pap endometrial cells or AGC Pap

Who Needs an EMB?Who Needs an EMB?Who Needs an EMB?Who Needs an EMB?

Premenopausal Premenopausal WomenWomen Prolonged Prolonged metrometrorrhagia (3 months or more)rrhagia (3 months or more) Unexplained post-coital or intermenstrual bleedingUnexplained post-coital or intermenstrual bleeding Endometrial cells on Pap smear in anovulatory Endometrial cells on Pap smear in anovulatory

premenopausal womanpremenopausal woman Abnormal glandular cells (AGC) PapAbnormal glandular cells (AGC) Pap– Abnormal endometrial cellsAbnormal endometrial cells– Older than 35 years old Older than 35 years old – < 35 years old with abnormal bleeding< 35 years old with abnormal bleeding

Technique of EMBTechnique of EMBTechnique of EMBTechnique of EMB

Bimanual exam to evaluate uterine axis, sizeBimanual exam to evaluate uterine axis, size Cleanse cervix with antisepticCleanse cervix with antiseptic S-l-o-w-l-y apply tenaculum ( S-l-o-w-l-y apply tenaculum ( ++ local anesthetic) local anesthetic) Use of the sampling deviceUse of the sampling device– Choose correct type (rigidity) of samplerChoose correct type (rigidity) of sampler– ““Crack” stylet to ensure easy movementCrack” stylet to ensure easy movement– Gently advance to fundus; expect resistance at Gently advance to fundus; expect resistance at

internal osinternal os– Note depth of sounding with side markingsNote depth of sounding with side markings– Pull back stylet to establish vacuumPull back stylet to establish vacuum

Tips for Internal Os StenosisTips for Internal Os StenosisTips for Internal Os StenosisTips for Internal Os Stenosis

Pain reliefPain relief– Use para-cervical or intra-cervical blockUse para-cervical or intra-cervical block– Intrauterine instillation of lidocaineIntrauterine instillation of lidocaine

Cervical dilationCervical dilation– Freeze endometrial sampler to increase rigidityFreeze endometrial sampler to increase rigidity– Grasp sampler with sponge forceps 3-4 cm from tipGrasp sampler with sponge forceps 3-4 cm from tip– Use cervical “os finder” deviceUse cervical “os finder” device– Use small size Pratt or Hegar dilatorsUse small size Pratt or Hegar dilators– Give sublingual or vaginal misoprostol to soften Give sublingual or vaginal misoprostol to soften

cervix 4 hours before procedurecervix 4 hours before procedure

EMB Result: Non-NeoplasticEMB Result: Non-Neoplastic Proliferative: E-induced growth, but no ovulationProliferative: E-induced growth, but no ovulation Secretory: ovulatory or recent progestin exposureSecretory: ovulatory or recent progestin exposure Menstrual: glandular breakdown, non-neoplastic Menstrual: glandular breakdown, non-neoplastic Disordered: out-of-phase glands (often anovulation) Disordered: out-of-phase glands (often anovulation) Chronic endometritis/inflammation: plasma cells Chronic endometritis/inflammation: plasma cells ++ wbc wbc Atrophic: hypoplastic glands and stromaAtrophic: hypoplastic glands and stroma Cystic hyperplasia: hypoplastic glands and stromaCystic hyperplasia: hypoplastic glands and stroma Insufficient: not enough tissue for interpretationInsufficient: not enough tissue for interpretation– If adequate sampling, atrophic endometrium likelyIf adequate sampling, atrophic endometrium likely– If sounding <5 cm, may not have entered cavityIf sounding <5 cm, may not have entered cavity

EMB Result: NeoplasmsEMB Result: Neoplasms

Endometrial polypEndometrial polyp Simple endometrial hyperplasiaSimple endometrial hyperplasia– Gland proliferation and crowding, but no atypiaGland proliferation and crowding, but no atypia– Reversible with continuous progestin exposureReversible with continuous progestin exposure

