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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