Period Problems: From Puberty to the Post-Menopause

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Period Problems: From Puberty to the Post-Menopause

JodySteinauer,MD,MAS

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No Disclosures, July 4th, 2019• Ihavenothingtodisclose

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Objectives• Whatisnewwiththeperiod• Workupandtreatmentofuterinebleeding• Treatmentofabnormalbleedingduetocontraceptives

1:Periods

3:Fibroids

2:PerimenopausalAUB

4:ContraceptiveSideEffects

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Case 1A23year-oldwomantellsyouaboutanappsheisusingtotrackhercycleandwondersifitiseffectiveasnaturalcontraception.Shealsowonderswhatyouthinkofthemenstrualcuporthenewdiscshereadabout– dotheyworkaswellastampons?

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What’s new with the period? • Mail-orderproducts

– Manywithdonationstolow-resourcesettings• Products

– Menstrualcupsanddiscs– Combotampon+liner– Organiccottontampons– Underwear– Washablepads

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Menstrual Cups• Highacceptability• Higheracceptabilitythantampons

• Lowercostanddecreasedwaste

Howard,FLOW,CFP,2011.Liswood,ObGynm1959.

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Menstrual Cycle Apps!• Systematicreviewoffreeapps• Of108only20wereaccurate(19%)• 80%conception/50%contraception• Only1/8womenhavea28daycycle

• Accuracy:averaged4ofpriorcycles,includingoutsideofusualrange

Moglia,ObGyn,2016

!Vox.com

• Collectdata,fewprivacypolicies• Advertising• Mostfertilityoriented• Incorrectlymarketedaseffectivebc• Assumptionsaboutgender/sexuality,oddemojis/images

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Free App by Planned Parenthood

Plannedparenthood.org

This one from Planned Parenthood is “Spot On”!

• Includesbirthcontrolinformationandreminders

• Noassumptionsaboutgenderorsexuality

• “Nopinkflowersorbutterflies”• Allowslimitedimportfromotherapps

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Case 2A46year-oldwomanreportsherperiodshavebecomeincreasinglyirregularandheavyoverthelast6-8months.Sometimestheycome2timespermonthandsometimesthereare2monthsbetween.Shebleeds10dayswithclotsandfrequentlybleedsthroughpadstoherclothes.Shealsohasdiabetesandisobese.HerLMPwas2monthsago.

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1. FSH2. Testosterone&DHEAS3. Urinehcg4. TSH5. Transvaginal Ultrasound(TVUS)6. EndometrialBiopsy(EMB)

Q1: Which is the first test should you order in this patient?

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Step 1: Pregnant?Pregnant• Ectopic• SpontaneousAbortion• ThreatenedAbortion• (MolarPregnancy)• (Trauma)• (Othercauses)

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

* = Most likely for this patient

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Terminology: What is abnormal?• Normal:Cycle=28days+- 7d(21-35);Length=2-7days;Heaviness=self-defined

• Toolittlebleeding:amenorrheaoroligomenorrhea• Toomuchbleeding:Menorrhagia(regulartimingbutheavy(accordingtopatientor>80cc)ORlongflow(>7days)

• Irregularbleeding:Metrorrhagia,intermenstrual orpost-coitalbleeding

• IrregularandExcessive:Menometrorrhagia

Preferredtermfornon-pregnantheavyand/orirregularbleeding=AbnormalUterineBleeding(AUB)

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Pathophysiology: AnovulatoryBleeding

Bricks&MortarEstrogen=Bricks,buildendometriumProgesterone(P)=Mortar,stabilizes,onlyhavePifovulateNormalmenses:WithdrawalofPcauseswalltofalldown,allatonce(heavywhenhemostatic&vaso-constrictionnotworking,highPG)

Anovulation: NoPsowhenwallgrowstootall,itfalls–irregularly,irregular(Fibroids: Un-steady vasculature, abnlcontraction)

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Abnormal Uterine Bleeding

Bradley,AJOG,2016

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History and Physical Examination• Hx:bleedingpattern,symptomsofanemia,sexual&reproductivehistory,chronicmedicalillness,meds

• Acutev.chronic• PE:signsofanemia,thyroidexamination,abd andgyn exam,(cervicaldysplasia/STIscreening?)

