曼月乐的非避孕临床应用

ReviewNon-contraceptiveusesoflevonorgestrel-releasinghormonesystem(LNG-IUS)—AsystematicenquiryandoverviewRajeshVarma*,DeepaliSinha,JaneshK.GuptaAcademicDepartmentofObstetricsandGynaecology,BirminghamWomen’sHospital,BirminghamB152TG,UKReceived31March2005;receivedinrevisedform12August2005;accepted28October2005AbstractLevonorgestrelreleasing-intrauterinesystems(LNG-IUS)wereoriginallydevelopedasamethodofcontraceptioninthemid1970s.TheonlyLNG-IUSapprovedforgeneralpublicuseistheMirena1LNG-IUS,whichreleases20mcgoflevonorgestrelperdaydirectlyintotheuterinecavity.However,newlowerdose(10and14mcgperday)andsmallersizedLNG-IUS(MLS,FibroPlant-LNG)arecurrentlyunderclinicaldevelopmentandinvestigation.Researchintothenon-contraceptiveusesofLNG-IUSisrapidlyexpanding.IntheUK,LNG-IUSislicensedforuseinmenorrhagiaandtoprovideendometrialprotectiontoperimenopausalandpostmenopausalwomenonestrogenreplacementtherapy.ThereislimitedevidencetosuggestthatLNG-IUSmayalsobebeneficialinwomenwithendometriosis,adenomyosis,fibroids,endometrialhyperplasiaandearlystageendometrialcancer(wherethepatientisdeemedunfitforprimarysurgicaltherapy).Thissystematicenquiryandoverviewevaluatesthequalityofevidencerelatingtothenon-contraceptivetherapeuticusesofLNG-IUSingynaecology.#2005ElsevierIrelandLtd.Allrightsreserved.Keywords:Levonorgestrel;Intrauterinedevices;Medicated;Menorrhagia;Endometriosis;Estrogenreplacementtherapy;Endometrialhyperplasia;Progestogen;TherapyContents1.Introduction...............................................................................102.Materialsandmethods........................................................................103.Results...................................................................................103.1.Menorrhagia..........................................................................103.2.Uterinefibroidsandfibroidrelatedmenorrhagia..................................................143.3.Endometriosis.........................................................................143.4.Adenomyosis..........................................................................163.5.Endometrialprotectionduringestrogenreplacementtherapyortamoxifeninperi-menopausalwomen............163.6.Endometrialhyperplasia..................................................................183.7.Endometrialcancer......................................................................183.8.Dysmenorrhoeaandpain..................................................................183.9.LNG-IUSandeffectonpelvicinflammatorydisease..............................................223.10.Othernon-contraceptivetherapeuticindications..................................................223.11.Adverseeffects........................................................................224.Discussion................................................................................23Acknowledgements..........................................................................24References................................................................................24(2006)9–28*Correspondingauthor.Tel.:[phone]/4751;fax:[phone].E-mailaddress:[e-mail](R.Varma).0301-2115/$–seefrontmatter#2005ElsevierIrelandLtd.Allrightsreserved.doi:10.1016/j.ejogrb.2005.10.0291.IntroductionTheonlylevonorgestrel-releasingintrauterinesystem(LNG-IUS)approvedforgeneralpublicuseistheMirena1(ScheringAG),whichisaT-shapedplasticintrauterinedevice(IUD)thatreleaseslevonorgestrel(20mcgperday)directlyintotheuterinecavity.ThemeansystemiclevelsoflevonorgestrelwiththisLNG-IUS(425pg/mlat1month,330pg/mlat6months,meanageofsubjectswas31years(range18–42))[1]arelessthanthoseachievedwiththerapeuticoralorparenteraldosesofprogestogens(henceminimizingsystemicsideeffects)andexceedsthecriticalvalueof200pg/mlbelowwhichovulationoccurs[2].MirenawasfirstlaunchedinFinlandin1990andhasbeenmarketedintheUKsince1995asacontraceptivedevice.TwonewlowerlevonorgestreldoseandsmallersizedLNG-IUSdevicesarecurrentlyunderclinicaldevelopmentandinvestigation:FibroPlantTM-LNG(framelessdevice,ContrelResearch,Belgium)andMLSsystem,releasing14and10mcglevonorgestrelperday,respectively[3,4].Mirena1LNG-IUSiscurrentlylicensedintheUKasa5-yearcontraceptiveagent(licenseawarded1995),treatmentforidiopathicmenorrhagia(licenseawarded2001),andtoprovideuterineprotectionduringestrogenreplacementtherapyinperimenopausalandpostmenopausalwomen(licenseawarded2005).ThelattertwoapplicationsforMirena1LNG-IUSarenotlicensedinUSAorCanada.ThefertilitycontrolprovidedbyLNG-IUSiscomparablewiththatoffemalesterilisation,andiscompletelyreversible[5].Therearemanyothernon-contraceptivebeneficialeffectsofLNG-IUSthathaveimportantpublichealthimplications.Thesehavebeensummarisedbyseveralreviews[6–9]andpolicystatements[10],andincorporatedwithinonesystematicreviewexaminingalltypesofintrauterinedevice[11].However,therehassincebeenaconsiderableexpansionofpublicationsinthisarea,manyofwhic