Atypical endometrial hyperplasiaAtypical endometrial hyperplasia– Hyperplasia with nuclear atypia of gland cellsHyperplasia with nuclear atypia of gland cells– Premalignant; often not reversible with progestinPremalignant; often not reversible with progestin

Endometrial carcinomaEndometrial carcinoma– Stromal invasion of malignant glandsStromal invasion of malignant glands

AVB: Presentation-based ManagementAVB: Presentation-based ManagementAVB: Presentation-based ManagementAVB: Presentation-based Management

Acute dysfunctional (anovulatory) bleedingAcute dysfunctional (anovulatory) bleeding Recurrent dysfunctional bleedingRecurrent dysfunctional bleeding Post-coital bleedingPost-coital bleeding Recurrent (ovulatory) menorrhagiaRecurrent (ovulatory) menorrhagia Postmenopausal bleeding (PMB)Postmenopausal bleeding (PMB)

Note: a menstrual calendar will help to differentiate these Note: a menstrual calendar will help to differentiate these conditionsconditions

Management of Acute DUBManagement of Acute DUBManagement of Acute DUBManagement of Acute DUB

Substitute a pharmacologic luteal phase for missed Substitute a pharmacologic luteal phase for missed physiologic luteal phasephysiologic luteal phase

If If minimal bleedingminimal bleeding for a few days for a few days– Rx MPA 10-20 mg QD (or microP, 200 BID) x10dRx MPA 10-20 mg QD (or microP, 200 BID) x10d– Bleeding stops < 3 days; menses after progestin endedBleeding stops < 3 days; menses after progestin ended

Moderate or heavy bleeding > 3 daysModerate or heavy bleeding > 3 days – Monophasic OC taken BID-TID x 7 days, then daily Monophasic OC taken BID-TID x 7 days, then daily

OC for 3 weeks (or longer)OC for 3 weeks (or longer)– Using “OC taper” Using “OC taper” and then stoppingand then stopping is illogical is illogical

Torrential bleedTorrential bleed: surgical curettage (MUA): surgical curettage (MUA)

Mechanism of “Chemical Curettage”Mechanism of “Chemical Curettage”Mechanism of “Chemical Curettage”Mechanism of “Chemical Curettage”

Estrogen

Progesterone

anovulation

High dose OCs x 7 daysHigh dose OCs x 7 days- E stabilizes EM- E stabilizes EM- P matures EM - P matures EM

OCs

Oral MPA and COCs for Acute Oral MPA and COCs for Acute Uterine Bleeding (AUB)Uterine Bleeding (AUB)

Munro MG, et al Obstet Gynecol 2006;108:924-9Munro MG, et al Obstet Gynecol 2006;108:924-9

Oral MPA and COCs for Acute Oral MPA and COCs for Acute Uterine Bleeding (AUB)Uterine Bleeding (AUB)

Munro MG, et al Obstet Gynecol 2006;108:924-9Munro MG, et al Obstet Gynecol 2006;108:924-9

40 women with non-anatomic AUB randomized to40 women with non-anatomic AUB randomized to– MPA 20 mg TID, then QD for 3 weeks vs MPA 20 mg TID, then QD for 3 weeks vs – COC (1 mg nor + 35 mcg EE) TID x1 week, QD x3 wksCOC (1 mg nor + 35 mcg EE) TID x1 week, QD x3 wks

ResultsResults– Median time to bleeding cessation was 3 daysMedian time to bleeding cessation was 3 days– Cessation in 88% OC group, 76% in MPA groupCessation in 88% OC group, 76% in MPA group– Surgery avoided in 100% MPA, 95% COC subjectsSurgery avoided in 100% MPA, 95% COC subjects– Compliance similar in both groupsCompliance similar in both groups– ““Would use again”…81% MPA, 69% COCWould use again”…81% MPA, 69% COC

Management of Recurrent DUBManagement of Recurrent DUBManagement of Recurrent DUBManagement of Recurrent DUB

