ashraf - managing pcos at a young agepcoschallenge.org/.../managing-pcos-at-a-young-age... · •...
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ManagingPCOSataYoungAgeAmbikaAshraf,MDAssociateProfessor
PediatricEndocrinology
Disclosures• Otsuka– Researchgrant• Merck– Researchgrant• ThrasherResearchFund
EducationObjectives1) UnderstandthediagnosisofPolycysticOvary
Syndromeinteenagers2) Beawareoftheconditionsthatcanbemislabeled
asPCOS3) Describethecomponentsofmanagement4) DiscussthemetabolicconsequencesofPCOSin
teenagers
PolycysticOvarySyndrome• Mostcommonsymptoms:• Menstrualirregularity• Infrequentmenses(oligomenorrhea >45days, <8cycles/year)• Primaryamenorrhea(nocyclebyage15or3yearsafterbreastdevelopment)• Secondaryamenorrhea(absentmenses >90days)• Canhave‘regular’periodswithoutovulation(10-15%)• Frequentheavybleeding(<21days)*** Persists2yearsbeyondmenarche
PolycysticOvarySyndrome• Othercommonsymptoms:• Hirsuitism- terminalhairgrowthinamalepattern- darkcoarse• Acne- severe,cystic- occuralongjawline,back,chest
• Obesity:inUS~2/3rd ofpatientswithPCOS-ObesityunmasksoramplifiesPCOS
RosenfieldRL.NEnglJMed2005;353:2578-2588.
The Ferriman–Gallwey Scoring System for HirsutismVisual grading over 9 body areas
Otherassociatedskinconditions• Acanthosisnigricans:neck,groin,skinfolds,underarms.Frominsulinresistance
• Rarelyalopecia:scalphairthinninginmalepattern
PCOSinadolescents- DiagnosticCriteria
• Onlyneed2criteria:• Hyperandrogenism:clinicalorbiochemical*Centraltodiagnosis• Menstrualirregularities:thatpersists>2yearsafteronsetoffirstperiod
• Absenceofanotherunderlyingendocrinopathy
Required
Hyperandrogenism Clinical/biochemical
X
Oligo-/amenorrhea Persistent XPCOmorphology Maybenormal NO
PCOS“Look-alikes”• Adolescence• Hypothyroidism• Hyperprolactinemia• OvarianFailure• Obesity• CushingSyndrome/Disease• HypothalamicDysfunction• Non-classicalCongenitalAdrenalHyperplasia• Androgen-SecretingTumor
PCOS“Look-alikes”• Non-classicalCongenitalAdrenalHyperplasia• Resultsinmenstrualirregularitiesandhyperandrogenism• Enzymedefectinsteroidpathway(adrenalandovary)• Measure17-hydroxyprogesteronetodiagnose
PCOS“Look-alikes”• Androgen-secretingTumor(adrenalorovariantumors)• Consideriftotaltestosteroneis>200ng/dL• Unusualsymptoms:voicedeepening,clitoromegaly,malepatternbalding• Rapidonsetofsymptoms• Mayneedpelvicultrasound(ovaries)andCTScan(adrenals)
PCOS“Look-alikes”• CushingSyndrome/Disease• Cortisolexcess• FromACTH-producingtumor• Fromcortisol-producingtumor• Steroidexposure• Clinicalfeatures:-Obesity-Hypertension-Striae-Muscleweakness
Laboratoryevaluation• SerumTestosterone:totalandfreeVariabilityofassays,diurnalfluctuations,lackofwelldefinedadolescentcut-offpointsTestosteronereachadultlevelsbyage15Reliableassay:LCMS/MS
• FSH/LH/estradiol• TSH,FT4• Prolactin• 17-hydroxyprogesterone• DHEAS• Midnightsalivarycortisol• Urine24-hrfreecortisol• Pelvicultrasound
Evaluatingassociatedrisks• Bloodpressure• Bodymassindex• Signsofinsulinresistance:acanthosis,skintags• Increasedabdominaladiposity• Diabetesscreening• 5-10foldincreasedriskofdiabetes• impairedglucosetolerance30-35%
• Cholesterolissues:hightriglyceride,lowHDL,highLDL• Screenfordepression,anxiety,panic,poorbodyimage,eatingdisorders
• Screenforfattyliverdisease:liverenzymes• Sleepapnea
Whentodoultrasound?1. Ifsuspicionofovarianoradrenaltumor:markedly
elevatedtestosterone,rapidonsetofseverevirilization,ifthereispainorapalpablemass
2. Toevaluateanatomy:Inpatientswhoneverhadacycle3. CystsinPCOS(maybenormalinadolescence):
- Arrestedfollicles(>12)- Lessthan10mminsize- Donotcausediscomfort,painorswelling- Increasedovarianvolume>10cm3 (withoutacystordominantfollicleineitherovary)- NoneedforUSmonitoring
IsPCOSthewrongname?• Thecystsin“PCOS”areanultrasoundfinding• Canbemisleading
