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UpdateinWomen’sHealth

JudithWalshMD,MPHDivisionofGeneralInternalMedicineWomen’sHealthCenterofExcellence

Planfortoday…• Reviewsomeofthemostsignificantpublishedadvancesin

theWomen’sHealthmedicalliteratureoverthepastyear– Toparticles– Keyarticles– Guidelines

• Assessthestrengthandscopeoftheevidencepresentedintheselectedliterature

• Applythisnewinformationtoourclinicalpractice– Take-homepoints

• SGIMAnnualMeeting,April2017– ErinContratto MD,Bimla Schwarz,MDandLydiaPaceMD

Process

16JournalsMarch12016-Feb20174Independentreviewers:ranked1-4stars

Criteria

• Hownew/innovativeisthisinformation?• Strengthoftheevidence?• Howwillitchangemypractice?

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• OCPsandCancer• BingeEating• CranberryandUTIs• Tomosynthesis

• Lymphedema&blooddraws

• HormonetherapyandCVD

• DXAmonitoringontherapy

• Atypicalfractures

ISSUESAFFECTINGREPRODUCTIVEAGEWOMEN

Case

• 39yearoldwomanwhohasbeenonOCPssinceshewas19,whenshestartedthemforirregularandpainfulmenses.Shedoesnotdesirechildrenandishappywithherlightandrelativelypainlessmenses.Shewouldliketocontinuebutisworriedthattheymaynotbesafeforwomenafter40.Whatdoyoutellher?

TheNews

• Lifetimecancerriskandcombinedoralcontraceptives:theRoyalCollegeofGeneralPractitioners'Oral Contraception Study– Iversen etal.AJOG2017

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UKRoyalCollegeofGeneralPractitioners'Oral Contraception Study

• 46,022womenrecruited1968-1969• Followedforupto44years

– 4661everCOCuserswithatleastonecancerduring884,895woman-yearsofobservation

– 2341neverCOCuserswithatleastonecancerduring388,505woman-yearsofobservation.

Iversen etal.AJOG2017

Results

• Previousconcernsofanyincreasedriskofbreast andcervical cancerlostwithinfiveyearsofstoppingCOC– noevidenceofincreasedriskofeithercancerrecurringwithtime.

– Suggestsearlierdiagnosisratherthantrueharm• Increasedriskoflung cancerwasseenonly

amongeveruserswhosmoked

ImportantcancerreductionspersistmanyyearsafterstoppingCOCuse

• Poissonregressiontoestimateincidencerateratios(IRR)betweeneverandneverCOCusers– adjustedforage,parity,smoking,andsocialclass

EveruseofCOCassociatedwithreducedcancer:• Endometrial (IRR0·66,99%CI0·48-0·89)• Ovarian (IRR0·67,99%CI0·50-0·89)• Colorectal (IRR0·81,99%CI0·66-0·99)• Lymphatic/ (IRR0·74,99%CI0·58-0·94)Hematopoietic

Iversen etal.AJOG2017

Implicationsforpractice

• Hormonal“contraception”maybeimportantforcancerprevention– EspeciallyifBMI>30– Evenifshewerenotseekingcontraception– Evenifshewere50yearsofage

• Levonorgestrel IntrauterineDeviceasanEndometrialCancerPreventionStrategyinObeseWomen:ACost-EffectivenessAnalysis

– Dottino JA,etal.ObGyn 2016

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Irregularbleedinginpremenopausalwomen?

• Bodymassindextrumpsageindecisionforendometrialbiopsy:cohortstudyofsymptomaticpremenopausalwomen– Wiseetal.AJOG2016

• AIM:Toassesstheeffectofbodymassindexonriskofendometrialhyperplasiaorcancerinyoungsymptomaticpremenopuasal women

Methods

• Retrospectivecohortof916premenopausal womenreferredforendometrialbiopsyforabnormaluterinebleeding– Noknownhistoryofendometrialcancer

• SinglesiteinNewZealand,2008-2014• Meanage=42yo• 50%obese(BMI>30)

Wiseetal.AJOG2017

4.9%had“primaryoutcome”1.4%endometrialadenocarcinoma1.1%complexhyperplasiawithatypia2.4%complexhyperplasiaNOatypia