Pregnancy: cycle with clomiphene or metforminPregnancy: cycle with clomiphene or metformin Contraception: cycle with OC Contraception: cycle with OC Not interested in pregnancy or contraceptionNot interested in pregnancy or contraception– MPA or microP first 10-14 days each month or every MPA or microP first 10-14 days each month or every

other other month if pt prefers fewer mensesmonth if pt prefers fewer menses– Place LNG-IUS (Mirena)Place LNG-IUS (Mirena)– Consider endometrial ablation if childbearing completedConsider endometrial ablation if childbearing completed

Perimenopausal bleedingPerimenopausal bleeding– Once hyperplasia excluded, the goal is cycle controlOnce hyperplasia excluded, the goal is cycle control»Low estrogen dose OCLow estrogen dose OC»Cyclic sequential EPTCyclic sequential EPT

Post-coital Bleeding (PCB) Post-coital Bleeding (PCB) Differential DiagnosisDifferential Diagnosis

Post-coital Bleeding (PCB) Post-coital Bleeding (PCB) Differential DiagnosisDifferential Diagnosis

AnatomicAnatomic– Fragile (friable) ectropionFragile (friable) ectropion– Urethral lesionUrethral lesion

InfectionsInfections– Endocervix: GC, Ct, Endocervix: GC, Ct, Ureaplasma, M genitaliumUreaplasma, M genitalium– Cervical or vaginal wartsCervical or vaginal warts– Endometritis (acute or chronic)Endometritis (acute or chronic)

NeoplasticNeoplastic– Endocervical or endometrial polypEndocervical or endometrial polyp– Vaginal, cervical, endocervical, or endometrial invasive Vaginal, cervical, endocervical, or endometrial invasive

cancer (not VaIN, CIN)cancer (not VaIN, CIN)

Post-coital Bleeding: EvaluationPost-coital Bleeding: EvaluationPost-coital Bleeding: EvaluationPost-coital Bleeding: Evaluation

Vaginal examVaginal exam – Epithelial lesions; foreign body; urethral lesionEpithelial lesions; foreign body; urethral lesion

Cervical examCervical exam – Ectropion, cervical leukoplakia or warts, cervical Ectropion, cervical leukoplakia or warts, cervical

mucopus, endocervical polypmucopus, endocervical polyp Cervical testsCervical tests– GC/Ct test, Pap (if not performed recently)GC/Ct test, Pap (if not performed recently)– Endocervical curettage (ECC), as Pap is often falsely Endocervical curettage (ECC), as Pap is often falsely

negative in women with endocervical adenocarcinomanegative in women with endocervical adenocarcinoma If at risk for endometrial hyperplasia, consider EMBIf at risk for endometrial hyperplasia, consider EMB If all negative, SIS to evaluate endometrial polypIf all negative, SIS to evaluate endometrial polyp

Post-coital Bleeding: TreatmentPost-coital Bleeding: TreatmentPost-coital Bleeding: TreatmentPost-coital Bleeding: Treatment Endocervicitis Endocervicitis – GC, Ct: treat with cefixime, azithromycinGC, Ct: treat with cefixime, azithromycin– If If UreaplasmaUreaplasma or or MycoplasmaMycoplasma suspected, treat with suspected, treat with

doxycycline for 7 days or azithromycin 1 gmdoxycycline for 7 days or azithromycin 1 gm Cervical or vaginal wartsCervical or vaginal warts– After biopsy, cryotherapy or 5-FU creamAfter biopsy, cryotherapy or 5-FU cream

Fragile ectropionFragile ectropion– After infection and CIN excluded, cryotherapyAfter infection and CIN excluded, cryotherapy

Endometritis Endometritis – Doxycycline 100 mg PO BID x 14 daysDoxycycline 100 mg PO BID x 14 days

