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OBG Management is a leading publication in the ObGyn specialty addressing patient care and practice management under one cover.
gambling
compulsive behaviors
ammunition
assault rifle
black jack
Boko Haram
bondage
child abuse
cocaine
Daech
drug paraphernalia
explosion
gun
human trafficking
ISIL
ISIS
Islamic caliphate
Islamic state
mixed martial arts
MMA
molestation
national rifle association
NRA
nsfw
pedophile
pedophilia
poker
porn
pornography
psychedelic drug
recreational drug
sex slave rings
slot machine
terrorism
terrorist
Texas hold 'em
UFC
substance abuse
abuseed
abuseer
abusees
abuseing
abusely
abuses
aeolus
aeolused
aeoluser
aeoluses
aeolusing
aeolusly
aeoluss
ahole
aholeed
aholeer
aholees
aholeing
aholely
aholes
alcohol
alcoholed
alcoholer
alcoholes
alcoholing
alcoholly
alcohols
allman
allmaned
allmaner
allmanes
allmaning
allmanly
allmans
alted
altes
alting
altly
alts
analed
analer
anales
analing
anally
analprobe
analprobeed
analprobeer
analprobees
analprobeing
analprobely
analprobes
anals
anilingus
anilingused
anilinguser
anilinguses
anilingusing
anilingusly
anilinguss
anus
anused
anuser
anuses
anusing
anusly
anuss
areola
areolaed
areolaer
areolaes
areolaing
areolaly
areolas
areole
areoleed
areoleer
areolees
areoleing
areolely
areoles
arian
arianed
arianer
arianes
arianing
arianly
arians
aryan
aryaned
aryaner
aryanes
aryaning
aryanly
aryans
asiaed
asiaer
asiaes
asiaing
asialy
asias
ass
ass hole
ass lick
ass licked
ass licker
ass lickes
ass licking
ass lickly
ass licks
assbang
assbanged
assbangeded
assbangeder
assbangedes
assbangeding
assbangedly
assbangeds
assbanger
assbanges
assbanging
assbangly
assbangs
assbangsed
assbangser
assbangses
assbangsing
assbangsly
assbangss
assed
asser
asses
assesed
asseser
asseses
assesing
assesly
assess
assfuck
assfucked
assfucker
assfuckered
assfuckerer
assfuckeres
assfuckering
assfuckerly
assfuckers
assfuckes
assfucking
assfuckly
assfucks
asshat
asshated
asshater
asshates
asshating
asshatly
asshats
assholeed
assholeer
assholees
assholeing
assholely
assholes
assholesed
assholeser
assholeses
assholesing
assholesly
assholess
assing
assly
assmaster
assmastered
assmasterer
assmasteres
assmastering
assmasterly
assmasters
assmunch
assmunched
assmuncher
assmunches
assmunching
assmunchly
assmunchs
asss
asswipe
asswipeed
asswipeer
asswipees
asswipeing
asswipely
asswipes
asswipesed
asswipeser
asswipeses
asswipesing
asswipesly
asswipess
azz
azzed
azzer
azzes
azzing
azzly
azzs
babeed
babeer
babees
babeing
babely
babes
babesed
babeser
babeses
babesing
babesly
babess
ballsac
ballsaced
ballsacer
ballsaces
ballsacing
ballsack
ballsacked
ballsacker
ballsackes
ballsacking
ballsackly
ballsacks
ballsacly
ballsacs
ballsed
ballser
ballses
ballsing
ballsly
ballss
barf
barfed
barfer
barfes
barfing
barfly
barfs
bastard
bastarded
bastarder
bastardes
bastarding
bastardly
bastards
bastardsed
bastardser
bastardses
bastardsing
bastardsly
bastardss
bawdy
bawdyed
bawdyer
bawdyes
bawdying
bawdyly
bawdys
beaner
beanered
beanerer
beaneres
beanering
beanerly
beaners
beardedclam
beardedclamed
beardedclamer
beardedclames
beardedclaming
beardedclamly
beardedclams
beastiality
beastialityed
beastialityer
beastialityes
beastialitying
beastialityly
beastialitys
beatch
beatched
beatcher
beatches
beatching
beatchly
beatchs
beater
beatered
beaterer
beateres
beatering
beaterly
beaters
beered
beerer
beeres
beering
beerly
beeyotch
beeyotched
beeyotcher
beeyotches
beeyotching
beeyotchly
beeyotchs
beotch
beotched
beotcher
beotches
beotching
beotchly
beotchs
biatch
biatched
biatcher
biatches
biatching
biatchly
biatchs
big tits
big titsed
big titser
big titses
big titsing
big titsly
big titss
bigtits
bigtitsed
bigtitser
bigtitses
bigtitsing
bigtitsly
bigtitss
bimbo
bimboed
bimboer
bimboes
bimboing
bimboly
bimbos
bisexualed
bisexualer
bisexuales
bisexualing
bisexually
bisexuals
bitch
bitched
bitcheded
bitcheder
bitchedes
bitcheding
bitchedly
bitcheds
bitcher
bitches
bitchesed
bitcheser
bitcheses
bitchesing
bitchesly
bitchess
bitching
bitchly
bitchs
bitchy
bitchyed
bitchyer
bitchyes
bitchying
bitchyly
bitchys
bleached
bleacher
bleaches
bleaching
bleachly
bleachs
blow job
blow jobed
blow jober
blow jobes
blow jobing
blow jobly
blow jobs
blowed
blower
blowes
blowing
blowjob
blowjobed
blowjober
blowjobes
blowjobing
blowjobly
blowjobs
blowjobsed
blowjobser
blowjobses
blowjobsing
blowjobsly
blowjobss
blowly
blows
boink
boinked
boinker
boinkes
boinking
boinkly
boinks
bollock
bollocked
bollocker
bollockes
bollocking
bollockly
bollocks
bollocksed
bollockser
bollockses
bollocksing
bollocksly
bollockss
bollok
bolloked
bolloker
bollokes
bolloking
bollokly
bolloks
boner
bonered
bonerer
boneres
bonering
bonerly
boners
bonersed
bonerser
bonerses
bonersing
bonersly
bonerss
bong
bonged
bonger
bonges
bonging
bongly
bongs
boob
boobed
boober
boobes
boobies
boobiesed
boobieser
boobieses
boobiesing
boobiesly
boobiess
boobing
boobly
boobs
boobsed
boobser
boobses
boobsing
boobsly
boobss
booby
boobyed
boobyer
boobyes
boobying
boobyly
boobys
booger
boogered
boogerer
boogeres
boogering
boogerly
boogers
bookie
bookieed
bookieer
bookiees
bookieing
bookiely
bookies
bootee
booteeed
booteeer
booteees
booteeing
booteely
bootees
bootie
bootieed
bootieer
bootiees
bootieing
bootiely
booties
booty
bootyed
bootyer
bootyes
bootying
bootyly
bootys
boozeed
boozeer
boozees
boozeing
boozely
boozer
boozered
boozerer
boozeres
boozering
boozerly
boozers
boozes
boozy
boozyed
boozyer
boozyes
boozying
boozyly
boozys
bosomed
bosomer
bosomes
bosoming
bosomly
bosoms
bosomy
bosomyed
bosomyer
bosomyes
bosomying
bosomyly
bosomys
bugger
buggered
buggerer
buggeres
buggering
buggerly
buggers
bukkake
bukkakeed
bukkakeer
bukkakees
bukkakeing
bukkakely
bukkakes
bull shit
bull shited
bull shiter
bull shites
bull shiting
bull shitly
bull shits
bullshit
bullshited
bullshiter
bullshites
bullshiting
bullshitly
bullshits
bullshitsed
bullshitser
bullshitses
bullshitsing
bullshitsly
bullshitss
bullshitted
bullshitteded
bullshitteder
bullshittedes
bullshitteding
bullshittedly
bullshitteds
bullturds
bullturdsed
bullturdser
bullturdses
bullturdsing
bullturdsly
bullturdss
bung
bunged
bunger
bunges
bunging
bungly
bungs
busty
bustyed
bustyer
bustyes
bustying
bustyly
bustys
butt
butt fuck
butt fucked
butt fucker
butt fuckes
butt fucking
butt fuckly
butt fucks
butted
buttes
buttfuck
buttfucked
buttfucker
buttfuckered
buttfuckerer
buttfuckeres
buttfuckering
buttfuckerly
buttfuckers
buttfuckes
buttfucking
buttfuckly
buttfucks
butting
buttly
buttplug
buttpluged
buttpluger
buttpluges
buttpluging
buttplugly
buttplugs
butts
caca
cacaed
cacaer
cacaes
cacaing
cacaly
cacas
cahone
cahoneed
cahoneer
cahonees
cahoneing
cahonely
cahones
cameltoe
cameltoeed
cameltoeer
cameltoees
cameltoeing
cameltoely
cameltoes
carpetmuncher
carpetmunchered
carpetmuncherer
carpetmuncheres
carpetmunchering
carpetmuncherly
carpetmunchers
cawk
cawked
cawker
cawkes
cawking
cawkly
cawks
chinc
chinced
chincer
chinces
chincing
chincly
chincs
chincsed
chincser
chincses
chincsing
chincsly
chincss
chink
chinked
chinker
chinkes
chinking
chinkly
chinks
chode
chodeed
chodeer
chodees
chodeing
chodely
chodes
chodesed
chodeser
chodeses
chodesing
chodesly
chodess
clit
clited
cliter
clites
cliting
clitly
clitoris
clitorised
clitoriser
clitorises
clitorising
clitorisly
clitoriss
clitorus
clitorused
clitoruser
clitoruses
clitorusing
clitorusly
clitoruss
clits
clitsed
clitser
clitses
clitsing
clitsly
clitss
clitty
clittyed
clittyer
clittyes
clittying
clittyly
clittys
cocain
cocaine
cocained
cocaineed
cocaineer
cocainees
cocaineing
cocainely
cocainer
cocaines
cocaining
cocainly
cocains
cock
cock sucker
cock suckered
cock suckerer
cock suckeres
cock suckering
cock suckerly
cock suckers
cockblock
cockblocked
cockblocker
cockblockes
cockblocking
cockblockly
cockblocks
cocked
cocker
cockes
cockholster
cockholstered
cockholsterer
cockholsteres
cockholstering
cockholsterly
cockholsters
cocking
cockknocker
cockknockered
cockknockerer
cockknockeres
cockknockering
cockknockerly
cockknockers
cockly
cocks
cocksed
cockser
cockses
cocksing
cocksly
cocksmoker
cocksmokered
cocksmokerer
cocksmokeres
cocksmokering
cocksmokerly
cocksmokers
cockss
cocksucker
cocksuckered
cocksuckerer
cocksuckeres
cocksuckering
cocksuckerly
cocksuckers
coital
coitaled
coitaler
coitales
coitaling
coitally
coitals
commie
commieed
commieer
commiees
commieing
commiely
commies
condomed
condomer
condomes
condoming
condomly
condoms
coon
cooned
cooner
coones
cooning
coonly
coons
coonsed
coonser
coonses
coonsing
coonsly
coonss
corksucker
corksuckered
corksuckerer
corksuckeres
corksuckering
corksuckerly
corksuckers
cracked
crackwhore
crackwhoreed
crackwhoreer
crackwhorees
crackwhoreing
crackwhorely
crackwhores
crap
craped
craper
crapes
craping
craply
crappy
crappyed
crappyer
crappyes
crappying
crappyly
crappys
cum
cumed
cumer
cumes
cuming
cumly
cummin
cummined
cumminer
cummines
cumming
cumminged
cumminger
cumminges
cumminging
cummingly
cummings
cummining
cumminly
cummins
cums
cumshot
cumshoted
cumshoter
cumshotes
cumshoting
cumshotly
cumshots
cumshotsed
cumshotser
cumshotses
cumshotsing
cumshotsly
cumshotss
cumslut
cumsluted
cumsluter
cumslutes
cumsluting
cumslutly
cumsluts
cumstain
cumstained
cumstainer
cumstaines
cumstaining
cumstainly
cumstains
cunilingus
cunilingused
cunilinguser
cunilinguses
cunilingusing
cunilingusly
cunilinguss
cunnilingus
cunnilingused
cunnilinguser
cunnilinguses
cunnilingusing
cunnilingusly
cunnilinguss
cunny
cunnyed
cunnyer
cunnyes
cunnying
cunnyly
cunnys
cunt
cunted
cunter
cuntes
cuntface
cuntfaceed
cuntfaceer
cuntfacees
cuntfaceing
cuntfacely
cuntfaces
cunthunter
cunthuntered
cunthunterer
cunthunteres
cunthuntering
cunthunterly
cunthunters
cunting
cuntlick
cuntlicked
cuntlicker
cuntlickered
cuntlickerer
cuntlickeres
cuntlickering
cuntlickerly
cuntlickers
cuntlickes
cuntlicking
cuntlickly
cuntlicks
cuntly
cunts
cuntsed
cuntser
cuntses
cuntsing
cuntsly
cuntss
dago
dagoed
dagoer
dagoes
dagoing
dagoly
dagos
dagosed
dagoser
dagoses
dagosing
dagosly
dagoss
dammit
dammited
dammiter
dammites
dammiting
dammitly
dammits
damn
damned
damneded
damneder
damnedes
damneding
damnedly
damneds
damner
damnes
damning
damnit
damnited
damniter
damnites
damniting
damnitly
damnits
damnly
damns
dick
dickbag
dickbaged
dickbager
dickbages
dickbaging
dickbagly
dickbags
dickdipper
dickdippered
dickdipperer
dickdipperes
dickdippering
dickdipperly
dickdippers
dicked
dicker
dickes
dickface
dickfaceed
dickfaceer
dickfacees
dickfaceing
dickfacely
dickfaces
dickflipper
dickflippered
dickflipperer
dickflipperes
dickflippering
dickflipperly
dickflippers
dickhead
dickheaded
dickheader
dickheades
dickheading
dickheadly
dickheads
dickheadsed
dickheadser
dickheadses
dickheadsing
dickheadsly
dickheadss
dicking
dickish
dickished
dickisher
dickishes
dickishing
dickishly
dickishs
dickly
dickripper
dickrippered
dickripperer
dickripperes
dickrippering
dickripperly
dickrippers
dicks
dicksipper
dicksippered
dicksipperer
dicksipperes
dicksippering
dicksipperly
dicksippers
dickweed
dickweeded
dickweeder
dickweedes
dickweeding
dickweedly
dickweeds
dickwhipper
dickwhippered
dickwhipperer
dickwhipperes
dickwhippering
dickwhipperly
dickwhippers
dickzipper
dickzippered
dickzipperer
dickzipperes
dickzippering
dickzipperly
dickzippers
diddle
diddleed
diddleer
diddlees
diddleing
diddlely
diddles
dike
dikeed
dikeer
dikees
dikeing
dikely
dikes
dildo
dildoed
dildoer
dildoes
dildoing
dildoly
dildos
dildosed
dildoser
dildoses
dildosing
dildosly
dildoss
diligaf
diligafed
diligafer
diligafes
diligafing
diligafly
diligafs
dillweed
dillweeded
dillweeder
dillweedes
dillweeding
dillweedly
dillweeds
dimwit
dimwited
dimwiter
dimwites
dimwiting
dimwitly
dimwits
dingle
dingleed
dingleer
dinglees
dingleing
dinglely
dingles
dipship
dipshiped
dipshiper
dipshipes
dipshiping
dipshiply
dipships
dizzyed
dizzyer
dizzyes
dizzying
dizzyly
dizzys
doggiestyleed
doggiestyleer
doggiestylees
doggiestyleing
doggiestylely
doggiestyles
doggystyleed
doggystyleer
doggystylees
doggystyleing
doggystylely
doggystyles
dong
donged
donger
donges
donging
dongly
dongs
doofus
doofused
doofuser
doofuses
doofusing
doofusly
doofuss
doosh
dooshed
doosher
dooshes
dooshing
dooshly
dooshs
dopeyed
dopeyer
dopeyes
dopeying
dopeyly
dopeys
douchebag
douchebaged
douchebager
douchebages
douchebaging
douchebagly
douchebags
douchebagsed
douchebagser
douchebagses
douchebagsing
douchebagsly
douchebagss
doucheed
doucheer
douchees
doucheing
douchely
douches
douchey
doucheyed
doucheyer
doucheyes
doucheying
doucheyly
doucheys
drunk
drunked
drunker
drunkes
drunking
drunkly
drunks
dumass
dumassed
dumasser
dumasses
dumassing
dumassly
dumasss
dumbass
dumbassed
dumbasser
dumbasses
dumbassesed
dumbasseser
dumbasseses
dumbassesing
dumbassesly
dumbassess
dumbassing
dumbassly
dumbasss
dummy
dummyed
dummyer
dummyes
dummying
dummyly
dummys
dyke
dykeed
dykeer
dykees
dykeing
dykely
dykes
dykesed
dykeser
dykeses
dykesing
dykesly
dykess
erotic
eroticed
eroticer
erotices
eroticing
eroticly
erotics
extacy
extacyed
extacyer
extacyes
extacying
extacyly
extacys
extasy
extasyed
extasyer
extasyes
extasying
extasyly
extasys
fack
facked
facker
fackes
facking
fackly
facks
fag
faged
fager
fages
fagg
fagged
faggeded
faggeder
faggedes
faggeding
faggedly
faggeds
fagger
fagges
fagging
faggit
faggited
faggiter
faggites
faggiting
faggitly
faggits
faggly
faggot
faggoted
faggoter
faggotes
faggoting
faggotly
faggots
faggs
faging
fagly
fagot
fagoted
fagoter
fagotes
fagoting
fagotly
fagots
fags
fagsed
fagser
fagses
fagsing
fagsly
fagss
faig
faiged
faiger
faiges
faiging
faigly
faigs
faigt
faigted
faigter
faigtes
faigting
faigtly
faigts
fannybandit
fannybandited
fannybanditer
fannybandites
fannybanditing
fannybanditly
fannybandits
farted
farter
fartes
farting
fartknocker
fartknockered
fartknockerer
fartknockeres
fartknockering
fartknockerly
fartknockers
fartly
farts
felch
felched
felcher
felchered
felcherer
felcheres
felchering
felcherly
felchers
felches
felching
felchinged
felchinger
felchinges
felchinging
felchingly
felchings
felchly
felchs
fellate
fellateed
fellateer
fellatees
fellateing
fellately
fellates
fellatio
fellatioed
fellatioer
fellatioes
fellatioing
fellatioly
fellatios
feltch
feltched
feltcher
feltchered
feltcherer
feltcheres
feltchering
feltcherly
feltchers
feltches
feltching
feltchly
feltchs
feom
feomed
feomer
feomes
feoming
feomly
feoms
fisted
fisteded
fisteder
fistedes
fisteding
fistedly
fisteds
fisting
fistinged
fistinger
fistinges
fistinging
fistingly
fistings
fisty
fistyed
fistyer
fistyes
fistying
fistyly
fistys
floozy
floozyed
floozyer
floozyes
floozying
floozyly
floozys
foad
foaded
foader
foades
foading
foadly
foads
fondleed
fondleer
fondlees
fondleing
fondlely
fondles
foobar
foobared
foobarer
foobares
foobaring
foobarly
foobars
freex
freexed
freexer
freexes
freexing
freexly
freexs
frigg
frigga
friggaed
friggaer
friggaes
friggaing
friggaly
friggas
frigged
frigger
frigges
frigging
friggly
friggs
fubar
fubared
fubarer
fubares
fubaring
fubarly
fubars
fuck
fuckass
fuckassed
fuckasser
fuckasses
fuckassing
fuckassly
fuckasss
fucked
fuckeded
fuckeder
fuckedes
fuckeding
fuckedly
fuckeds
fucker
fuckered
fuckerer
fuckeres
fuckering
fuckerly
fuckers
fuckes
fuckface
fuckfaceed
fuckfaceer
fuckfacees
fuckfaceing
fuckfacely
fuckfaces
fuckin
fuckined
fuckiner
fuckines
fucking
fuckinged
fuckinger
fuckinges
fuckinging
fuckingly
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ruskis
sadism
sadismed
sadismer
sadismes
sadisming
sadismly
sadisms
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scag
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scager
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scantily
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scantilyer
scantilyes
scantilying
scantilyly
scantilys
schlong
schlonged
schlonger
schlonges
schlonging
schlongly
schlongs
scrog
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scroging
scrogly
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scrote
scroted
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scroteer
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scruded
scruder
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scruding
scrudly
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scum
scumed
scumer
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scuming
scumly
scums
seaman
seamaned
seamaner
seamanes
seamaning
seamanly
seamans
seamen
seamened
seamener
seamenes
seamening
seamenly
seamens
seduceed
seduceer
seducees
seduceing
seducely
seduces
semen
semened
semener
semenes
semening
semenly
semens
shamedame
shamedameed
shamedameer
shamedamees
shamedameing
shamedamely
shamedames
shit
shite
shiteater
shiteatered
shiteaterer
shiteateres
shiteatering
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shiteaters
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shitholeing
shitholely
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shithouse
shithouseed
shithouseer
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shithouseing
shithousely
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shiting
shitly
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shitsed
shitser
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shitt
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shitteder
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shitteding
shittedly
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shitter
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shitterer
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shittering
shitterly
shitters
shittes
shitting
shittly
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shitty
shittyed
shittyer
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shittying
shittyly
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shiz
shized
shizer
shizes
shizing
shizly
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shooted
shooter
shootes
shooting
shootly
shoots
sissy
sissyed
sissyer
sissyes
sissying
sissyly
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skag
skaged
skager
skages
skaging
skagly
skags
skank
skanked
skanker
skankes
skanking
skankly
skanks
slave
slaveed
slaveer
slavees
slaveing
slavely
slaves
sleaze
sleazeed
sleazeer
sleazees
sleazeing
sleazely
sleazes
sleazy
sleazyed
sleazyer
sleazyes
sleazying
sleazyly
sleazys
slut
slutdumper
slutdumpered
slutdumperer
slutdumperes
slutdumpering
slutdumperly
slutdumpers
sluted
sluter
slutes
sluting
slutkiss
slutkissed
slutkisser
slutkisses
slutkissing
slutkissly
slutkisss
slutly
sluts
slutsed
slutser
slutses
slutsing
slutsly
slutss
smegma
smegmaed
smegmaer
smegmaes
smegmaing
smegmaly
smegmas
smut
smuted
smuter
smutes
smuting
smutly
smuts
smutty
smuttyed
smuttyer
smuttyes
smuttying
smuttyly
smuttys
snatch
snatched
snatcher
snatches
snatching
snatchly
snatchs
sniper
snipered
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sniperes
snipering
sniperly
snipers
snort
snorted
snorter
snortes
snorting
snortly
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snuffes
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sodom
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sodomer
sodomes
sodoming
sodomly
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spic
spiced
spicer
spices
spicing
spick
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spicker
spickes
spicking
spickly
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spik
spoof
spoofed
spoofer
spoofes
spoofing
spoofly
spoofs
spooge
spoogeed
spoogeer
spoogees
spoogeing
spoogely
spooges
spunk
spunked
spunker
spunkes
spunking
spunkly
spunks
steamyed
steamyer
steamyes
steamying
steamyly
steamys
stfu
stfued
stfuer
stfues
stfuing
stfuly
stfus
stiffy
stiffyed
stiffyer
stiffyes
stiffying
stiffyly
stiffys
stoneded
stoneder
stonedes
stoneding
stonedly
stoneds
stupided
stupider
stupides
stupiding
stupidly
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suckeded
suckeder
suckedes
suckeding
suckedly
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suckes
sucking
suckinged
suckinger
suckinges
suckinging
suckingly
suckings
suckly
sucks
sumofabiatch
sumofabiatched
sumofabiatcher
sumofabiatches
sumofabiatching
sumofabiatchly
sumofabiatchs
tard
tarded
tarder
tardes
tarding
tardly
tards
tawdry
tawdryed
tawdryer
tawdryes
tawdrying
tawdryly
tawdrys
teabagging
teabagginged
teabagginger
teabagginges
teabagginging
teabaggingly
teabaggings
terd
terded
terder
terdes
terding
terdly
terds
teste
testee
testeed
testeeed
testeeer
testeees
testeeing
testeely
testeer
testees
testeing
testely
testes
testesed
testeser
testeses
testesing
testesly
testess
testicle
testicleed
testicleer
testiclees
testicleing
testiclely
testicles
testis
testised
testiser
testises
testising
testisly
testiss
thrusted
thruster
thrustes
thrusting
thrustly
thrusts
thug
thuged
thuger
thuges
thuging
thugly
thugs
tinkle
tinkleed
tinkleer
tinklees
tinkleing
tinklely
tinkles
tit
tited
titer
tites
titfuck
titfucked
titfucker
titfuckes
titfucking
titfuckly
titfucks
titi
titied
titier
tities
titiing
titily
titing
titis
titly
tits
titsed
titser
titses
titsing
titsly
titss
tittiefucker
tittiefuckered
tittiefuckerer
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tittiefuckering
tittiefuckerly
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titties
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tittieser
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tittiesing
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titty
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tittyer
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tittyfuck
tittyfucked
tittyfucker
tittyfuckered
tittyfuckerer
tittyfuckeres
