“Why am I bleeding?” Diagnosis and Treatment

JodySteinauer,MD,MASDept.Ob/Gyn &ReproductiveSciences

Disclosures

July,2016Ihavenodisclosures.

The Questions

• Toomuch(&tooearlyortoolate)– Differentialandapproachtowork‐up

– Doessheneedanendometrialbiopsy(EMB)oru/s?

• Toofast:She’shemorrhaging—whatdoIdo?

• Sideeffect:duetohormonalcontraception

• Toolittle:Aquickreviewofamenorrhea

Case 1

A46yo G3P2T1reportsherperiodshavebecomeincreasinglyirregularandheavyoverthelast6‐8months.Sometimestheycome2timespermonthandsometimesthereare2monthsbetween.LMP2monthsago.Shebleeds10dayswithclotsandfrequentlybleedsthroughpadstoherclothes.Sheoccasionallyhashotflashes.Shealsohasdiabetesandisobese.

1. Whattermdescribeshersymptoms?

2. Physiologically,whatcausesthistypeofbleedingpattern?

3. Whatisthedifferential?

Q1: In addition to a urine pregnancy test and TSH, which of the following is the most appropriate test to obtain at this time?

1. FSH2. Testosterone&DHEAS3. Serumbeta‐HCG4. Transvaginal Ultrasound(TVUS)5. EndometrialBiopsy(EMB)

Terminology: What is abnormal?

• Normal:Cycle=28days+‐ 7d(21‐35);Length=2‐7days;Heaviness=self‐defined

• Toolittlebleeding:amenorrheaoroligomenorrhea

• Toomuchbleeding:Menorrhagia(regulartimingbutheavy(accordingtopatient)ORlongflow(>7days)

• Irregularbleeding:Metrorrhagia,intermenstrual orpost‐coitalbleeding

• IrregularandExcessive:Menometrorrhagia

• Preferredtermfornon‐pregnantbleedingissues=AbnormalUterineBleeding(AUB)– Avoid“DUB”‐ dysfunctionaluterinebleeding.

Pathophysiology: Anovulatory Bleeding

Bricks&MortarEstrogen=Bricks,buildendometrium

Progesterone(P)=Mortar,stabilizes,onlyhavePifovulate

Normalmenses:WithdrawalofPcauseswalltofalldown,allatonce(orderlybleed)

Anovulation: NoPsowhenwallgrowstootall,itfalls.Itisheavywhenwallistall.Brickscanalsofallintermittently&incompletely–irregularly,irregular

Differential: AUBStep 1: Pregnant?

Pregnant• Ectopic• SpontaneousAbortion• ThreatenedAbortion• MolarPregnancy• Trauma• Somenon‐pregnantcauses

NotPregnant• Anovulation***• Anatomic/structural**• Neoplastic*• Infectious• Iatrogenic• Non‐gynecologic

* = Most likely for this patient

PCOS Hypo/HyperThyroid

Anorexia/Over‐exercise

menopause

Peri‐menarche/Peri‐menopause

Physiologic Hyperandrogenic CNS Iatrogenic

Obesity

Causes of Anovulation Reference: Causes of Anovulation

Pregnancy*Peri‐menarche+Peri‐menopause+Breast‐feeding*Obesity(viainsulineffectinovary)+

PCOS+Adult‐onsetcongenitaladrenalhyperplasia+

Pituitary adenoma (prolactin-secreting)*

Neuroleptic agents (via increased prolactin)*

Hypo or hyper thyroid (* or +)

Hypothalamic (stress, anorexia)*

LevonorgestrelIUD#Progestininjection*#Progestinimplant#Combinedhormonalcontraception#

*Typicallyamenorrhea#Typicallyspotting/lightirregularbleeding+Typicallyirregularheavybleeding(q1.5‐6mos)