Agedoesnotpredictendometrialrisk

Wiseetal.AJOG2017

PredictorsofPremenopausalEndometrialhyperplasia/cancer

Wiseetal.AJOG2017

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Implicationsforpractice

• Thinkaboutpreventingendometrialcancerwhencaringforobesewomen

• Considerultrasoundtoassessendometriallining+/- Biopsy– Especiallyifmenorrhagiaresultsinanemia

Case:HPV• 25yearoldwomanreceived2dosesofHPVvaccineseveralyearsagoandwantstoknowifsheshouldrestarttheHPVseries?Youtellher…

A. Sincelastdose>12monthsago,sheshouldrestartthefull3doseseries.

B. Ifshereceived2dosesbeforeage15,nofurtherdosesareneeded.

C.HPVvaccineisonly2dosesnow,regardlessofage.

Background:HPVvaccination

v9vHPVvaccine– Gardasil9(Merck®)– FDAapprovedDec2014– 2016:onlyvaccinedistributedinUS– 6,11 (genitalwarts)– 16,18+31,33,45,52,58(oncogenic)

MMWRDec16,2016

TheNewsv TwovsThreeDosesofHumanPapillomavirusVaccineNewPolicyforthe

SecondDecadeoftheVaccinationProgram- Markowitzetal.JAMA.2016

v Immunogenicityof9-valentHPVvaccineUsing2-DoseRegimeninGirlsandBoysvsa3-DoseRegimeninWomen– Iversen etal.JAMA2016§ 1377boys&girlsages9-14§ 97.9%seroconversion4weeksafter2nd dose

vACIPDec2016(AdvisoryCommitteeonImmunizationPractices)• Routinevaccine11-12yo• 2doseseriesages9-14(0,6-12mo)• 15-26:3doseseries(0,1-2,6mo)

MMWRDec16,2016

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Conclusion

vHowmanydosesofHPVvaccineshouldpatientsreceive?

• If2dosesinitiatedbeforeage15years,nofurtherdoses.

• Ifseriesstartedafterage15,3dosesgiven.• Ifvaccinationscheduleisinterrupted,donotrestartseries.

MMWRDec16,2016

Case:BingeEatingDisorder38yo womanpresentstodiscussweightlossoptions.Shehasdifficultywithportioncontrolanddescribesweeklyepisodesofeatinglargequantitiesoffoodinashortperiodoftime.Shefeelsthatshecannotcontrolherselfduringthesebinges.RecentlysheconsumedanentirebagofOreosin30minutes.Shedoesnotinducevomitingorexerciseexcessivelyafterbinges.BMIis29.Whattherapywillpreventbingeeating&reduceweight?

A.sibutramineB.self-directed- cognitivebehaviortherapyC.lisdexamfetamineD.sertraline

BingeEatingDisorder• MostcommoneatingdisorderintheUS

• Lifetimeprevalence– women 3.5%(vsmen2%)– obese 5-30%

• DSMVCriteria– recurrent(>1x/wk)over3mo– brief(<2hrs)– psychologicallydistressedbinge-eating:consumelargeramountsoffoodthanmostpeoplewouldundersimilarcircumstances&lackcontrolovereating

• Currenttreatmentguidelinesareconflicting(AmericanPsychiatricAssociation,NationalInstituteforHealth&CareExcellence)

News:LisdexamfetamineforBingeEatingdisorders

vBinge-EatingDisordersinAdults:AsystematicReviewandMeta-analysis

- Brownley etal.AnnalsofInternalMedicine2016.

Objective:summarizeevidenceaboutbenefits&harmsofpsychological&pharmacologictherapiesforadultswithbinge-eatingdisorder.Methods:systematicreviewFunding:AHRQ

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Results

• 34trialswithlow/mediumriskofbias• Female:77%• Meanage:36-47years• MeanBMI:28.8-41• Treatments:6weeks– 6months

Brownley etal.Annals2016.