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Initial Work-up: Menometrorrhagia• Always:Urinepregnancy• Usually:TSH• Maybe:Hct,r/ocoagulopathy• Maybe:EMB(EndometrialBiopsy)• Maybebutlater:Transvaginal Ultrasound• Usuallynotnecessary:FSH,LH,Testost,Estradiol

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ACOG, July 2012

ACOGPracticeBulletin128,DiagnosisofAUBinReproductive-AgedWomen

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Perimenopause

• Averages4years

•12%suddenlystopmenstruating

•18%havelonger,heaviermenses

•70%haveshort,irregularmenses

ShouldwethereforeperformEMB onallbut12%ofwomen?

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A Rational Approach to EMB• Naturalhistory:Endometrialcatakesyearstodevelop- noatypia→atypia →invasion.

• Bleedingpatterncues:Cancer&hyperplasiacommonlypresentwithmenometrorrhagia,sometimeswithintermenstrualbleeding,rarelywithregularly-timedmenses.

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A Rational Approach to EMBPost-Menopause:ALLwomenWITHANY BLEEDING(except4-6months

afterstartingHT)

Recentonsetirregularbleeding: Considertreatingfirstandifbleedingnormalizes,noneedforEMB

>50: Allwomenwithrecurrent,irregular bleeding(considernotdoingifperiodslightandspacingout)

45-50: Recurrentirregularbleedingplus>1riskfactorOR>6mosmenometrorrhagia (considernotdoingifperiodslightandspacingout)

<45:Longhistory(>2yr?)ofuntreatedanovulatory bleedingorfailedmedicalmanagement

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Otherreasons:Papwithatypicalglandularcellsorendometrialcells(ifnotdoneattimeofmenses).

EMB isnotperfectlysensitivesofurtherevaluationmandatoryif:

1.PersistentAUB afternegativeEMB2.PersistentAUB after3-6monthsofmedicaltherapy

A Rational Approach to EMB

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Do all women with AUB need an ultrasound?AlthoughTVUSisthebestimagingchoiceforpelvicpathology(betterthanMR,CT)….• 80%withheavymenstrualbleedinghavenoanatomicpathology

• Incidentalfindingssuchasfunctionalovariancystsandsmallfibroids(~50%)areoftenfoundleadingtoanxietyandunnecessarytreatments

• SO….treatfirst,TVUSiftreatmentfails

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What about U/S instead of EMB for post-menopausal bleeding?Transvaginal Ultrasound

• Measureendometrialstripe• Abnormal=>4mm(or5)• Non-specific:myomas,polypsalsocausethickEM• Operatorskillmandatory• NOTUSEFULPRE-MENOPAUSE

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!!!!!!TVUS! ! !!!!!!!!!!EMB!

96%! Sensitivity! 94%!

61%! Specificity! 99%!

99%! NPV! 99%!

40;50%! Further!w/u!necessary!

?!<5%!!

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CanofferpatientchoiceaslongaseitherisquicklyavailableandpatientunderstandsshemayneedEMBafterU/S

TVUS vs EMB to detect cancer (in post-menopausal women)

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Q2: You decide to do a urine pregnancy test and check her TSH – which is the most appropriate next test?1. FSH2. Testosterone&DHEAS3. Serumbeta-HCG4. Transvaginal Ultrasound5. EndometrialBiopsy

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

Ultrasound5. EndometrialBiopsy

A 46 year-old woman reports her periods have become increasingly irregular and heavy over the last 6-8 months. Sometimes they come 2 times per month and sometimes there are 2 months between. LMP 2 months ago. She bleeds 10 days with clots and frequently bleeds through pads to her clothes. She also has diabetes and is obese.

Q2: You decide to do a urine pregnancy test and check her TSH – which is the most appropriate next test?