Physiologic Hyperandrogenic CNS Iatrogenic

Reference:  AUB Differential 

Uterus:Polyp,adenomyosis,leiomyoma,atrophy

Cervix:polyp,atrophy,trauma

Vagina:atrophy,trauma

Uterus:Hyperplasia,malignancy

Cervix:Dysplasia,malignancy

Ovary:hormoneproducingtumor

Uterus:Endometritis,PID

Cervix:Cervicitis

Vagina:Vaginitis(eg Trich)

Coagulopathy(vWD),severerenalorliverdz,GIorGUsource

Non-Gynecologic

Infectious

Neoplastic

Anatomic

Hormonal

Not Pregnant

Anovulation

NotPregnant

PALM-COEINInitial Work‐up:  Menometrorrhagia

• Always:Urinepregnancy

• Usually:TSH

• Maybe:Hct,r/ocoagulopathy

• Maybe:EMB(EndometrialBiopsy)

• Maybebutlater:TransvaginalUltrasound

• Usuallynotnecessary:FSH,LH,Testosterone,Estradiol

Does she need an EMB?

EndometrialCancerFacts• 4thmostcommoncancerinwomen;averageage61but25%occurinpremenopause.

• 10%ofpost‐menopausalwomenwithbleedinghavecancer.

• Presentsatearlystagewithbleeding;rareintheabsenceofbleeding.Vastmajorityareeffectivelytreatedwithsimplehysterectomy.

• Riskfactor=Increasedestrogen(longh/oanovulatione.g.PCOS,obesity).Protective=smoking,OCP’s.

The Problem

• Irregularbleedingiscommon• Endometrialcancerisrelativelycommon• Riskpredictionmodelsarenotuseful• LittleevidencetoguideusaboutwhentodoEMB• ACOGguidelines(expertopinion)recommendbiopsyinMANYwomen

ACOG, July 2012

ACOGPracticeBulletin128,DiagnosisofAUBinReproductive‐AgedWomen

Perimenopause

• Averages4years

•12%suddenlystopmenstruating

•18%havelonger,heaviermenses

•70%haveshort,irregularmenses

ShouldwethereforeperformEMB onallbut12%of

women?

The Evidence…

• Oneprospectivecohortstudyof1000womentotestlessaggressiveEMBClinicalPathway

• AlleligibleforbiopsyusingACOGguidelines.Onlybiopsiedthosethatwerepost‐menopausalorhadatleast1riskfactor(n=570)

• Nocancers/hyperplasiain2yrs f/uinthosethatweren’tbiopsied.(under‐poweredtoanswerthisquestion)

Dunn,JReprodMed. 2001Sep;46(9):831‐4

A Rational Approach to EMB

• Naturalhistory:Endometrialcancertakesmanyyearstodevelop.Wehavetimetodetectit.

• Bleedingpatterncues:Cancer&hyperplasiapresentmostcommonlywithmenometrorrhagia,sometimeswithintermenstrual bleeding.Rarelywithregularly‐timedmenses.

• Progestins (IUD,progestin‐onlypill)havebeenshowntotreathyperplasiaandcancer.

A Rational Approach to EMB

Post‐Menopause:ALLwomen WITHANY BLEEDING(except4‐6monthsafterstartingHRT)

Recentonsetirregularbleeding: Considertreatingfirstandifbleedingnormalizes,noneedEMB

>50: Allwomenwithrecurrent,irregular bleeding(considernotdoingifperiodslightandspacingout)

45‐50: Recurrentirregularbleedingplus>1riskfactorOR>6mosmenometrorrhagia

<45:Longhistory(>2yr?>5yr?)ofuntreatedanovulatory bleeding(eg PCOS)

A Rational Approach to EMB (cont’d)

Otherreasons:Papwithatypicalglandularcellsorendometrialcells(ie ifpapnotdoneattimeofmenses).

EMB isnotperfectlysensitivesofurtherevaluationmandatoryif:

1.PersistentAUB afternegativeEMB

2.PersistentAUB after3‐6monthsofmedicaltherapy

Do all women with AUB need an ultrasound?

