ObstetGynecolClinNAm33(2006)111

EpidemiologyofMyomasMarkPayson,MDa,b,
a,b

PhyllisLeppert,MD,PhD ,
JamesSegars,MD

a,b,

ReproductiveBiologyandMedicineBranch,NICHD,NationalInstitutesofHealth,Building10,
b
CRC,1E3140,9000RockvillePike,Bethesda,MD20892,USA DepartmentofObstetricsand
Gynecology,UniformedServicesUniversityoftheHealthSciences,8900WisconsinAvenue,
Bethesda,MD20814,USA

Uterineleiomyomas(orfibroids)areaprevalentandmorbiddisease.Leio
myomasplaceanenormoushealthcareburdenonAmericanwomen,anddis
proportionatelyaffectAfricanAmericanwomen.Despitetheirprevalence,the
diseasehasremainedenigmatic,withtheincidence,naturalhistory,andpro
gressionincompletelyunderstood[1].Ascholarlyexaminationoftheepidemi
ologyoffibroiddiseasefacesfivesizeablechallenges.
First,isfibroiddiseaseasingleentityormorethanonedisease?Itisnow
appreciatedthatleiomyomadevelopmentisaphenotypefeaturedinseveral
geneticdiseases;leiomyomaencounteredclinicallymaynotrepresentasingle
diseaseentity.Mostobviously,diseaseprogressionandoutcomemightvary
betweenthedifferenttypesofdisease,perhapsindifferentethnicgroups.The
appreciationthattheremaybedifferentphenotypesoffibroiddiseaseissug
gestedbyrecentmolecularprofilingstudies,describedlaterinthisarticle.
Second,thereisnotawidelyaccepted,standardizedclassificationsystemfor
leiomyomas;fibroidsaredifferentsizesandoccurindifferentareasoftheuterus.
Theabsenceofascoringsystemtoclassifydiseasemakescomparativeassess
mentofdiseaseproblematic.Theinabilityaccuratelytoclassifydiseasestage
compromisesstudiesofdiseaseepidemiology.
Thisresearchwassupported,inpart,bytheIntramuralResearchProgramoftheReproductive
BiologyandMedicineBranch,NICHD,NationalInstitutesofHealth.
Theopinionsorassertionsaretheprivateviewsoftheauthorsandarenottobeconstruedas
officialorasreflectingtheviewsoftheDepartmentofHealthandHumanServices.

TCorrespondingauthor.ReproductiveBiologyandMedicineBranch,NICHD,National
InstitutesofHealth,Building10,CRC,1E3140,9000RockvillePike,Bethesda,MD20892.
Emailaddress:segarsj@mail.nih.gov(J.Segars).
08898545/06/$seefrontmatter.PublishedbyElsevierInc.doi:10.1016/j.ogc.2005.12.004
obgyn.theclinics.com

2paysonetal

Third,theincidenceofdisease(fibroids)variesaswomenageandwithrace.If
thesevariablesarenottakenintoconsiderationorcarefullycontrolled,itiseasyto
drawfalseconclusions,ortobemisledbytheconfoundingvariablesthatareage
orracedependentandnotanelementofthefibroidevolutionperse.
Fourth,diagnosticmethodsusedtodetectdiseasevaryinsensitivityand
specificity,andsomearenotablyoperatordependent.Thisfactfurtherobfuscates
assessmentofdiseaseprogressionandcomparisonacrossstudies.
Fifth,theincidenceoffibroidsthataresonographicallydetectable,butasymp
tomatic,isremarkablyhigh,andinfactencompassesmostAmericanwomenby
theageofmenopause.Studiesthatsimplyuseselfreportingunderestimate
prevalenceofdiseaseinaconsiderablenumberofpatientswithleiomyomas,and
tendtodrawincorrectconclusions.Thisformofbiasmaycausethedetrimental
natureoffibroidstobeoveremphasizedorsymptomstobeassignedincorrectlyto
leiomyomas.Stateddifferently,themedicalliteratureisnaturallybiasedtoward
assignmentofclinicalconditionstofibroiddisease,aproblemcompoundedbythe
factthatfewstudieshaveincludedappropriateagematchedcontrolgroups.
Bearinginmindtheseformidableobstacles,thisarticlereviewstheepidemiology
ofuterinefibroids.Cluestotheetiologyoffibroidsmaybegleanedby
identificationofindividualsatriskandelucidationofriskfactors.Furthermore,
identificationofmodifiableriskfactorsmayleadtostrategiesforprevention.
Prevalenceindifferentpopulations
AnoftcitedstudyfromtheUnitedStatesassessedtheprevalenceoffibroidsina
populationofpatientsundergoingtubalsterilization[2].Theprevalenceinwhite
womenwas9%,andinAfricanAmericanwomen16%.Interestingly,onlyone
thirdofthewomenwhohadfibroidsdiagnosedduringtheirtubalprocedurehad
previouslybeengivenadiagnosisoffibroids,indicatingthatfibroidshadeither
notbeendetectedonpreviousexaminationsorthatthepatientshadnotreported
sufficientsymptomstohavebeendiagnosed.Thisfactemphasizesthatthe