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EMB=“Disordered Proliferative”. How do I stop the bleeding?MedicalNSAID’sE+Ppill,patch,ringOralProgestinProgestinIUDIMProgestinGnRH agonistTranexamic Acid

SurgicalEndometrialablationD&C/HysteroscopyHysterectomy

Disorderedproliferative=Anovulation

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Treatment of AUB: NSAIDs• Suppressprostaglandinsynthesis,increasesplateletaggregation,andreducesmenstrualbloodloss

• Reducesbloodlossby40%• Usealoneorwithothertreatments• Prescribe5daysATC

– Ibuprofen,mefenamic acid,naproxen

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Treatment of AUB: Estrogen• CHC– pill,patch,ring– improvecyclecontrol,decreasemenstrualbloodloss,decreaseirregularbleeding,whenusedtraditionallyorcontinuously– OneapprovedbyFDAforheavymenstrualbleeding– OftenusedtotreatacuteandchronicAUB– despitelimited(butsome)evidencetosupportit

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Treatment of AUB: Progestins• Oralprogestin

– IfovulatoryAUB:daily progestindecreasesbloodloss(MPA2.5-10mgqd,norethindrone 2.5-5mgqd)

– Ifanovulatory:cyclicprogestin-12-14d/monthimprovesmensesinhalfofwomen

• Injectableprogestin– 50%amenorrheaafter1year,irreg.bleedinginfirstfewmonthsand50%atoneyear

• Intrauterineprogestin– Significantdecreaseinbloodloss,superiortootherprogestins andCHCs

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First Line Hormonal Treatments• Firstchoice:Levonorgestrel IUD

– >80%reductioninbloodloss,decreasedcramping,prevents/treatshyperplasia,highlyeffectivebirthcontrol

– Veryfewcontraindicationstousing– Bloodlosscomparabletoablation,satisfactioncomparabletohyst.

• 2nd choice:combinedcontraceptives(pill,patch,ring)ororalprogestin(cyclicv.daily)orprogestininjection– Proventodecreaseirregularperi-menopausalbleeding– Anytypeok,20mcgpreferredforwomen>40– Estrogencontraindications:smokers>35,HTN,complicatedDM,multipleRFforCAD,h/oDVT,migraines

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Treatment of AUB: Tranexamic Acid• Preventsplasmaformation,fibrindegradation,andclotdegradation

• Moreeffectivethanplacebo,NSAID,cyclicprogestin

• Dose:1gto1.3gevery6-8hoursduringmenses• Risks:TheoreticriskofVTE,noincreaseinlargestudies.Contraindicatedwithhistoryof/riskfactorsforVTE.ProbablysafeinconjunctionwithCHC.

• Sideeffects:Minimal

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Surgical Treatments• D&C,Hysteroscopy:

– Temporaryreductioninbleeding.Curativeiffibroidorpolypremoved.

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

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Perimenopausal / Anovulatory Bleeding: SummaryR/opregnancy,thyroiddz

EMBifmeetscriteria

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

Ifpersists:– U/Stor/oanatomiccauses(andEMBifnotalreadydone)– Discusssurgicaloptionsifrefractorytomedicalmanagement.

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Case 3: Is it the fibroids?SamehistoryasCase2exceptshehasfibroids….Onexaminationheruterusis16weeks’size.• Verycommonà 80%ofhysterectomyspecimens(doneforanyreason)and~75%haveonU/Satage50.

• About50%areasymptomatic• Growslowlyuntilmenopauseandthendecreaseby~50%(canstillcausebleedingpost-menopause)

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AUB with Known Fibroids: Work-up and Treatment• R/ocancer(using“rationalemb algorithm”andpregnancy(don’tblamefibroidsforthebleeding)

• NSAID’sandLNGIUD,CHC,tranexamicacid

• Ifnobetter,blamethefibroids

• +/- Lupron--asabridgetomenopauseorpre-optoshrinktoobtainlessinvasiverouteofhysterectomy

• Othertx (hysteroscopic resectionif<3cm,myomectomy,MR-guidedfocusedu/s,RFA,UAE,hysterectomy)

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Case 4: Because of her contraceptive…• A32year-oldwomanhasrecentlyinitiatedthebirthcontrolpill.

• Shehashadspottingfor30straightdays!Sheisannoyed.

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Case 4: Because of the injection…• A32year-oldwomanhasrecentlyinitiatedthecontraceptiveinjection.


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Case 4: Because of the implant…• A32year-oldwomanhasrecentlyinitiatedthecontraceptiveimplant.


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Case 4: Because of the IUD…• A32year-oldwomanhasrecentlyinitiatedthelevonorgestrel IUD.


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Condom Pill Injection LNGimplant

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 contraceptive discontinuation

MoreauC,etal.Contraception,2005.