BingeEatingDisorderTherapiesTherapy Abstinencefrom

bingeeatingDepressionsymptoms

Weight

Second-generationantidepressants*

Improved(RR1.67)

Improved(MD-1.97)

Nochange

Therapist led-CBT

Improved(RR4.95)

Nochange Nochange

lisdexamfetamine Improved(RR2.61)

- Decreased(5.2-6.3%)

topiramate Moderate benefit(58-64%vs29-30%)2 trials

- Decreased(4.7kg)

*citalopram, escitalopram, duloxetine, bupropion,fluvoxamine,paroxetine,sertraline

Brownley etal.Annals2016

HarmsofTreatment

• Notreportedin– Psychologicalstudies– 20/25pharmacologicstudies

• 3Trials=lisdexamfetamine– Sympatheticnervoussystemarousal:RR4.28– Insomnia:RR2.8(CI1.74-4.51)– GIupset:RR2.71– Generalsleepdisturbances:RR2.19– Headache:RR1.63

Brownley etal.Annals2016

Conclusions

• Inadultswithbingeeatingdisorder:– Increaseabstinencefrombingeeating

• therapistled- CBT• topiramate• lisdexamfetamine• 2nd generationantidepressants(i.e.citalopram,escitalopram,fluoxetine,fluvoxamine,paroxetine,sertraline)

– Reduceweight• topiramate• lisdexamfetamine

Brownley etal.Annals2016

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Case:Cranberryjuice• 36yo womanrecoveringfromrecentE.coliUTIstates,“mymothertoldmecranberryjuicetreatsUTI’s,isthistrue?”Youtellher…

A) ThereisnoevidenceoncranberryjuiceandUTIsB) Cranberryjuice/capsuleshavenotbeenproved

effectiveatpreventingUTIC) Cranberryjuice/capsulespreventUTIsfornursing

homepatientsD) Wrongjuice- tryorangejuice

Background• Cranberryproanthocyanidins

– inhibitadherenceofE.colitouroepithelial cells

• PriorstudiesUTIprophylaxis– women78.5yrs– 300mL(~10oz)=36mg– dailyx6months– decreasedbacteria&pyuria

Howelletal.NEngl JMed.1998Lavigne etal. Clin Microbiol Infect.2008Avorn etal. JAMA.1994

TheNews

• Effectof Cranberry Capsules onBacteriuriaPlus Pyuria Among Older Women in NursingHomes.– Juthani-Mehtaetal.JAMA. 2016

• Objectives– effectof2cranberry capsules/day

(72mgproanthocyanidin)• bacteriuria+ pyuria• womennursinghomeresidents

MethodsStudyDesign

– Double-blindplacebo-controlled,efficacyRCT– 21NursingHomes:Aug2012-Oct2014

Outcomes– Bacteriuria(>100KCFU)+pyuria(WBC)

• assessedq2months,followed12months

Exclusioncriteria– chronicsuppressiveantibiotics– ESRD– Unabletoprovidebaselinecleancatchurinespecimen– warfarin– hx ofnephrolithiasis– indwellingbladdercatheter– nursinghomeresidence<4weeks

Juthani-Mehtaetal.JAMA. 2016

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ResultsNoDifferences

Outcome Cranberrytablets(n=92)

Placebo(n=93)

Bacteriuria +pyuria 29.1% 29.0%SymptomaticUTI 17 16

Allcausehospitalization 33 50

MDRGNBBacteriuria 9 24

AntibioticsforsuspectedUTI 692 909

Totalantimicrobials 1415 1883

Juthani-Mehtaetal.JAMA. 2016

Conclusions

• CranberrycapsulesunlikelytopreventUTIforwomen>65years,residinginnursinghomes

• SupportedbyCochraneReview2012– CranberryunlikelytopreventUTIover12months

MammographyScreening

TheOngoingSaga

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Case

Ms.Smithisa50yearoldwomanwhojusthadherfirstscreeningmammogramwhichshowsheterogeneouslydensebreastsbutnootherabnormalities.• Menarcheat12,firstchildat32• Nohistoryofabreastbiopsy• Nofhx ofbreastcancer

Sheasksifsheshouldhave“oneofthose3Dmammograms”?

Yousay:

• No,Digital(2D)mammograms,every2yearsarefineforyou

• Yes,Digital3Dmammograms(tomosynthesis),every3years

• 2Dor3Dmammogramsevery1yeararefine• Let’sreviewyourriskfordevelopingbreastcancerandyourpreferences

Background

Wangetal,MayoClin Proc2014

• 50%ofbreastsaredense• Tomosynthesis (3Dmammography)

• Nowavailable~22%ofU.S.facilities• Variablycoveredbyinsurance

TheNews• Raffertyetal,BreastCancerScreeningUsingTomosynthesis

andDigitalMammographyinDenseandNondense Breasts,JAMAApril2016

• Objective:– screeningperformanceaccordingtobreastdensitylevel– digitalmammogram+tomosynthesis vsdigitalmammogramalone

• Funding– Hologic

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Methods

– Retrospectivepre/postanalysisofscreeningperformancemetricsfrom13centers

– 452,320screeningmammograms• 278, 906digitalmammos (2D)• 173,414digitalmammos +tomosynthesis (3D)

– Compareddifferencesin(a)recalland(b)cancerdetectionrates,amongwomenwithdensevs.nondensebreasts

Results

AddingTomosynthesis (3D)todigital(2D)mammography1.Decreasedrecallrates2.Increasedcancerdetectionrates3.Effectslargerfordensebreasts

Resultsbybreastdensity

Raffertyetal.JAMAApril2016.