tittyfuckering
tittyfuckerly
tittyfuckers
tittyfuckes
tittyfucking
tittyfuckly
tittyfucks
tittying
tittyly
tittys
toke
tokeed
tokeer
tokees
tokeing
tokely
tokes
toots
tootsed
tootser
tootses
tootsing
tootsly
tootss
tramp
tramped
tramper
trampes
tramping
tramply
tramps
transsexualed
transsexualer
transsexuales
transsexualing
transsexually
transsexuals
trashy
trashyed
trashyer
trashyes
trashying
trashyly
trashys
tubgirl
tubgirled
tubgirler
tubgirles
tubgirling
tubgirlly
tubgirls
turd
turded
turder
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turding
turdly
turds
tush
tushed
tusher
tushes
tushing
tushly
tushs
twat
twated
twater
twates
twating
twatly
twats
twatsed
twatser
twatses
twatsing
twatsly
twatss
undies
undiesed
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undiesing
undiesly
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uzi
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uzier
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uziing
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uzis
vag
vaged
vager
vages
vaging
vagly
vags
valium
valiumed
valiumer
valiumes
valiuming
valiumly
valiums
venous
virgined
virginer
virgines
virgining
virginly
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vixen
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vixening
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vodkaing
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voyeuring
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wang
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wanges
wanging
wangly
wangs
wank
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wankering
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wanking
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wazoo
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wazooing
wazooly
wazoos
wedgie
wedgieed
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wedgieing
wedgiely
wedgies
weeded
weeder
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weeding
weedly
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weenie
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weinering
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weirdo
weirdoed
weirdoer
weirdoes
weirdoing
weirdoly
weirdos
wench
wenched
wencher
wenches
wenching
wenchly
wenchs
wetback
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wetbacking
wetbackly
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whiteyes
whiteying
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whorealicious
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whorehopper
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whorehoppering
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whorehouse
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whorehouseing
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whoreing
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whoress
whoring
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whoringly
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wigger
wiggered
wiggerer
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wiggerly
wiggers
woody
woodyed
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woodying
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woper
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woply
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wtfing
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xxx
xxxed
xxxer
xxxes
xxxing
xxxly
xxxs
yeasty
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yeastyer
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yeastying
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yobbo
yobboed
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yobboing
yobboly
yobbos
zoophile
zoophileed
zoophileer
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zoophileing
zoophilely
zoophiles
anal
ass
ass lick
balls
ballsac
bisexual
bleach
causas
cheap
cost of miracles
cunt
display network stats
fart
fda and death
fda AND warn
fda AND warning
fda AND warns
feom
fuck
gfc
humira AND expensive
illegal
madvocate
masturbation
nuccitelli
overdose
porn
shit
snort
texarkana
Cost-conscious minimally invasive hysterectomy: A case illustration
CASE Cost-conscious benign laparoscopic hysterectomy
A 43-year-old woman undergoes laparoscopic hysterectomy for treatment of presumed benign uterine fibroids and menorrhagia. Once she is prepped with ChloraPrep with tint, a RUMI II uterine manipulator is placed. Laparoscopic ports include a Kii Balloon Blunt Tip system, a Versaport Plus Pyramidal Bladed Trocar, and 2 Kii Fios First Entry trocars.
The surgeon uses the Harmonic ACE +7 device (a purely ultrasonic device) to perform most of the procedure. The uterus is morcellated and removed using the US Food and Drug Administration (FDA)-approved Olympus Contained Tissue Extraction System, and the vaginal cuff is closed using a series of 2-0 PDS II sutures. Skin incisions are closed using Dermabond skin adhesive.
Total cost of the products used in this case: $1,592.40. Could different product choices have reduced this figure?
Health-care costs continue to rise faster than inflation: Total health-care expenditures account for approximately 18% of gross domestic product in the United States. Physicians therefore face increasing pressure to take cost into account in their care of patients.1 Cost-effectiveness and outcome quality continue to increase in importance as measures in many clinical trials that compare standard and alternative therapies. And women’s health—specifically, minimally invasive gynecologic surgery—invites such comparisons.
Overall, conventional laparoscopic gynecologic procedures tend to cost less than laparotomy, a consequence of shorter hospital stays, faster recovery, and fewer complications.2-5 What is not fully appreciated, however, is how choice of laparoscopic instrumentation and associated products affects surgical costs. In this article, which revisits and updates a 2013 OBG Management examination of cost-consciousness in the selection of equipment and supplies for minimally invasive gynecologic surgery,6 we review these costs in 2018. Our goal is to raise awareness of the role of cost in care among minimally invasive gynecologic surgeons.
In the sections that follow, we highlight several aspects of laparoscopic gynecologic surgery that can affect your selection of instruments and products, describing differences in cost as well as some distinctive characteristics of products. Note that our comparisons focus solely on cost—not on ease of utility, effectiveness, surgical technique, risk of complications, or any other assessment. Note also that numerous other instruments and devices are commercially available besides those we list.
Importantly, 2013 and 2018 costs are included in TABLE 1. Unless otherwise noted, costs are per unit. Changes in manufacturers and material costs and technologic advances have contributed to some, but not all, of the changes in cost between 2013 and 2018.

Continue to: Variables to keep in mind
Variables to keep in mind
Even when taking cost into consideration, tailor your selection of instruments and supplies to your capabilities and comfort, as well as to the particular characteristics of the patient and the planned procedure. Also, remember that your institution might have arrangements with companies that supply minimally invasive instruments, and that such arrangements might limit your options, to some degree. Last, be aware that reprocessed ports and instruments are now available at a reduced cost. In short, we believe that it is crucial for surgeons to be cognizant of all products available to them prior to attending a surgical case.
Skin preparation and other preop considerations
Multiple preoperative skin preparations are available (TABLE 1). Traditionally, a povidone–iodine topical antiseptic, such as Betadine, has been used for skin and vaginal preparation prior to gynecologic surgery. Hibiclens and ChloraPrep are different combinations of chlorhexidine gluconate and isopropyl alcohol that act as broad-spectrum antiseptics.
ChloraPrep is applied with a wand-like applicator and contains a much higher concentration of isopropyl alcohol than Hibiclens (70% and 4%, respectively), rendering it more flammable. It also requires longer drying time before surgery can be started. Clear and tinted ChloraPrep formulations are available.
Continue to: Uterine manipulators
Uterine manipulators
Cannulation of the cervical canal allows for uterine manipulation, increasing intraoperative traction and exposure as well as visualization of the adnexae and peritoneal surfaces.
The Hulka-Kenwick is a reusable uterine manipulator that is fairly standard and easy to apply. Specialized, single-use manipulators also are available, including the Advincula Delineator and VCare Plus uterine manipulator/elevator. The VCare Plus manipulator consists of 2 opposing cups: one cup (available in 4 sizes, small to extra-large) fits around the cervix and defines the site for colpotomy; the other helps maintain pneumoperitoneum once a colpotomy is created.
The ZUMI (Zinnanti Uterine Manipulator Injector) is a rigid, curved shaft with an intrauterine balloon to help prevent expulsion. It also has an integrated injection channel to allow for intraoperative chromotubation.
The RUMI II System fits individual patient anatomy with various tip lengths and colpotomy cup sizes. The Advincula Arch Uterine Manipulator Handle is a reusable alternative to the articulating RUMI II and works with the RUMI II System Disposable Tip (TABLE 1).
Continue to: Entry style and ports
Entry style and ports
The peritoneal cavity can be entered using either a closed (Veress needle) or open (Hasson) technique.7,8 Closed entry might allow for quicker access to the peritoneal cavity. A 2015 Cochrane review of 46 randomized, controlled trials of 7,389 patients undergoing laparoscopy compared outcomes between laparoscopic entry techniques and found no difference in major vascular or visceral injury between closed and open techniques at the umbilicus.9 However, open entry was associated with a greater likelihood of successful entry into the peritoneal cavity.9
Left upper-quadrant (Palmer’s point) entry is another option when adhesions are anticipated or abnormal anatomy is encountered at the umbilicus.
In general, complications related to laparoscopic entry are rare in gynecologic surgery, ranging from 0.18% to 0.5% of cases in studies.8,10,11 A minimally invasive surgeon might prefer one entry technique over another but should be able to perform both methods competently and recognize when a particular technique is warranted.
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Choosing a port
Laparoscopic ports usually range from 5 mm to 12 mm and can be fixed or variable in size.
The primary port, usually placed through the umbilicus, can be a standard, blunt, 10-mm (Bluntport Plus Hasson) port, or it can be specialized to ease entry of the port or stabilize the port once it is introduced through the skin incision.
Optical trocars have a transparent tip that allows the surgeon to visualize the abdominal wall entry layer by layer using a 0° laparoscope, sometimes after pneumoperitoneum is created with a Veress needle. Other specialized ports include those that have balloons or foam collars, or both, to secure the port without traditional stay sutures on the fascia and to minimize leakage of pneumoperitoneum.
Continue to: Accessory ports
Accessory ports
When choosing an accessory port type and size, it is important to anticipate which instruments and devices, such as an Endo Catch bag, suture, or needle, will need to pass through it. Also, know whether 5-mm and 10-mm laparoscopes are available, and anticipate whether a second port with insufflation capabilities will be required.
The Pediport Locking Trocar is a user-friendly, 5-mm bladed port that deploys a mushroom-shaped stabilizer to prevent dislodgement. The Versaport bladed trocar has a spring-loaded entry shield, which slides over the blade to protect it once the peritoneal cavity is entered.
VersaStep Bladeless Trocars are introduced after a Step Insufflation Needle has been inserted. These trocars create a smaller fascial defect than conventional bladed trocars for an equivalent cannula size (TABLE 1).
Cutting and coagulating
Both monopolar and bipolar electrosurgical techniques are commonly employed in gynecologic laparoscopy. A wide variety of disposable and reusable instruments are available for monopolar energy, such as scissors, a hook, and a spatula.
Bipolar devices also can be disposable or reusable. Although bipolar electrosurgery minimizes injury to surrounding tissues by containing the current within the jaws of the forceps, it cannot cut or seal large vessels. As a result, several advanced bipolar devices with sealing and transecting capabilities have emerged (the LigaSure line of devices, Enseal). Ultrasonic devices, such as the Harmonic ACE, also can coagulate and cut at lower temperatures by converting electrical energy to mechanical energy (TABLE 1).
Continue to: Suture material
Suture material
Aspects of minimally invasive gynecologic surgery that require the use of suture include, but are not limited to, closure of the vaginal cuff, oophoropexy, and reapproximation of the ovarian cortex after cystectomy. Synthetic and delayed absorbable sutures, such as PDS II, are used frequently. The barbed suture also has gained popularity because it anchors to tissue without the need for intracorporeal or extracorporeal knots (TABLE 1).
Tissue removal
Adnexae and pathologic tissue, such as dermoid cysts, can be removed intact from the peritoneal cavity using an Endo Catch Single Use Specimen Pouch, a polyurethane sac. Careful use, with placement of the ovary with the cyst into the pouch prior to cystectomy, can contain or prevent spillage outside the bag.
A large uterus that cannot be extracted through a colpotomy can be manually morcellated. Appropriate candidates can undergo power morcellation using an FDA-approved device. (TABLE 1), allowing for the removal of smaller pieces through a small laparoscopic incision or the colpotomy.
Issues surrounding morcellation continue to require that gynecologic surgeons understand FDA recommendations. In 2014, the FDA issued a safety communication that morcellation is “contraindicated in gynecologic surgery if tissue is known or suspected to be malignant; it is contraindicated for uterine tissue removal with presumed benign fibroids in perimenopausal women.”12 A black-box warning was issued that uterine tissue might contain unsuspected cancer.
A task force created by AAGL addressed key issues in this controversy.
AAGL then provided guidelines related to morcellation13:
- Do not use morcellate in the setting of known malignancy.
- Provide appropriate preoperative evaluation with up-to-date Pap smear screening and image analysis.
- Increasing age significantly increases the risk of leiomyosarcoma, especially in a postmenopausal woman.
- Fibroid growth is not a reliable sign of malignancy.
- Do not use a morcellator if the patient is at high risk for malignancy.
- If leiomyosarcoma is the presumed pathology, await the final pathology report before proceeding with hysterectomy.
- Concomitant use of a bag might mitigate the risk of tissue spread.
- Obtain informed consent before proceeding with morcellation.
Continue to: Skin closure
Skin closure
Final subcuticular closure can be accomplished using sutures or skin adhesive. Sutures can be synthetic, absorbable monofilament (Caprosyn), or synthetic, absorbable, braided multifilament (Polysorb).
Skin adhesive closes incisions quickly, avoids inflammation related to foreign bodies, and can ease patients’ concerns that sometimes arise when absorbable suture persists postoperatively (TABLE 1).
The impact of physician experience
Physician experience has been shown to reduce cost while maintaining quality of care.14 That was the conclusion of researchers who undertook a retrospective study, addressing cost and clinical outcomes, of senior and junior attending physicians who performed laparoscopic-assisted vaginal hysterectomy on 120 patients. Studies such as these often lead to clinical pathways to facilitate cost-effective quality care.
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CASE Same outcome at lower cost
The hypothetical 43-year-old patient in the opening case undergoes laparoscopic hysterectomy for treatment of uterine fibroids and menorrhagia. In this scenario, however, the surgeon makes the following product choices:
- The patient is prepped with Hibiclens.
- A VCare Plus uterine manipulator is placed.
- Laparoscopic ports include a VersaStep Plus Bladeless Trocar with Step Insufflation Needle; Versaport Plus Pyramidal Bladed Trocar; and 2 VersaOne Bladed trocars.
- The surgeon uses the PKS LYONS Dissecting Forceps and reprocessed Endo Shears to perform the hysterectomy.
- The uterus is enclosed in an Endo Catch bag and removed through the minilaparotomy site.
- The vaginal cuff is closed using 2-0 V-Loc barbed suture. Skin incisions are closed with 4-0 Polysorb, a polyglycolic acid absorbable suture.
The cost of this set of products? $360.44 or, roughly, $1,231.96 less than the set-up described in the case at the beginning of this article (TABLE 2).
Continue to: Summing up
Summing up
Here are key points to take away from this analysis and discussion:
- As third-party payers and hospitals continue to evaluate surgeons individually and compare procedures from surgeon to surgeon, reimbursement might be stratified—thereby favoring physicians who demonstrate both quality outcomes and cost containment.
- There are many ways a minimally invasive surgeon can implement cost-conscious choices that have little or no impact on the quality of outcome.
- Surgeons who are familiar with surgical instruments and models available at their institution are better prepared to make wise cost-conscious decisions. (See “Caregivers should keep cost in mind: Here’s why,” in the Web version of this article at https://www.mdedge.com/obgyn.)
- Cost is not the only indicator of value: The surgeon must know how to apply tools correctly and be familiar with their limitations, and should choose instruments and products for their safety and ease of use. More often than not, a surgeon’s training and personal experience define—and sometimes restrict—the choice of devices.
- Last, it makes sense to have instruments and devices readily available in the operating room at the start of a case, to avoid unnecessary surgical delays. However, we recommend that you refrain from opening these tools until they are required intraoperatively. It is possible that the case will require conversion to laparotomy or that, after direct visualization of the pathology, different ports or instruments are required.
Acknowledgments
The authors would like to thank Meredith Snook, MD, who was coauthor of the original 2013 article6 and Kathleen Riordan, BSN, RN, for assistance in gathering specific cost-related information for this article.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Centers for Medicare & Medicaid Services. National health expenditure projections 2017-2026: Forecast summary. www.cms.gov/Research-Statistics-Data-and-Systems /Statistics-Trends-and-Reports/NationalHealthExpendData /Downloads/ForecastSummary.pdf. Accessed November 3, 2018.
- Vilos GA, Alshimmiri MM. Cost-benefit analysis of laparoscopic versus laparotomy salpingo-oophorectomy for benign tubo-ovarian disease. J Am Assoc Gynecol Laparosc. 1995;2(3):299-303.
- Gray DT, Thorburn J, Lundor P, et al. A cost-effectiveness study of a randomised trial of laparoscopy versus laparotomy for ectopic pregnancy. Lancet. 1995;345(8958):1139-1143.
- Chapron C, Fauconnier A, Goffinet F, et al. Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a metaanalysis. Hum Reprod. 2002;17(5):1334-1342.
- Benezra V, Verma U, Whitted RW. Comparison of laparoscopy versus laparotomy for the surgical treatment of ovarian dermoid cysts. Obstet Gynecol Surv. 2006;61(1): 20-21.
- Sanfilippo JS, Snook ML. Cost-conscious choices for minimally invasive gynecologic surgery. OBG Manag. 2013;25(11):40-41,44,46-48,72.
- Hasson HM. A modified instrument and method for laparoscopy. Am J Obstet Gynecol. 1971;110(6):886-887.
- Ott J, Jaeger-Lansky A, Poschalko G, et al. Entry techniques in gynecologic laparoscopy—a review. Gynecol Surg. 2012;9(2):139-146.
- Ahmad G, Gent D, Henderson D, et al. Laparoscopic entry techniques. Cochrane Database Syst Rev. 2015;8:CD006583.
- Hasson HM, Rotman C, Rana N, et al. Open laparoscopy: 29-year experience. Obstet Gynecol. 2000;96(5 Pt 1):763-766.
- Schäfer M, Lauper M, Krähenbühl L. Trocar and Veress needle injuries during laparoscopy. Surg Endosc. 2001;15(3):275- 280.
- Immediately in effect guidance document: product labeling for laparoscopic power morcellators. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration Center for Devices and Radiological Health; November 25, 2014. www.fda.gov/downloads /MedicalDevices/DeviceRegulationandGuidance /GuidanceDocuments/UCM424123.pdf. Accessed November 3, 2018.
- Tissue Extraction Task Force Members. Morcellation during uterine tissue extraction: an update. J Minim Invasive Gynecol. 2018;25(4):543-550.
- Chang WC, Li TC, Lin CC. The effect of physician experience on costs and clinical outcomes of laparoscopic-assisted vaginal hysterectomy: a multivariate analysis. J Am Assoc Gynecol Laparosc. 2003;10(3):356-359.