Recurrent MenorrhagiaRecurrent MenorrhagiaRecurrent MenorrhagiaRecurrent Menorrhagia Differential diagnosis Differential diagnosis – Endometrial polypEndometrial polyp– Submucus myomaSubmucus myoma– Coagulpathy: vWD, ITP, liver disease Coagulpathy: vWD, ITP, liver disease – IdiopathicIdiopathic

DiagnosticDiagnostic – Coag panel: consult with hematologistCoag panel: consult with hematologist– SSaline aline IInfusion nfusion SSonography (SIS)onography (SIS)– HysteroscopyHysteroscopy– NOT endometrial biopsy or pelvic US aloneNOT endometrial biopsy or pelvic US alone

Recurrent MenorrhagiaRecurrent MenorrhagiaRecurrent MenorrhagiaRecurrent Menorrhagia

Submucous myoma (fibroids)Submucous myoma (fibroids)– Medical: OCs, progestins, tranexamic acidMedical: OCs, progestins, tranexamic acid– LNG-IUS (Mirena)LNG-IUS (Mirena)– MyomectomyMyomectomy»Laparoscopy, hysteroscopy, or laparotomyLaparoscopy, hysteroscopy, or laparotomy

– Uterine artery embolization (UAE)Uterine artery embolization (UAE)– Hysterectomy (VH, LAVH, LASH)Hysterectomy (VH, LAVH, LASH)– GnRH-a (Lupron) is given for 1-3 months GnRH-a (Lupron) is given for 1-3 months onlyonly »To facilitate surgery by reducing myoma volumeTo facilitate surgery by reducing myoma volume»To induce amenorrhea to treat severe anemiaTo induce amenorrhea to treat severe anemia

LNG-IUS and Fibroids LNG-IUS and Fibroids LNG-IUS and Fibroids LNG-IUS and Fibroids

Small studies with mixed resultsSmall studies with mixed results– Mercorio (2003): 75% persistent menorrhagiaMercorio (2003): 75% persistent menorrhagia– Starczewski (2000): 92% reduced bleedingStarczewski (2000): 92% reduced bleeding

RecommendationsRecommendations– Off-label use; may violate precaution regarding Off-label use; may violate precaution regarding

cavity depth and distortion of uterine cavitycavity depth and distortion of uterine cavity– Reasonable to attempt treatment with MirenaReasonable to attempt treatment with Mirena– Documentation of informed consent content a mustDocumentation of informed consent content a must

56

Tips for IUC Insertion in Tips for IUC Insertion in Women with FibroidsWomen with Fibroids

Tips for IUC Insertion in Tips for IUC Insertion in Women with FibroidsWomen with Fibroids

Determine fibroid location by ultrasoundDetermine fibroid location by ultrasound– Fundal fibroids (intramural, sub-serous) that do not Fundal fibroids (intramural, sub-serous) that do not

distort uterine cavity do not preclude IUC usedistort uterine cavity do not preclude IUC use– Large sub-mucous fibroids, especially in lower Large sub-mucous fibroids, especially in lower

uterine segment, contraindicate IUC useuterine segment, contraindicate IUC use– Evaluate for other pathology, e.g., polypEvaluate for other pathology, e.g., polyp

Ultrasound guidance may facilitate safe placementUltrasound guidance may facilitate safe placement No data on efficacy, but probably not compromised No data on efficacy, but probably not compromised

with LNG-IUS or with Cu-T if fundal placementwith LNG-IUS or with Cu-T if fundal placement

Recurrent MenorrhagiaRecurrent MenorrhagiaRecurrent MenorrhagiaRecurrent Menorrhagia

Idiopathic menorrhagiaIdiopathic menorrhagia– Oral contraceptives (extended regimen or cycle)Oral contraceptives (extended regimen or cycle)– NSAIDS (before and during menses)NSAIDS (before and during menses)» Ibuprofen (400 mg tid), naproxen sodium (275 Ibuprofen (400 mg tid), naproxen sodium (275

mg every 6 hours after a loading dose of 550 mg)mg every 6 hours after a loading dose of 550 mg)– LNG intrauterine system (Mirena)LNG intrauterine system (Mirena)– Tranexamic acid (Lysteda)Tranexamic acid (Lysteda)– Endometrial ablationEndometrial ablation– Hysterectomy (VH, LAVH, LASH)Hysterectomy (VH, LAVH, LASH)