AlthoughTVUS isthebestimagingchoiceforpelvicpathology(ie betterthanMRI,CT)….• 80%withheavymenstrualbleedinghavenoanatomicpathology

• Incidentalfindingssuchasfunctionalovariancystsandsmallfibroids(~50%)areoftenfoundleadingtoanxietyandunnecessarytreatments

• SO….treatfirst,TVUS iftreatmentfails

What about U/S instead of EMB for post‐menopausal bleeding?

Transvaginal Ultrasound

• Measureendometrialstripe

• Abnormal=>4mm(or5)

• Non‐specific:myomas,polypsalsocausethickEM

• Operatorskillmandatory

• NOTUSEFULPRE‐MENOPAUSE

TVUS vs EMB to Detect Cancer (in post‐menopausal women)

TVUS EMB

96% Sensitivity 94%

61% Specificity 99%

99% NPV 99%

40‐50% Furtherw/unecessary

?<5%

CanofferpatientchoiceaslongaseitherisquicklyavailableandpatientunderstandsshemayneedEMBafterU/S

Q1: In addition to a urine pregnancy test and TSH, which of the following is the most appropriate test to order at this time?

1. FSH2. Testosterone&DHEAS3. Serumbeta‐HCG4. Transvaginal

Ultrasound5. EndometrialBiopsy

A46yo G3P2T1reportsherperiodshavebecomeincreasinglyirregularandheavyoverthelast6‐8months.Sometimestheycome2timespermonthandsometimesthereare2monthsbetween.LMP2monthsago.Shebleeds10dayswithclotsandfrequentlybleedsthroughpadstoherclothes.Sheoccasionallyhashotflashes.Shealsohasdiabetesandisobese.

EMB=“Disordered Proliferative”. How do I stop the bleeding?

MedicalNSAID’sTranexamic AcidOralE+PE+Ppatch,ringHRT(lowerdoseE+P)HRTpatchOralProgestinProgestinIUDIMProgestinGnRH agonist

SurgicalEndometrialablation

(D&C/Hysteroscopy)

Hysterectomy(failedmedicalmanagement)

Disorderedproliferative=Anovulation

Non‐hormonal Treatment: NSAID’s

• 5daysaroundtheclock(eg 600mgtid)

• ManydosagesandtypesproveneffectiveinmultipleRCT’stodecreasebleedingby~40%

• Usealoneorwithothertherapies

DON’TFORGETNSAIDs!

First Line Hormonal Treatments

• Firstchoice:Levonorgestrel IUD– >80%reductioninbloodloss,decreasedcramping,prevents/treatshyperplasia,highlyeffectivebirthcontrol

– Veryfewcontraindicationstousing– Bloodlossandsatisfactioncomparabletoablation,satisfactioncomparabletohyst.

• 2nd choice:combinedcontraceptives(pill,patch,ring)orprogestininjection– Proventodecreaseirregularperi‐menopausalbleeding– Anytypeok,20mcgdosepreferredforwomen>40– Estrogencontraindications:smokers>35,HTN,complicatedDM,multipleRFforCAD,h/oDVT,migraines>35orwithaura

Second Line Hormonal Options

• CyclicProgestins:– LesseffectivethanNSAID’sandLevo IUD– 21‐daytherapymoreeffectivethan10‐day‐ poorlytolerated

• HT(post‐menopausaldosing):– MoredifficulttogaincyclecontrolcomparedwithOCP– SamecontraindicationsasCombinedHormonalContraception

Tranexamic Acid

• Anti‐fibrinolytic;availableinEuropeformanyyears‐availableinUS2011

• InRCT’s,moreeffectivethanNSAID,cyclicprovera.– LesseffectivethanMirena.ImprovesQOLby80%by3rdcycle

• Dose:2tabstid for5days(1300mgq8=3900mg/day)

• Risks:TheoreticriskofVTE.Noincreaseinlargestudies.ContraindicatedinthosewithhistoryoforriskfactorsforVTE.UnknownifsafeinconjunctionwithCHC.

• Sideeffects:Minimal

Surgical Treatments

• D&C,Hysteroscopy:– Notreallyatreatment.Temporaryreductioninbleeding.Diagnostic,notcurative(exceptifpolypremoved).