CASE Cost-conscious benign laparoscopic hysterectomy
A 43-year-old woman undergoes laparoscopic hysterectomy for treatment of presumed benign uterine fibroids and menorrhagia. Once she is prepped with ChloraPrep with tint, a RUMI II uterine manipulator is placed. Laparoscopic ports include a Kii Balloon Blunt Tip system, a Versaport Plus Pyramidal Bladed Trocar, and 2 Kii Fios First Entry trocars.
The surgeon uses the Harmonic ACE +7 device (a purely ultrasonic device) to perform most of the procedure. The uterus is morcellated and removed using the US Food and Drug Administration (FDA)-approved Olympus Contained Tissue Extraction System, and the vaginal cuff is closed using a series of 2-0 PDS II sutures. Skin incisions are closed using Dermabond skin adhesive.
Total cost of the products used in this case: $1,592.40. Could different product choices have reduced this figure?
Health-care costs continue to rise faster than inflation: Total health-care expenditures account for approximately 18% of gross domestic product in the United States. Physicians therefore face increasing pressure to take cost into account in their care of patients.1 Cost-effectiveness and outcome quality continue to increase in importance as measures in many clinical trials that compare standard and alternative therapies. And women’s health—specifically, minimally invasive gynecologic surgery—invites such comparisons.
Overall, conventional laparoscopic gynecologic procedures tend to cost less than laparotomy, a consequence of shorter hospital stays, faster recovery, and fewer complications.2-5 What is not fully appreciated, however, is how choice of laparoscopic instrumentation and associated products affects surgical costs. In this article, which revisits and updates a 2013 OBG Management examination of cost-consciousness in the selection of equipment and supplies for minimally invasive gynecologic surgery,6 we review these costs in 2018. Our goal is to raise awareness of the role of cost in care among minimally invasive gynecologic surgeons.
In the sections that follow, we highlight several aspects of laparoscopic gynecologic surgery that can affect your selection of instruments and products, describing differences in cost as well as some distinctive characteristics of products. Note that our comparisons focus solely on cost—not on ease of utility, effectiveness, surgical technique, risk of complications, or any other assessment. Note also that numerous other instruments and devices are commercially available besides those we list.
Importantly, 2013 and 2018 costs are included in TABLE 1. Unless otherwise noted, costs are per unit. Changes in manufacturers and material costs and technologic advances have contributed to some, but not all, of the changes in cost between 2013 and 2018.

Continue to: Variables to keep in mind
Variables to keep in mind
Even when taking cost into consideration, tailor your selection of instruments and supplies to your capabilities and comfort, as well as to the particular characteristics of the patient and the planned procedure. Also, remember that your institution might have arrangements with companies that supply minimally invasive instruments, and that such arrangements might limit your options, to some degree. Last, be aware that reprocessed ports and instruments are now available at a reduced cost. In short, we believe that it is crucial for surgeons to be cognizant of all products available to them prior to attending a surgical case.
Skin preparation and other preop considerations
Multiple preoperative skin preparations are available (TABLE 1). Traditionally, a povidone–iodine topical antiseptic, such as Betadine, has been used for skin and vaginal preparation prior to gynecologic surgery. Hibiclens and ChloraPrep are different combinations of chlorhexidine gluconate and isopropyl alcohol that act as broad-spectrum antiseptics.
ChloraPrep is applied with a wand-like applicator and contains a much higher concentration of isopropyl alcohol than Hibiclens (70% and 4%, respectively), rendering it more flammable. It also requires longer drying time before surgery can be started. Clear and tinted ChloraPrep formulations are available.
Continue to: Uterine manipulators
Uterine manipulators
Cannulation of the cervical canal allows for uterine manipulation, increasing intraoperative traction and exposure as well as visualization of the adnexae and peritoneal surfaces.
The Hulka-Kenwick is a reusable uterine manipulator that is fairly standard and easy to apply. Specialized, single-use manipulators also are available, including the Advincula Delineator and VCare Plus uterine manipulator/elevator. The VCare Plus manipulator consists of 2 opposing cups: one cup (available in 4 sizes, small to extra-large) fits around the cervix and defines the site for colpotomy; the other helps maintain pneumoperitoneum once a colpotomy is created.
The ZUMI (Zinnanti Uterine Manipulator Injector) is a rigid, curved shaft with an intrauterine balloon to help prevent expulsion. It also has an integrated injection channel to allow for intraoperative chromotubation.
The RUMI II System fits individual patient anatomy with various tip lengths and colpotomy cup sizes. The Advincula Arch Uterine Manipulator Handle is a reusable alternative to the articulating RUMI II and works with the RUMI II System Disposable Tip (TABLE 1).
Continue to: Entry style and ports
Entry style and ports
The peritoneal cavity can be entered using either a closed (Veress needle) or open (Hasson) technique.7,8 Closed entry might allow for quicker access to the peritoneal cavity. A 2015 Cochrane review of 46 randomized, controlled trials of 7,389 patients undergoing laparoscopy compared outcomes between laparoscopic entry techniques and found no difference in major vascular or visceral injury between closed and open techniques at the umbilicus.9 However, open entry was associated with a greater likelihood of successful entry into the peritoneal cavity.9
Left upper-quadrant (Palmer’s point) entry is another option when adhesions are anticipated or abnormal anatomy is encountered at the umbilicus.
In general, complications related to laparoscopic entry are rare in gynecologic surgery, ranging from 0.18% to 0.5% of cases in studies.8,10,11 A minimally invasive surgeon might prefer one entry technique over another but should be able to perform both methods competently and recognize when a particular technique is warranted.
--
Choosing a port
Laparoscopic ports usually range from 5 mm to 12 mm and can be fixed or variable in size.
The primary port, usually placed through the umbilicus, can be a standard, blunt, 10-mm (Bluntport Plus Hasson) port, or it can be specialized to ease entry of the port or stabilize the port once it is introduced through the skin incision.
Optical trocars have a transparent tip that allows the surgeon to visualize the abdominal wall entry layer by layer using a 0° laparoscope, sometimes after pneumoperitoneum is created with a Veress needle. Other specialized ports include those that have balloons or foam collars, or both, to secure the port without traditional stay sutures on the fascia and to minimize leakage of pneumoperitoneum.
Continue to: Accessory ports
Accessory ports
When choosing an accessory port type and size, it is important to anticipate which instruments and devices, such as an Endo Catch bag, suture, or needle, will need to pass through it. Also, know whether 5-mm and 10-mm laparoscopes are available, and anticipate whether a second port with insufflation capabilities will be required.
The Pediport Locking Trocar is a user-friendly, 5-mm bladed port that deploys a mushroom-shaped stabilizer to prevent dislodgement. The Versaport bladed trocar has a spring-loaded entry shield, which slides over the blade to protect it once the peritoneal cavity is entered.
VersaStep Bladeless Trocars are introduced after a Step Insufflation Needle has been inserted. These trocars create a smaller fascial defect than conventional bladed trocars for an equivalent cannula size (TABLE 1).
Cutting and coagulating
Both monopolar and bipolar electrosurgical techniques are commonly employed in gynecologic laparoscopy. A wide variety of disposable and reusable instruments are available for monopolar energy, such as scissors, a hook, and a spatula.
Bipolar devices also can be disposable or reusable. Although bipolar electrosurgery minimizes injury to surrounding tissues by containing the current within the jaws of the forceps, it cannot cut or seal large vessels. As a result, several advanced bipolar devices with sealing and transecting capabilities have emerged (the LigaSure line of devices, Enseal). Ultrasonic devices, such as the Harmonic ACE, also can coagulate and cut at lower temperatures by converting electrical energy to mechanical energy (TABLE 1).
Continue to: Suture material
Suture material
Aspects of minimally invasive gynecologic surgery that require the use of suture include, but are not limited to, closure of the vaginal cuff, oophoropexy, and reapproximation of the ovarian cortex after cystectomy. Synthetic and delayed absorbable sutures, such as PDS II, are used frequently. The barbed suture also has gained popularity because it anchors to tissue without the need for intracorporeal or extracorporeal knots (TABLE 1).
Tissue removal
Adnexae and pathologic tissue, such as dermoid cysts, can be removed intact from the peritoneal cavity using an Endo Catch Single Use Specimen Pouch, a polyurethane sac. Careful use, with placement of the ovary with the cyst into the pouch prior to cystectomy, can contain or prevent spillage outside the bag.
A large uterus that cannot be extracted through a colpotomy can be manually morcellated. Appropriate candidates can undergo power morcellation using an FDA-approved device. (TABLE 1), allowing for the removal of smaller pieces through a small laparoscopic incision or the colpotomy.
Issues surrounding morcellation continue to require that gynecologic surgeons understand FDA recommendations. In 2014, the FDA issued a safety communication that morcellation is “contraindicated in gynecologic surgery if tissue is known or suspected to be malignant; it is contraindicated for uterine tissue removal with presumed benign fibroids in perimenopausal women.”12 A black-box warning was issued that uterine tissue might contain unsuspected cancer.
A task force created by AAGL addressed key issues in this controversy.
AAGL then provided guidelines related to morcellation13:
- Do not use morcellate in the setting of known malignancy.
- Provide appropriate preoperative evaluation with up-to-date Pap smear screening and image analysis.
- Increasing age significantly increases the risk of leiomyosarcoma, especially in a postmenopausal woman.
- Fibroid growth is not a reliable sign of malignancy.
- Do not use a morcellator if the patient is at high risk for malignancy.
- If leiomyosarcoma is the presumed pathology, await the final pathology report before proceeding with hysterectomy.
- Concomitant use of a bag might mitigate the risk of tissue spread.
- Obtain informed consent before proceeding with morcellation.
Continue to: Skin closure
Skin closure
Final subcuticular closure can be accomplished using sutures or skin adhesive. Sutures can be synthetic, absorbable monofilament (Caprosyn), or synthetic, absorbable, braided multifilament (Polysorb).
Skin adhesive closes incisions quickly, avoids inflammation related to foreign bodies, and can ease patients’ concerns that sometimes arise when absorbable suture persists postoperatively (TABLE 1).
The impact of physician experience
Physician experience has been shown to reduce cost while maintaining quality of care.14 That was the conclusion of researchers who undertook a retrospective study, addressing cost and clinical outcomes, of senior and junior attending physicians who performed laparoscopic-assisted vaginal hysterectomy on 120 patients. Studies such as these often lead to clinical pathways to facilitate cost-effective quality care.
--
CASE Same outcome at lower cost
The hypothetical 43-year-old patient in the opening case undergoes laparoscopic hysterectomy for treatment of uterine fibroids and menorrhagia. In this scenario, however, the surgeon makes the following product choices:
- The patient is prepped with Hibiclens.
- A VCare Plus uterine manipulator is placed.
- Laparoscopic ports include a VersaStep Plus Bladeless Trocar with Step Insufflation Needle; Versaport Plus Pyramidal Bladed Trocar; and 2 VersaOne Bladed trocars.
- The surgeon uses the PKS LYONS Dissecting Forceps and reprocessed Endo Shears to perform the hysterectomy.
- The uterus is enclosed in an Endo Catch bag and removed through the minilaparotomy site.
- The vaginal cuff is closed using 2-0 V-Loc barbed suture. Skin incisions are closed with 4-0 Polysorb, a polyglycolic acid absorbable suture.
The cost of this set of products? $360.44 or, roughly, $1,231.96 less than the set-up described in the case at the beginning of this article (TABLE 2).
Continue to: Summing up
Summing up
Here are key points to take away from this analysis and discussion:
- As third-party payers and hospitals continue to evaluate surgeons individually and compare procedures from surgeon to surgeon, reimbursement might be stratified—thereby favoring physicians who demonstrate both quality outcomes and cost containment.
- There are many ways a minimally invasive surgeon can implement cost-conscious choices that have little or no impact on the quality of outcome.
- Surgeons who are familiar with surgical instruments and models available at their institution are better prepared to make wise cost-conscious decisions. (See “Caregivers should keep cost in mind: Here’s why,” in the Web version of this article at https://www.mdedge.com/obgyn.)
- Cost is not the only indicator of value: The surgeon must know how to apply tools correctly and be familiar with their limitations, and should choose instruments and products for their safety and ease of use. More often than not, a surgeon’s training and personal experience define—and sometimes restrict—the choice of devices.
- Last, it makes sense to have instruments and devices readily available in the operating room at the start of a case, to avoid unnecessary surgical delays. However, we recommend that you refrain from opening these tools until they are required intraoperatively. It is possible that the case will require conversion to laparotomy or that, after direct visualization of the pathology, different ports or instruments are required.
Acknowledgments
The authors would like to thank Meredith Snook, MD, who was coauthor of the original 2013 article6 and Kathleen Riordan, BSN, RN, for assistance in gathering specific cost-related information for this article.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
CASE Cost-conscious benign laparoscopic hysterectomy
A 43-year-old woman undergoes laparoscopic hysterectomy for treatment of presumed benign uterine fibroids and menorrhagia. Once she is prepped with ChloraPrep with tint, a RUMI II uterine manipulator is placed. Laparoscopic ports include a Kii Balloon Blunt Tip system, a Versaport Plus Pyramidal Bladed Trocar, and 2 Kii Fios First Entry trocars.
The surgeon uses the Harmonic ACE +7 device (a purely ultrasonic device) to perform most of the procedure. The uterus is morcellated and removed using the US Food and Drug Administration (FDA)-approved Olympus Contained Tissue Extraction System, and the vaginal cuff is closed using a series of 2-0 PDS II sutures. Skin incisions are closed using Dermabond skin adhesive.
Total cost of the products used in this case: $1,592.40. Could different product choices have reduced this figure?
Health-care costs continue to rise faster than inflation: Total health-care expenditures account for approximately 18% of gross domestic product in the United States. Physicians therefore face increasing pressure to take cost into account in their care of patients.1 Cost-effectiveness and outcome quality continue to increase in importance as measures in many clinical trials that compare standard and alternative therapies. And women’s health—specifically, minimally invasive gynecologic surgery—invites such comparisons.
Overall, conventional laparoscopic gynecologic procedures tend to cost less than laparotomy, a consequence of shorter hospital stays, faster recovery, and fewer complications.2-5 What is not fully appreciated, however, is how choice of laparoscopic instrumentation and associated products affects surgical costs. In this article, which revisits and updates a 2013 OBG Management examination of cost-consciousness in the selection of equipment and supplies for minimally invasive gynecologic surgery,6 we review these costs in 2018. Our goal is to raise awareness of the role of cost in care among minimally invasive gynecologic surgeons.
In the sections that follow, we highlight several aspects of laparoscopic gynecologic surgery that can affect your selection of instruments and products, describing differences in cost as well as some distinctive characteristics of products. Note that our comparisons focus solely on cost—not on ease of utility, effectiveness, surgical technique, risk of complications, or any other assessment. Note also that numerous other instruments and devices are commercially available besides those we list.
Importantly, 2013 and 2018 costs are included in TABLE 1. Unless otherwise noted, costs are per unit. Changes in manufacturers and material costs and technologic advances have contributed to some, but not all, of the changes in cost between 2013 and 2018.

Continue to: Variables to keep in mind
Variables to keep in mind
Even when taking cost into consideration, tailor your selection of instruments and supplies to your capabilities and comfort, as well as to the particular characteristics of the patient and the planned procedure. Also, remember that your institution might have arrangements with companies that supply minimally invasive instruments, and that such arrangements might limit your options, to some degree. Last, be aware that reprocessed ports and instruments are now available at a reduced cost. In short, we believe that it is crucial for surgeons to be cognizant of all products available to them prior to attending a surgical case.
Skin preparation and other preop considerations
Multiple preoperative skin preparations are available (TABLE 1). Traditionally, a povidone–iodine topical antiseptic, such as Betadine, has been used for skin and vaginal preparation prior to gynecologic surgery. Hibiclens and ChloraPrep are different combinations of chlorhexidine gluconate and isopropyl alcohol that act as broad-spectrum antiseptics.
ChloraPrep is applied with a wand-like applicator and contains a much higher concentration of isopropyl alcohol than Hibiclens (70% and 4%, respectively), rendering it more flammable. It also requires longer drying time before surgery can be started. Clear and tinted ChloraPrep formulations are available.
Continue to: Uterine manipulators
Uterine manipulators
Cannulation of the cervical canal allows for uterine manipulation, increasing intraoperative traction and exposure as well as visualization of the adnexae and peritoneal surfaces.
The Hulka-Kenwick is a reusable uterine manipulator that is fairly standard and easy to apply. Specialized, single-use manipulators also are available, including the Advincula Delineator and VCare Plus uterine manipulator/elevator. The VCare Plus manipulator consists of 2 opposing cups: one cup (available in 4 sizes, small to extra-large) fits around the cervix and defines the site for colpotomy; the other helps maintain pneumoperitoneum once a colpotomy is created.
The ZUMI (Zinnanti Uterine Manipulator Injector) is a rigid, curved shaft with an intrauterine balloon to help prevent expulsion. It also has an integrated injection channel to allow for intraoperative chromotubation.
The RUMI II System fits individual patient anatomy with various tip lengths and colpotomy cup sizes. The Advincula Arch Uterine Manipulator Handle is a reusable alternative to the articulating RUMI II and works with the RUMI II System Disposable Tip (TABLE 1).
Continue to: Entry style and ports
Entry style and ports
The peritoneal cavity can be entered using either a closed (Veress needle) or open (Hasson) technique.7,8 Closed entry might allow for quicker access to the peritoneal cavity. A 2015 Cochrane review of 46 randomized, controlled trials of 7,389 patients undergoing laparoscopy compared outcomes between laparoscopic entry techniques and found no difference in major vascular or visceral injury between closed and open techniques at the umbilicus.9 However, open entry was associated with a greater likelihood of successful entry into the peritoneal cavity.9
Left upper-quadrant (Palmer’s point) entry is another option when adhesions are anticipated or abnormal anatomy is encountered at the umbilicus.
In general, complications related to laparoscopic entry are rare in gynecologic surgery, ranging from 0.18% to 0.5% of cases in studies.8,10,11 A minimally invasive surgeon might prefer one entry technique over another but should be able to perform both methods competently and recognize when a particular technique is warranted.
--
Choosing a port
Laparoscopic ports usually range from 5 mm to 12 mm and can be fixed or variable in size.
The primary port, usually placed through the umbilicus, can be a standard, blunt, 10-mm (Bluntport Plus Hasson) port, or it can be specialized to ease entry of the port or stabilize the port once it is introduced through the skin incision.
Optical trocars have a transparent tip that allows the surgeon to visualize the abdominal wall entry layer by layer using a 0° laparoscope, sometimes after pneumoperitoneum is created with a Veress needle. Other specialized ports include those that have balloons or foam collars, or both, to secure the port without traditional stay sutures on the fascia and to minimize leakage of pneumoperitoneum.
Continue to: Accessory ports
Accessory ports
When choosing an accessory port type and size, it is important to anticipate which instruments and devices, such as an Endo Catch bag, suture, or needle, will need to pass through it. Also, know whether 5-mm and 10-mm laparoscopes are available, and anticipate whether a second port with insufflation capabilities will be required.
The Pediport Locking Trocar is a user-friendly, 5-mm bladed port that deploys a mushroom-shaped stabilizer to prevent dislodgement. The Versaport bladed trocar has a spring-loaded entry shield, which slides over the blade to protect it once the peritoneal cavity is entered.
VersaStep Bladeless Trocars are introduced after a Step Insufflation Needle has been inserted. These trocars create a smaller fascial defect than conventional bladed trocars for an equivalent cannula size (TABLE 1).
Cutting and coagulating
Both monopolar and bipolar electrosurgical techniques are commonly employed in gynecologic laparoscopy. A wide variety of disposable and reusable instruments are available for monopolar energy, such as scissors, a hook, and a spatula.
Bipolar devices also can be disposable or reusable. Although bipolar electrosurgery minimizes injury to surrounding tissues by containing the current within the jaws of the forceps, it cannot cut or seal large vessels. As a result, several advanced bipolar devices with sealing and transecting capabilities have emerged (the LigaSure line of devices, Enseal). Ultrasonic devices, such as the Harmonic ACE, also can coagulate and cut at lower temperatures by converting electrical energy to mechanical energy (TABLE 1).
Continue to: Suture material
Suture material
Aspects of minimally invasive gynecologic surgery that require the use of suture include, but are not limited to, closure of the vaginal cuff, oophoropexy, and reapproximation of the ovarian cortex after cystectomy. Synthetic and delayed absorbable sutures, such as PDS II, are used frequently. The barbed suture also has gained popularity because it anchors to tissue without the need for intracorporeal or extracorporeal knots (TABLE 1).
Tissue removal
Adnexae and pathologic tissue, such as dermoid cysts, can be removed intact from the peritoneal cavity using an Endo Catch Single Use Specimen Pouch, a polyurethane sac. Careful use, with placement of the ovary with the cyst into the pouch prior to cystectomy, can contain or prevent spillage outside the bag.
A large uterus that cannot be extracted through a colpotomy can be manually morcellated. Appropriate candidates can undergo power morcellation using an FDA-approved device. (TABLE 1), allowing for the removal of smaller pieces through a small laparoscopic incision or the colpotomy.
Issues surrounding morcellation continue to require that gynecologic surgeons understand FDA recommendations. In 2014, the FDA issued a safety communication that morcellation is “contraindicated in gynecologic surgery if tissue is known or suspected to be malignant; it is contraindicated for uterine tissue removal with presumed benign fibroids in perimenopausal women.”12 A black-box warning was issued that uterine tissue might contain unsuspected cancer.
A task force created by AAGL addressed key issues in this controversy.