prevalenceoffibroidsymptomsreflectsafractionoftheoverallprevalenceof
disease.
Thebestdesignedstudiesexaminingoverallprevalencehaveappliedultrasound
diagnosistoarandomlysampledpopulation.InanotherstudyfromtheUnited
States[3]1364women35to49yearsoldwerescreenedbyultrasound.Athirdof
thewomenhadalreadybeengivenadiagnosisoffibroids,andhalfofthosewho
hadnothadapreviousdiagnosishadultrasoundevidenceoffibroids.The
cumulativeincidenceoffibroidsbyage50includedmostAmericanwomen,
almost70%forwhitesand80%forAfricanAmericans.Includedinthisnumberis
19%ofwomenwhodidnothaveafocalfibroididentified,butsimplyhad
diffuselyheterogeneousechopatternsindicativeoffibroids.Itispossiblethatnot
allofthesepatientshadfibroids,thatsomehadadenomyosisorsimply
myometrialcontractions;however,evenifthissubsetisexcluded,uterinefibroids
epidemiologyofmyomas3

werestillfoundinmostcases.BytheageofmenopauseinAmerica,thepresence
ofuterinefibroidsseemstobethenorm,nottheexception.
ThestrikingincreasedprevalenceofdiseaseinAfricanAmericanwomenbrings
intoquestiontheincidenceoffibroidsinpopulationsinAfrica,andwhetherthe
highprevalenceofdiseasemightreflectageneticpredisposition,orconversely
dietorotherenvironmentalinfluences.Fewstudieshavespecificallyaddressed
thispoint.InaNigerianstudythenumberofhospitaladmissionsthatcouldbe
attributedtofibroidswasexamined.Althoughnotcontrolledforthepopulation,
13.4%ofnewgynecologicadmissionsinNigeriawereadmittedasadirectresult
offibroids[4].
FibroiddiseaseseemstobelessprevalentinEuropeanpopulations.InaGerman
studybeganin1998[5],theGermanCohortStudy,aquestionnairebasedsurvey
ofwomenshealthamong10,241women,theincidenceoffibroiddiseasewas
only12.7per100,000years.Ifprevalenceiscalculatedfromtheirnumbers,it
seemstobesurprisinglylowat5%.Thisdoesnotinclude,however,anequal
numberofpatientswhorespondedthattheyweregivenadiagnosisofbenign
tumorsoftheuterus,whichpresumablywerealsofibroids.Includingthese
patients,theprevalencedoublesto10.7%.Thisreflectsthenumberofwomenof
meanage39.6whoreportedhavingbeengiventhosediagnoses,whichcertainly
underestimatesasymptomaticorundiagnosedfibroidburden.Despitethese
methodologiclimitations,theresultssuggestthatfibroiddiseasemaybeless
commonincentralEurope.