Tranexamic Acid (Lysteda) for HMBTranexamic Acid (Lysteda) for HMBTranexamic Acid (Lysteda) for HMBTranexamic Acid (Lysteda) for HMB

FDA: treatment of cyclic heavy menstrual bleeding FDA: treatment of cyclic heavy menstrual bleeding Mechanism of action is antifibrinolyticMechanism of action is antifibrinolytic Use: 1,300 mg (two 650 mg tablets) TID for up to 5 daysUse: 1,300 mg (two 650 mg tablets) TID for up to 5 days ContraindicationsContraindications– Active thromboembolic diseaseActive thromboembolic disease– History or intrinsic risk of DVTHistory or intrinsic risk of DVT

CautionsCautions– Concomitant therapy with OCs may further increase the Concomitant therapy with OCs may further increase the

risk of blood clots, stroke, or MIrisk of blood clots, stroke, or MI– Women using CHC should use only if a strong medical Women using CHC should use only if a strong medical

need and benefit outweighs risk of TE event need and benefit outweighs risk of TE event

Menorrhagia Medical Therapy: Bleeding Reduction Menorrhagia Medical Therapy: Bleeding Reduction with LNG-IUS vs NSAID and Tranexamic Acidwith LNG-IUS vs NSAID and Tranexamic Acid

Menorrhagia Medical Therapy: Bleeding Reduction Menorrhagia Medical Therapy: Bleeding Reduction with LNG-IUS vs NSAID and Tranexamic Acidwith LNG-IUS vs NSAID and Tranexamic Acid

-100

-75

-50

-25

0

LNG IUS

NSAID

Tranexamic Acid(antifibrinolyticagent)

Milsom et al. Am J Obstet Gynecol 1991;164:879-83.

Meta-Analysis: MirenaMeta-Analysis: Mirena®® vs. Ablation for vs. Ablation for Heavy Menstrual BleedingHeavy Menstrual Bleeding

Meta-Analysis: MirenaMeta-Analysis: Mirena®® vs. Ablation for vs. Ablation for Heavy Menstrual BleedingHeavy Menstrual Bleeding

No difference between rates of treatment failuresNo difference between rates of treatment failures– 21.2% LNG-IUS vs. 17.9% endometrial ablation21.2% LNG-IUS vs. 17.9% endometrial ablation

Both methods resulted in similar improvements in Both methods resulted in similar improvements in quality of lifequality of life

Less need for analgesia/anesthesia in LNG-IUS groupLess need for analgesia/anesthesia in LNG-IUS group Ablation requires additional effective contraceptionAblation requires additional effective contraception

Kaunitz, et al. OG. 2009 May;113(5):1104-16b.

11stst Generation Treatment: Generation Treatment:“Rollerball” Endometrial Ablation“Rollerball” Endometrial Ablation

11stst Generation Treatment: Generation Treatment:“Rollerball” Endometrial Ablation“Rollerball” Endometrial Ablation

TechniqueTechnique– Hysteroscopy, with fluid distention of endometriumHysteroscopy, with fluid distention of endometrium– Rollerball electrocautery of EM, fundus in stripsRollerball electrocautery of EM, fundus in strips

AdvantagesAdvantages– Direct visualization of the endometrial cavityDirect visualization of the endometrial cavity– Permits removal of polyps, submucous fibroidsPermits removal of polyps, submucous fibroids

DisadvantagesDisadvantages– Requires general or regional anesthesiaRequires general or regional anesthesia– Risk of fluid overload, burn injuries, perforationRisk of fluid overload, burn injuries, perforation– Training and expertise in hysteroscopyTraining and expertise in hysteroscopy