Takehome

• Forwomenwithdensebreasts,tomosynthesisMAYbepreferable(ifavailable)

• Butlong-termclinicalimplicationsstillunknown– Over-diagnosisrates– Breastcancermortality– Costeffectiveness

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USPSTFGuidelinesMammography• Age 50-74: screening mammography every 2 years• Age 40-49: individualize decision to begin biennial

screening according to patient’s context and values• Age ≥75: no recommendation (insufficient evidence)

BreastExam• Clinicalbreastexaminationalone– insufficientevidence• Recommendagainstteachingwomentoperformroutine

breastself-examination– Nomortalitybenefit– Higherratesofbenignbreastbiopsies

» USPSTF2016

USPSTFGuidelines

• Evidenceisinsufficienttoassessthebalanceofbenefitsandharmsfordigitalbreasttomosynthesis(DBT)

• Theevidenceisinsufficienttoassesstherisksandbenefitsofadjunctivescreening(ultrasound,MRIorDBT)forwomenwithdensebreastsandanotherwisenegativescreeningmammogram

– January,2016

TheNews

• TailoringBreastCancerScreeningIntervalsbyBreastDensityandRiskforWomenAged50YearsorOlder:CollaborativeModelingofScreeningOutcomes– Trentham-Dietzetal,AnnInt Med2016

• Modelingstudyofwomenaged50-74at4differentrisklevelsand4breastdensitylevels

• Examinedoutcomesfromannual,biennialandtriennialscreening

IfMs.Smithwasinthemodel….• BreastCancerRiskAssessmentTool(GailModel)https://www.cancer.gov/bcrisktool/– 5-yearrisk1.3%(average);lifetimerisk12.1%(average11.3%)

Lifetimescreeningoutcomesfor1000womenataverageriskwithheterogeneouslydensebreasts….

Triennial Biennial AnnualDeathsaverted 4.8 6.3 8.4Falsepositiveresults 917 1197 2123Overdiagnosis 16 20 28

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Ratiooffalsepositivestodeathsaverted(harm:benefit)byrisk,densityandscreeninginterval

Studylimitations

• Harm:benefitratiosconsiderfalsepositivesnotoverdiagnosis– Highlydependentonpatientpreferences

• Magnitudeofoverdiagnosis consideredinstudyisunclear

• Strategyforriskestimationisalsonotclear

Take-home

• “Screeningbenefitsandharmsexistonacontinuumacrossage,riskanddensity,withtheoptimalscreeningintervaldependingonwomen’svaluesandpreferencesforbenefitsandharms.”

• Triennialscreeningmaybereasonableforlow-riskwomenparticularlythosewithnondense breasts,dependingonpatientpreferences– NotcurrentlyrecommendedinU.S.guidelines

Yousay:

• No,Digital(2D)mammograms,every2yearsarefineforyou

• Yes,Digital3Dmammograms(tomosynthesis),every3years

• Ifyouwant,2Dor3Dmammograms,every1yeararefine

• Let’sgetsupplementalimagingwithMRInow• Let’sreviewyourriskfordevelopingbreastcancerandyourpreferences

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Case• Ms Jonesisa75FwithahistoryofHTNandLbreastcancer12yearsago,s/pmastectomy,chemo,tamoxifen

• Today,BPis175/80ontheR.Yousuggestcheckingbotharms,butshestopsyou,sayingaboutherLarm,“that’smymastectomyarm!”

Yousay:a) Oh,you’reright,thankyousomuchforremindingmeb) Thatisaloadofbaloney,anybreastcancersurvivor

canhaveBPchecksonbotharms.c) Whatkindofmastectomydidyouhave?