AAGL then provided guidelines related to morcellation13:
- Do not use morcellate in the setting of known malignancy.
- Provide appropriate preoperative evaluation with up-to-date Pap smear screening and image analysis.
- Increasing age significantly increases the risk of leiomyosarcoma, especially in a postmenopausal woman.
- Fibroid growth is not a reliable sign of malignancy.
- Do not use a morcellator if the patient is at high risk for malignancy.
- If leiomyosarcoma is the presumed pathology, await the final pathology report before proceeding with hysterectomy.
- Concomitant use of a bag might mitigate the risk of tissue spread.
- Obtain informed consent before proceeding with morcellation.
Continue to: Skin closure
Skin closure
Final subcuticular closure can be accomplished using sutures or skin adhesive. Sutures can be synthetic, absorbable monofilament (Caprosyn), or synthetic, absorbable, braided multifilament (Polysorb).
Skin adhesive closes incisions quickly, avoids inflammation related to foreign bodies, and can ease patients’ concerns that sometimes arise when absorbable suture persists postoperatively (TABLE 1).
The impact of physician experience
Physician experience has been shown to reduce cost while maintaining quality of care.14 That was the conclusion of researchers who undertook a retrospective study, addressing cost and clinical outcomes, of senior and junior attending physicians who performed laparoscopic-assisted vaginal hysterectomy on 120 patients. Studies such as these often lead to clinical pathways to facilitate cost-effective quality care.
--
CASE Same outcome at lower cost
The hypothetical 43-year-old patient in the opening case undergoes laparoscopic hysterectomy for treatment of uterine fibroids and menorrhagia. In this scenario, however, the surgeon makes the following product choices:
- The patient is prepped with Hibiclens.
- A VCare Plus uterine manipulator is placed.
- Laparoscopic ports include a VersaStep Plus Bladeless Trocar with Step Insufflation Needle; Versaport Plus Pyramidal Bladed Trocar; and 2 VersaOne Bladed trocars.
- The surgeon uses the PKS LYONS Dissecting Forceps and reprocessed Endo Shears to perform the hysterectomy.
- The uterus is enclosed in an Endo Catch bag and removed through the minilaparotomy site.
- The vaginal cuff is closed using 2-0 V-Loc barbed suture. Skin incisions are closed with 4-0 Polysorb, a polyglycolic acid absorbable suture.
The cost of this set of products? $360.44 or, roughly, $1,231.96 less than the set-up described in the case at the beginning of this article (TABLE 2).
Continue to: Summing up
Summing up
Here are key points to take away from this analysis and discussion:
- As third-party payers and hospitals continue to evaluate surgeons individually and compare procedures from surgeon to surgeon, reimbursement might be stratified—thereby favoring physicians who demonstrate both quality outcomes and cost containment.
- There are many ways a minimally invasive surgeon can implement cost-conscious choices that have little or no impact on the quality of outcome.
- Surgeons who are familiar with surgical instruments and models available at their institution are better prepared to make wise cost-conscious decisions. (See “Caregivers should keep cost in mind: Here’s why,” in the Web version of this article at https://www.mdedge.com/obgyn.)
- Cost is not the only indicator of value: The surgeon must know how to apply tools correctly and be familiar with their limitations, and should choose instruments and products for their safety and ease of use. More often than not, a surgeon’s training and personal experience define—and sometimes restrict—the choice of devices.
- Last, it makes sense to have instruments and devices readily available in the operating room at the start of a case, to avoid unnecessary surgical delays. However, we recommend that you refrain from opening these tools until they are required intraoperatively. It is possible that the case will require conversion to laparotomy or that, after direct visualization of the pathology, different ports or instruments are required.
Acknowledgments
The authors would like to thank Meredith Snook, MD, who was coauthor of the original 2013 article6 and Kathleen Riordan, BSN, RN, for assistance in gathering specific cost-related information for this article.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Centers for Medicare & Medicaid Services. National health expenditure projections 2017-2026: Forecast summary. www.cms.gov/Research-Statistics-Data-and-Systems /Statistics-Trends-and-Reports/NationalHealthExpendData /Downloads/ForecastSummary.pdf. Accessed November 3, 2018.
- Vilos GA, Alshimmiri MM. Cost-benefit analysis of laparoscopic versus laparotomy salpingo-oophorectomy for benign tubo-ovarian disease. J Am Assoc Gynecol Laparosc. 1995;2(3):299-303.
- Gray DT, Thorburn J, Lundor P, et al. A cost-effectiveness study of a randomised trial of laparoscopy versus laparotomy for ectopic pregnancy. Lancet. 1995;345(8958):1139-1143.
- Chapron C, Fauconnier A, Goffinet F, et al. Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a metaanalysis. Hum Reprod. 2002;17(5):1334-1342.
- Benezra V, Verma U, Whitted RW. Comparison of laparoscopy versus laparotomy for the surgical treatment of ovarian dermoid cysts. Obstet Gynecol Surv. 2006;61(1): 20-21.
- Sanfilippo JS, Snook ML. Cost-conscious choices for minimally invasive gynecologic surgery. OBG Manag. 2013;25(11):40-41,44,46-48,72.
- Hasson HM. A modified instrument and method for laparoscopy. Am J Obstet Gynecol. 1971;110(6):886-887.
- Ott J, Jaeger-Lansky A, Poschalko G, et al. Entry techniques in gynecologic laparoscopy—a review. Gynecol Surg. 2012;9(2):139-146.
- Ahmad G, Gent D, Henderson D, et al. Laparoscopic entry techniques. Cochrane Database Syst Rev. 2015;8:CD006583.
- Hasson HM, Rotman C, Rana N, et al. Open laparoscopy: 29-year experience. Obstet Gynecol. 2000;96(5 Pt 1):763-766.
- Schäfer M, Lauper M, Krähenbühl L. Trocar and Veress needle injuries during laparoscopy. Surg Endosc. 2001;15(3):275- 280.
- Immediately in effect guidance document: product labeling for laparoscopic power morcellators. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration Center for Devices and Radiological Health; November 25, 2014. www.fda.gov/downloads /MedicalDevices/DeviceRegulationandGuidance /GuidanceDocuments/UCM424123.pdf. Accessed November 3, 2018.
- Tissue Extraction Task Force Members. Morcellation during uterine tissue extraction: an update. J Minim Invasive Gynecol. 2018;25(4):543-550.
- Chang WC, Li TC, Lin CC. The effect of physician experience on costs and clinical outcomes of laparoscopic-assisted vaginal hysterectomy: a multivariate analysis. J Am Assoc Gynecol Laparosc. 2003;10(3):356-359.
- Centers for Medicare & Medicaid Services. National health expenditure projections 2017-2026: Forecast summary. www.cms.gov/Research-Statistics-Data-and-Systems /Statistics-Trends-and-Reports/NationalHealthExpendData /Downloads/ForecastSummary.pdf. Accessed November 3, 2018.
- Vilos GA, Alshimmiri MM. Cost-benefit analysis of laparoscopic versus laparotomy salpingo-oophorectomy for benign tubo-ovarian disease. J Am Assoc Gynecol Laparosc. 1995;2(3):299-303.
- Gray DT, Thorburn J, Lundor P, et al. A cost-effectiveness study of a randomised trial of laparoscopy versus laparotomy for ectopic pregnancy. Lancet. 1995;345(8958):1139-1143.
- Chapron C, Fauconnier A, Goffinet F, et al. Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a metaanalysis. Hum Reprod. 2002;17(5):1334-1342.
- Benezra V, Verma U, Whitted RW. Comparison of laparoscopy versus laparotomy for the surgical treatment of ovarian dermoid cysts. Obstet Gynecol Surv. 2006;61(1): 20-21.
- Sanfilippo JS, Snook ML. Cost-conscious choices for minimally invasive gynecologic surgery. OBG Manag. 2013;25(11):40-41,44,46-48,72.
- Hasson HM. A modified instrument and method for laparoscopy. Am J Obstet Gynecol. 1971;110(6):886-887.
- Ott J, Jaeger-Lansky A, Poschalko G, et al. Entry techniques in gynecologic laparoscopy—a review. Gynecol Surg. 2012;9(2):139-146.
- Ahmad G, Gent D, Henderson D, et al. Laparoscopic entry techniques. Cochrane Database Syst Rev. 2015;8:CD006583.
- Hasson HM, Rotman C, Rana N, et al. Open laparoscopy: 29-year experience. Obstet Gynecol. 2000;96(5 Pt 1):763-766.
- Schäfer M, Lauper M, Krähenbühl L. Trocar and Veress needle injuries during laparoscopy. Surg Endosc. 2001;15(3):275- 280.
- Immediately in effect guidance document: product labeling for laparoscopic power morcellators. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration Center for Devices and Radiological Health; November 25, 2014. www.fda.gov/downloads /MedicalDevices/DeviceRegulationandGuidance /GuidanceDocuments/UCM424123.pdf. Accessed November 3, 2018.
- Tissue Extraction Task Force Members. Morcellation during uterine tissue extraction: an update. J Minim Invasive Gynecol. 2018;25(4):543-550.
- Chang WC, Li TC, Lin CC. The effect of physician experience on costs and clinical outcomes of laparoscopic-assisted vaginal hysterectomy: a multivariate analysis. J Am Assoc Gynecol Laparosc. 2003;10(3):356-359.
Dienogest as an option for endometriosis pain
Dienogest as an option for endometriosis pain
For treatment of endometriosis-related pain, what about the drug dienogest and the cyclic oral contraceptive Qlaira, which contains dienogest?
Chow Kah Kiong, MBBS
Singapore
--
--
Norethindrone’s conversion to ethinyl estradiol
Dr. Barbieri’s editorial on the medical treatment of endometriosis is excellent! Does norethindrone acetate metabolize to ethinyl estradiol in a higher percentage when the dose is higher, or is it still 1%? We were taught that at doses of greater than 15 mg daily, norethindrone can contribute significant amounts of estrogen.
Lauren Barnes, MD
Albuquerque, New Mexico
Endometriosis is a surgical, not a medical, disease
I read with some dismay Dr. Barbieri’s editorial on medical treatment of endometriosis. As a long-time disciple of the eminent Dr. David Redwine, I have dedicated my practice focus over the past 28 years to minimally invasive curative solutions to many gynecologic problems. The data on the histology, qualitative hormonal differences, and inconsistent and poor long-term response of endometriosis to traditional hormonal suppressive therapies falls strongly in favor of complete and thorough laparoscopic excision—not “biopsy”—as the only truly curative treatment, certainly not medical therapy. Endometriosis is a surgical disease. The experience of the dedicated few in our field who have taken the time and effort to become experts in excision (not ablation) of endometriosis bears this out.
The tragedy is that the only Current Procedural Terminology code that is usable for reimbursement is 58662. Sadly, this code was assigned a resource-based relative value scale “value” many years ago, when the operation consisted of putting a scope in the abdomen and taking a sampling biopsy (which took all of 10 minutes). Of course, we know that a prolonged, delicate procedure requiring retroperitoneal dissection, ureterolysis, excision of deeply infiltrating rectovaginal septum endometriosis, and discoid or segmental bowel resection requires the kind of surgical expertise developed only by those who put in the time and effort to get good at this type of surgery. The majority of ObGyns who have a full obstetric practice and low surgical volumes simply are not going to struggle in the operating room over the many cases that it takes to become good, and safe, at this procedure only to receive an insulting reimbursement.
It is emblematic of this travesty that many of the best minimally invasive surgery practitioners do not accept insurance or other thirdparty payment such as Medicaid as they would otherwise not cover their overhead.
Putting premenopausal women into a severely hypoestrogenic state with medication is cruel and, even worse, does not cure the disease.
Balanced information on surgical management should have been presented in the article. And physicians who are not capable of proper laparoscopic excision should refer the patient.
Hugo Ribot, MD
Cartersville, Georgia
Continue to: Dr. Barbieri responds
Dr. Barbieri responds
I thank Drs. Chow, Barnes, and Ribot for their interest in my recent editorial on the medical treatment of endometriosis. I agree with Dr. Chow that dienogest, a synthetic progestin, is effective in the treatment of pelvic pain caused by endometriosis. In one observational study, norethindrone acetate 2.5 mg daily and dienogest 2 mg daily had similar efficacy in the treatment of pelvic pain. Dienogest treatment was associated with fewer side effects but was much more expensive than norethindrone acetate.1 The US Food and Drug Administration has approved a combination estradiol- progestin pill (Natazia, Qlaira) as a contraceptive, and I have occasionally used this medication in my practice for women with pelvic pain caused by endometriosis. Dienogest monotherapy is not available in the United States.
Dr. Barnes reminds us that norethindrone is a substrate for the aromatase enzyme system and can be converted to ethinyl estradiol.2 The conversion occurs at a very low rate, likely less than 0.4%.3 At a norethindrone acetate dose of 5 mg daily, aromatization would result in the production of less than 2 μg of ethinyl estradiol daily.
Dr. Ribot advocates for surgery as the primary treatment of pelvic pain caused by endometriosis. I agree with Dr. Ribot that, for severe pain caused by deep infiltrating endometriosis, surgery is an optimal approach. However, for women with pelvic pain and Stage I endometriosis, hormonal treatment after initial surgical diagnosis and treatment reduces pain recurrence and repetitive surgical procedures.4
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Vercellini P, Bracco B, Mosconi P, et al. Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study. Fertil Steril. 2016;105:734-743.
- Barbieri RL, Petro Z, Canick JA, et al. Aromatization of norethindrone to ethinyl estradiol by human placental microsomes. J Clin Endocrinol Metab. 1983;57:299-303.
- Chu MC, Zhang X, Gentzschein E, et al. Formation of ethinyl estradiol in women during treatment with norethindrone acetate. J Clin Endocrinol Metab. 2007;92:2205-2207.
- Soliman AM, Bonafede M, Farr AM, et al. Analysis of subsequent surgery rates among endometriosis patients who underwent surgery with and without concomitant leuprolide acetate therapy. Curr Med Res Opin. 2016;32:1073-1082.
Dienogest as an option for endometriosis pain
For treatment of endometriosis-related pain, what about the drug dienogest and the cyclic oral contraceptive Qlaira, which contains dienogest?
Chow Kah Kiong, MBBS
Singapore
--
--
Norethindrone’s conversion to ethinyl estradiol
Dr. Barbieri’s editorial on the medical treatment of endometriosis is excellent! Does norethindrone acetate metabolize to ethinyl estradiol in a higher percentage when the dose is higher, or is it still 1%? We were taught that at doses of greater than 15 mg daily, norethindrone can contribute significant amounts of estrogen.
Lauren Barnes, MD
Albuquerque, New Mexico
Endometriosis is a surgical, not a medical, disease
I read with some dismay Dr. Barbieri’s editorial on medical treatment of endometriosis. As a long-time disciple of the eminent Dr. David Redwine, I have dedicated my practice focus over the past 28 years to minimally invasive curative solutions to many gynecologic problems. The data on the histology, qualitative hormonal differences, and inconsistent and poor long-term response of endometriosis to traditional hormonal suppressive therapies falls strongly in favor of complete and thorough laparoscopic excision—not “biopsy”—as the only truly curative treatment, certainly not medical therapy. Endometriosis is a surgical disease. The experience of the dedicated few in our field who have taken the time and effort to become experts in excision (not ablation) of endometriosis bears this out.
The tragedy is that the only Current Procedural Terminology code that is usable for reimbursement is 58662. Sadly, this code was assigned a resource-based relative value scale “value” many years ago, when the operation consisted of putting a scope in the abdomen and taking a sampling biopsy (which took all of 10 minutes). Of course, we know that a prolonged, delicate procedure requiring retroperitoneal dissection, ureterolysis, excision of deeply infiltrating rectovaginal septum endometriosis, and discoid or segmental bowel resection requires the kind of surgical expertise developed only by those who put in the time and effort to get good at this type of surgery. The majority of ObGyns who have a full obstetric practice and low surgical volumes simply are not going to struggle in the operating room over the many cases that it takes to become good, and safe, at this procedure only to receive an insulting reimbursement.
It is emblematic of this travesty that many of the best minimally invasive surgery practitioners do not accept insurance or other thirdparty payment such as Medicaid as they would otherwise not cover their overhead.
Putting premenopausal women into a severely hypoestrogenic state with medication is cruel and, even worse, does not cure the disease.
Balanced information on surgical management should have been presented in the article. And physicians who are not capable of proper laparoscopic excision should refer the patient.
Hugo Ribot, MD
Cartersville, Georgia
Continue to: Dr. Barbieri responds
Dr. Barbieri responds
I thank Drs. Chow, Barnes, and Ribot for their interest in my recent editorial on the medical treatment of endometriosis. I agree with Dr. Chow that dienogest, a synthetic progestin, is effective in the treatment of pelvic pain caused by endometriosis. In one observational study, norethindrone acetate 2.5 mg daily and dienogest 2 mg daily had similar efficacy in the treatment of pelvic pain. Dienogest treatment was associated with fewer side effects but was much more expensive than norethindrone acetate.1 The US Food and Drug Administration has approved a combination estradiol- progestin pill (Natazia, Qlaira) as a contraceptive, and I have occasionally used this medication in my practice for women with pelvic pain caused by endometriosis. Dienogest monotherapy is not available in the United States.
Dr. Barnes reminds us that norethindrone is a substrate for the aromatase enzyme system and can be converted to ethinyl estradiol.2 The conversion occurs at a very low rate, likely less than 0.4%.3 At a norethindrone acetate dose of 5 mg daily, aromatization would result in the production of less than 2 μg of ethinyl estradiol daily.
Dr. Ribot advocates for surgery as the primary treatment of pelvic pain caused by endometriosis. I agree with Dr. Ribot that, for severe pain caused by deep infiltrating endometriosis, surgery is an optimal approach. However, for women with pelvic pain and Stage I endometriosis, hormonal treatment after initial surgical diagnosis and treatment reduces pain recurrence and repetitive surgical procedures.4
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Dienogest as an option for endometriosis pain
For treatment of endometriosis-related pain, what about the drug dienogest and the cyclic oral contraceptive Qlaira, which contains dienogest?
Chow Kah Kiong, MBBS
Singapore
--
--
Norethindrone’s conversion to ethinyl estradiol
Dr. Barbieri’s editorial on the medical treatment of endometriosis is excellent! Does norethindrone acetate metabolize to ethinyl estradiol in a higher percentage when the dose is higher, or is it still 1%? We were taught that at doses of greater than 15 mg daily, norethindrone can contribute significant amounts of estrogen.
Lauren Barnes, MD
Albuquerque, New Mexico
Endometriosis is a surgical, not a medical, disease
I read with some dismay Dr. Barbieri’s editorial on medical treatment of endometriosis. As a long-time disciple of the eminent Dr. David Redwine, I have dedicated my practice focus over the past 28 years to minimally invasive curative solutions to many gynecologic problems. The data on the histology, qualitative hormonal differences, and inconsistent and poor long-term response of endometriosis to traditional hormonal suppressive therapies falls strongly in favor of complete and thorough laparoscopic excision—not “biopsy”—as the only truly curative treatment, certainly not medical therapy. Endometriosis is a surgical disease. The experience of the dedicated few in our field who have taken the time and effort to become experts in excision (not ablation) of endometriosis bears this out.
The tragedy is that the only Current Procedural Terminology code that is usable for reimbursement is 58662. Sadly, this code was assigned a resource-based relative value scale “value” many years ago, when the operation consisted of putting a scope in the abdomen and taking a sampling biopsy (which took all of 10 minutes). Of course, we know that a prolonged, delicate procedure requiring retroperitoneal dissection, ureterolysis, excision of deeply infiltrating rectovaginal septum endometriosis, and discoid or segmental bowel resection requires the kind of surgical expertise developed only by those who put in the time and effort to get good at this type of surgery. The majority of ObGyns who have a full obstetric practice and low surgical volumes simply are not going to struggle in the operating room over the many cases that it takes to become good, and safe, at this procedure only to receive an insulting reimbursement.
It is emblematic of this travesty that many of the best minimally invasive surgery practitioners do not accept insurance or other thirdparty payment such as Medicaid as they would otherwise not cover their overhead.
Putting premenopausal women into a severely hypoestrogenic state with medication is cruel and, even worse, does not cure the disease.
Balanced information on surgical management should have been presented in the article. And physicians who are not capable of proper laparoscopic excision should refer the patient.
Hugo Ribot, MD
Cartersville, Georgia
Continue to: Dr. Barbieri responds
Dr. Barbieri responds
I thank Drs. Chow, Barnes, and Ribot for their interest in my recent editorial on the medical treatment of endometriosis. I agree with Dr. Chow that dienogest, a synthetic progestin, is effective in the treatment of pelvic pain caused by endometriosis. In one observational study, norethindrone acetate 2.5 mg daily and dienogest 2 mg daily had similar efficacy in the treatment of pelvic pain. Dienogest treatment was associated with fewer side effects but was much more expensive than norethindrone acetate.1 The US Food and Drug Administration has approved a combination estradiol- progestin pill (Natazia, Qlaira) as a contraceptive, and I have occasionally used this medication in my practice for women with pelvic pain caused by endometriosis. Dienogest monotherapy is not available in the United States.
Dr. Barnes reminds us that norethindrone is a substrate for the aromatase enzyme system and can be converted to ethinyl estradiol.2 The conversion occurs at a very low rate, likely less than 0.4%.3 At a norethindrone acetate dose of 5 mg daily, aromatization would result in the production of less than 2 μg of ethinyl estradiol daily.