TheSevesoWomensHealthStudy[6]followedacohortofwomeninItaly.In
thisstudyof341womenaged30to60withauterus,theincidenceof
ultrasonographicallydetectablefibroidswas21.4%.Thisprovidesoneofthebest
prevalenceestimatesforfibroidsinaEuropeanpopulationbecausethepresenceor
absenceoffibroidswasdeterminedindependentofsymptomatology.
ASwedishstudyalsousingultrasoundfordetectionofdiseasereporteda
relativelylowprevalenceoffibroids[7].Fivehundredfiftyfourwomenaged25
to50,allSwedishcitizens,wererandomlyselectedfromthenationalpopulation
registerandaskedtojointhestudy;threequartersaccepted.Fibroidswere
diagnosedin3.3%of25to32yearoldsandin7.8%ofthe33to40yearolds.
Althoughnotspecificallyaddressingthepopulationprevalenceofdisease,a
Japanesestudy[8]examinedtheprevalenceoffibroiddiseaseinfirstdegree
relativesofwomenundergoingsurgeryforfibroids.Thirtyonepercentofwomen
undergoingfibroidsurgeryreportedafirstdegreerelativewithfibroids,as
opposedto15%ofcontrols.Despitethelimitationsofaquestionnairebasedsur
veyaboutrelativeshealthstatus,itdoesprovideinformationaboutthepreva
lenceoffibroiddiseaseintheJapanesepopulation,andhintsatafamiliallink.
Prevalenceindifferentraceandethnicgroups
Studiesthathaveexaminedprevalenceindifferentracialgroupsprincipallyhave
beenconductedintheUnitedStates.Becauseofthehomogeneousnature
4paysonetal

ofsomeofthepopulationsinthesamplesreferencedintheprecedingsection,it
canbeinferredthattheremaybesignificantdifferencesindiseaseprevalence
betweenwomenofdifferentracialandethnicbackground.Unfortunately,many
reportsdonotspecificallyassesstheincidenceoffibroidsbetweenraceswithin
theirpopulation.Inastudycomparingprevalenceoffibroidsasdiagnosedby
ultrasoundorhysterectomyacrossracesonlyAfricanAmericanshadanin
creasedrisk.BothHispanicsandAsiansintheUnitedStateshadriskssimilarto
whites[9].
SeveralstudieshaveshownanincreasedprevalenceoffibroidsinAfrican
Americans[2,3,10,11].Thisdisproportionatediseaseburdenismanifestinthe
numberofhysterectomiesperformedonAfricanAmericanwomen,75%ofwhich
wereperformedfortheindicationoffibroids[12].StudiesintheUnitedStates
revealedanincidencetwofoldtothreefoldgreaterinAfricanAmericanthanwhite
women.Thelikelihoodofbeingdiagnosedwithfibroidswasapproximately3%
peryearforreproductiveageAfricanAmericanwomen[10].Inoneultrasound

studythatconfirmedthehighprevalenceoffibroidsinAmericanwomen[3],there
wasanincreasedprevalenceinAfricanAmericans.Fibroidswerediagnosedata
youngerage,weremoreoftenmultiple,andtendedtobelargerinAfrican
Americans,withthecumulativeincidenceinexcessof80%byage50.
Acarefullyconductedcasecontrolstudy[11]foundselfreportedAfrican
Americanheritagetobeassociatedwitharelativerisk(RR)offibroidsof9.4
comparedwithwhitewomen.Thesubjectsinthisstudywerewomenbeingseen
forsymptomsoffibroiddiseaseandhadfibroidsconfirmedeithersono
graphicallyorsurgically.
Aretheredifferenttypesoffibroiddisease?
Theliteratureoffibroidepidemiologytreatsfibroidsasasingledisease.
Clinically,however,leiomyomaseemtoexhibitatleastthreesomewhatdistinct
phenotypesthatalthoughtheyhavenotbeenclearlydefined,seemtocarry
differentprognoses.Specifically,leiomyoma(1)maybesingle;(2)maybemul
tipleandtheuterusvirtuallypepperedwithmultipleleiomyomaofvaryingsize;
and(3)maybefoundinassociationwithadenomyosis,oralone.Forexample,in
aninterestingstudy[3]thediagnosisoffibroidswassubcategorizedastowhether
fibroidsweremultipleornot.Seventythreepercentofblackwomenhadmultiple
fibroidtumorsversus45%ofwhitewomen.Analysisatmyomectomysuggests
thatfibroidsfromAfricanAmericansarelargerthanthosefromwhites[1].At
myomectomytheaffecteduterusmayfeatureasingletumor,ormanytumorsthat
arepracticallyimpossibletoextirpate.
Insomewomenthetumorsaresingular,andifremovedrarelyrecur.Incontrastin
otherwomenauterusnormalizedbyremovalofseveraltumorsmayrapidly
developseveralmoretumorswithinafewmonths.Itiscertainlypossiblethatthe
myometriumofsomewomenismorepronetodevelopfibroidsandonce
epidemiologyofmyomas5