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Mechanism for Abnormal Bleeding with Hormonal Contraceptives

Irregularbleeding

Transitionfromthicktothinendometrium

Fragileandsuperficial

bloodvesselsinendometrium

Unstableendometrialstromaandglands

Alteredendometrialremodeling

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Abnormal Bleeding from Contraceptives

Settingexpectations

Bleedingsideeffects Treatment

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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

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COCs: General Counseling

• Takepillatthesametimeeachday– Inconsistentpilluseassociatedwithincreasedriskofunscheduledbleeding1

• Stopsmoking!– Smokersmorelikelytoexperienceunscheduledbleeding/spotting1

– Amongsmokers,bleedingmorelikelytopersistthroughsubsequentcycles

1. Rosenberg WJ et al. Contraception, 1996.

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COCs: Regimens

• CyclicUse • ExtendedCycle

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Treating Bleeding on Cyclic COCs• Supplementalestrogen1

– OralCEE1.25mgx7days– Oralestradiol2mgx7days

• IncreasedoseofestrogenifwomanusingCOCwith< 20mcgestrogen– SeveralCOCscontaining20mcgethinylestradiolresultedin:

• Higherratesofearlytrialdiscontinuation• Increasedriskofbleedingdisturbances2

• Switchtovaginalring1.SperoffL,DarneyPD.ClinicalGuideforContraception.4th Ed.2011.

2.Gallo,MF.CochraneDatabaseofSystematicReviews,2013.

Double or triple the birth control pill?

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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

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DMPA: Setting Expectations• Abnormalbleedingiscommoninthefirstyear• Ratesofunscheduledbleeding1

– Upto70%inthefirstyear– Approximately10%afterthefirstyear

• Amenorrheaismorelikelyovertime1

Within3months After1year At5years

Rateofamenorrhea 12% 46% 80%


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Treating Injection Bleeding

EnhancedCounseling• Bleedingpatterns• Reassurance

ContinueDMPA• Moreinjections,lessbleeding

TREAT• NSAIDsx5-7days

• Estrogen(COCsorsupplementalestrogenx10-20days)

• Tranexamicacid

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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


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Contraceptive Implant: Bleeding Patterns

• Numberofunscheduledbleedingdays:– IsHIGHESTinthefirst3months

– DECREASESoverthefirstyear

– PLATEAUSinthesecondandthirdyear

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

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Contraceptive Implant: Bleeding Patterns

• Moreunpredictablebleedingpattern1– Amenorrheamaynotbesustainedifachieved

– “Favorable”patterninthefirst3monthspredictsacontinuedfavorablepattern

– Forthosewithan“unfavorable”bleedingpattern,50%reportimprovementovertime

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

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Treating Implant Bleeding

EXPECTANTMANAGEMENT

for6-12months

Supplementalestrogen

COCs-10-20days

Oralestrogen-1.25mgCEE-2mgestradiol

Transdermalestrogen-0.1mg/day

NSAIDsx5-7days

USSelectedPracticeRecommendationfor

ContraceptiveUse,2013

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LNG IUS: Setting Expectations• Unscheduledspottingorlightbleedingiscommon,especiallyduringthefirst3–6months

• ForLNG52/5,spottingwaspresentin25%oftheusersat6monthsanddecreasedovertime.1

1. Hidalgo M et al. Contraception, 2002.

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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

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Treating LNG IUS Bleeding

• Pre-insertioncounseling– Discussbleeding/spottinginfirst3-6months

– Discussamenorrhea

• Providereassuranceasbleedinglikelytoimprove

• CheckIUDlocation• NSAIDsATCq4wks mayhelp,noevidenceforestrogen

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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

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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-14 6% 12%at2years

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US Selected Practice Recommendation for Contraceptive Use, 2013

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Conclusions• Abnormaluterinebleeding – thinkofanovulation• Work-up:Alwaysruleoutpregnancy.Usually:TSH,PLN,PossibleHCT,EMB,TVUSifinitialtx fails.

• Treatment:allbleedingtreatedsimilarly• NSAID’splushormones.Persistentrequirescontinuedwork-upevenifEMBand/orultrasoundarenegative.

• Hormonalorcopperbirthcontrol:setexpectations

ThankyoutoRebeccaJacksonandSaraWhetstoneforsharingslides!

Period Problems: From Puberty to the Post-Menopause

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