Hormones and Mental Health - Dr. Leslie Korn · • HT can be an effective adjunct to mental health...

HormonesandMentalHealth

MaryAnnOsborne,DNP,ARNP

Objectives

• DiscusssymptomsofAndropause

• Assessdifferencesbetweenperi-menopauseandmenopause

• Identifysymptomsofhormoneimbalancerelatedtomentalhealth

• IdentifyVitaminsandMedicationswhichaffecthormonebalance

Andropause,Peri-Menopause&Menopause

• Middleagerange

• Changesinmoodcommon

• Anxiety

• Insomnia

• Depression

• Fatigue

• Cognitivechanges

Andropause

• Malemen-o-pause

• Declineoftestosteroneoccursmoreslowlythanmenopause

• LowlevelofVitaminD

• Cholesterol-loweringstatinmedicationsdecreasetestosterone

HormoneImbalanceinMen

• Symptomsinclude:– LackofMotivation– DecreaseStamina– Decreaselibido–Muscleloss– Depression,anxiety,moodswings– Insomnia– EnlargedProstate– HairLoss

HormoneReplacementinMen

• Prescriptionorcompoundedtestosteroneoptionsformen

• Lifestylechangestosupportloweringoreliminatingcholesterolloweringdrugs

• Progesteroneisprecursortotestosterone• Lowdoseprogesterone(compounded)forinsomnia

• VitaminDreplacementtoadequatelevel(normalrange30-110andgoalrange55-75)

Case1

• 72yomalewithc/omildcognitivedecline,decreasedstamina

• Lifestyleandsignificantdietarychangesoverpast4years.

• Begantestosteronepatch

• Improvedmemoryandnowbiking20-30milesatatime;severaldaysaweek

Case2

• 69yomalewithc/odecreasedmood,libidoanddifficultymaintainingerection;increasedstresswithparents'illness,impairedglucosetoleranceandhyperlipidemia

• Begantestosteronecreamappliedqd

• Improvedmood,libidoanderection;improvedrelationshipwithwifeandatwork;improvedlipids

Peri-menopause

• Peri-menopause:8-10years

• AverageageofProgesteronedeclineinU.S.isage36

• InitialdropofProgesterone

• Symptoms:includemoodchanges,agitation,irritability,insomnia,fatigue,weightgain,bodyaches,headaches,irregularmenses

• Doyouseethisinyourpractice?

PerimenopausalDepression

• Closeto16%ofperimenopausalwomenexperienceonedepressiveepisode

• SignificantriskwithhistoryofPMDDand/orpostpartumdepressionBUTupto2xriskof1stonsetdepression

• Aftermenopausetheriskgraduallyreturnstobaseline

PerimenopausalDepression

• Contributingfactorisfluctuationofestrogenlevelsfromlossofnormalmenstrualcycleswhichleadstocompromisedmoodregulatorymechanismsinthebrain

• Perimenopausaldepression– Unrelatedtoserumestradiollevels– Earlymenopauseorprolongedmenopausaltransition

– HistoryofPMDDarehigherrisk

PerimenopausalDepression

• ResearchshowswomenwhoaretreatedwithHTcutriskbyhalf

• Useofprogesteroneneededinsteadofprogestinswhichseemtomodifyeffect

• Estradioltreatmentimprovesmood(patchhadhadbestresponse)

• Oralcontraceptiveshavebeenusedtostabilizehormonefluctuations

• DepressionmayrecurwhenHTdiscontinued

Peri-Menopause

• Typicallytestosteronedeclines

• Symptomsinclude:– Lackofmotivation

– Lackofstamina

– Difficultywithexercise–Muscleloss

– Troublespeakingupforthemselves

TreatmentofPeri-menopause

• Initiallyincreaseprogesterone– Improveestrogen:progesteroneratio

– Cycleprogesteronewithmenstrualcycle

• Increasetestosteroneasneeded

• Eventuallywillseedeclineinestrogen

Case3

• 45yofemaleadmittedtolocalmentalhealthfacilityoverweekend– Agitation– Anxiety– Insomnia– Depression

• Physicianondutyrecommendedsheseekassistanceforhormonetherapy

• HistoryofTrauma

Menopause

• Definition:cessationofmensesfor12months

• Menopause:Averageage53yo

• Manywomenhavenotsoughttreatmentduetostigma/misinformationofhormonetherapy

• Replaceestrogen/progesterone/testosteronepersonallyprescribed

• Greatdealofvariationamongwomen

WhataboutSurgicalMenopause?