• NIH-calledmeeting2013“ThenamePCOSisadistractionthatimpedesprogress.Itistimetoassignanamethatreflectsthecomplexinteractionsthatcharacterizethesyndrome”
• E.g.FemaleMetabolicReproductiveSyndrome
TheSyndrome• MenstrualIrregularities• AndrogenExcess• Hirsutism• Acne
• Infertility• Cardio-metabolicConsequences• Diabetes• CardiovascularDisease
• Depression
UnderlyingcauseofPCOS• Notwelldefined:complexpolygenic• Affects5-10ofevery100adolescents• Higherprevalenceinobeseadolescents• Associatedwithinsulinresistancein50-70%ofpatients:- Increasedinsulinlevels- Decreasedinsulinsensitivity/resistanceà increasemalehormoneeffects
• Inherentabnormalityofsteroidproduction(dysregulatedhyperactivityofcytochromeP450c17αenzymaticactivity)inovariesandadrenalgland
• Manygenesimplicated• Lowbirthweight• Precociouspuberty
Overproductionofandrogensfromtheadrenalglandsandovaries
ImbalanceofLHandFSHfromthepituitarygland
Insulinresistance
RapidGnRH pulses
Understandingpathophysiology• Insulinresistance(IR)àplayacardinalroleinthepathogenesisofPCOSandhyperandrogenism
• Desynchronization ofLHandFSHsecretionfromthepituitaryglandà highLH,lowFSH-LowFSH:abnormalfolliclematuraiton/anovulation-HighLH:stimulatestestosteroneproductionfromthecacells
• Overproductionofandrogensfromtheadrenalglandsandovaries
Treatment• Symptomatic• NoCure• MainGoalsofTreatment:
ØMenstrualregulation:lifestylechanges,OCP,metforminØ Improveinsulinresistance:lifestylechanges,metforminØReducemalehormoneeffects:lifestylechanges,OCP,metformin,spironolactone,skintreatments
Treatment:MenstrualRegulation• Combinedoralcontraceptives=1st linetherapy• Predictablecycles,improvesacne• Improveshirsuitism:noticeablein6months• Protectendometriumfromprolongedestrogen• NoevidenceforOCPincreasingriskfordiabetes• Improveslipids• Continueuntil5yearsaftermenarcheorhaslostasubstantialamountofweight
Treatment:Insulinresistance• Insulinsensitizer:Metformin-Ifdiabetic,prediabetic, orhasimpairedglucosetolerance orwhennosuccesswithoutmedication
- 30%reductioninprogressiontodiabetes-1500-2000mg/day-Maycauseweightlossinsome-Mayimprovemenstrualirregularity- Reducetestosteroneby20-25%
-Otherdrugs–notapproved• NoadequatelypoweredRCTsofarinadolescents
Lifestylemodification• Maintainingoptimalbodyweight• Exercise:30minutesofmoderate-vigorousphysicalactivity• 5-10%weightlossà canimprovemenstrualfunction• Reducesdiabetesriskandothermetabolicabnormalities
• Behaviormodification• Maintainingselfcontrol• Assessingdepressionandanxiety
• Diet (nodietisshowntobesuperior)• Calorierestricteddiet• Manyrecommendlowercarbohydratediet,lowglycemicloaddiet
Hirsuitism:pharmaceuticalRx• Combinedoralcontraceptive=1st line• Takesawhiletoseeeffect(6monthsà alteredhairshafts)
• Spironolactone• Antiandrogen:reducehairgrowth, preventnewgrowth,alreadypresentfolliclesmaynotregress• Antihypertensive,adiuretic(can↑K)• Teratogenic:mayaffectformationofmalegenitaliaoffetusà needreliablecontraception
• Otherantiandrogens:flutamide,finasteride- notusedinteens• Topicaleflornithine (vaniqa)
Treatment:HirsutismCosmeticManagementOptions• Mechanical• Shaving• Waxing• Creams• Electrolysis• Depilatories
• Lasertreatment• Worksasfollicularmelaninabsorbsthelaserwavelength,selectivethermaldamage• Besttocombinewithamedicaltreatment
Multi-DisciplinaryApproach• MenstrualRegulation• Hirsutism• Obesity• Monitoringforcardio-metabolicrisk• Regularfollow–up
PediatricEndocrinologyPediatricGynecology
DermatologyPrimaryCareNutritionist
FamilysupportMotivation
Importanceofearlydiagnosis
Timelyinitiationoftherapy
Improvedqualityoflife
Summary• PropermanagementcanimprovePCOS• Beawareoftheconditionsthatcanbe
mislabeledasPCOStoensureanaccuratediagnosis
• PCOSisasyndromeandtreatmentisamulti-facetedapproach