• EndometrialAblation– Reducesbutdoesn’teliminatemenses– ~25%repeatablationorhyst in5years– Mustruleoutcancerfirst– Can’tbedonein>12weekuteriorforwomenwhowantfertility

Perimenopausal/AnovulatoryBleeding: Summary

R/opregnancy,thyroiddz

EMBifmeetscriteria

Treatfirstasifanovulatory bleeding:– NSAID’s+– Hormones(Levo IUD,CHC,DMPA)

Ifpersists:– U/Stocheckforanatomiccauses(andEMBifnotalreadydone)

– Discusssurgicaloptionsforbleedingrefractorytomedicalmanagement.

Case 2: Is it the fibroids?

SamehistoryasCase1exceptshehasfibroids….

A46yo G2P2womanpresentsstatingthatherfibroidsarecausingirregularbleeding.

Shehasaknownfibroiduterusandcomplainsofincreasinglyirregularandheavyperiods.Sometimestheycome2timespermonthandsometimesthereare2monthsbetween.LMP 2monthsago.Shebleeds10dayswithclotsandfrequentlybleedsthroughpadstoherclothes.Sheoccasionallyhashotflashes.Shealsohasdiabetesandisobese.

Onexam,heruterusis16weekssizeandirregular.

Fibroids…...

• Verycommon 80%ofhysterectomyspecimens(doneforanyreason)and~75%haveonU/Satage50.

• 2‐3foldhigherincidenceinblackwomen

• About50%areasymptomatic

• Growslowlyuntilmenopauseandthendecreaseby~50%(canstillcausebleedingpost‐menopause)

Fibroid Symptoms• Bleeding

– Usuallynormal ormenorrhagia(heavybutregular).Fibroidsstretchendometrium=morebleeding

– Occasionallymenometrorrhagiaifsubmucous orintracavitary(Fibroidsdistortendometriumsoitcan’tbestable)

• Pressure(notpain)• Dysmenorrhea

Heavy,irregularbleeding

NoeffectHeavy,regularbleeding

Is the bleeding due to the fibroids? 

• Fibroidsarecommoninlater40s• Anovulationiscommoninlater40s• Theincreasedbleedingseenwithfibroidsistypicallyduetoincreasedvolumeordistortionoftheendometrium

• Therefore:Decreasetheamountofendometriumbytreatingasanovulatory bleeding.Thisoftenworks.

AUB with Known Fibroids: Work‐up and Treatment

• R/ocancer(using“rationalemb algorithm”)andpregnancy(don’tblamefibroidsforthebleeding)

• NSAID’sandhormones

• Ifnobetter,blamethefibroids!

• +/‐ Lupron‐‐asabridgetomenopauseorpre‐optoshrinktoobtainlessinvasiverouteofhysterectomy

• Surgicaltherapies(hysteroscopic resectionif<3cm,myomectomy,hysterectomy,UAE)

Hysterectomy

• Veryhighpatientsatisfaction(90%)(higherthanablation)

• Improvedqualityoflife,sexualsatisfactionanddecreasedpain

• Increasedlong‐termrisksofprolapse,incontinence

Uterine Artery Embolization• Benefits:40%decreasesize,75‐90%improvedbleeding

• Re‐grow?In5yrf/uofRCT,25%hadhysterectomy

• Notfor:womenwhowantfertility• A“major”non‐surgicalprocedure:

– Oftenrequireshospitalizationforpaincontrol

– ~2weekstoreturntofullactivities(duetopainandfever)

– Risks:emergenthyst (1‐2%),5%expelmyoma throughcervix,40%havefever

Case 3… Too Fast

41yearoldwomanpresentswithdizzinessandheavyvaginalbleedingfor2weeksstraight.

Priortothis,occasionalirregularperiodsbutnothinglikethis!