fibroidsdeveloptheymaygrowmorerapidly.Fewstudies[13]havereportedthe
numberoffibroidsratherthansimplytheirpresenceorabsence.Thesemarkedly
differentclinicalphenotypesofonepathologicconditionbegthequestion:isthere
morethanonetypeoffibroiddisease?
Theanswertothisquestionseemstobe,yes.Someleiomyomaclearlyreflect
underlyinggeneticpredispositiontotumordevelopment.Forexample,several
reportedgeneticsyndromesfeatureleiomyomadevelopment,suchashereditary
leiomyomatosisandrenalcellcancer,Reedssyndrome,andAlportssyndrome
[1416].Theleiomyomainsuchconditionsareassociatedwithknownmuta

tions,orabnormalities,suchasfumaratehydrataseinhereditaryleiomyomatosis
andrenalcellcancer[17].Leiomyomaassociatedwiththeseraregeneticsyn
dromesaregrosslyindistinguishablefromcommonleiomyomata,butclearlythese
leiomyomadonotportendthesameriskanddisease,becauseinsuchacondition
ashereditaryleiomyomatosisandrenalcellcancer,leiomyosarcomamaybea
concern.Interestingly,preliminaryreportsofgeneprofilingstudiessuggestthat
fibroidsfromatleastonesyndrome,hereditaryleiomyomatosisandrenalcell
cancer,maynotresemblethoseofcommonleiomyoma(MayersCandcoworkers,
unpublisheddata).
Recentmolecularprofilingstudiesoffibroidslendsupporttothenotionthat
fibroidsmayexistasdifferentclinicalphenotypes.Thatthesetwopresentations
mayrepresentdifferenttypesoffibroiddiseaseissupportedbygeneprofiling
studiescomparingfibroidsfromAfricanAmericanswithwhites[18].This
observation,coupledwiththegeneticsyndromesmentioned,suggeststhatfi
broidsmayrepresentacommonsmoothmuscleresponsetoseveraldifferent
disordersratherthanadiscretedisease.Ifthisisindeedthecase,itisimportantto
elucidatetheprevalenceofdifferenttypesoffibroidsandtheclinicalcourseofthe
subtypes.
Incidenceatdifferentagesandprogression
Theincidenceofpathologicallydiagnosedfibroidsincreasessteadilywithage
[19].At25to30yearstheincidenceoffibroidsisonly0.31per1000women
years,butbyages45to50theincidencehasincreased20foldto6.20per1000
womenyears.Advancingageincreasestheriskforfibroidsmanyfold,andmirrors
theunderstandingofthebiologicdevelopmentoffibroids:mostgrowintimeand
areexpectedtobediagnosedingreaternumbersinoldercohorts.Asmallsample
ofpatientswhohadtheirfibroidsfollowedupultrasonographically[20]sawan
averagegrowthof1.2cmin2.5years.Thechanceofbeingdiagnosedwith
fibroidsincreaseswithageuntilabout50yearsandthendeclinessharply[8,11].
Howquicklyfibroidsgroworrecurwasexaminedinastudyof145women
followedafterabdominalmyomectomy[21].Therecurrenceoffibroidswas
diagnosedbyultrasounddemonstratingfibroidsatleast2cmindiameter.The5
yearriskofrecurrencewas62%,witha9%riskofanadditionalmajorsurgery,
6paysonetal

animportantnumbertobeawareofwhencounselingpatientsformyomectomy.
Therecurrenceriskwaslowerinpatientswithasolitaryfibroid,asmallertotal
uterinesize,andthosewhosubsequentlyhadasuccessfulpregnancy.