• Ovariesarespared

• Conventionalmedicinedoesnotbelievethatprogesteroneisneededafterhysterectomy

• Increaseriskofauto-immunediseaseinwomenwithhysterectomywhoarenotgivenprogesteronealongwithestrogen

• Flores,VA;Pal,L.(2018).Managingmenopausebycombiningevidencewithclinicaljudgment.ClinicalObstetricsandGynecology;61(3):496-507.

Case4

• 50yofemalewithdepression,anxiety,hypervigilance,insomnia,lostsenseofwell-beingsincehysterectomy

• BeganBiestandTestosteronetopicaloilwithoralProgesterone

• Returnvisit:stillnotfeelingwellbutwasabletobeginshortmeditation,journaling

• Changedtoestrogenpatchformoreconstantdelivery

Case4

• Encouragedtoincreasemindbodyactivities

• 4/7/8Breath

• Offeredreassurance

• Difficultcaseduetofactthatovariesarecontinuingtoproducesomeestrogenintermittently

• Discussedlossofuterus/grief

• Recommendcounseling

Estrogen

• Stimulate

• Animate

• HelpwithStressResponse

• Stimulatebreastglandulartissue

• Stimulateuterinelining

• “Estrogensmakeyoufeelsensual.Itbringsglowtotheskin…moisturetotheeyes,fullnesstothebreastsandclaritytothemind.Itkeepsthevaginalubricated.Itupliftsandstabilizesyourmood.Itinfluencesyourbrainandyourbonesandprotectsyouagainstcardiovascular

disease….”• UziRice,MD• NaturalHormoneBalanceinWomen

EstrogenDeficiency

• Hotflashes(75%)• NightSweats• Warmrushes• Coldflash• Racingmindatnight(outpouringofadrenaline)

• SleepDisturbance• MemoryImpairment

EstrogenDeficiency

• Dryvagina,eyes,skin

• Painwithintercourse(maritalissues/counseling)

• Urinarysymptoms(frequency,urgency,nocturia)

• MentalFog

• Forgetfulness

• CognitiveDecline

• MenstrualMigraines

• Fatigue

EstrogenDeficiency

• Palpitations

• Decreaselibidoandsenseofsexuality

• Weightgain

• Senseofnormalcyduring2ndhalfofmenstrualcycleiftheyarestillmenstruating

• IntestinalBloating

EstrogenandMood

• Lifetimeprevalenceofmajordepression20%womenvs10%men

• Riskhighestattimesofhormonevariation– Puberty– Premenstrual– Postpartum– Peri-menopause

• Asubgroupofwomenseemtobemorevulnerabletothesefluctuations

EffectsofEstrogenonNeurotransmitters

• Actsasaserotoninagonist

• Increasesserotonin,dopamine,andendorphinsynthesisandavailabilityofatsynapses

• Inhibitstheenzymethatinactivatesnorepinephrine

• ReducesMAOactivity(likeaMAOinhibitor)furtherincreasesserotoninandcatecholamineactivityinthebrainBUTestrogeninHTactsonlyasaweakantidepressant

EstrogenasMoodRegulator

• MRIfindings– Estrogenstimulatesareasofthebrainassociatedwithcognitiveregulationofemotions

– Estrogendecreasesactivityinareasassociatedwithnegativemoods

EstrogenasMoodRegulators

• Inmostwomen,thebrainadaptsthismechanismtocopewithcyclichormonalfluctuations– Premenstrualsymptoms

• PremenstrualDysphoricDisorder(PMDD)andotherhormone-relateddepressions– Normalhormonelevels– Reducedabilitytoadapttohormonalchanges,regulatemoods

PostpartumDepression

• Depressionoranxietythatbeginsduringpregnancyorwithin4weeksofchildbirth

• Requiredfordiagnosis–lowmoodoranhedonia

• Oftenaccompaniedbysignificantanxietysymptomsthatmayincluderuminatingthoughts,agitationorrestlessness

• Affects10-15%ofpostpartumwomen

PostpartumDepression

• Differentiatebetween"BabyBlues"– Affectsatleast50%ofwomen

– Heightenedemotionalreactivity

– Peaks3-5daysafterchildbirth– Resolvesspontaneously

PostpartumDepression

• RiskFactors– Historyofdepression,PMDDorpriorpostpartumdepression

– Familyhistoryofpostpartumdepression

• EnvironmentalContributors– Psychosocialstress,espDomesticViolence

– Inadequatesocialsupport(teens)– Unintendedpregnancy

PostpartumDepression

• Precipitousfallinhormones(cortisol,progesterone,estrogen)whichleadstomoodderegulation– CanbesimulatedinwomenwithPMDDbywithdrawalofhighdoseestrogenandprogesterone