Hemoglobin=9

Acute Menorrhagia Treatment

ABC’sandStopthebleeding!• ConsiderEDfortransfusion• Estrogen—2‐4OCPs(30‐35mcgE2)

– OralaseffectiveasIV(souseoral)

• Givewithanti‐emetic• SmallRCTsuggestshigh‐doseprovera maybeeffectiveas

well,20mgtid• Ifnoteffective,options:D&C,Foleybulbtamponade,

emergencyhysterectomy

OCP Taper

• Don’twanttogive2‐4OCP’s perdayandthenstopsuddenlyb/cwillhavelargewithdrawalbleed

• Taper:4x4days,3x4days,2x4daysthen1 perdayfor1‐2months(66‐96pillsrequired).

• Instructnottotakeplacebosandgiveatleast3packsofpillsatonce.

• Givewithanti‐emetic,splitbid(i.e.2bidratherthan4allatonce)

Case 4:  Because of her contraceptive…

• A32year‐oldwomanhasrecentlyinitiatedthebirthcontrolpill.

• Shehashadspottingfor30straightdays!Sheisannoyed.

Case 4:  Because of the injection…

• A32year‐oldwomanhasrecentlyinitiatedthecontraceptiveinjection.

• Shehashadspottingfor30straightdays!Sheisannoyed.

Case 4:  Because of the implant…

• A32year‐oldwomanhasrecentlyinitiatedthecontraceptiveimplant.

• Shehashadspottingfor30straightdays!Sheisannoyed.

Case 4:  Because of the IUD…

• A32year‐oldwomanhasrecentlyinitiatedthelevonorgestrel IUD.

• Shehashadspottingfor30straightdays!Sheisannoyed.

Condom Pill InjectionLNGimplant

n=705 n=1637 n=579 n=66%Reportingthefollowingreasons

Tooexpensive 2.2 3.2 2.1 1

Toodifficultormessytouse 15.2 5.7 1.2 10.4Partnerunsatisfied 38.6 2.8 2.6 1.2Experiencedsideeffects 17.9 64.6 72.3 70.6Worriedaboutsideeffects 2 13.1 4.2 4.2

Didnotlikethechangesinmenstrualperiods 1.5 12.7 33.7 19.3

Experiencedcontraceptivefailure 7.5 10.4 5.7 8.3Worriedabouteffectiveness 13.2 3 2.2 0NoprotectionagainstSTIs 1.1 2.1 1.3 0Otherhealthproblems/doctor'sadvice 2.5 8.5 5.7 9.2Methoddecreasedsexualpleasure 37.9 4.1 8.2 1.1Toodifficulttoobtain 1.5 1.8 2 0Otherreason 15.4 10.6 8.1 10.2

Reasons for dissatisfaction leading to pill, condom, implant or injection discontinuation

MoreauC,etal.Contraception,2005.

Mechanism for Abnormal Bleeding with Hormonal Contraceptives

IrregularbleedingIrregularbleeding

Transitionfromthicktothinendometrium

Transitionfromthicktothinendometrium

Fragileandsuperficial

bloodvesselsinendometrium

Fragileandsuperficial

bloodvesselsinendometrium

Unstableendometrialstromaandglands

Unstableendometrialstromaandglands

Alteredendometrialremodeling

Alteredendometrialremodeling

COCs: Setting Expectations

• Ratesofunscheduledbleeding– 10‐30%inthefirstmonth– Lessthan10%bythethirdmonth

• Ratesofamenorrhea– Lessthan2%inthefirstyear– Upto5%after1year

1. Speroff L, Darney PD. Clinical Guide for Contraception. 4th Ed. 2011

COCs: General Counseling

• Takepillatthesametimeeachday– Inconsistentpilluseassociatedwithincreasedriskofunscheduledbleeding1

• Stopsmoking!– Smokersmorelikelytoexperienceunscheduledbleeding/spotting1

– Amongsmokers,bleedingmorelikelytopersistthroughsubsequentcycles

1. Rosenberg WJ et al. Contraception, 1996.

CyclicUse ExtendedCycle

COCs: Regimens

Treating Bleeding on Cyclic COCs

• Supplementalestrogen1– OralCEE1.25mgx7days– Oralestradiol2mgx7days

• IncreasedoseofestrogenifwomanusingCOCwith<20mcgestrogen– SeveralCOCscontaining20mcgethinylestradiolresultedin:

• Higherratesofearlytrialdiscontinuation• Increasedriskofbleedingdisturbances2

• Switchtovaginalring

1.SperoffL,DarneyPD.ClinicalGuideforContraception.4th Ed.2011.2.Gallo,MF.CochraneDatabaseofSystematicReviews,2013.