PreliminaryresultsfromtheongoingNIEHSstudy[22]suggestedthatanyfibroid
documentedonMRIdoesgrowovertimebutatvariablerates.Notably,no
fibroidswereseenthatregressedduringtheirobservations[22].Thedisappear
anceorshrinkingseeninotherstudies[20]maybecausedbytheimprecisenature
ofultrasoundexaminations,whereafibroidcouldbeincorrectlymappedorother
featuresofthemyometrium,suchasamyometrialcontraction,maybeincorrectly
scoredasafibroid,whichmightthenlaterbeseentodisappear.
Hormonesandfibroids
Acasecontrolstudyof535womenwhodevelopedfibroidsfromacohortselected
fromafamilyplanningclinicfoundriskfactorsassociatedwitheventsthatcould
changeestrogenlevels[19].Inthisstudythediagnosisoffibroidswasconfinedto
thosepatientswhohadsurgerytoremovethem.Oralcontraceptiveusedecreased
associationwithfibroids,withtheRRdecreasinginadosedependentfashionto
thedurationoforalcontraceptiveuse.Inthegroupwiththelongestuse(N145
months),theriskoffibroidswashalfthatofcontrols.Whatcanbeseenasa
dramaticprotectiveeffectinthesepatients,however,canbeattributedtothe
populationstudied.Thepatientswithfibroidshadamoredifficulttimeachieving
pregnancy,andwouldhavelesstimeduringwhichtheywereusingcontraception.
Iftheanalysishadincludedanytypeofcontraception,ratherthanjusthormonal
contraception,itmighthaveshownasimilareffect.Otherstudies[11]also
reportedaprotectiveeffectoforalcontraceptiveswithaRRof0.2,butthe
confoundersmentionedneedtobekeptinmind.
Ofnote,alargestudythatexaminedsimilarfactorsin95,000premenopausal
nurses[23]foundtheonlychangeinriskassociatedwithoralcontraceptiveswas
ageatfirstuse;womenwhohadfirstusedoralcontraceptivesbetween13and16
yearsofagehadasignificantlyincreasedriskofuterinefibroids(RR1.9).This
couldbeattributedtoeithertheknownincreasedincidenceofsexuallytransmitted
diseaseamongearlyinitiatorsofsexualactivity,orasamarkerformetrorrhagia,
whichinandofitselfcouldbeauterineirritant.Startingoralcontraceptivesata
youngagecouldbeamarkerforotherriskfactorsforfibroids,ratherthanacause
itself.
Obesityincreasedriskroughly18%foreach10kgincrease,whereastwopacksof
cigarettesadaydecreasedtheriskthesameamount.Anotherstudy[11]showed
anincreasedriskof2.3forfibroidsforwomenintheupperquartileofbodymass
index.Althoughhigherestrogenlevelsarepresentinobesity,onestudythat
examinedthisvariable[24]reportedareducedRRoffibroidsinthesepatients
(RR0.6).Thismaybeattributabletothedifficultyofdiagnosingfibroidsinthe
obesepopulationratherthanatrueprotectiveeffect,butitdoesnotseemthat