Dr. Ribot advocates for surgery as the primary treatment of pelvic pain caused by endometriosis. I agree with Dr. Ribot that, for severe pain caused by deep infiltrating endometriosis, surgery is an optimal approach. However, for women with pelvic pain and Stage I endometriosis, hormonal treatment after initial surgical diagnosis and treatment reduces pain recurrence and repetitive surgical procedures.4
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Vercellini P, Bracco B, Mosconi P, et al. Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study. Fertil Steril. 2016;105:734-743.
- Barbieri RL, Petro Z, Canick JA, et al. Aromatization of norethindrone to ethinyl estradiol by human placental microsomes. J Clin Endocrinol Metab. 1983;57:299-303.
- Chu MC, Zhang X, Gentzschein E, et al. Formation of ethinyl estradiol in women during treatment with norethindrone acetate. J Clin Endocrinol Metab. 2007;92:2205-2207.
- Soliman AM, Bonafede M, Farr AM, et al. Analysis of subsequent surgery rates among endometriosis patients who underwent surgery with and without concomitant leuprolide acetate therapy. Curr Med Res Opin. 2016;32:1073-1082.
- Vercellini P, Bracco B, Mosconi P, et al. Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study. Fertil Steril. 2016;105:734-743.
- Barbieri RL, Petro Z, Canick JA, et al. Aromatization of norethindrone to ethinyl estradiol by human placental microsomes. J Clin Endocrinol Metab. 1983;57:299-303.
- Chu MC, Zhang X, Gentzschein E, et al. Formation of ethinyl estradiol in women during treatment with norethindrone acetate. J Clin Endocrinol Metab. 2007;92:2205-2207.
- Soliman AM, Bonafede M, Farr AM, et al. Analysis of subsequent surgery rates among endometriosis patients who underwent surgery with and without concomitant leuprolide acetate therapy. Curr Med Res Opin. 2016;32:1073-1082.
Maternal health benefits of breastfeeding
In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.1 While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.
Infant health benefits of breastfeeding
There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.2 In addition, breastfeeding greatly benefits maternal health.
Maternal health benefits of breastfeeding
Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.
filler
Type 2 diabetes
In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.3 In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.4
Hypertension
In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.5 For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.5 Similar results were observed in the Nurses’ Health Study II.6
Myocardial infarction and coronary heart disease
In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.7 In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).5
Breast cancer
In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.8 In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.9 In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.10 Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.
Continue to: Ovarian Cancer
Ovarian cancer
In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.8 In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.11
Endometrial cancer
In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.12 In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.13
Let’s support our patients’ health by encouraging successful breastfeeding
Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.14,15 Birth practices that help to increase successful breastfeeding include:
- inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
- initiate skin-to-skin contact at birth
- encourage the initiation of breastfeeding within 1 hour of birth
- ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
- encourage breastfeeding women to not use pacifiers or artificial nipples.15
When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.16
Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Centers for Disease Control and Prevention. Breastfeeding Among U.S. Children Born 2009–2015, CDC National Immunization Survey. https://www.cdc.gov/breastfeeding/data/nis_data/results.html. Updated August 2018. Accessed November 19, 2018.
- Ip S, Chung M, Raman G, et al. A summary of the Agency for Healthcare Research and Quality’s evidence report on breastfeeding in developed countries. Breastfeed Med. 2009;4 (suppl 1):S17.
- Gunderson Ep, Lewis CE, Lin Y, et al. Lactation duration and progression to diabetes in women across the childbearing years: the 30-year CARDIA study. JAMA Int Med. 2018;178:328-337.
- Stuebe AM, Rich-Edwards JW, Willett WC, et al. Duration of lactation and incidence of type 2 diabetes. JAMA. 2005;294:2601-2610.
- Schwarz EB, Ray RM, Stuebe AM, et al. Duration of lactation and risk factors for maternal cardiovascular disease. Obstet Gynecol. 2009;113:974-982.
- Stuebe Am, Schwarz EB, Grewen K, et al. Duration of lactation and incidence of maternal hypertension: a longitudinal cohort study. Am J Epidemiol. 2011;174:1147-1158.
- Stuebe AM, Michels KB, Willett WC, et al. Duration of lactation and incidence of myocardial infarction in middle to late adulthood. Am J Obstet Gynecol. 2009;200:138.e1-e8.
- Chowdhury R, Sinha B, Sankar MJ, et al. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr. 2015;104:96-113.
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries including 50,302 women with breast cancer and 96,973 women without the disease. Lancet. 2002;360:187-195.
- Islami F, Liu Y, Jemal A, et al. Breastfeeding and breast cancer risk by receptor status—a systematic review and meta-analysis. Ann Oncol. 2015;26:2398-2407.
- Gaitskell K, Green J, Pirie K, et al. Million Women Study Collaborators. Histological subtypes of ovarian cancer associated with parity and breastfeeding in the Million Women Study. Int J Cancer. 2018;142:281-289.
- Jordan SJ, Na R, Johnatty SE, et al. Breastfeeding and endometrial cancer risk: an analysis from the epidemiology of endometrial cancer consortium. Obstet Gynecol. 2017;129:1059-1067.
- Zhan B, Liu X, Li F, Zhang D, et al. Breastfeeding and the incidence of endometrial cancer: a meta-analysis. Oncotarget. 2015;6:38398-38409.
- Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012;CD003517.
- ACOG Committee Opinion No. 756. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;132:e187-e196.
- McFadden A, Gavine A, Renfrew M, et al. Support for healthy breastfeeding mothers with healthy term babies. Cochrane Database Syst Rev. 2017;CD001141.
In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.1 While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.
Infant health benefits of breastfeeding
There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.2 In addition, breastfeeding greatly benefits maternal health.
Maternal health benefits of breastfeeding
Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.
filler
Type 2 diabetes
In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.3 In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.4
Hypertension
In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.5 For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.5 Similar results were observed in the Nurses’ Health Study II.6
Myocardial infarction and coronary heart disease
In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.7 In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).5
Breast cancer
In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.8 In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.9 In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.10 Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.
Continue to: Ovarian Cancer
Ovarian cancer
In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.8 In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.11
Endometrial cancer
In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.12 In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.13
Let’s support our patients’ health by encouraging successful breastfeeding
Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.14,15 Birth practices that help to increase successful breastfeeding include:
- inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
- initiate skin-to-skin contact at birth
- encourage the initiation of breastfeeding within 1 hour of birth
- ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
- encourage breastfeeding women to not use pacifiers or artificial nipples.15
When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.16
Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.1 While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.
Infant health benefits of breastfeeding
There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.2 In addition, breastfeeding greatly benefits maternal health.
Maternal health benefits of breastfeeding
Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.
filler
Type 2 diabetes
In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.3 In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.4
Hypertension
In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.5 For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.5 Similar results were observed in the Nurses’ Health Study II.6
Myocardial infarction and coronary heart disease
In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.7 In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).5
Breast cancer
In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.8 In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.9 In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.10 Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.
Continue to: Ovarian Cancer
Ovarian cancer
In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.8 In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.11
Endometrial cancer
In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.12 In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.13
Let’s support our patients’ health by encouraging successful breastfeeding
Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.14,15 Birth practices that help to increase successful breastfeeding include:
- inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
- initiate skin-to-skin contact at birth
- encourage the initiation of breastfeeding within 1 hour of birth
- ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
- encourage breastfeeding women to not use pacifiers or artificial nipples.15
When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.16
Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Centers for Disease Control and Prevention. Breastfeeding Among U.S. Children Born 2009–2015, CDC National Immunization Survey. https://www.cdc.gov/breastfeeding/data/nis_data/results.html. Updated August 2018. Accessed November 19, 2018.
- Ip S, Chung M, Raman G, et al. A summary of the Agency for Healthcare Research and Quality’s evidence report on breastfeeding in developed countries. Breastfeed Med. 2009;4 (suppl 1):S17.
- Gunderson Ep, Lewis CE, Lin Y, et al. Lactation duration and progression to diabetes in women across the childbearing years: the 30-year CARDIA study. JAMA Int Med. 2018;178:328-337.
- Stuebe AM, Rich-Edwards JW, Willett WC, et al. Duration of lactation and incidence of type 2 diabetes. JAMA. 2005;294:2601-2610.
- Schwarz EB, Ray RM, Stuebe AM, et al. Duration of lactation and risk factors for maternal cardiovascular disease. Obstet Gynecol. 2009;113:974-982.
- Stuebe Am, Schwarz EB, Grewen K, et al. Duration of lactation and incidence of maternal hypertension: a longitudinal cohort study. Am J Epidemiol. 2011;174:1147-1158.
- Stuebe AM, Michels KB, Willett WC, et al. Duration of lactation and incidence of myocardial infarction in middle to late adulthood. Am J Obstet Gynecol. 2009;200:138.e1-e8.
- Chowdhury R, Sinha B, Sankar MJ, et al. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr. 2015;104:96-113.
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries including 50,302 women with breast cancer and 96,973 women without the disease. Lancet. 2002;360:187-195.
- Islami F, Liu Y, Jemal A, et al. Breastfeeding and breast cancer risk by receptor status—a systematic review and meta-analysis. Ann Oncol. 2015;26:2398-2407.
- Gaitskell K, Green J, Pirie K, et al. Million Women Study Collaborators. Histological subtypes of ovarian cancer associated with parity and breastfeeding in the Million Women Study. Int J Cancer. 2018;142:281-289.
- Jordan SJ, Na R, Johnatty SE, et al. Breastfeeding and endometrial cancer risk: an analysis from the epidemiology of endometrial cancer consortium. Obstet Gynecol. 2017;129:1059-1067.
- Zhan B, Liu X, Li F, Zhang D, et al. Breastfeeding and the incidence of endometrial cancer: a meta-analysis. Oncotarget. 2015;6:38398-38409.
- Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012;CD003517.
- ACOG Committee Opinion No. 756. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;132:e187-e196.
- McFadden A, Gavine A, Renfrew M, et al. Support for healthy breastfeeding mothers with healthy term babies. Cochrane Database Syst Rev. 2017;CD001141.
- Centers for Disease Control and Prevention. Breastfeeding Among U.S. Children Born 2009–2015, CDC National Immunization Survey. https://www.cdc.gov/breastfeeding/data/nis_data/results.html. Updated August 2018. Accessed November 19, 2018.
- Ip S, Chung M, Raman G, et al. A summary of the Agency for Healthcare Research and Quality’s evidence report on breastfeeding in developed countries. Breastfeed Med. 2009;4 (suppl 1):S17.
- Gunderson Ep, Lewis CE, Lin Y, et al. Lactation duration and progression to diabetes in women across the childbearing years: the 30-year CARDIA study. JAMA Int Med. 2018;178:328-337.
- Stuebe AM, Rich-Edwards JW, Willett WC, et al. Duration of lactation and incidence of type 2 diabetes. JAMA. 2005;294:2601-2610.
- Schwarz EB, Ray RM, Stuebe AM, et al. Duration of lactation and risk factors for maternal cardiovascular disease. Obstet Gynecol. 2009;113:974-982.
- Stuebe Am, Schwarz EB, Grewen K, et al. Duration of lactation and incidence of maternal hypertension: a longitudinal cohort study. Am J Epidemiol. 2011;174:1147-1158.
- Stuebe AM, Michels KB, Willett WC, et al. Duration of lactation and incidence of myocardial infarction in middle to late adulthood. Am J Obstet Gynecol. 2009;200:138.e1-e8.
- Chowdhury R, Sinha B, Sankar MJ, et al. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr. 2015;104:96-113.
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries including 50,302 women with breast cancer and 96,973 women without the disease. Lancet. 2002;360:187-195.
- Islami F, Liu Y, Jemal A, et al. Breastfeeding and breast cancer risk by receptor status—a systematic review and meta-analysis. Ann Oncol. 2015;26:2398-2407.
- Gaitskell K, Green J, Pirie K, et al. Million Women Study Collaborators. Histological subtypes of ovarian cancer associated with parity and breastfeeding in the Million Women Study. Int J Cancer. 2018;142:281-289.
- Jordan SJ, Na R, Johnatty SE, et al. Breastfeeding and endometrial cancer risk: an analysis from the epidemiology of endometrial cancer consortium. Obstet Gynecol. 2017;129:1059-1067.
- Zhan B, Liu X, Li F, Zhang D, et al. Breastfeeding and the incidence of endometrial cancer: a meta-analysis. Oncotarget. 2015;6:38398-38409.
- Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012;CD003517.
- ACOG Committee Opinion No. 756. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;132:e187-e196.
- McFadden A, Gavine A, Renfrew M, et al. Support for healthy breastfeeding mothers with healthy term babies. Cochrane Database Syst Rev. 2017;CD001141.
To prevent fractures, treating only women with osteoporosis is not enough
The conventional bone mineral density threshold for initiating treatment to prevent fragility fractures is a T-score of less than -2.5 (the World Health Organization criteria for osteoporosis).1 However, most fractures experienced by postmenopausal women occur not in osteoporotic women but in those with low bone mass (osteopenia).2
Investigators in New Zealand recently published the results of a randomized controlled trial they conducted to determine the efficacy of zoledronate (zoledronic acid) in preventing fractures in postmenopausal women.3 They enrolled women age 65 years or older with osteopenia of the hip and randomly assigned the participants to 4 intravenous infusions of 5 mg zoledronic acid or placebo at 18-month intervals for 6 years.
Zoledronic acid reduced fracture risk
The trial included 2,000 postmenopausal women (mean age at baseline, 71 years; 94% European ethnicity) with a T-score of -1.0 to -2.5 at either the total hip or the femoral neck on either side. Both hips were assessed. The women received either zoledronic acid treatment or placebo in a 1:1 ratio. Candidates were excluded if they regularly used bone-active drugs in the previous year.
Fragility fractures were noted in 190 women in the placebo group and in 122 women treated with zoledronic acid (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50–0.79, P<.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15.
Compared with placebo, zoledronic acid also lowered the risk of nonvertebral, symptomatic, and vertebral fractures as well as height loss (P≤.003 for these 4 comparisons). Relatively few adverse events occurred with zoledronic acid treatment. No atypical femoral fractures or cases of osteonecrosis of the jaw occurred in either group.
Trial closes the knowledge gap regarding treatment thresholds
This trial’s findings underscore the importance of age as a risk factor for fragility fracture and clarify that pharmacologic treatment is appropriate not only for women with osteoporosis but also for older postmenopausal women with osteopenia.
As the authors point out, administration of zoledronic acid less often than annually can be highly effective in preventing fractures; they recommend future trials of administration of this intravenous bisphosphonate at intervals less frequent than 18 months. Although the absence of atypical femoral fractures or cases of osteonecrosis of the jaw is reassuring, the authors note that their trial was underpowered to assess these uncommon events.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- World Health Organization. WHO Scientific Group on the assessment of osteoporosis at primary health care level. Summary meeting report, Brussels, Belgium, 5-7 May 2004. https://www. who.int/chp/topics/Osteoporosis.pdf. Accessed November 19, 2018.
- Siris ES, Chen YT, Abbott TA, et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med. 2004;164:1108-1112.
- Reid IR, Horne AM, Mihov B, et al. Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med. 2018. doi:10.1056/NEJMoa1808082.
The conventional bone mineral density threshold for initiating treatment to prevent fragility fractures is a T-score of less than -2.5 (the World Health Organization criteria for osteoporosis).1 However, most fractures experienced by postmenopausal women occur not in osteoporotic women but in those with low bone mass (osteopenia).2
Investigators in New Zealand recently published the results of a randomized controlled trial they conducted to determine the efficacy of zoledronate (zoledronic acid) in preventing fractures in postmenopausal women.3 They enrolled women age 65 years or older with osteopenia of the hip and randomly assigned the participants to 4 intravenous infusions of 5 mg zoledronic acid or placebo at 18-month intervals for 6 years.
Zoledronic acid reduced fracture risk
The trial included 2,000 postmenopausal women (mean age at baseline, 71 years; 94% European ethnicity) with a T-score of -1.0 to -2.5 at either the total hip or the femoral neck on either side. Both hips were assessed. The women received either zoledronic acid treatment or placebo in a 1:1 ratio. Candidates were excluded if they regularly used bone-active drugs in the previous year.
Fragility fractures were noted in 190 women in the placebo group and in 122 women treated with zoledronic acid (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50–0.79, P<.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15.
Compared with placebo, zoledronic acid also lowered the risk of nonvertebral, symptomatic, and vertebral fractures as well as height loss (P≤.003 for these 4 comparisons). Relatively few adverse events occurred with zoledronic acid treatment. No atypical femoral fractures or cases of osteonecrosis of the jaw occurred in either group.
Trial closes the knowledge gap regarding treatment thresholds
This trial’s findings underscore the importance of age as a risk factor for fragility fracture and clarify that pharmacologic treatment is appropriate not only for women with osteoporosis but also for older postmenopausal women with osteopenia.
As the authors point out, administration of zoledronic acid less often than annually can be highly effective in preventing fractures; they recommend future trials of administration of this intravenous bisphosphonate at intervals less frequent than 18 months. Although the absence of atypical femoral fractures or cases of osteonecrosis of the jaw is reassuring, the authors note that their trial was underpowered to assess these uncommon events.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
The conventional bone mineral density threshold for initiating treatment to prevent fragility fractures is a T-score of less than -2.5 (the World Health Organization criteria for osteoporosis).1 However, most fractures experienced by postmenopausal women occur not in osteoporotic women but in those with low bone mass (osteopenia).2
Investigators in New Zealand recently published the results of a randomized controlled trial they conducted to determine the efficacy of zoledronate (zoledronic acid) in preventing fractures in postmenopausal women.3 They enrolled women age 65 years or older with osteopenia of the hip and randomly assigned the participants to 4 intravenous infusions of 5 mg zoledronic acid or placebo at 18-month intervals for 6 years.
Zoledronic acid reduced fracture risk
The trial included 2,000 postmenopausal women (mean age at baseline, 71 years; 94% European ethnicity) with a T-score of -1.0 to -2.5 at either the total hip or the femoral neck on either side. Both hips were assessed. The women received either zoledronic acid treatment or placebo in a 1:1 ratio. Candidates were excluded if they regularly used bone-active drugs in the previous year.
Fragility fractures were noted in 190 women in the placebo group and in 122 women treated with zoledronic acid (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50–0.79, P<.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15.
Compared with placebo, zoledronic acid also lowered the risk of nonvertebral, symptomatic, and vertebral fractures as well as height loss (P≤.003 for these 4 comparisons). Relatively few adverse events occurred with zoledronic acid treatment. No atypical femoral fractures or cases of osteonecrosis of the jaw occurred in either group.
Trial closes the knowledge gap regarding treatment thresholds
This trial’s findings underscore the importance of age as a risk factor for fragility fracture and clarify that pharmacologic treatment is appropriate not only for women with osteoporosis but also for older postmenopausal women with osteopenia.
As the authors point out, administration of zoledronic acid less often than annually can be highly effective in preventing fractures; they recommend future trials of administration of this intravenous bisphosphonate at intervals less frequent than 18 months. Although the absence of atypical femoral fractures or cases of osteonecrosis of the jaw is reassuring, the authors note that their trial was underpowered to assess these uncommon events.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- World Health Organization. WHO Scientific Group on the assessment of osteoporosis at primary health care level. Summary meeting report, Brussels, Belgium, 5-7 May 2004. https://www. who.int/chp/topics/Osteoporosis.pdf. Accessed November 19, 2018.
- Siris ES, Chen YT, Abbott TA, et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med. 2004;164:1108-1112.
- Reid IR, Horne AM, Mihov B, et al. Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med. 2018. doi:10.1056/NEJMoa1808082.
- World Health Organization. WHO Scientific Group on the assessment of osteoporosis at primary health care level. Summary meeting report, Brussels, Belgium, 5-7 May 2004. https://www. who.int/chp/topics/Osteoporosis.pdf. Accessed November 19, 2018.
- Siris ES, Chen YT, Abbott TA, et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med. 2004;164:1108-1112.
- Reid IR, Horne AM, Mihov B, et al. Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med. 2018. doi:10.1056/NEJMoa1808082.
Meaningful endometriosis treatment requires a holistic approach and an understanding of chronic pain
Although it has been more than 100 years since endometriosis was first described in the literature, deciphering the mechanisms that cause pain in women with this enigmatic disease is an ongoing pursuit.
Pain is the most debilitating symptom of endometriosis.1,2 In many cases, it has a profoundly negative impact on a patient’s quality of life, and contributes significantly to disease burden, as well as to personal and societal costs from lost productivity.3,4 Women with endometriosis often experience chronic pelvic pain, deep dyspareunia, dysmenorrhea, and subfertility.5 The majority of women with the disease also have one or more comorbidities, including adenomyosis, adhesive disease, and other pelvic pain conditions such as interstitial cystitis, irritable bowel disease, inflammatory bowel disease, and pelvic floor myalgia.6-8
Recent studies have yielded new insights into the development of endometriosis-associated pelvic pain. The role of peritoneal inflammation, de novo innervation of endometriosis implants, and changes in the central nervous system are becoming increasingly clear.5,9,10 These discoveries have important treatment implications.
In this article, Andrea J. Rapkin, MD, Professor of Obstetrics and Gynecology at the University of California, Los Angeles, and Founder and Director of the UCLA Pelvic Pain Center, offers her expert opinion on the findings of key studies and their clinical implications, including the importance of a multidisciplinary treatment approach that focuses on the whole patient.
Q What mechanisms underlie the chronic pain that many women with endometriosis feel?
Although pain is the primary symptom experienced by women with endometriosis, the disease burden and symptom severity do not often correlate.11,12 “This was the first conundrum presented to clinicians,” noted Dr. Rapkin. “In fact, we do not know the true prevalence of endometriosis because women with endometriosis only come to diagnosis either based on pain or infertility. When infertility is the problem, very often we are surprised by how much disease is present in an individual with either no pain or minimal pain. Conversely, in other individuals with very severe pain, upon laparoscopic surgery, have minimal or mild endometriosis.”