Global Endometrial AblationGlobal Endometrial AblationGlobal Endometrial AblationGlobal Endometrial Ablation

Bipolar Dessication (NovaSure Bipolar Dessication (NovaSure ™™)) Cryoablation (Her OptionCryoablation (Her Option™™)) Thermal Balloon (Thermachoice Thermal Balloon (Thermachoice ™™, Caviturm, Caviturm®®)) Microwave Endometrial Ablation (MicrosulisMicrowave Endometrial Ablation (Microsulis)) Hydrothermal Ablation (Hydro ThermAblator Hydrothermal Ablation (Hydro ThermAblator ™™)) Radiofrequency Thermal BalloonRadiofrequency Thermal Balloon

Endometrial Ablation vs HysterectomyEndometrial Ablation vs HysterectomyEndometrial Ablation vs HysterectomyEndometrial Ablation vs Hysterectomy

AdvantagesAdvantages – Office procedure or outpatient surgeryOffice procedure or outpatient surgery– Very low rate of major complicationsVery low rate of major complications– Rapid post operative recovery periodRapid post operative recovery period– Less time consuming and costly vs hysterectomyLess time consuming and costly vs hysterectomy

DisadvantagesDisadvantages– Amenorrhea in 50-70%, but >95% have less bleedingAmenorrhea in 50-70%, but >95% have less bleeding– May fail over time; 2nd ablation required in 5-10%May fail over time; 2nd ablation required in 5-10%– Reduces fertility, but not highly effective Reduces fertility, but not highly effective

contraceptioncontraception– Cervical, endometrial cancer may occur (vs Cervical, endometrial cancer may occur (vs

hysterectomy)hysterectomy)

Postmenopausal Bleeding (PMB) Postmenopausal Bleeding (PMB) Differential DiagnosisDifferential Diagnosis

Postmenopausal Bleeding (PMB) Postmenopausal Bleeding (PMB) Differential DiagnosisDifferential Diagnosis

Hormonal Hormonal – Exogenous estrogens: hormone therapy (HT)Exogenous estrogens: hormone therapy (HT)– Endogenous estrogens: acute stress, estrogen-secreting Endogenous estrogens: acute stress, estrogen-secreting

ovarian tumorovarian tumor Anatomic Anatomic – Atrophic vaginitis, foreign bodyAtrophic vaginitis, foreign body– Endometrial hypoplasia (atrophy)Endometrial hypoplasia (atrophy)– Endometrial hyperplasiaEndometrial hyperplasia– Uterine cancer: endometrial adenocarcinoma, corpus Uterine cancer: endometrial adenocarcinoma, corpus

sarcomasarcoma– Cervical cancer: squamous, adenocarcinomaCervical cancer: squamous, adenocarcinoma

Postmenopausal Bleeding: EvaluationPostmenopausal Bleeding: EvaluationPostmenopausal Bleeding: EvaluationPostmenopausal Bleeding: Evaluation

If If notnot using HT, evaluation is required by either using HT, evaluation is required by either – Endometrial biopsy, or Endometrial biopsy, or – Endovaginal ultrasound (normal stripe is < 5 mm)Endovaginal ultrasound (normal stripe is < 5 mm)

If If usingusing HT, endometrial biopsy (EMB) to evaluate HT, endometrial biopsy (EMB) to evaluate – Cont Combined -EPT: persistent bleeding > 3 months Cont Combined -EPT: persistent bleeding > 3 months

after HT initiationafter HT initiation– Cont Sequential -EPT: persistent unscheduled bleedingCont Sequential -EPT: persistent unscheduled bleeding

Single episode of PMB; limited time and volume; explained Single episode of PMB; limited time and volume; explained – Observation is an acceptable optionObservation is an acceptable option– If recurrent, endometrial evaluation is mandatoryIf recurrent, endometrial evaluation is mandatory

Ultrasound Diagnosis of Ultrasound Diagnosis of Endometrial HyperplasiaEndometrial HyperplasiaUltrasound Diagnosis of Ultrasound Diagnosis of Endometrial HyperplasiaEndometrial Hyperplasia