obesitycausesamarkedincreaseinfibroidrisk.
epidemiologyofmyomas7

Pregnancyandfibroids
Severalstudieshaveshownaprotectiveeffectofpregnancyonthedevelopment
offibroids[2],withparitydecreasingtheriskoffibroidsuptofivefold.These
numbersmaybedeceptivelyhigh,however,giventheknowndecrementin
fertilityattributabletofibroids.Ifawomandoesnothavefibroidssheismore
likelytohavebeenpregnantanddeliveredachild,andbecausemanyofthe
studieslookatparityratherthansimplyahistoryofbeingpregnant,theeffectmay
beinflatedevenmore,becausefibroidsnotonlyinterferewithimplantation,but
withsuccessfuldelivery.Thereisbiologicplausibilitytotheprotectiveeffectof
progestinsonfibroidgrowth,however,becauseintheEkerrattheincidenceof
fibroiddiseasewasreducedwithprogestins[25].
Theconfoundingeffectsthatsubfertilitycausedbyfibroidshasonanalysisof
effectofpregnancyonfibroidsiswellillustratedinastudyexaminingtheriskof
fibroidsandageatdelivery[19].Adiagnosisoffibroidsdidnotchangetheageof
deliveryoffirstchildren,butdidchangetheageoflasttermdelivery.Havinga
childlaterinlifewasconveyedasbeingprotective,wheninfactitmaymerely
illustratethefactthattherewasagreaterdiseaseburdenoffibroidslaterinlifeand
thesewomendidnothavetheirfertilityaffectedatage19,butfertilitywasaffected
atage38.
Menstrualcyclecharacteristics
Fibroidsaregenerallyassociatedwithanincreasedriskofheavymenstrualflowor
alongerdurationofmenses[2].Thebiologicplausibilitywasattributedto
submucosalfibroidsinterruptingthenormalendometrialdevelopment,orthe
burdenoffibroidsinfluencingnormalmyometrialcontractility.Notallstudies,
however,haveshownthisrelationship.Inacohortofwomenbeingfollowed
independentoffibroidrisk[6],73ofwhohadultrasonographicallydetectable
fibroids,therewasnosignificantdifferenceintheirmenstrualcyclecharacter
isticscomparedwithcontrols.Becausebydefinitionthesewomenwerenot
selectedforsymptomsoffibroids,however,thesamplesizewasnotlargeenough
todemonstratetheeffect.Thisillustratesthepointthatdisruptionofthemenstrual
cycleisfarfromaninevitableoutcomeinwomenwithfibroids.Thereisabiasto
attributesymptomstothetumorsinwomenwithfibroids.
Hypertension

Arecentstudydemonstratedanintriguinglinkbetweendiastolicbloodpressure
andfibroids[26].Inlinewiththeoriesthatshowagradedresponseofdiastolic
bloodpressurestoatherogenesis,itwassuggestedthatelevatedbloodpressure
couldcauseinjuryorcytokinereleaseintheuterinesmoothmusclethat
8paysonetal

promotesfibroidgrowth.Ina10yearanalysisofmorethan100,000nursesthere
were7466diagnosesoffibroidsbyultrasoundorhysterectomy.Afteradjustingfor
age,race,bodymassindex,andotherfactors,anindependentriskofdiastolic
bloodpressurewasfound.Hypertensivewomenwere24%morelikelytoreport
fibroids,andtheriskincreasedwithdurationofhypertension.Theriskforfibroids
alsoincreasedwiththedegreeofhypertension.Forevery10mmHGincreasein
diastolicbloodpressure,theriskforfibroidsincreased8%to10%.Theincreased
pressuremaybeaffectinguterinesmoothmuscle,causingdamagewithasimilar
mechanismasinvascularsmoothmuscleandhypertension.
Infectionandfibroids
Iffibroidsmaybetriggeredbymyometrialinjuryassuggested[27],eitherthrough
ischemia,pressure,orirritationfromatherogenictypemechanisms,suchas
hypertension,itislogicaltoinquireabouttheaffectofinfectiononfibroid
development.Acasecontrolstudyof318women[28]thatadjustedforhyper
tension,diabetes,age,ethnicity,bodymassindex,smoking,andoralcontra
ceptiveuse,foundapositiveassociationwithpelvicinfection.Ahistoryofpelvic
inflammatorydiseaseincreasedtheriskoffibroids,withtheriskincreasingwith
thenumberofinfectiousepisodes.Ahistoryofthreeepisodesofpelvicinflam
matorydiseaseconferredaRRof3.7.Likewise,ahistoryofChlamydiacon
ferredaRRof3.2.Sexuallytransmitteddiseasesthatmainlyaffectedtheexternal
genitalia(genitalwartsandherpes)showednoassociation.Itseemsthatthe
intrauterineirritationmaycontributetotheappearanceorgrowthoffibroids.
Chagasdisease,theresultofaparasiticinfectionendemictoportionsofSouth
America,hasbeenreportedtoleadtoanincreasedriskofvariouscancers.Inan
intriguingstudy[29]itwasshownthattheincidenceofapositivehistoryof
Chagasdisease,diagnosedbyserology,wassignificantlyhigherinwomen
presentingforleiomyomasurgery.Twentysevenpercentofwomenundergoing
fibroidsurgeryhadaserologicallydocumentedChagasinfectionversus16%of
controls.Whenthegroupswerefurtheranalyzedbyrace,whitewomenwith
fibroidshada40%prevalenceofChagasversus10%fornonwhitecontrols.Itis
knownthatChagascanparasitizetheuterinesmoothmuscle,andthisirritation
mayexplaintheassociationobserved.