Efforts to solve this clinical puzzle began decades ago. “Dr. Michael Vernon discovered that the small, red, endometriosis implants that looked like petechial hemorrhages produced more prostaglandin E2 (PGE2) in vitro than the older black-brown lesions. PGE2 is a pain-producing (algesic) chemical produced after cytokines stimulation,” said Dr. Rapkin. “This was the first evidence that, yes, there is a reason for pain in many individuals with lower-stage disease.”
“Prostaglandins are known to be a major cause of dysmenorrhea. Prostaglandins induce uterine cramping, sensitize nerve endings, and promote other inflammatory factors responsible for attracting monocytes that become macrophages, further contributing to inflammation,” Dr. Rapkin continued. “PGE2 also stimulates the enzyme aromatase, which allows androgens to be converted to estrogen, which promotes growth of endometriotic lesions. This is a self-feeding aspect of endometriosis.”
Continue to: These discoveries were followed by the realization that deeply infiltrating endometriosis...
These discoveries were followed by the realization that deeply infiltrating endometriosis (defined by disease infiltration of more than 5 mm, often in the uterosacral ligaments) was more likely to be painful than superficial disease, said Dr. Rapkin. “In some women with endometriosis, the disease we see laparoscopically is really the tip of the iceberg.”
In 2005, landmark studies performed by Karen J. Berkley, PhD, were summarized in a paper coauthored by Dr. Berkley, Dr. Rapkin, and Raymond E. Papka, PhD.13 “In a rodent model where endometriosis was developed by suturing pieces of endometrium in the mesentery, the endometriosis implants developed a vascular supply and a nerve supply. These nerves were not just functioning to govern the dilation and contraction of the blood vessels (in other words the sympathetic type nerves), but these nerves stained for neurotransmitters associated with pain (algesic agents, such as substance P and CGRP),” said Dr. Rapkin. “At UCLA, we acquired tissue from women with endometriosis and analyzed in Dr. Papka’s lab. Those tissues also showed nerves staining for pain-producing chemicals.” Other studies performed worldwide also demonstrated nerve endings with neurotrophic and algesic chemicals in endometriotic tissues. In addition to prostaglandins and cytokines, increased expression of various neuropeptides, neurotrophins, and alterations in ion channels contribute to hypersensitivity and pain.
Q What other chronic pain conditions might women with endometriosis experience?
Overlapping chronic pain conditions are common in women with endometriosis. “There is a very high co-occurrence of interstitial cystitis/painful bladder syndrome,” said Dr. Rapkin. “Irritable bowel syndrome is more common in women with endometriosis, as is vulvodynia. Fibromyalgia, migraine headache, temporo-mandibular joint pain (TMJ), anxiety, and depression also commonly co-occur in women with endometriosis.”
“Two concepts may be relevant to why these overlapping pain conditions develop,” Dr. Rapkin continued. “First, visceral sensitization: If one organ or tissue is inflamed and becomes hyperalgesic then other organs in the adjacent region with shared thoracolumbar and sacral innervation can become sensitized through shared cell bodies in the spinal cord, cross-sensitization in the cord, or at higher regions of the CNS. In addition, visceral somatic conversion occurs, whereby somatic tissues such as muscles and subcutaneous tissues with the same nerve supply as the affected organs become sensitized. This process may explain why abdominal wall and pelvic floor muscles become painful. The involvement of surrounding musculature is an important contributor to the pain in many women with endometriosis.”
“Finally, genetic studies of alterations in genes that encode for chemicals affecting the sensitivity and perception of pain are shedding light on the development of chronic pain. Ultimately these studies will advance our understanding of pain related to endometriosis.”
Continue to: Q How have new understandings about the pain mechanisms...
Q How have new understandings about the pain mechanisms involved with endometriosis-caused pelvic pain improved treatment?
According to Dr. Rapkin, the increased understanding of the mechanisms involved in endometriosis-associated pain gained from these key studies led to a paradigm shift, with endometriosis being viewed not just as a condition with mechanical hypersensitivity due to altered anatomy and inflammation but also as a neurologic condition, or a nerve pain condition with peripheral and central sensitization. “This means there is upregulation or hyperactivity both in the periphery (in the pelvis) and centrally (in the spinal cord and brain),” said Dr. Rapkin.
“In the periphery, the endometriotic lesions develop an afferent sensory innervation and communicate with the brain. Stimulation of these nerves by the inflammatory milieu contributes to pain.” Dr. Rapkin noted research by Maria Adele Giamberardino, which demonstrated that women with endometriosis and pain have a lower threshold for feeling pain in the tissues overlying the pelvis (the abdominal wall and back).14 This also has been shown by Dr. Berkley in rodents given endometriosis.
“The muscles develop trigger points and tender hyperalgesic points as part of the sensitization process. In addition, distant sensitization develops—women with pelvic pain and endometriosis have a lower threshold for sensing experimental pain in areas outside the pelvis, for example the back, leg, or shoulder. These discoveries clearly reflect up regulation for pain processing in the central nervous system.”
Dr. Rapkin also pointed to research published in 2016 by Sawson As-Sanie, MD, MPH, that showed an association between endometriosis-associated pelvic pain and altered brain chemistry and function.16 “Dr. As-Sanie demonstrated a decrease in gray matter volume in key neural pain processing areas in the brain in women with pain with endometriosis. This was not found in women with endometriosis who did not have pain,” she said. “Altered connectivity in brain areas related to perception and inhibition of pain is important in maintaining pain. Dr. As-Sanie’s studies also found that these changes are correlated with anxiety, depression, and pain intensity in patients with endometriosis and chronic pain.”
Continue to: Q What are some newer treatment approaches to chronic pain with endometriosis?
Q What are some newer treatment approaches to chronic pain with endometriosis?
“Multidisciplinary approaches to endometriosis-related pain are important,” said Dr. Rapkin. “Although it is important to excise or cauterize endometriosis lesions, or debulk as much as can safely be removed during laparoscopic surgery, it is now standard of care that medical therapy, not surgery, is the first approach to treatment. Endometriosis is a chronic condition. Inflammatory factors will continue to proliferate in patients who menstruate and produce high levels of estrogen with ovulation. The goal of medical therapy is to decrease the levels of estrogen that contribute to maintenance and proliferation of the implants. We want to suppress estrogen in a way that is compatible with long-term quality of life for our patients. Wiping out estrogen and placing patients into a chemical or surgical menopause for most of their reproductive years is not desirable.”
Approaches to hormonally modulate endometriosis include combined hormonal contraceptives and progestin-only medications, such as the levonogestrol-containing IUD, progestin-containing contraceptive implants, injections, or tablets. Second-line medical therapy consists of gonadotropin-releasing hormone agonists and antagonists that can be used for 6 months to 2 years and allows for further lowering of estrogen levels. These may not provide sufficient pain relief for some patients. “There is some evidence from Dr. Giamberadino’s studies that after women with dysmenorrhea were treated with oral contraceptives, the abdominal wall hyperalgesia decreased,” said Dr. Rapkin. “The question is, why don’t we see this in all patients? We come to the realization that endometriosis has to be treated as a neurologically mediated disorder. We have to treat the peripheral and central sensitization in a multidisciplinary way.”
A holistic approach to endometriosis is a new and exciting area for the field, said Dr. Rapkin. “We have to treat ‘bottom-up’, and ‘top-down.’ Bottom-up means we are addressing the peripheral factors that contribute to pain: endometriotic lesions, other pelvic organ pain, myofascial pain, trigger points, the tender points, and the muscle dysfunction in the abdominal wall, the back, and the pelvic floor. Pelvic floor physical therapists help women with pain and endometriosis. Often, women with endometriosis have myofascial pain and pain related to the other comorbid pain conditions they may have developed. Peripheral nerve blocks and medications used for neuropathic pain that alter nerve firing can be helpful in many situations. Pain can be augmented by cognitions and beliefs about pain, and by anxiety and depression. So the top-down approach addresses the cognitions, depression, and anxiety. We do not consider endometriosis a psychosomatic condition, but we know that if you do not address the central upregulation, including anxiety and depression, we may not get anywhere.”
“Interestingly, neurotransmitters and brain regions governing mood contribute to nerve pain. Medications such as tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, anticonvulsants, and calcium channel blocking agents may prove fruitful. Cognitive behavioral therapy is another approach—to stimulate the prefrontal cortex, the area that is involved in pain inhibition, and other areas of the brain that may produce endogenous opioids to help with inhibiting pain. Bringing in complementary approaches is very important—for example, mindfulness-based meditation or yoga. There is growing evidence for acupuncture as well. Physical therapists, pain psychologists, anesthesiologists, or gynecologists who are facile with nerve blocks, to help tone down hyperalgesic tissues, in addition to medical and surgical therapy, have the possibility of really improving the lives of women with endometriosis.”
Q What key pearls would you like to share with readers?
“It is important to evaluate the entire individual,” she said. “Do not just viscerally focus on the uterus, the ovaries, fallopian tubes, and the peritoneum; investigate the adjacent organs and somatic tissues. Think about the abdominal wall, think about the pelvic floor. Learn how to evaluate these structures. There are simple evaluation techniques that gynecologists can learn and should include with every patient with pelvic pain, whether or not they are suspected of having endometriosis. You also want to get a complete history to determine if there are other co-occurring pain conditions. If there are, it is already a sign that there may be central sensitization.”
“Very often, it is necessary to bring in a pain psychologist—not because the disease is psychosomatic but because therapy can help the patient to learn how to use their brain to erase pain memory, and of course to address the concomitant anxiety, depression, and social isolation that happens with pain.”
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Olive DL, Lindheim SR, Pritts EA. New medical treatments for endometriosis. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):319-328.
- Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447): 1789-1799.
- Nnoaham KE, Hummelshoj L, Webster P, et al; World Endometriosis Research Foundation Global Study of Women’s Health consortium. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011;96(2):366-373.e8.
- Simoens S, Dunselman G, Dirksen C, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012;27(5):1292–1299.
- Bruner-Tran KL, Mokshagundam S, Herington JL. Rodent models of experimental endometriosis: identifying mechanisms of disease and therapeutic targets. Curr Womens Health Rev. 2018;14(2):173-188.
- Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715-2724.
- Struble J, Reid S, Bedaiwy MA. Adenomyosis: a clinical review of a challenging gynecologic condition. J Minim Invasive Gynecol. 2016;23(2):164-185.
- Tirlapur SA, Kuhrt K, Chaliha C. The ‘evil twin syndrome’ in chronic pelvic pain: a systematic review of prevalence studies of bladder pain syndrome and endometriosis. Int J Surg. 2013;11(3):233-237.
- Coxon L, Horne AW, Vincent K. Pathophysiology of endometriosis-associated pain: a review of pelvic and central nervous system mechanisms. Best Pract Res Clin Obstet Gynaecol. 2018 Feb 15. pii: S1521-6934(18)30032-4. doi: 10.1016/j.bpobgyn.2018.01.014. [Epub ahead of print]
- Yan D, Liu X, Guo SW. Nerve fibers and endometriotic lesions: partners in crime in inflicting pains in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2017;209:14-24.
- Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22(1):266-271.
- Fedele L, Parazzini F, Bianchi S. Stage and localization of pelvic endometriosis and pain. Fertil Steril. 1990;53(1):155-158.
- Berkley KJ, Rapkin AJ, Papka RE. The pains of endometriosis. Science. 2005;308(5728):1587-1589.
- Giamberardino MA, Tana C, Costantini R. Pain thresholds in women with chronic pelvic pain. Curr Opin Obstet Gynecol. 2014;26(4):253-259.
- Giamberardino MA, Berkley KJ, Affaitati G. Influence of endometriosis on pain behaviors and muscle hyperalgesia induced by a ureteral calculosis in female rats. Pain. 2002;95(3):247-257.
- As-Sanie S, Kim J, Schmidt-Wilcke T. Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain. J Pain. 2016;17(1):1-13.
Although it has been more than 100 years since endometriosis was first described in the literature, deciphering the mechanisms that cause pain in women with this enigmatic disease is an ongoing pursuit.
Pain is the most debilitating symptom of endometriosis.1,2 In many cases, it has a profoundly negative impact on a patient’s quality of life, and contributes significantly to disease burden, as well as to personal and societal costs from lost productivity.3,4 Women with endometriosis often experience chronic pelvic pain, deep dyspareunia, dysmenorrhea, and subfertility.5 The majority of women with the disease also have one or more comorbidities, including adenomyosis, adhesive disease, and other pelvic pain conditions such as interstitial cystitis, irritable bowel disease, inflammatory bowel disease, and pelvic floor myalgia.6-8
Recent studies have yielded new insights into the development of endometriosis-associated pelvic pain. The role of peritoneal inflammation, de novo innervation of endometriosis implants, and changes in the central nervous system are becoming increasingly clear.5,9,10 These discoveries have important treatment implications.
In this article, Andrea J. Rapkin, MD, Professor of Obstetrics and Gynecology at the University of California, Los Angeles, and Founder and Director of the UCLA Pelvic Pain Center, offers her expert opinion on the findings of key studies and their clinical implications, including the importance of a multidisciplinary treatment approach that focuses on the whole patient.
Q What mechanisms underlie the chronic pain that many women with endometriosis feel?
Although pain is the primary symptom experienced by women with endometriosis, the disease burden and symptom severity do not often correlate.11,12 “This was the first conundrum presented to clinicians,” noted Dr. Rapkin. “In fact, we do not know the true prevalence of endometriosis because women with endometriosis only come to diagnosis either based on pain or infertility. When infertility is the problem, very often we are surprised by how much disease is present in an individual with either no pain or minimal pain. Conversely, in other individuals with very severe pain, upon laparoscopic surgery, have minimal or mild endometriosis.”
Efforts to solve this clinical puzzle began decades ago. “Dr. Michael Vernon discovered that the small, red, endometriosis implants that looked like petechial hemorrhages produced more prostaglandin E2 (PGE2) in vitro than the older black-brown lesions. PGE2 is a pain-producing (algesic) chemical produced after cytokines stimulation,” said Dr. Rapkin. “This was the first evidence that, yes, there is a reason for pain in many individuals with lower-stage disease.”
“Prostaglandins are known to be a major cause of dysmenorrhea. Prostaglandins induce uterine cramping, sensitize nerve endings, and promote other inflammatory factors responsible for attracting monocytes that become macrophages, further contributing to inflammation,” Dr. Rapkin continued. “PGE2 also stimulates the enzyme aromatase, which allows androgens to be converted to estrogen, which promotes growth of endometriotic lesions. This is a self-feeding aspect of endometriosis.”
Continue to: These discoveries were followed by the realization that deeply infiltrating endometriosis...
These discoveries were followed by the realization that deeply infiltrating endometriosis (defined by disease infiltration of more than 5 mm, often in the uterosacral ligaments) was more likely to be painful than superficial disease, said Dr. Rapkin. “In some women with endometriosis, the disease we see laparoscopically is really the tip of the iceberg.”
In 2005, landmark studies performed by Karen J. Berkley, PhD, were summarized in a paper coauthored by Dr. Berkley, Dr. Rapkin, and Raymond E. Papka, PhD.13 “In a rodent model where endometriosis was developed by suturing pieces of endometrium in the mesentery, the endometriosis implants developed a vascular supply and a nerve supply. These nerves were not just functioning to govern the dilation and contraction of the blood vessels (in other words the sympathetic type nerves), but these nerves stained for neurotransmitters associated with pain (algesic agents, such as substance P and CGRP),” said Dr. Rapkin. “At UCLA, we acquired tissue from women with endometriosis and analyzed in Dr. Papka’s lab. Those tissues also showed nerves staining for pain-producing chemicals.” Other studies performed worldwide also demonstrated nerve endings with neurotrophic and algesic chemicals in endometriotic tissues. In addition to prostaglandins and cytokines, increased expression of various neuropeptides, neurotrophins, and alterations in ion channels contribute to hypersensitivity and pain.
Q What other chronic pain conditions might women with endometriosis experience?
Overlapping chronic pain conditions are common in women with endometriosis. “There is a very high co-occurrence of interstitial cystitis/painful bladder syndrome,” said Dr. Rapkin. “Irritable bowel syndrome is more common in women with endometriosis, as is vulvodynia. Fibromyalgia, migraine headache, temporo-mandibular joint pain (TMJ), anxiety, and depression also commonly co-occur in women with endometriosis.”
“Two concepts may be relevant to why these overlapping pain conditions develop,” Dr. Rapkin continued. “First, visceral sensitization: If one organ or tissue is inflamed and becomes hyperalgesic then other organs in the adjacent region with shared thoracolumbar and sacral innervation can become sensitized through shared cell bodies in the spinal cord, cross-sensitization in the cord, or at higher regions of the CNS. In addition, visceral somatic conversion occurs, whereby somatic tissues such as muscles and subcutaneous tissues with the same nerve supply as the affected organs become sensitized. This process may explain why abdominal wall and pelvic floor muscles become painful. The involvement of surrounding musculature is an important contributor to the pain in many women with endometriosis.”
“Finally, genetic studies of alterations in genes that encode for chemicals affecting the sensitivity and perception of pain are shedding light on the development of chronic pain. Ultimately these studies will advance our understanding of pain related to endometriosis.”
Continue to: Q How have new understandings about the pain mechanisms...
Q How have new understandings about the pain mechanisms involved with endometriosis-caused pelvic pain improved treatment?
According to Dr. Rapkin, the increased understanding of the mechanisms involved in endometriosis-associated pain gained from these key studies led to a paradigm shift, with endometriosis being viewed not just as a condition with mechanical hypersensitivity due to altered anatomy and inflammation but also as a neurologic condition, or a nerve pain condition with peripheral and central sensitization. “This means there is upregulation or hyperactivity both in the periphery (in the pelvis) and centrally (in the spinal cord and brain),” said Dr. Rapkin.
“In the periphery, the endometriotic lesions develop an afferent sensory innervation and communicate with the brain. Stimulation of these nerves by the inflammatory milieu contributes to pain.” Dr. Rapkin noted research by Maria Adele Giamberardino, which demonstrated that women with endometriosis and pain have a lower threshold for feeling pain in the tissues overlying the pelvis (the abdominal wall and back).14 This also has been shown by Dr. Berkley in rodents given endometriosis.
“The muscles develop trigger points and tender hyperalgesic points as part of the sensitization process. In addition, distant sensitization develops—women with pelvic pain and endometriosis have a lower threshold for sensing experimental pain in areas outside the pelvis, for example the back, leg, or shoulder. These discoveries clearly reflect up regulation for pain processing in the central nervous system.”
Dr. Rapkin also pointed to research published in 2016 by Sawson As-Sanie, MD, MPH, that showed an association between endometriosis-associated pelvic pain and altered brain chemistry and function.16 “Dr. As-Sanie demonstrated a decrease in gray matter volume in key neural pain processing areas in the brain in women with pain with endometriosis. This was not found in women with endometriosis who did not have pain,” she said. “Altered connectivity in brain areas related to perception and inhibition of pain is important in maintaining pain. Dr. As-Sanie’s studies also found that these changes are correlated with anxiety, depression, and pain intensity in patients with endometriosis and chronic pain.”
Continue to: Q What are some newer treatment approaches to chronic pain with endometriosis?
Q What are some newer treatment approaches to chronic pain with endometriosis?
“Multidisciplinary approaches to endometriosis-related pain are important,” said Dr. Rapkin. “Although it is important to excise or cauterize endometriosis lesions, or debulk as much as can safely be removed during laparoscopic surgery, it is now standard of care that medical therapy, not surgery, is the first approach to treatment. Endometriosis is a chronic condition. Inflammatory factors will continue to proliferate in patients who menstruate and produce high levels of estrogen with ovulation. The goal of medical therapy is to decrease the levels of estrogen that contribute to maintenance and proliferation of the implants. We want to suppress estrogen in a way that is compatible with long-term quality of life for our patients. Wiping out estrogen and placing patients into a chemical or surgical menopause for most of their reproductive years is not desirable.”
Approaches to hormonally modulate endometriosis include combined hormonal contraceptives and progestin-only medications, such as the levonogestrol-containing IUD, progestin-containing contraceptive implants, injections, or tablets. Second-line medical therapy consists of gonadotropin-releasing hormone agonists and antagonists that can be used for 6 months to 2 years and allows for further lowering of estrogen levels. These may not provide sufficient pain relief for some patients. “There is some evidence from Dr. Giamberadino’s studies that after women with dysmenorrhea were treated with oral contraceptives, the abdominal wall hyperalgesia decreased,” said Dr. Rapkin. “The question is, why don’t we see this in all patients? We come to the realization that endometriosis has to be treated as a neurologically mediated disorder. We have to treat the peripheral and central sensitization in a multidisciplinary way.”
A holistic approach to endometriosis is a new and exciting area for the field, said Dr. Rapkin. “We have to treat ‘bottom-up’, and ‘top-down.’ Bottom-up means we are addressing the peripheral factors that contribute to pain: endometriotic lesions, other pelvic organ pain, myofascial pain, trigger points, the tender points, and the muscle dysfunction in the abdominal wall, the back, and the pelvic floor. Pelvic floor physical therapists help women with pain and endometriosis. Often, women with endometriosis have myofascial pain and pain related to the other comorbid pain conditions they may have developed. Peripheral nerve blocks and medications used for neuropathic pain that alter nerve firing can be helpful in many situations. Pain can be augmented by cognitions and beliefs about pain, and by anxiety and depression. So the top-down approach addresses the cognitions, depression, and anxiety. We do not consider endometriosis a psychosomatic condition, but we know that if you do not address the central upregulation, including anxiety and depression, we may not get anywhere.”