TheNews• ImpactofIpsilateralBloodDraws,Injections,BloodPressure

Measurements,andAirTravelontheRiskofLymphedemaforPatientsTreatedforBreastCancer.– Fergusonetal,JournalofClinicalOncology 2016

• Objective:– Evaluateassociationbetweentrauma&armswellinginpatientstreatedforbreastcancer

Breastcancer–relatedlymphedema

• Armswelling,discomfort,andultimatelyimpairedfunctionduetocompromisedlymphaticdamage– Removedlymphnodes(sentinelbx orALND)/axillaryXRT

– Lifetimerisk;14.4mo.averagetimetoonset• Knownriskfactors:ALND,obesity,increasedageatDx

Commonrecommendationsforpreventinglymphedema

• Avoidtraumatoipsilateralarm– blooddraws,injections,BPchecks

• Onplaneflights(pressurechange),wearcompressionsleeves

• Theseguidelinesarebasedonanecdotalevidence,notrigorousstudies

• Placeburden/stressonpatients&providersACS: Lymphedema; NationalLymphedemaNetwork; www.hopkinsmedicine.org;http://ww5.komen.org/BreastCancer/Lymphedema.html

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MethodsStudyDesign:singlesite,prospectivecohortstudyofwomenscreenedforlymphedemainbreastsurgicalclinicParticipants:632womennewlydiagnosedbreastcancer• allhadmastectomyorlumpectomy• 65%hadsomeradiationMethods:

• Prospectivescreeningforlymphedemawperometer(infraredvolumeassessment)pre-op,post-op,thenq3-7months

• Patientsurveyateachvisit» #intervalblooddraws/injections/BPreadings/traumaatriskarm» #flights

Fergusonetal.JournalofClinicalOncology2016

Resultsofmultivariateanalysis

Fergusonetal.JournalofClinicalOncology2016

Conclusions• Ipsilateralblooddraws,injections,BPchecks&flightsdidnotincreasearmswellingatmedian24monthsposttreatment

• Increasedarmswellingisassociatedwith:– AxillaryLNdissection– RegionalLNirradiation– BMI≥25– Cellulitis

• Thesefindingsareconsistentwithotherstudiesbutamorerigorousdesignandlargersamplesizewasused

Fergusonetal.JournalofClinicalOncology2016

Takehome

• Strictprecautionsaboutlymphedemapreventionarenotevidence-basedandwarrantskepticism

• WhatwouldyousaytoMs.Jones?a) Oh,you’reright,thankyousomuchforstoppingme

b)Thatisaloadofbaloney,anybreastcancersurvivorcanhaveBPchecksonbotharms.

c) Whatkindofmastectomydidyouhave?

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Menopause

VasomotorSymptoms

• MinniePauseisa53yearoldwomanwhohadherlastmenstrualperiod18monthsago.Sheisstillhavinghotflashesandawakensatleasttwiceanightwiththem.Shefeelsexhaustedatworkeverydayandwantssomethingthatwill“reallywork.”Heronlymedicalhistoryishypertensionwellcontrolledonlisinopril.Sheisconsideringtakingestrogenbutwantstoknowifitissafe.Whatdoyoutellher?

Whatdoyoutellher?

• Whydon’tyoutryblackcohash- thatwillworkjustaswell

• Venlafaxineisaseffectiveashormonesanditisalotsafer

• Hormonetherapyisprobablyok,ifyoudon’ttakeitfortoolong

• Absolutelynot- noonetakeshormonesanymore

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Whatdoyoutellher?

• Whydon’tyoutryblackcohash- thatwillworkjustaswell

• Venlafaxineisaseffectiveashormonesanditisalotsafer

• Hormonetherapyisprobablyok,ifyoudon’ttakeitfortoolong

• Absolutelynot- noonetakeshormonesanymore

ShouldIusehormones?

• Ok,sotheymayhelpmysymptoms……butaretheysafe?