N=250N=250 Endometrial Stripe ThicknessEndometrial Stripe Thickness

DiagnosisDiagnosis <5mm<5mm 6-10mm6-10mm 11-15mm11-15mm >15mm>15mm

AtrophyAtrophy 93%93% 7%7%

HyperplasiaHyperplasia 58%58% 42%42%

PolypPolyp 53%53% 47%47%

CancerCancer 18%18% 41%41% 41%41%

Grigoriou: Maturitus 23:9-14,1996Grigoriou: Maturitus 23:9-14,1996

Postmenopausal Bleeding: ManagementPostmenopausal Bleeding: ManagementPostmenopausal Bleeding: ManagementPostmenopausal Bleeding: Management

Atrophic vaginitis: Atrophic vaginitis: topical estrogentopical estrogen Chronic endometritis: Chronic endometritis: ++ antibiotics antibiotics Polyp: observe or hysteroscopic excisionPolyp: observe or hysteroscopic excision– Depends upon size, persistent bleeding symptoms Depends upon size, persistent bleeding symptoms

Cystic Cystic hyperplasia or endometrial atrophy hyperplasia or endometrial atrophy – Observe or very low estrogen dose CC-EPTObserve or very low estrogen dose CC-EPT

Simple Simple endometrial hyperplasiaendometrial hyperplasia– Continuous high dose progestin; re-biopsy in 4 mosContinuous high dose progestin; re-biopsy in 4 mos

Atypical Atypical endometrial hyperplasia: hysterectomyendometrial hyperplasia: hysterectomy Endometrial cancer: hysterectomy Endometrial cancer: hysterectomy ++ XRT XRT

ReferencesReferencesReferencesReferences Kaunitz, et al. Meta-Analysis: MirenaKaunitz, et al. Meta-Analysis: Mirena®® vs. Ablation for Heavy vs. Ablation for Heavy

Menstrual Bleeding. Obstet Gynecol 2009 May;113(5):1104-16b.Menstrual Bleeding. Obstet Gynecol 2009 May;113(5):1104-16b. Pitkin J. Dysfunctional uterine bleeding. BMJ 2007;334:1110 Pitkin J. Dysfunctional uterine bleeding. BMJ 2007;334:1110 Munro MG, et al. Oral MPA and COCs for Acute Uterine Bleeding Munro MG, et al. Oral MPA and COCs for Acute Uterine Bleeding

Obstet Gynecol 2006;108:924-9Obstet Gynecol 2006;108:924-9 Dubinsky TJ. Value of sonography in the diagnosis of abnormal vaginal Dubinsky TJ. Value of sonography in the diagnosis of abnormal vaginal

bleeding. J Clin Ultrasound. 2004 Sep;32(7):348-53bleeding. J Clin Ultrasound. 2004 Sep;32(7):348-53 Learman LA, et al, Hysterectomy versus expanded medical treatment Learman LA, et al, Hysterectomy versus expanded medical treatment

for abnormal uterine bleeding: clinical outcomes in the medicine or for abnormal uterine bleeding: clinical outcomes in the medicine or surgery trial. Obstet Gynecol 2004;103(5 Pt 1):824-33surgery trial. Obstet Gynecol 2004;103(5 Pt 1):824-33

Daniels RV, Abnormal vaginal bleeding in the nonpregnant patient. Daniels RV, Abnormal vaginal bleeding in the nonpregnant patient. Emerg Med Clin North Am. 2003;21(3):751-72Emerg Med Clin North Am. 2003;21(3):751-72

Lethaby A, et al. Nonsteroidal anti-inflammatory drugs for heavy Lethaby A, et al. Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding. menstrual bleeding. Cochrane Database Syst RevCochrane Database Syst Rev. 2007;(4):CD000400. 2007;(4):CD000400

Documents

Abnormal Vaginal Bleeding Policar 051611-1