“Interestingly, neurotransmitters and brain regions governing mood contribute to nerve pain. Medications such as tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, anticonvulsants, and calcium channel blocking agents may prove fruitful. Cognitive behavioral therapy is another approach—to stimulate the prefrontal cortex, the area that is involved in pain inhibition, and other areas of the brain that may produce endogenous opioids to help with inhibiting pain. Bringing in complementary approaches is very important—for example, mindfulness-based meditation or yoga. There is growing evidence for acupuncture as well. Physical therapists, pain psychologists, anesthesiologists, or gynecologists who are facile with nerve blocks, to help tone down hyperalgesic tissues, in addition to medical and surgical therapy, have the possibility of really improving the lives of women with endometriosis.”
Q What key pearls would you like to share with readers?
“It is important to evaluate the entire individual,” she said. “Do not just viscerally focus on the uterus, the ovaries, fallopian tubes, and the peritoneum; investigate the adjacent organs and somatic tissues. Think about the abdominal wall, think about the pelvic floor. Learn how to evaluate these structures. There are simple evaluation techniques that gynecologists can learn and should include with every patient with pelvic pain, whether or not they are suspected of having endometriosis. You also want to get a complete history to determine if there are other co-occurring pain conditions. If there are, it is already a sign that there may be central sensitization.”
“Very often, it is necessary to bring in a pain psychologist—not because the disease is psychosomatic but because therapy can help the patient to learn how to use their brain to erase pain memory, and of course to address the concomitant anxiety, depression, and social isolation that happens with pain.”
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Although it has been more than 100 years since endometriosis was first described in the literature, deciphering the mechanisms that cause pain in women with this enigmatic disease is an ongoing pursuit.
Pain is the most debilitating symptom of endometriosis.1,2 In many cases, it has a profoundly negative impact on a patient’s quality of life, and contributes significantly to disease burden, as well as to personal and societal costs from lost productivity.3,4 Women with endometriosis often experience chronic pelvic pain, deep dyspareunia, dysmenorrhea, and subfertility.5 The majority of women with the disease also have one or more comorbidities, including adenomyosis, adhesive disease, and other pelvic pain conditions such as interstitial cystitis, irritable bowel disease, inflammatory bowel disease, and pelvic floor myalgia.6-8
Recent studies have yielded new insights into the development of endometriosis-associated pelvic pain. The role of peritoneal inflammation, de novo innervation of endometriosis implants, and changes in the central nervous system are becoming increasingly clear.5,9,10 These discoveries have important treatment implications.
In this article, Andrea J. Rapkin, MD, Professor of Obstetrics and Gynecology at the University of California, Los Angeles, and Founder and Director of the UCLA Pelvic Pain Center, offers her expert opinion on the findings of key studies and their clinical implications, including the importance of a multidisciplinary treatment approach that focuses on the whole patient.
Q What mechanisms underlie the chronic pain that many women with endometriosis feel?
Although pain is the primary symptom experienced by women with endometriosis, the disease burden and symptom severity do not often correlate.11,12 “This was the first conundrum presented to clinicians,” noted Dr. Rapkin. “In fact, we do not know the true prevalence of endometriosis because women with endometriosis only come to diagnosis either based on pain or infertility. When infertility is the problem, very often we are surprised by how much disease is present in an individual with either no pain or minimal pain. Conversely, in other individuals with very severe pain, upon laparoscopic surgery, have minimal or mild endometriosis.”
Efforts to solve this clinical puzzle began decades ago. “Dr. Michael Vernon discovered that the small, red, endometriosis implants that looked like petechial hemorrhages produced more prostaglandin E2 (PGE2) in vitro than the older black-brown lesions. PGE2 is a pain-producing (algesic) chemical produced after cytokines stimulation,” said Dr. Rapkin. “This was the first evidence that, yes, there is a reason for pain in many individuals with lower-stage disease.”
“Prostaglandins are known to be a major cause of dysmenorrhea. Prostaglandins induce uterine cramping, sensitize nerve endings, and promote other inflammatory factors responsible for attracting monocytes that become macrophages, further contributing to inflammation,” Dr. Rapkin continued. “PGE2 also stimulates the enzyme aromatase, which allows androgens to be converted to estrogen, which promotes growth of endometriotic lesions. This is a self-feeding aspect of endometriosis.”
Continue to: These discoveries were followed by the realization that deeply infiltrating endometriosis...
These discoveries were followed by the realization that deeply infiltrating endometriosis (defined by disease infiltration of more than 5 mm, often in the uterosacral ligaments) was more likely to be painful than superficial disease, said Dr. Rapkin. “In some women with endometriosis, the disease we see laparoscopically is really the tip of the iceberg.”
In 2005, landmark studies performed by Karen J. Berkley, PhD, were summarized in a paper coauthored by Dr. Berkley, Dr. Rapkin, and Raymond E. Papka, PhD.13 “In a rodent model where endometriosis was developed by suturing pieces of endometrium in the mesentery, the endometriosis implants developed a vascular supply and a nerve supply. These nerves were not just functioning to govern the dilation and contraction of the blood vessels (in other words the sympathetic type nerves), but these nerves stained for neurotransmitters associated with pain (algesic agents, such as substance P and CGRP),” said Dr. Rapkin. “At UCLA, we acquired tissue from women with endometriosis and analyzed in Dr. Papka’s lab. Those tissues also showed nerves staining for pain-producing chemicals.” Other studies performed worldwide also demonstrated nerve endings with neurotrophic and algesic chemicals in endometriotic tissues. In addition to prostaglandins and cytokines, increased expression of various neuropeptides, neurotrophins, and alterations in ion channels contribute to hypersensitivity and pain.
Q What other chronic pain conditions might women with endometriosis experience?
Overlapping chronic pain conditions are common in women with endometriosis. “There is a very high co-occurrence of interstitial cystitis/painful bladder syndrome,” said Dr. Rapkin. “Irritable bowel syndrome is more common in women with endometriosis, as is vulvodynia. Fibromyalgia, migraine headache, temporo-mandibular joint pain (TMJ), anxiety, and depression also commonly co-occur in women with endometriosis.”
“Two concepts may be relevant to why these overlapping pain conditions develop,” Dr. Rapkin continued. “First, visceral sensitization: If one organ or tissue is inflamed and becomes hyperalgesic then other organs in the adjacent region with shared thoracolumbar and sacral innervation can become sensitized through shared cell bodies in the spinal cord, cross-sensitization in the cord, or at higher regions of the CNS. In addition, visceral somatic conversion occurs, whereby somatic tissues such as muscles and subcutaneous tissues with the same nerve supply as the affected organs become sensitized. This process may explain why abdominal wall and pelvic floor muscles become painful. The involvement of surrounding musculature is an important contributor to the pain in many women with endometriosis.”
“Finally, genetic studies of alterations in genes that encode for chemicals affecting the sensitivity and perception of pain are shedding light on the development of chronic pain. Ultimately these studies will advance our understanding of pain related to endometriosis.”
Continue to: Q How have new understandings about the pain mechanisms...
Q How have new understandings about the pain mechanisms involved with endometriosis-caused pelvic pain improved treatment?
According to Dr. Rapkin, the increased understanding of the mechanisms involved in endometriosis-associated pain gained from these key studies led to a paradigm shift, with endometriosis being viewed not just as a condition with mechanical hypersensitivity due to altered anatomy and inflammation but also as a neurologic condition, or a nerve pain condition with peripheral and central sensitization. “This means there is upregulation or hyperactivity both in the periphery (in the pelvis) and centrally (in the spinal cord and brain),” said Dr. Rapkin.
“In the periphery, the endometriotic lesions develop an afferent sensory innervation and communicate with the brain. Stimulation of these nerves by the inflammatory milieu contributes to pain.” Dr. Rapkin noted research by Maria Adele Giamberardino, which demonstrated that women with endometriosis and pain have a lower threshold for feeling pain in the tissues overlying the pelvis (the abdominal wall and back).14 This also has been shown by Dr. Berkley in rodents given endometriosis.
“The muscles develop trigger points and tender hyperalgesic points as part of the sensitization process. In addition, distant sensitization develops—women with pelvic pain and endometriosis have a lower threshold for sensing experimental pain in areas outside the pelvis, for example the back, leg, or shoulder. These discoveries clearly reflect up regulation for pain processing in the central nervous system.”
Dr. Rapkin also pointed to research published in 2016 by Sawson As-Sanie, MD, MPH, that showed an association between endometriosis-associated pelvic pain and altered brain chemistry and function.16 “Dr. As-Sanie demonstrated a decrease in gray matter volume in key neural pain processing areas in the brain in women with pain with endometriosis. This was not found in women with endometriosis who did not have pain,” she said. “Altered connectivity in brain areas related to perception and inhibition of pain is important in maintaining pain. Dr. As-Sanie’s studies also found that these changes are correlated with anxiety, depression, and pain intensity in patients with endometriosis and chronic pain.”
Continue to: Q What are some newer treatment approaches to chronic pain with endometriosis?
Q What are some newer treatment approaches to chronic pain with endometriosis?
“Multidisciplinary approaches to endometriosis-related pain are important,” said Dr. Rapkin. “Although it is important to excise or cauterize endometriosis lesions, or debulk as much as can safely be removed during laparoscopic surgery, it is now standard of care that medical therapy, not surgery, is the first approach to treatment. Endometriosis is a chronic condition. Inflammatory factors will continue to proliferate in patients who menstruate and produce high levels of estrogen with ovulation. The goal of medical therapy is to decrease the levels of estrogen that contribute to maintenance and proliferation of the implants. We want to suppress estrogen in a way that is compatible with long-term quality of life for our patients. Wiping out estrogen and placing patients into a chemical or surgical menopause for most of their reproductive years is not desirable.”
Approaches to hormonally modulate endometriosis include combined hormonal contraceptives and progestin-only medications, such as the levonogestrol-containing IUD, progestin-containing contraceptive implants, injections, or tablets. Second-line medical therapy consists of gonadotropin-releasing hormone agonists and antagonists that can be used for 6 months to 2 years and allows for further lowering of estrogen levels. These may not provide sufficient pain relief for some patients. “There is some evidence from Dr. Giamberadino’s studies that after women with dysmenorrhea were treated with oral contraceptives, the abdominal wall hyperalgesia decreased,” said Dr. Rapkin. “The question is, why don’t we see this in all patients? We come to the realization that endometriosis has to be treated as a neurologically mediated disorder. We have to treat the peripheral and central sensitization in a multidisciplinary way.”
A holistic approach to endometriosis is a new and exciting area for the field, said Dr. Rapkin. “We have to treat ‘bottom-up’, and ‘top-down.’ Bottom-up means we are addressing the peripheral factors that contribute to pain: endometriotic lesions, other pelvic organ pain, myofascial pain, trigger points, the tender points, and the muscle dysfunction in the abdominal wall, the back, and the pelvic floor. Pelvic floor physical therapists help women with pain and endometriosis. Often, women with endometriosis have myofascial pain and pain related to the other comorbid pain conditions they may have developed. Peripheral nerve blocks and medications used for neuropathic pain that alter nerve firing can be helpful in many situations. Pain can be augmented by cognitions and beliefs about pain, and by anxiety and depression. So the top-down approach addresses the cognitions, depression, and anxiety. We do not consider endometriosis a psychosomatic condition, but we know that if you do not address the central upregulation, including anxiety and depression, we may not get anywhere.”
“Interestingly, neurotransmitters and brain regions governing mood contribute to nerve pain. Medications such as tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, anticonvulsants, and calcium channel blocking agents may prove fruitful. Cognitive behavioral therapy is another approach—to stimulate the prefrontal cortex, the area that is involved in pain inhibition, and other areas of the brain that may produce endogenous opioids to help with inhibiting pain. Bringing in complementary approaches is very important—for example, mindfulness-based meditation or yoga. There is growing evidence for acupuncture as well. Physical therapists, pain psychologists, anesthesiologists, or gynecologists who are facile with nerve blocks, to help tone down hyperalgesic tissues, in addition to medical and surgical therapy, have the possibility of really improving the lives of women with endometriosis.”
Q What key pearls would you like to share with readers?
“It is important to evaluate the entire individual,” she said. “Do not just viscerally focus on the uterus, the ovaries, fallopian tubes, and the peritoneum; investigate the adjacent organs and somatic tissues. Think about the abdominal wall, think about the pelvic floor. Learn how to evaluate these structures. There are simple evaluation techniques that gynecologists can learn and should include with every patient with pelvic pain, whether or not they are suspected of having endometriosis. You also want to get a complete history to determine if there are other co-occurring pain conditions. If there are, it is already a sign that there may be central sensitization.”
“Very often, it is necessary to bring in a pain psychologist—not because the disease is psychosomatic but because therapy can help the patient to learn how to use their brain to erase pain memory, and of course to address the concomitant anxiety, depression, and social isolation that happens with pain.”
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Olive DL, Lindheim SR, Pritts EA. New medical treatments for endometriosis. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):319-328.
- Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447): 1789-1799.
- Nnoaham KE, Hummelshoj L, Webster P, et al; World Endometriosis Research Foundation Global Study of Women’s Health consortium. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011;96(2):366-373.e8.
- Simoens S, Dunselman G, Dirksen C, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012;27(5):1292–1299.
- Bruner-Tran KL, Mokshagundam S, Herington JL. Rodent models of experimental endometriosis: identifying mechanisms of disease and therapeutic targets. Curr Womens Health Rev. 2018;14(2):173-188.
- Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715-2724.
- Struble J, Reid S, Bedaiwy MA. Adenomyosis: a clinical review of a challenging gynecologic condition. J Minim Invasive Gynecol. 2016;23(2):164-185.
- Tirlapur SA, Kuhrt K, Chaliha C. The ‘evil twin syndrome’ in chronic pelvic pain: a systematic review of prevalence studies of bladder pain syndrome and endometriosis. Int J Surg. 2013;11(3):233-237.
- Coxon L, Horne AW, Vincent K. Pathophysiology of endometriosis-associated pain: a review of pelvic and central nervous system mechanisms. Best Pract Res Clin Obstet Gynaecol. 2018 Feb 15. pii: S1521-6934(18)30032-4. doi: 10.1016/j.bpobgyn.2018.01.014. [Epub ahead of print]
- Yan D, Liu X, Guo SW. Nerve fibers and endometriotic lesions: partners in crime in inflicting pains in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2017;209:14-24.
- Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22(1):266-271.
- Fedele L, Parazzini F, Bianchi S. Stage and localization of pelvic endometriosis and pain. Fertil Steril. 1990;53(1):155-158.
- Berkley KJ, Rapkin AJ, Papka RE. The pains of endometriosis. Science. 2005;308(5728):1587-1589.
- Giamberardino MA, Tana C, Costantini R. Pain thresholds in women with chronic pelvic pain. Curr Opin Obstet Gynecol. 2014;26(4):253-259.
- Giamberardino MA, Berkley KJ, Affaitati G. Influence of endometriosis on pain behaviors and muscle hyperalgesia induced by a ureteral calculosis in female rats. Pain. 2002;95(3):247-257.
- As-Sanie S, Kim J, Schmidt-Wilcke T. Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain. J Pain. 2016;17(1):1-13.
- Olive DL, Lindheim SR, Pritts EA. New medical treatments for endometriosis. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):319-328.
- Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447): 1789-1799.
- Nnoaham KE, Hummelshoj L, Webster P, et al; World Endometriosis Research Foundation Global Study of Women’s Health consortium. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011;96(2):366-373.e8.
- Simoens S, Dunselman G, Dirksen C, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012;27(5):1292–1299.
- Bruner-Tran KL, Mokshagundam S, Herington JL. Rodent models of experimental endometriosis: identifying mechanisms of disease and therapeutic targets. Curr Womens Health Rev. 2018;14(2):173-188.
- Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715-2724.
- Struble J, Reid S, Bedaiwy MA. Adenomyosis: a clinical review of a challenging gynecologic condition. J Minim Invasive Gynecol. 2016;23(2):164-185.
- Tirlapur SA, Kuhrt K, Chaliha C. The ‘evil twin syndrome’ in chronic pelvic pain: a systematic review of prevalence studies of bladder pain syndrome and endometriosis. Int J Surg. 2013;11(3):233-237.
- Coxon L, Horne AW, Vincent K. Pathophysiology of endometriosis-associated pain: a review of pelvic and central nervous system mechanisms. Best Pract Res Clin Obstet Gynaecol. 2018 Feb 15. pii: S1521-6934(18)30032-4. doi: 10.1016/j.bpobgyn.2018.01.014. [Epub ahead of print]
- Yan D, Liu X, Guo SW. Nerve fibers and endometriotic lesions: partners in crime in inflicting pains in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2017;209:14-24.
- Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22(1):266-271.
- Fedele L, Parazzini F, Bianchi S. Stage and localization of pelvic endometriosis and pain. Fertil Steril. 1990;53(1):155-158.
- Berkley KJ, Rapkin AJ, Papka RE. The pains of endometriosis. Science. 2005;308(5728):1587-1589.
- Giamberardino MA, Tana C, Costantini R. Pain thresholds in women with chronic pelvic pain. Curr Opin Obstet Gynecol. 2014;26(4):253-259.
- Giamberardino MA, Berkley KJ, Affaitati G. Influence of endometriosis on pain behaviors and muscle hyperalgesia induced by a ureteral calculosis in female rats. Pain. 2002;95(3):247-257.
- As-Sanie S, Kim J, Schmidt-Wilcke T. Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain. J Pain. 2016;17(1):1-13.
Coding and reimbursement 101: How to maximize your payments
While reimbursement for ObGyn services seemingly should be a simple matter of putting codes on a claim form, the reality is that it is complex, and it requires a team approach to accomplish timely filing to receive fair and accurate reimbursement.
Reimbursement occurs over the length of the revenue cycle for a patient encounter and involves many steps. It starts when the patient makes an appointment for services and ends when the practice receives payment. Along the way, there must be good clinician documentation and sound knowledge about the billing process (including the Current Procedural Terminology [CPT] or Healthcare Common Procedure Coding System [HCPCS] codes for services), the International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes that establish medical necessity, the modifiers that alter the meaning of the codes, and, of course, the bundling issues that now accompany many coding situations.
In addition, ObGyn practices must contend with a multitude of payers—from federal to commercial—and must understand and adhere to each payer’s rules and policies to maximize and retain reimbursement.
In this article, I detail stumbling blocks to maximizing reimbursement and how to avoid them.
Coding considerations for office services
Good documentation before, during, and after a patient’s office visit is essential, along with accurate codes, modifiers, and order of services on the claims you submit.
Prep paperwork before the patient encounter
Once a patient makes an appointment, the front-end staff can handle some of the tasks in the cycle. This includes ensuring that the patient’s insurance coverage information is current, informing the patient of any additional information to bring at the time of the visit (such as a patient history form for a new patient visit or a list of current prescriptions), or, if an established patient will be having a procedure, making sure that prior authorization is complete. This streamlines the process, assists the clinician with documentation housekeeping, and ensures that incorrect or missing information does not cause a claim to be denied or not be filed in a timely manner (many payers require submission of an initial claim 30 days from the date of service).
Continue to: Document details of the clinician-patient interaction
Document details of the clinician-patient interaction
At the time of the encounter, you are responsible for documenting your contact with the patient in enough detail to support billing a CPT evaluation and management (E/M) code at the level selected and/or any procedures or other services performed. The TABLE provides an overview of the requirements for each level of office service.
If both an E/M and a procedure are performed on the same date of service, the E/M must be documented to show it was separate from the procedure and that the work was significantly more than would be required to accomplish the procedure. Documentation of the procedure should include the indication, steps performed, findings, the patient’s condition afterward, and instructions for aftercare or follow-up.
If you use an electronic health record for reporting, you may be the one responsible for selecting both the CPT code for services performed and an ICD-10-CM code(s) to establish the medical need for them. Select the most accurate CPT codes, and clearly link them to a supporting diagnosis for each service that will be billed. If more than one diagnosis is applicable, the first one linked to any given service should represent the most important justification, as not all payers will accept more than one diagnosis code on the claim per service billed.
If the billing staff is assigned the task of selecting the CPT and/or ICD-10-CM diagnostic codes based on your documentation, they should be well versed in the services, procedures, and diagnoses reported for their ObGyn practice.
The actual code selection may end up being a joint venture between the clinician and the staff to ensure that accurate information will be entered on the claim. Good and frequent clinician-staff communication on billing of services can transform average reimbursement into maximized reimbursement.
Be aware of bundles
Sometimes more than one service or procedure is listed on a claim on the same date of service. However, it is important to identify all potential bundles before billing to ensure correct payment. For instance, payers like to bundle an E/M service and a procedure, or you may be in the global period (defined below) of a surgery but need to report an unrelated service.
You and your staff must work together to ensure the claim is submitted with the correct modifiers; on the other hand, you may decide that a better method of coding is in order. Some payers, for example, will not reimburse both an insertion and a removal of an intrauterine device (IUD) on the same date of service. If that does happen, a modifier on the removal code might save the day, rather than billing 2 codes.
Continue to: Manage the modifiers
Manage the modifiers
Sometimes the code billed requires a modifier to ensure payment. Typical modifiers used in an ObGyn office setting include the following:
- 22, Increased procedural services (the clinician must assign a fee that is higher than the usual fee for the procedure and be able to document CPT equivalents to the work involved)
- 24, Unrelated E/M during the postoperative period (note that this modifier does not apply during the antepartum period for pregnancy)
- 25, Significant and separate E/M on the same date as another service or minor procedure
- 52, Reduced services (generally, the payer will expect an explanation of the reduced service and will determine payment accordingly)
- 57, Decision to perform major surgery the day of or the day before the surgery
- 59, Distinct procedural service (used when 2 procedures are bundled and a modifier is allowed). Note that payment reductions for multiple procedures will still apply.