Background

• ManyobservationalstudiesshowedaninverseassociationbetweenhormonetherapyandCHD

• Clinicaltrialshavesuggestedeithernooradverseeffects

• WomenintheobservationalstudiesweretypicallyyoungerwithHTinitiatedclosertomenopause– “TimingHypothesis”

TheNews

• VascularEffectsofEarlyvsLatePostmenopausalTreatmentwithEstradiol(ELITE)– Hodis etal.NEJM2016

• Objective– Tocomparetheimpactofhormonetherapyonsubclinicalatherosclerosiswhentherapyisinitiatedsoonaftermenopausevs alongtimetimeaftermenopause

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Methods:ELITE• 643healthypostmenopausalwomenwithoutdiabetesorclinicalCVD– Stratifiedbytimesincemenopause

• <6yearsvs.≥10years

• Randomizedto1mgestradiolpluscyclicprogesteronevaginalgel(45mg)vs.placebopillsandgel

• Primaryoutcome:changeincarotidarteryintimalthickness– Measuredevery6months– Secondaryoutcome:coronaryatherosclerosismeasuredbycardiacCT

Results:ELITE

• Amongwomen<6yearsfrommenopause– Inplacebogroup,CIMTincreasedby0.0078mm/year– Inestradiolgroup,CIMTonly0.00044mm/year

• P=0.008

• Amongwomen10+yearspostmenopause– CIMTincreased0.0088mm/yearvs0.0100mm/year

• P=0.29

• NodifferencesincardiacCTmeasuresofatherosclerosisineitherstratum

Conclusion

• Oralestradiolwasassociatedwithlessprogressionofsubclinicalatherosclerosiswheninitiatedwithin6yearsofmenopause,butnotwheninitiated10+yearsaftermenopause

TakeHome

• Estrogentherapygivenaroundthetimeofmenopausedoesnotappeartohavedeleteriouscardiovasculareffects

• Thiscanbetakenintoaccountfordecisionmakingaboutestrogentherapyformenopausalsymptoms

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Osteoporosis

BoneDensityMonitoringEmergingTherapies

Case

• Bonnie Bony is a 68 year old woman who wants to know whether she should have another bone mineral density test. You started her on alendronate last year after a t-score of -2.9. What do you tell her?

Bonnie

1) Let’s schedule it now2) We should do it next year3) There is no need to do it4) I have no idea…what do you think?

Background

• PriorstudieshavenotshownthatrepeatedBMDmeasurementsaremorepredictiveoffracturethanbaselinemeasurement

• WhetherornottomeasureBMDduringpharmacotherapyiscontroversial

• Treatmentfailureisuncommon

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TheNews

• ChangeinBoneMineralDensityisanIndicatorofTreatment-RelatedAntifracture EffectinRoutineClinicalPractice– LeslieWDetal.AnnInt Med2016

• Objective– ToevaluatewhetherrepeatBMDtestingisanindicatoroftreatment-relatedfractureriskreduction

Methods• PopulationbasedregistryinManitoba,Canada• CanadianGuidelines

– Baselinetestingatage65– 3yearfollowupformostpatients– 1yearfollowupforthoseonAIorsteroids– 5yearfollowupforthoseconsideredlowrisk

• DXAdatabase99%completeandaccurateandcanbelinkedwithotherpopulationbasedhealthdatabases

• Outcomes:Incidentnontraumatic hip,clinicalvertebral,forearmandhumerus fractures

Results

• 6629womeninitiatingosteoporosistreatmentwherechangeinBMDcouldbeassessedatoneormoreskeletalsites– 85%initiallyreceivedbisphosphonates

• DetectablechangeinBMD:– Detectableincreasein30.4%ofwomen– Detectabledecreasein18.8%ofwomen– Stablein50.8%

Results• 61,088personyearsoffollowup

– Median9.2years• WomenwithadetectabledecreaseintotalhipBMDhadincreasedriskoffracture– 2.9%(95%CI:1.5%to4.4%)at5yearfollowup– 5.5%(95%CI:2.8%to8.1%)at10yearfollowup

• WomenwithadetectableincreaseintotalhipBMDhadalowerriskoffracture– 1.3%(95%CI:0.4%to2.2%)at5yearfollowup– 2.6%(95%CI:0.7%to4.5%)at10yearfollowup

• ComparableresultsforfemoralneckBMDandlumbarspineBMD

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Conclusions

• TreatmentrelatedincreasesinBMDareassociatedwithadecreasedfracturerisk

• TreatmentrelateddecreasesinBMDareassociatedwithanincreasedfracturerisk

• BMDmonitoringamongwomenonosteoporosistreatmentmay behelpfulinidentifyingthosewithsuboptimalresponses

Take-home

• MonitoringBMDamongwomenonosteoporosistherapymaybeusefulinidentifyingwomenwhohave“suboptimalresponses”totherapy

• Unansweredquestions– Whatis“suboptimalresponse?”– Whatis“treatmentfailure”– IfBMDgoesdown,whatwillyoudodifferently?

