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JorgeFlechasMD,MPH Hendersonville,NC28792 OXYTOCIN,THEHORMONEOF FEMALEORGASM Oxytocin § Oxytocincanbestimulatedtobereleasedby § § § § Estrogen Secretionofoxytocinisinhibitedbyethanol Itcanbeliberatedbysucking PaincanreleaseoxytocinandAVP. Chronicpainwouldhencekeepthebrainina stateoflowoxytocinallthetime Oxytocin § Manipulationordistentionofthefemale genitaltractartificiallyorduringparturitionis astrongerstimulustocausereleaseof oxytocinfromthebrainthansucking § Harrison’sPrinciplesofInternalMedicine14th ed.1998pg2011 OTmaybefoundlowin § § § § Depression(EvansJ.1997) Autism(Panksepp1993;PankseppJ.1993) AIDS(Purbaetal.1993) Fibromyalgia(Anderberg,U.M.2000) OTmaybefoundlowin § MultipleSclerosis(Molleretal.1985) § LowEstrogenstates(Amicoetal.1981) § LowThyroidT3(Argiolasetal.1990) § ChronicStressSituations(Panksepp1992;Kalinetal. 1985;Argiolasetal.1990) OTmaybefoundlowin § ChronicOpioidUse(GreidanusVan Wimersma&TenHaaf1985;GreidanusVan Wimersma&TenHaaf1985) § PraderWilliSyndrome(EvansJ.1997) § Parkinsons(EvansJ.1997) Molecularmimicry § § § § OTbehavinglikeinterleukin2inthethymus(Johnson etal.1982) OTbehaveslikeinsulin.Ithasonefifththeactivityof insulin.(Hollenbergetal.1983) OTbehaveslikeAVPtovasodilatebrainbloodvessels (Oyamaetal.1993) OTbehaveslikeanopioid(Millanetal.1998;Yang 1994) OTisinhibited ú ú ú ú ú ú bystress byopioidpeptides byopioids byfear byanger (Speroffetal.1989) AutismandOxytocin § http://www.hugthemonkey.com/autism/ Green,L."Oxytocinandautisticdisorder:alterationsinpeptideforms."(2001). Hollander,E."Oxytocininfusionreducesrepetitivebehaviorsinadults withautisticandAsperger'sdisorders."(2003). Hollander,E.,etal."Oxytocinincreasesretentionofsocial cognitioninautism."BiolPsychiatry61.4(2007):498-503. Oxytocin § Oxytocinhastheabilitytostimulate enkephalinsandcontrolpainatthelevelof theCNS.Itwasfrommyworkinfibromyalgia thatwemadetheobservationsgivenduring thislecture. FemaleSexualDysfunction § InAmericaithits40millionwomen § 31%havelowsexualdesire § 43%havesexualdysfunction FemaleSexualDysfunction § Dysfunctioncanbebrokendownto § HypoactiveSexualDisorder § SexualAversionDisorder § SexualArousalDisorder § OrgasmicDisorder Inwomenthemainandrogen isDHEA § Itcanbeinhibitedbycarbamazepine, phenytoin,cytochromep450(CYP)3AA inhibitorsandalcohol.Alcoholalsoinhibits oxytocinproduction. § DHEAcanbestimulatedbybupropion, digoxin,diltiazem,andcigarettesmoking § CrenshawTL.GoldbergJP.Sexual pharmacology:drugsthataffectsexual function.NewYorkWWNorton&Co.1996 SexualAversionDisorder § Persistentorrecurrentphobicaversiontoand avoidanceofsexualcontactwithasexual partner.ThiscanbeduetoChronicpelvic pain.Thiscanaffect20millionwomenin Americawith90percentsufferingfrom sexualpain. § www.SecretSuffering.com SexualArousalDisorder § 23%ofallwomen § Seenmoreofteninmenopauseandpost menopause § Secondarytodepression § Childrenlivingathome § Fluctuationintestosteronelevels OrgasmicDisorder § 24%ofallwomen § SeenmoreofteninpatientstakingSSRI § Maleratsgivenfluoxetinehadinhibitedsexualorgasm. Inhumansthisoccuresinabout60%ofpatients. § Whentheratwasgivenoxytocin,theejaculatory