Double or triple the birth control pill?

Treating Bleeding on Extended COCs

• DiscontinuetheCOCsfor3‐4consecutivedays1

– A3‐dayhormonefreeintervalwasassociatedwithgreaterresolutioninbreakthroughbleeding/spottingincomparisontocontinuingactivepills2

– Afterthefirst21daysofthehormone

1. Godfrey EM et al. Contraception, 201; 2. Sulak PJ et al. AJOG, 2006

DMPA: Setting Expectations

• Abnormalbleedingiscommoninthefirstyear• Ratesofunscheduledbleeding1

– Upto70%inthefirstyear– Approximately10%afterthefirstyear

• Amenorrheaismorelikelyovertime1

Within3months

After1year At5years

Rateofamenorrhea 12% 46% 80%

1. Speroff L, Darney PD. Clinical Guide for Contraception. 4th Ed. 2011

Valdecoxib1

• Dose:40mgdailyx5d

• Morewomeninthetreatmentgrouphadcessationofbleeding(77%vs.33%)

• Treatmentgrouphadahighermeannumberofbleeding‐freedaysinthefollowingmonth(17.8vs.11.5days)*

*statisticallysignificant

Mefenamicacid2

• Dose:500mgbidx5d

• Morewomenintreatmentgrouphadcessationofbleedingintheweekfollowingtreatment(69%vs.40%)

• Nosignificantdifferenceinbleeding‐freedaysinthefollowingmonth(16.1intreatmentgrp vs.12.4inplacebogrp)

NSAIDs and Contraceptive Injection

1. Nathirojanakun P. Contraception, 2006.2. Tantiwattanakul. Contraception, 2004.

Estrogens and Contraceptive Injection

RCTofDMPAuserswithunscheduledbleeeding1

Ethinylestradiol50mcg

Estronesulfate2.5mg

Placebo

Conclusions Ethinylestradioleffective instoppingbleedingduringtreatment Bleedingtended torecurafterdiscontinuationofestrogen

1. Said S et al. Human Reproduction, 1996.

Tranexamic Acid and Injection

%stoppedbleedingin1stwk 88% 8.20%%stoppedbleedingin4wkf/u 68% 0%Meannumberofdaysofbleeding/spotting

5.7 17.5

RCTofDMPAuserswithunscheduledbleeeding1

Tranexamicacid250mgqidx5days

Placebo

1. Senthong AJ et al. Journal of Medical Association of Thailand, 2009.

Summary: Injection Bleeding

EnhancedCounseling• Bleedingpatterns

• Reassurance

EnhancedCounseling• Bleedingpatterns

• Reassurance

ContinueDMPA• Moreinjections,lessbleeding

ContinueDMPA• Moreinjections,lessbleeding

TREAT• NSAIDsx5‐7days• Estrogen(COCsorsupplementalestrogenx10‐20days)

• Tranexamicacid

TREAT• NSAIDsx5‐7days• Estrogen(COCsorsupplementalestrogenx10‐20days)

• Tranexamicacid

Etonogestrel Implant: Setting Expectations

• Mostwomenexperienceareductionofmenstrualbleeding1

• Bothersomebleedingreportedin25%ofpatients2

– 6.7%reportedfrequentbleeding– 17.7%prolongedbleeding

• Ratesofamenorrhea3

– Approximately20%infirstyear– 30‐40%after1year

1. Mansour D. Contraception, 2011.2. Mansour D. European Journal of

Contraception & Reproductive Health Care, 2008

3. Speroff L, Darney PD. Clinical Guide for Contraception. 4th Ed. 2011

Contraceptive Implant: Bleeding Patterns

• Numberofunscheduledbleedingdays:

– IsHIGHESTinthefirst3months

– DECREASESoverthefirstyear

– PLATEAUSinthesecondandthirdyear

1 Flores JB, International Journal of Gynecology & Obstetrics, 2005.

Contraceptive Implant: Bleeding Patterns

• Moreunpredictablebleedingpattern1– Amenorrheamaynotbesustainedifachieved

– “Favorable”patterninthefirst3monthspredictsacontinuedfavorablepattern

– Forthosewithan“unfavorable”bleedingpattern,50%reportimprovementovertime

1 Mansour D, European Journal of Contraception & Reproductive Health Care, 2008.

NSAIDs and Etonogestrel Implant

• Limiteddata

• VariableefficacyofNSAIDsinLNGimplant1,2

– Variousregimens– Smallnumberofstudiesandparticipants

• OneRCTevaluatedNSAIDsinwomenwithETGimplants3

– Randomizedtoplaceboormefenamicacid(500mgtid)– 65%stoppedbleedingwithin1weekinNSAIDgroupvs.21%intheplacebo

– Lessbleedinginthesubsequent4weeksinthewomenwhohadreceivedNSAIDs

1 Mansour D, European Journal of Contraception & Reproductive Health Care, 2008. 2. Abdel-Aleem H, Cochrane Database of Systematic Reviews, 2013.

3. Phaliwong P, Journal of Medical Association of Thailand, 2004.

Estrogen and LNG Implant

• RecommendationsbasedonstudiesofLNGimplant

• Systematicreviewofestrogenvs.placebotreatmentforirregularbleedingwithLNGimplant1

– Decreasedthedaysofongoingbleeding

– Effectlastedforseveralmonthsaftertreatment

– Moresideeffectsintreatmentgroup(nausea,GIupset)

1. Abdel-Aleem H, Cochrane Database of Systematic Reviews, 2013.

Implant Bleeding Management

EXPECTANTMANAGEMENT

for6‐12months

EXPECTANTMANAGEMENT

for6‐12months

Supplementalestrogen

Supplementalestrogen

COCs‐10‐20daysCOCs

‐10‐20days

Oralestrogen‐1.25mgCEE‐2mgestradiol

Oralestrogen‐1.25mgCEE‐2mgestradiol

Transdermalestrogen‐0.1mg/day

Transdermalestrogen‐0.1mg/day

NSAIDsx5‐7days

NSAIDsx5‐7days

US Selected Practice Recommendation for Contraceptive

Use, 2013

LNG‐IUS: Setting Expectations

• Unscheduledspottingorlightbleedingiscommon,especiallyduringthefirst3–6months

• ForLNG52/5,spottingwaspresentin25%oftheusersat6monthsanddecreasedovertime.1

1. Hidalgo M et al. Contraception, 2002.

LNG IUS: Setting Expectations

• 79‐97%reductioninbleeding• 33%developedoligo/amenorrheainfirst3months,70%at2yrs

• Amenorrheaat1yr:20%• Amenorrheaat2yrs:30‐40%

• Amenorrheaat1yr:6%• Amenorrheaat2yrs:12%

LNG 52/5

LNG13.5/3

Office1

LNG‐IUS: Interventions for Bothersome Bleeding

• Estrogen1– Estradiolpatchweeklyx12weeks– Greaternumberofbleeding/spottingdayscomparedtoplacebo(non‐significant)

– Moredissatisfactionwithtreatment

• NSAIDs1– Naproxen500mgbidx5daysevery4weeksfor12weeks

– Fewernumberofbleeding/spottingdayscomparedtoplacebo(non‐significant)

– Moredissatisfactionwithtreatment

“No direct evidence was found regarding

therapeutic treatments for bleeding

irregularities during LNG-IUD use.”