– Postpartumhighdoseestrogentherapytreatment

• Newresearchimplicatesallopregnanolone,aneurosteroidthatintersctswithGABAareceptors

ManagementofPostpartumDepression

• Estrogentherapyathigherdoses

• Typicaldosetherapyisnoteffective

• SupportforMomandBaby

• Psychotherapy

• Additionalmedicationsifneeded

Case5

• Currentclientpresentsfor"hormonalissues"andhistoryofdepression

• Perimenopausalandtreatedwithprogesterone• Discussedneedforcontraception• UnintendedpregnancyandPostpartumdepression

• Estrogentherapygivenbutlactationpreventsadditionofprogesterone

EstrogenandtheBrain

EffectsofEstrogenontheBrain

• Neuroprotectivefrom:– Oxidativestress– Ischemicinjury

– Hypoglycemicinjury

– Damagedbyamyloidprotein

EffectsofEstrogenontheBrain

• Neurotrophic(throughgrowthfactors)– Stimulatesneuronalgrowthandviability

– Repairsdamagedneurons

– Promotesdendriticbranching

EffectsofEstrogenontheBrain

• Increaseneurotransmitteractivity– Increasesconcentrationsofneurotransmitters• Affectsrelease,reuptakeandenzymaticinactivation

– Increasesreceptorstoneurotransmitters

• Anti-inflammatory

• Increasescerebralbloodflow

EstrogenandCognition

• Inpostmenopausalwomen,cognitivefunctioncanbecorrelatedwithbonedensity

• WomenwithsurgicalremovalofovarieshavemorememoryimpairmentthannaturallymenopausalwomenBUTnodifferenceifestrogentherapystartedimmediatelypost-opandcontinuedtoage50

• WomenwithAlzheimer'sare4-6xmorelikelytohaveendogenousestradiol<20pg/ml

HTandCognitioninMenopause

• UCSFstudyof3,393women>age65

• EstrogenuserswhowereAPOE4negativewerehalfaslikelysuffercognitivedecline

• Strongestbenefitwasamongcurrentestrogenusers,butsomeseenin'ever-users'

• Estrogenusewasassociatedwithlesscarotidwallthickening/atherosclerosis

DeliverySystemandFormofHT

• Studiesontransdermaldeliveryhaveyieldedmoreconsistentpositiveresultsoncognitivefunctionthanconjugatedequineestrogen/CEE

• Medroxyprogesteroneacetatemaycounterestrogen'spositiveeffectsonthebrain.Micronizedprogesteronedoesnotseemtohavethesameeffect.

Progesterone• TheGreatCalmer

• SupportsMood

• SupportsSleep

• Balancesthestimulatoryaffectsofestrogen

ProgesteroneDeficiency

• BackandJointPain

• BodyAches

• Ligamentpain

• Anxiety

• Insomnia

• Severeemotionalchanges

• Breasttenderness,pain,lumps

ProgesteroneDeficiency

• PreMenstrualSyndrome

• Fibroids

• Endometriosis

• Declineinlibido

• Decreasedthyroidfunction

• Declinesearlierandmoreprominently

Testosterone

• Menhaveaccesstopharmaceuticalorcompoundedtestosterone.

• Deliveryingelorcream

• Womendonothaveapharmaceuticaloption

Testosterone

• Associatedwithreducedobesity,fatmassandwaistcircumferenceandimprovedglycemiccontrol

• >22studiesshowbeneficialeffectoncardiovascularrisksandmortality

• LingeringconcernoftestosteronesupplementationandCVriskinmenbutlargemeta-analysisdoesnotsupporttheconcern– Morgantaler,et.al.(2015).MayoClinProc.;90(2):224-251

Summary

• HTcanbeaneffectiveadjuncttomentalhealthduringtimesofhormonalfluctuations

• HTcanhelpimprovemoodandassistsclientinfindingastableplaceto"dothework"oftherapy

• Continuedresearchisurgentlyneededontheeffectsofhormonesandthebrain

Resources

• HappyHealthyHormones,DavidRosensweet,MD

• EstrogenMattersbyAvrumBluming,MD