responsewasrestored. § CantorJMinPsychopharmacology(Berl) § 1999;144(4):355-362 SexualDysfunctionbyAge OxytocinandOrgasm § Orgasminbothmenandwomenisprimarilyunder adrenergiccontrol. § Ejaculationaswellasorgasminwomenisasacralspinal reflexmediatedprimarilybyadrenergicactivity. § Oxytocinplasmalevelsareincreasedduringorgasmin menandwomen.Oxytocinlevelscorrelatewithorgasmic intensity § Pharmacotherapy19(7):823-831.1999 TheTemporalLobe § Language(hearing,reading) § Readingsocialcues § Short-termmemory § Gettingmemoriesintolong-termstorage § Processingmusic § Toneofvoice § Moodstability TemporalLobe § Recognizingobjectsandfacesbysightand namingthem § Hippocampuslocatedinsidetemporallobes; encodesnewinformationandstoresitupto severalweeks § Whendamaged,youcanneitherstorenew experiencesnorretrieveexperienceslearned withinlastseveralweeks TemporalLobes § Thehippocampusisoneoffirstareasdamagedby Alzheimer’sdisease § Infrontofthehippocampusinsidethetemporallobeis analmond-shapedstructurecalledtheamygdala.The amygdalacoordinatesemotionalresponses.Strong emotionscanimprovetheencodingprocessesof hippocampalneuronsandmakeiteasiertoretrievethe experience.Emotionallystimulatingevents(e.g.good sex,beingmugged,etc)aremoreeasierrecalled. DamagedTemporalLobes § Damagedtemporallobesleadtobothshort andlongtermmemoryproblems,reading difficulty,troublefindrightwordsin conversation,troublereadingsocialcues, moodinstability.Occasionallyreligiousor moralpreoccupationoralackofspiritual sensitivitycanoccur. § Left-sidetemporallobedamagerelatedto temperproblems. RightTemporalLobe § Spiritualexperiencesandinsightssuch § § § § asfeelingGod’spresence Orgasmshavebeenfoundtoactivate thispartofthebrain Peoplewhohaveseizuresinthisareaof thebraincansometimeexperiencean orgasmpriortoseizure Thisareastronglystimulatedby oxytocin Fromthebookin2007:SexontheBrain byD.G.Amen,MD OxytocinandOrgasm § Inmen,releasednorepinephrineactsona- adrenergicreceptorsofsmoothmusclesof thevasdeferens,prostate,andseminal vesselstocontractandpropelseminalfluid intothebulbarurethra(emission). § Pharmacotherapy19(7):823-831.1999 § § DefinitionofOrgasmby C.Meston:J.ofSexual Orgasmisasensationofintensepleasurecreating MedicineVol.1,No.1, analteredconsciousnessstate 2004pg66-68 accompaniedbypelvicstriatedcircumvaginal musculatureanduterine/analcontractionsand § myotoniathatresolvessexually-induced vasocongestionandinduceswell-being/ contentment.In1,749randomly-sampledU.S. women,24%reportedanorgasmicdysfunction. OxytocinandHugging § Huggingyourhusbands/partnersin premenopausalwomenendedupinthebody producinghigherlevelsofoxytocin,whichisa vasodilatorandhenceloweredtheBPofthe women.P<0.05 § LightK.C.,BiolPsychol2005:69(1):5-21 OxytocinandMultiple Orgasms § Womenwhoaremultiorgasmichavemuch highlevelsofplasmaoxytocinandahigher subjectiveintensity. § CarmichaelMSArchivesofSexualBehavior vol23,number1,Feb1994 Orgasmisaspinalcordreflex § Orgasmisaspinalcordreflexinitiatedby stimulationofthedorsalhornnuclei § Thedorsalrootgangliadevelopinthe embryofromneuralcrestcells,not neuraltube.Hence,thespinalgangliacanbe regardedasgraymatterofthespinalcord thatbecametranslocatedtotheperiphery. Dorsalrootganglionneurons § Theaxonsofdorsalrootganglionneuronsare knownasafferents.Inthe peripheralnervoussystem,afferentsreferto theaxonsthatrelaysensoryinformationinto thecentralnervoussystem(i.e.thebrainand thespinalcord). Dorsalrootganglionneurons § Unlikethemajorityofneuronsfoundin thecentralnervoussystem,an actionpotentialinposteriorrootganglion neuronmayinitiateinthedistalprocessinthe periphery,bypassthecellbody,andcontinue topropagatealongtheproximalprocessuntil reachingthesynapticterminalin theposteriorhornofspinalcord OxytocinandtheSpinalCord § Theresultssuggestthattheparaventriculo-spinal pathwayisparticularlyrelatedtospecificgroupsof sympatheticandparasympatheticpreganglionic neurons,andtothemarginalzone,whichisinvolved intherelayofascendingnociceptiveinformation throughthespinothalamictract. § JCompNeurol.1979Nov1;188(1):87-106. § Thedistributionofoxytocin-andneurophysin- stainedfibersinthespinalcordoftheratand monkey. § SwansonLW,McKellarS. Topicaloxytocinreversesvaginal atrophyinpostmenopausalwomen:a double-blindrandomizedpilotstudy § Twentypostmenopausalwomen(atleasttwoyearsafter menopause)withsymptomsofvaginalatrophysuchas vaginaldryness,pain,itching,discomfortandbleeding duringintercoursewereenrolledinthestudywhenvisual inspectionofthevaginahadconfirmedthattheirmucosa wasatrophic.Theparticipantswererandomizedto intravaginaltreatmentwitheitheroxytocinorplacebogel forsevendays.Beforeandaftertreatment,a gynaecologicalexaminationandavisualandcolposcopic inspectionofthevaginawereperformed,biopsiesfromthe vaginalmucosaweretakenandbloodsampleswere collectedforanalysisofcirculatinglevelsofestradioland oxytocin. OxytocinandvaginalAtrophy § Aftertreatmentwiththeoxytocingel,the examinationshowedthatthevaginal epitheliumofsevenofthe10participantsin theoxytocingrouphadbecomehealthierand normalized.Nochangeintheseparameters wasobservedamongthe10participantsin theplacebogroup.Thisdifferencebetween theoxytocinandplacebogroupswas significant(P=0.003). Oxytocinandvaginalatrophy § Topicaloxytocinreversesvaginalatrophyin postmenopausalwomen:adouble-blind randomizedpilotstudyAinoFianuJonasson, § LenaEdwall, § andKerstinUvnäs-Moberg § MenopauseInt,December 2011;vol.17,4:pp.120-125. Oxytocinlevels § Oxytocinlevelsinwomenareelevatedin responsetorelaxationmassageand decreasedwhenexperiencingunpleasant emotionalreactions. § TurnerRAetal.1999Plasmaoxytocinin normalwomenetc.. OxytocinafteranOrgasm § Oneminuteafteranorgasmoxytocinlevels aresignificantlyhigher.Thishormoneplaysa majorpartinthehumansexualresponse. § W.Blaicheretal.1999 Levelsofoxytocin § Womenwhoaremultiorgasmichavemuch higherlevelsofoxytocin,andthelevelsof oxytocincorrelatessignificantlywiththe orgasmintensity. § M.S.Carmichaeletal.ArchivesofSexual Behavior1994Feb;23(1):59-79 § C.S.CarterOxytocinandSexualbehavior 1992 OxytocinaAphrodisiac § Oxytocinhasapotentialaphrodisiacor prosexualeffectonwomen. § M.Anderson-Hunt,L.Dennerstein1995 § Oxytocinandfemalesexuality. OxytocinandbreastCancer § Oxytocinisprotectiveagainstbreastcancer. Thisisconsistentwiththelowerriskofbreast canceramongwomenwhohavehadchildren andbreastfed,comparedtothosewhohave not. § T.G.MurrellThepotentialforoxytocinto preventbreastcancer:ahypothesis1995