AtypicalFemoralFractures

• Althoughbisphosphonatesclearlyreduceriskofhipfracture,therehasbeenincreasingconcernaboutatypicalfemoralfractures

• Atypicalfemoralfractures:– Transversefracturesoriginatingatlateralfemoralcortex

– Subtrochanteric orfemoralshaft– Non-comminutedandassociatedwithcorticalthickening

TheNews

• Riskofhip,subtrochanteric andfemoralshaftfracturesamongmidandlongtermusersofalendronate:nationwidecohortandnestedcasecontrolstudy

• Objective– Todetermineoverallsafetyandefficacyoflongtermuseofalendronateinpatientswithosteoporosis

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Methods

• NationwidepopulationbasedstudyinDenmark• 61,990menandwomenaged50-94atthestartoftreatmentwhohadnotpreviouslytakenalendronate

• Outcomes– Incidentfractureofhip,subtrochanteric femurorfemoralshaft

• Non-fracturecontrolsmatchedbysex,yearofbirthandyearofalendronateinitiation

Results• Incidenceofsubtrochanteric/femoralneckfracture

– 3.4/1000personyears(95%CI:3.2-3.6)• Incidenceofhipfracture

– 16.2/1000personyears(95%CI:15.8to16.6)• Risknohigherinlongtermusersthanincurrentorpastusers

• Highermedicationadherenceandlongerdurationofusewereassociatedwithareducedriskofhipfracture– 0.73(95%CI:0.68to0.78)forMPR>80%– 0.74(95%CI:0.56to0.97)foruse≥10years

Conclusion

• Thebenefit/riskratiosupportsabenefitofalendronateevenwithuseformorethan10years

TakeHome

• Theoverallbenefittoriskratioisfavorableforalendronate,evenwithlongtermuse.

• Longtermalendronateusewillavertmanymorehipfracturesthanwillitcauseatypicalfemoralfractures

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CurrentTherapies

• Bisphosphonates• SelectiveEstrogenReceptorModulators• ParathyroidHormone• Calcitonin• Denosumab

NewTherapies

• Abaloparatide– PeptidethatselectivelybindstheRGconformationoftheparathyroidhormonetypeIreceptor

• Romosozumab– Monoclonalantibodythatbindssclerostin,increasesboneformationanddecreasedresorption

QuickTake:Abaloparatide

• Abaloparatide-ComparatorTrialinVertebralEndpoints(ACTIVE)Phase3doubleblindRCTwith2463women

• Over18months,abaloparatide reducedtheriskofnewvertebralandnonvertebral fractures

• Moreinformationaboutthebenefitsandrisksneeded

• Howdoesitcomparewithotherosteoporosistreatments?

– MillerPDetalJAMA2016

QuickTake:Romosozumab• FractureStudyinPostmenopausalWomenwithOsteoporosis(FRAME)doubleblindplacebocontrolstudyrandomized7180womentoreceiveromosozumab orplacebo

• Monthlysubcutaneousinjectionfor12monthsfollowedbydenosumab (every6months)for12months

• Lowerriskofvertebralfractureat12monthsandat24monthsaftertransitiontodenosumab

• OnecasesofONJandtwoatypicalfemoralfracturesinromosozumab group

• Howdoesitcomparetootherosteoporosistherapies?

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TakeHome

• Twonewosteoporosismedicationsonthehorizonandornewlyapproved

• Wheretheyfitinwithothermoreestablishedmedicationsremainstobeseen

TakeHome

• OCPsappeartobesafeforlongtermuse• NewHPVVaccinerecommendationsarefortwodosesifseriesinitiatedbeforeage15

• Newevidencefortreatmentofbingeeatingdisorder.

• Roleoftomosynthesis needsadditionalstudy• CranberrydoesnotpreventUTIs• Newevidenceforlymphedemariskdependingonmastectomycharacteristics

Summary• Estrogengivenaroundthetimeofmenopausedoesnotappeartohaveanydeleteriouscardiovasculareffects

• MonitoringBMDinwomenontherapymayidentifythosehavingasuboptimalresponse

• Overallbenefittoharmratioforalendronatefavorsbenefitforlongtermtreatment

• Romosozumab andAbaloparatide bothpromisingnewtreatments– Needadditionalinformationabouthowtheycomparewithexistingtreatments

Questions?