Smoking,alcohol,andcaffeine
Ithasbeensuggestedthatcigarettesmokingcouldlowertheriskoffibroids
becauseitisassociatedwithlowerestrogenlevelsinsomestudies.Thedataare
conflicting,withaRRof1.6forgreaterthanonepackperday[2]toadecreasein
risk(RR0.7)[19,24].InthewelldoneBlackWomensHealthStudyfollow
epidemiologyofmyomas9

ingalmost22,000womentherewasnochangeinriskassociatedwithtobacco
smoking[30].
TheBlackWomensHealthStudywasabletodemonstratenochangeinrisk
relatedtocaffeineconsumption,butdidseeasmall(RR1.57)increaseinriskfor
morethansevendrinksofbeerperweek.Lesseramountsofbeerandother
alcoholsshowedsmallerrisksbutdidnotreachstatisticalsignificance.
Dietandfibroids
Onestudy[31]hasspecificallyaddressedthequestionofdietaryinfluencesonthe
prevalenceoffibroids.InanItalianpopulation,843womenwithfibroidswere
comparedwith1557womenwithout.Adietweightedtowardgreenvegetables
wasprotective(RR0.5),whereasahigherintakeofmeatswasassociatedwitha
greaterincidenceoffibroids(RR1.7).Giventhatdietisanessentialcomponentof
lifestyletherearemultipleconfoundingfactors.Thisstudydoessuggest,however,
thatlifestyleandenvironmentalexposuresseemtoaffecttheincidenceoffibroid
disease.
Summary
FibroidsareaprevalentdisorderoccurringinatleasthalfofAmerican
reproductiveagewomen.Ingeneral,theincidenceandsizeincreaseswithage.
Mostwomenneverattributeorreportanysymptomsfromtheirfibroids,and
becauseofthistheactualcontributionofdiseasetosymptomsofpelvicpain,
menstrualsymptoms,andinfertilityispoorlyunderstood.Thepresenceoffibroids
canleadtomultipleanddisablingdifficulties.Fibroidsmaycausepainand
menstrualbleedingtothepointofanemia.Fibroidsclearlyreducefertility,
increasepretermlaboranddelivery,andmarkedlyincreasetheriskforcesarean
delivery.Becausetheincidencevariesaccordingtopopulationofinterest,fi
broidsmayexplainsomehealthdisparitiesindifferentpopulations.Forexample,
AfricanAmericanshavearelativelypooroutcomewithassistedreproductive
techniquescomparedwithwhites[32].Controllingforfibroiddiseasemayex
plainthisdisparity,atleastinpart[33].

Fibroidsrepresentatremendouspublichealthburdenonwomenandeconomic
costonsociety.Strategiestoprevent,limitgrowth,andtreatnonsurgicallyare
needed.Fundamentalandsignificantquestionsremainaboutfibroiddisease,such
aswhetherdifferentclinicaldiseasephenotypes(multipleversussingle
leiomyomas)contributeequallytosymptomsandpossessanequallikelihoodof
diseaseprogression.Forepidemiologicassessmentofdisease,ascoringsystemis
urgentlyneeded.Welldesigned,controlled,prospectivestudiesarestillneededto
definethenaturalhistoryandcorrelatethepresenceofdiseasewithsymptom
atologyinwomen[34].
10paysonetalAcknowledgments

TheauthorsacknowledgethehelpfuldiscussionsofcolleaguesDr.William
Catherino,Dr.LynnetteNieman,andDr.JohnTsibris.SupportfromDrs.
Chrousos,Haffner,andSatinhelpedtomakethisworkpossible.
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