-US SPR, 2013

1. Madden T et al. AJOG, 2012.2. Abdel-Aleem H, Cochrane Database of

Systematic Reviews, 2013.

LNG IUD Bleeding

• Provideexcellentcounselingpre‐insertion– Discussbleeding/spottinginfirst3‐6months

– Discussamenorrhea

• Providereassuranceasbleedinglikelytoimprove

• ConfirmappropriatelocationofIUD

Irregular Bleeding by Contraceptive Ratesofirregularbleeding

COCs • 10‐30%infirstmonthofuse• <10%bythethirdmonthofuse

VaginalRing • Lesscommonin comparisontoCOCs• Upto6%infirstyear

Patch • SimilartoCOCs exceptslightlyhigherrateofspottinginfirst2cycles

Injectable • 70%in first year• 10% afterthefirstyear

Implant • Upto25% infirst2years

Cu‐IUD • Lessirregularbleedingcompared toLNG‐IUS

LNG‐IUS • Upto25% at6months• 8‐11%at18‐24months

Slide 67

Office1 Image?Microsoft Office User, 6/17/2016

Amenorrhea by ContraceptiveRATESOFAMENORRHEAWithin 1st year At1year Beyond

COCs <2% Upto5%

VaginalRing SimilartoCOCs

Patch SimilartoCOCs

Injectable 12% 46% 80%at5yrs

Implant 21% 30‐40%

Cu‐IUD 0% 0% 0%

LNG‐20 20% 30‐40% at2yrs

LNG‐146% 12%at2years

US Selected Practice Recommendation for Contraceptive Use, 2013

What about too little bleeding?

Sevenquestionsinevaluationof2° amenorrhea

1. Pregnant?2. Excessivehairgrowthoracne? PCOS3. Overweight? Obesity‐inducedanovulation4. Breastsecretions? Hyperprolactinemia5. Verythin,over‐exercise,stress? Functional

hypothalamicamenorrhea6. Hotflashes? Prematureovarianfailure7. Pregnantrecentlycomplicatedwithinfectionoruterine

surgery(D&C)? Asherman’s syndrome

Size of words reflects frequency.

WORK‐UP:  Amenorrhea

• Always:– Urinepregnancytest

– IfNeg:TSH&Prolactin

• Ifhotflashes:– FSH

• Ifhirsute/obese:

– Usuallynofurthertestingneeded.(Ifdeepvoiceorclitoromegaly:testosterone.Iffamilyhistoryhirsutism oronsetatpuberty:17OH‐P)

Reference: Progestin Challenge Test

• Progestinchallengetest:(10mgProverax10days)– Bleedingafterconfirmsendogenousestrogenispresent

– Distinguisheshypothalamicamenorrhea(nobleedingorjustspots)fromPCOS/anovulation(fullwithdrawalbleed)

• Estrogenchallengetest:(Premarin 2.5mgqd x3wksthenProverax10days)distinguisheshypothalamicamenorrhea(fullwithdrawalbleed)fromAsherman’s (nobleedingorjustspots)

Amenorrhea Treatment

1. PCOS Protecttheendometrium!(fromhyperplasiaduetounopposedE2) combinedcontraceptives,DMPA,LNGIUD

2. Obesityinducedanovulation same

3. Hyperprolactinemia duetomicroadenoma OCPsornothing,Bromocriptine ifdesirespregnancyortotreatsxs

4. Functionalhypothalamicamenorrhea‐‐ protectthebones!(fromlackofE2) estrogen‐containingcontraceptives

5. Prematureovarianfailure same

6. Asherman’s syndrome Hysteroscopy

Conclusions

• Diagnosis:thinkofanovulation• Work‐up:Alwaysruleoutpregnancy.Usually:TSH,PLN,?HCT,?EMB,TVUSifinitialtx fails.

• Treatment:allbleedingtreatedsimilarly• NSAID’splushormones.Persistentabnormalbleedingrequirescontinuedwork‐upevenifEMBand/orultrasoundarenegative.

• Hormonalorcopperbirthcontrol:setexpectations