- 79, Unrelated procedure during the postoperative period (usually paid at the full allowable).
Organize the order of services on the claim
For an outpatient claim that includes both an E/M service and procedures, the order of the services—not the order in which they were performed—may be important to obtaining maximum reimbursement. In general, payers will pay in full for a supported E/M service no matter where it appears on the claim, but they apply reductions only for multiple procedures.
For instance, if you insert levonorgestrel implants on the same date as you remove a large polyp from the cervix, you would want to report the code with the highest relative value unit (RVU) first. In this case, it would be 11981 (4.05 RVUs), 57500 (3.61 RVUs).
In the IUD case mentioned earlier (removal and insertion of IUDs on the same date), the order of the codes, assuming the payer reimburses for both, will be even more important since removal usually has a higher payment: 58301 (2.70 RUVs), 58300 (1.54 RVUs).
Coding considerations for surgical services
Surgical services performed in a hospital or ambulatory surgical center present another set of must-dos to ensure timely and fair reimbursement.
Grasp the ‘global package’ concept
Understanding this concept can be crucial to getting paid for additional services during this time period and correct billing for any E/M services performed prior to surgery. In general, the routine history and physical examination performed prior to a major surgery is considered included in the work and should not be billed separately. Surgical clearance for a patient’s condition, such as hypertension, a heart condition, or lung issues, can be billed separately, but these generally are performed by someone other than the operating surgeon.
Procedures performed in the hospital setting generally will have a 10- or 90-day global period. During this time, any related E/M service should not be billed separately, and the use of modifiers becomes even more important than with office services.
Applicable modifiers for use with hospital surgery can include all those for outpatient services plus:
- 50, Bilateral procedure (for which you may be paid up to 150% of the allowable)
- 58, Staged or related procedure during the postoperative period (this may be paid at the full allowable)
- 62, Co-surgeons (both surgeons bill the same CPT code and both document their involvement in the surgery). Medicare will reimburse each surgeon 62.5% of the allowable.
- 78, Return to the operating room for an unplanned related procedure (the full allowable may be reduced by some payers owing to their belief that this is soon after the original procedure so intraoperative time only is considered).
Be savvy about surgical bundles
Here, it is important to understand all published bundling edits for multiple procedures performed by the same surgeon at the same surgical session. If a code combination is never allowed but the surgery is more intense due to additional work required, a modifier -22 may be your only option. Again, clear, concise documentation of the additional work is imperative to receive the additional payment.
When a modifier is allowed, it generally will be one that denotes a procedure done on bilateral organs (such as the ovaries) when there is no extensive code to cover all of the work or when the additional procedure is “distinct” and meets the criteria for using a modifier 59.
Medicare has expanded the modifier -59 into additional modifiers to further explain the situation. These additional modifiers are:
- XE, A service that is distinct because it occurred during a separate encounter on the same date of service
- XS, A service that is distinct because it was performed on a separate organ/structure
- XP, A service that is distinct because it was performed by a different practitioner
- XU, The use of a service that is distinct because it does not overlap usual components of the main service.
Standards of care: Some steps are inherent to the surgery
Expect to receive claim denials if you bill separately for adhesiolysis during a surgical procedure. Every payer considers this procedure related to access to the surgical site and will deny separate coding. If the lysis was truly significant in terms of work, try reporting the modifier 22 and provide adequate documentation.
Other procedures at the time of surgery that generally are not paid for include 1) examination under anesthesia, 2) any procedure done to check the surgeon’s work (for example, cystoscopy, especially when done after urinary or pelvic reconstruction procedures, or chromotubation following extensive ovariolysis), 3) placement of catheters, and 4) placement of devices to alleviate postsurgical pain.
Bottom line
Maximizing reimbursement involves good documentation, correct CPT codes linked to specific and accurate medical indications, the use of appropriate modifiers, and listing codes in order of their relative values from highest to lowest.
Should a denial or unfair reduction in payment come your way, analyze the rejection to determine the cause and make billing and reporting changes as needed to improve your future reimbursements.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
While reimbursement for ObGyn services seemingly should be a simple matter of putting codes on a claim form, the reality is that it is complex, and it requires a team approach to accomplish timely filing to receive fair and accurate reimbursement.
Reimbursement occurs over the length of the revenue cycle for a patient encounter and involves many steps. It starts when the patient makes an appointment for services and ends when the practice receives payment. Along the way, there must be good clinician documentation and sound knowledge about the billing process (including the Current Procedural Terminology [CPT] or Healthcare Common Procedure Coding System [HCPCS] codes for services), the International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes that establish medical necessity, the modifiers that alter the meaning of the codes, and, of course, the bundling issues that now accompany many coding situations.
In addition, ObGyn practices must contend with a multitude of payers—from federal to commercial—and must understand and adhere to each payer’s rules and policies to maximize and retain reimbursement.
In this article, I detail stumbling blocks to maximizing reimbursement and how to avoid them.
Coding considerations for office services
Good documentation before, during, and after a patient’s office visit is essential, along with accurate codes, modifiers, and order of services on the claims you submit.
Prep paperwork before the patient encounter
Once a patient makes an appointment, the front-end staff can handle some of the tasks in the cycle. This includes ensuring that the patient’s insurance coverage information is current, informing the patient of any additional information to bring at the time of the visit (such as a patient history form for a new patient visit or a list of current prescriptions), or, if an established patient will be having a procedure, making sure that prior authorization is complete. This streamlines the process, assists the clinician with documentation housekeeping, and ensures that incorrect or missing information does not cause a claim to be denied or not be filed in a timely manner (many payers require submission of an initial claim 30 days from the date of service).
Continue to: Document details of the clinician-patient interaction
Document details of the clinician-patient interaction
At the time of the encounter, you are responsible for documenting your contact with the patient in enough detail to support billing a CPT evaluation and management (E/M) code at the level selected and/or any procedures or other services performed. The TABLE provides an overview of the requirements for each level of office service.
If both an E/M and a procedure are performed on the same date of service, the E/M must be documented to show it was separate from the procedure and that the work was significantly more than would be required to accomplish the procedure. Documentation of the procedure should include the indication, steps performed, findings, the patient’s condition afterward, and instructions for aftercare or follow-up.
If you use an electronic health record for reporting, you may be the one responsible for selecting both the CPT code for services performed and an ICD-10-CM code(s) to establish the medical need for them. Select the most accurate CPT codes, and clearly link them to a supporting diagnosis for each service that will be billed. If more than one diagnosis is applicable, the first one linked to any given service should represent the most important justification, as not all payers will accept more than one diagnosis code on the claim per service billed.
If the billing staff is assigned the task of selecting the CPT and/or ICD-10-CM diagnostic codes based on your documentation, they should be well versed in the services, procedures, and diagnoses reported for their ObGyn practice.
The actual code selection may end up being a joint venture between the clinician and the staff to ensure that accurate information will be entered on the claim. Good and frequent clinician-staff communication on billing of services can transform average reimbursement into maximized reimbursement.
Be aware of bundles
Sometimes more than one service or procedure is listed on a claim on the same date of service. However, it is important to identify all potential bundles before billing to ensure correct payment. For instance, payers like to bundle an E/M service and a procedure, or you may be in the global period (defined below) of a surgery but need to report an unrelated service.
You and your staff must work together to ensure the claim is submitted with the correct modifiers; on the other hand, you may decide that a better method of coding is in order. Some payers, for example, will not reimburse both an insertion and a removal of an intrauterine device (IUD) on the same date of service. If that does happen, a modifier on the removal code might save the day, rather than billing 2 codes.
Continue to: Manage the modifiers
Manage the modifiers
Sometimes the code billed requires a modifier to ensure payment. Typical modifiers used in an ObGyn office setting include the following:
- 22, Increased procedural services (the clinician must assign a fee that is higher than the usual fee for the procedure and be able to document CPT equivalents to the work involved)
- 24, Unrelated E/M during the postoperative period (note that this modifier does not apply during the antepartum period for pregnancy)
- 25, Significant and separate E/M on the same date as another service or minor procedure
- 52, Reduced services (generally, the payer will expect an explanation of the reduced service and will determine payment accordingly)
- 57, Decision to perform major surgery the day of or the day before the surgery
- 59, Distinct procedural service (used when 2 procedures are bundled and a modifier is allowed). Note that payment reductions for multiple procedures will still apply.
- 79, Unrelated procedure during the postoperative period (usually paid at the full allowable).
Organize the order of services on the claim
For an outpatient claim that includes both an E/M service and procedures, the order of the services—not the order in which they were performed—may be important to obtaining maximum reimbursement. In general, payers will pay in full for a supported E/M service no matter where it appears on the claim, but they apply reductions only for multiple procedures.
For instance, if you insert levonorgestrel implants on the same date as you remove a large polyp from the cervix, you would want to report the code with the highest relative value unit (RVU) first. In this case, it would be 11981 (4.05 RVUs), 57500 (3.61 RVUs).
In the IUD case mentioned earlier (removal and insertion of IUDs on the same date), the order of the codes, assuming the payer reimburses for both, will be even more important since removal usually has a higher payment: 58301 (2.70 RUVs), 58300 (1.54 RVUs).
Coding considerations for surgical services
Surgical services performed in a hospital or ambulatory surgical center present another set of must-dos to ensure timely and fair reimbursement.
Grasp the ‘global package’ concept
Understanding this concept can be crucial to getting paid for additional services during this time period and correct billing for any E/M services performed prior to surgery. In general, the routine history and physical examination performed prior to a major surgery is considered included in the work and should not be billed separately. Surgical clearance for a patient’s condition, such as hypertension, a heart condition, or lung issues, can be billed separately, but these generally are performed by someone other than the operating surgeon.
Procedures performed in the hospital setting generally will have a 10- or 90-day global period. During this time, any related E/M service should not be billed separately, and the use of modifiers becomes even more important than with office services.
Applicable modifiers for use with hospital surgery can include all those for outpatient services plus:
- 50, Bilateral procedure (for which you may be paid up to 150% of the allowable)
- 58, Staged or related procedure during the postoperative period (this may be paid at the full allowable)
- 62, Co-surgeons (both surgeons bill the same CPT code and both document their involvement in the surgery). Medicare will reimburse each surgeon 62.5% of the allowable.
- 78, Return to the operating room for an unplanned related procedure (the full allowable may be reduced by some payers owing to their belief that this is soon after the original procedure so intraoperative time only is considered).
Be savvy about surgical bundles
Here, it is important to understand all published bundling edits for multiple procedures performed by the same surgeon at the same surgical session. If a code combination is never allowed but the surgery is more intense due to additional work required, a modifier -22 may be your only option. Again, clear, concise documentation of the additional work is imperative to receive the additional payment.
When a modifier is allowed, it generally will be one that denotes a procedure done on bilateral organs (such as the ovaries) when there is no extensive code to cover all of the work or when the additional procedure is “distinct” and meets the criteria for using a modifier 59.
Medicare has expanded the modifier -59 into additional modifiers to further explain the situation. These additional modifiers are:
- XE, A service that is distinct because it occurred during a separate encounter on the same date of service
- XS, A service that is distinct because it was performed on a separate organ/structure
- XP, A service that is distinct because it was performed by a different practitioner
- XU, The use of a service that is distinct because it does not overlap usual components of the main service.
Standards of care: Some steps are inherent to the surgery
Expect to receive claim denials if you bill separately for adhesiolysis during a surgical procedure. Every payer considers this procedure related to access to the surgical site and will deny separate coding. If the lysis was truly significant in terms of work, try reporting the modifier 22 and provide adequate documentation.
Other procedures at the time of surgery that generally are not paid for include 1) examination under anesthesia, 2) any procedure done to check the surgeon’s work (for example, cystoscopy, especially when done after urinary or pelvic reconstruction procedures, or chromotubation following extensive ovariolysis), 3) placement of catheters, and 4) placement of devices to alleviate postsurgical pain.
Bottom line
Maximizing reimbursement involves good documentation, correct CPT codes linked to specific and accurate medical indications, the use of appropriate modifiers, and listing codes in order of their relative values from highest to lowest.
Should a denial or unfair reduction in payment come your way, analyze the rejection to determine the cause and make billing and reporting changes as needed to improve your future reimbursements.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
While reimbursement for ObGyn services seemingly should be a simple matter of putting codes on a claim form, the reality is that it is complex, and it requires a team approach to accomplish timely filing to receive fair and accurate reimbursement.
Reimbursement occurs over the length of the revenue cycle for a patient encounter and involves many steps. It starts when the patient makes an appointment for services and ends when the practice receives payment. Along the way, there must be good clinician documentation and sound knowledge about the billing process (including the Current Procedural Terminology [CPT] or Healthcare Common Procedure Coding System [HCPCS] codes for services), the International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes that establish medical necessity, the modifiers that alter the meaning of the codes, and, of course, the bundling issues that now accompany many coding situations.
In addition, ObGyn practices must contend with a multitude of payers—from federal to commercial—and must understand and adhere to each payer’s rules and policies to maximize and retain reimbursement.
In this article, I detail stumbling blocks to maximizing reimbursement and how to avoid them.
Coding considerations for office services
Good documentation before, during, and after a patient’s office visit is essential, along with accurate codes, modifiers, and order of services on the claims you submit.
Prep paperwork before the patient encounter
Once a patient makes an appointment, the front-end staff can handle some of the tasks in the cycle. This includes ensuring that the patient’s insurance coverage information is current, informing the patient of any additional information to bring at the time of the visit (such as a patient history form for a new patient visit or a list of current prescriptions), or, if an established patient will be having a procedure, making sure that prior authorization is complete. This streamlines the process, assists the clinician with documentation housekeeping, and ensures that incorrect or missing information does not cause a claim to be denied or not be filed in a timely manner (many payers require submission of an initial claim 30 days from the date of service).
Continue to: Document details of the clinician-patient interaction
Document details of the clinician-patient interaction
At the time of the encounter, you are responsible for documenting your contact with the patient in enough detail to support billing a CPT evaluation and management (E/M) code at the level selected and/or any procedures or other services performed. The TABLE provides an overview of the requirements for each level of office service.
If both an E/M and a procedure are performed on the same date of service, the E/M must be documented to show it was separate from the procedure and that the work was significantly more than would be required to accomplish the procedure. Documentation of the procedure should include the indication, steps performed, findings, the patient’s condition afterward, and instructions for aftercare or follow-up.
If you use an electronic health record for reporting, you may be the one responsible for selecting both the CPT code for services performed and an ICD-10-CM code(s) to establish the medical need for them. Select the most accurate CPT codes, and clearly link them to a supporting diagnosis for each service that will be billed. If more than one diagnosis is applicable, the first one linked to any given service should represent the most important justification, as not all payers will accept more than one diagnosis code on the claim per service billed.
If the billing staff is assigned the task of selecting the CPT and/or ICD-10-CM diagnostic codes based on your documentation, they should be well versed in the services, procedures, and diagnoses reported for their ObGyn practice.
The actual code selection may end up being a joint venture between the clinician and the staff to ensure that accurate information will be entered on the claim. Good and frequent clinician-staff communication on billing of services can transform average reimbursement into maximized reimbursement.
Be aware of bundles
Sometimes more than one service or procedure is listed on a claim on the same date of service. However, it is important to identify all potential bundles before billing to ensure correct payment. For instance, payers like to bundle an E/M service and a procedure, or you may be in the global period (defined below) of a surgery but need to report an unrelated service.
You and your staff must work together to ensure the claim is submitted with the correct modifiers; on the other hand, you may decide that a better method of coding is in order. Some payers, for example, will not reimburse both an insertion and a removal of an intrauterine device (IUD) on the same date of service. If that does happen, a modifier on the removal code might save the day, rather than billing 2 codes.
Continue to: Manage the modifiers
Manage the modifiers
Sometimes the code billed requires a modifier to ensure payment. Typical modifiers used in an ObGyn office setting include the following:
- 22, Increased procedural services (the clinician must assign a fee that is higher than the usual fee for the procedure and be able to document CPT equivalents to the work involved)
- 24, Unrelated E/M during the postoperative period (note that this modifier does not apply during the antepartum period for pregnancy)
- 25, Significant and separate E/M on the same date as another service or minor procedure
- 52, Reduced services (generally, the payer will expect an explanation of the reduced service and will determine payment accordingly)
- 57, Decision to perform major surgery the day of or the day before the surgery
- 59, Distinct procedural service (used when 2 procedures are bundled and a modifier is allowed). Note that payment reductions for multiple procedures will still apply.
- 79, Unrelated procedure during the postoperative period (usually paid at the full allowable).
Organize the order of services on the claim
For an outpatient claim that includes both an E/M service and procedures, the order of the services—not the order in which they were performed—may be important to obtaining maximum reimbursement. In general, payers will pay in full for a supported E/M service no matter where it appears on the claim, but they apply reductions only for multiple procedures.
For instance, if you insert levonorgestrel implants on the same date as you remove a large polyp from the cervix, you would want to report the code with the highest relative value unit (RVU) first. In this case, it would be 11981 (4.05 RVUs), 57500 (3.61 RVUs).
In the IUD case mentioned earlier (removal and insertion of IUDs on the same date), the order of the codes, assuming the payer reimburses for both, will be even more important since removal usually has a higher payment: 58301 (2.70 RUVs), 58300 (1.54 RVUs).
Coding considerations for surgical services
Surgical services performed in a hospital or ambulatory surgical center present another set of must-dos to ensure timely and fair reimbursement.
Grasp the ‘global package’ concept
Understanding this concept can be crucial to getting paid for additional services during this time period and correct billing for any E/M services performed prior to surgery. In general, the routine history and physical examination performed prior to a major surgery is considered included in the work and should not be billed separately. Surgical clearance for a patient’s condition, such as hypertension, a heart condition, or lung issues, can be billed separately, but these generally are performed by someone other than the operating surgeon.
Procedures performed in the hospital setting generally will have a 10- or 90-day global period. During this time, any related E/M service should not be billed separately, and the use of modifiers becomes even more important than with office services.
Applicable modifiers for use with hospital surgery can include all those for outpatient services plus:
- 50, Bilateral procedure (for which you may be paid up to 150% of the allowable)
- 58, Staged or related procedure during the postoperative period (this may be paid at the full allowable)
- 62, Co-surgeons (both surgeons bill the same CPT code and both document their involvement in the surgery). Medicare will reimburse each surgeon 62.5% of the allowable.
- 78, Return to the operating room for an unplanned related procedure (the full allowable may be reduced by some payers owing to their belief that this is soon after the original procedure so intraoperative time only is considered).
Be savvy about surgical bundles
Here, it is important to understand all published bundling edits for multiple procedures performed by the same surgeon at the same surgical session. If a code combination is never allowed but the surgery is more intense due to additional work required, a modifier -22 may be your only option. Again, clear, concise documentation of the additional work is imperative to receive the additional payment.
When a modifier is allowed, it generally will be one that denotes a procedure done on bilateral organs (such as the ovaries) when there is no extensive code to cover all of the work or when the additional procedure is “distinct” and meets the criteria for using a modifier 59.
Medicare has expanded the modifier -59 into additional modifiers to further explain the situation. These additional modifiers are:
- XE, A service that is distinct because it occurred during a separate encounter on the same date of service
- XS, A service that is distinct because it was performed on a separate organ/structure
- XP, A service that is distinct because it was performed by a different practitioner
- XU, The use of a service that is distinct because it does not overlap usual components of the main service.
Standards of care: Some steps are inherent to the surgery
Expect to receive claim denials if you bill separately for adhesiolysis during a surgical procedure. Every payer considers this procedure related to access to the surgical site and will deny separate coding. If the lysis was truly significant in terms of work, try reporting the modifier 22 and provide adequate documentation.
Other procedures at the time of surgery that generally are not paid for include 1) examination under anesthesia, 2) any procedure done to check the surgeon’s work (for example, cystoscopy, especially when done after urinary or pelvic reconstruction procedures, or chromotubation following extensive ovariolysis), 3) placement of catheters, and 4) placement of devices to alleviate postsurgical pain.
Bottom line
Maximizing reimbursement involves good documentation, correct CPT codes linked to specific and accurate medical indications, the use of appropriate modifiers, and listing codes in order of their relative values from highest to lowest.
Should a denial or unfair reduction in payment come your way, analyze the rejection to determine the cause and make billing and reporting changes as needed to improve your future reimbursements.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Does low-dose aspirin decrease a woman’s risk of ovarian cancer?
EXPERT COMMENTARY
Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.
Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.2-6
_
Details of the study
This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.
Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).
The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.
Study strengths and weaknesses
This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.
However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.
In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.
Based on these current data, there is insufficient evidence to suggest the use of low-dose aspirin for chemoprophylaxis of ovarian cancer. In order to suggest the use of a drug for prophylaxis the benefits must outweigh the risks, and in the case of NSAIDs, this has yet to be confirmed.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Poole EM, Lee IM, Ridker PM, et al. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol. 2013;178:1256-1264.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.
- Peres LC, Camacho F, Abbott SE, et al. Analgesic medication use and risk of epithelial ovarian cancer in African American women. Br J Cancer. 2016;114(7):819-825.
- Murphy MA, Trabert B, Yang HP, et al. Non-steroidal antiinflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control. 2012;23:1839-1852.
- Brasky TM, Liu J, White E, et al. Non-steroidal antiinflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer. 2014;135:1869-1883.
- Lacey JV Jr, Sherman ME, Hartge P, et al. Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer. 2004;108:281-286.
EXPERT COMMENTARY
Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.
Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.2-6
_
Details of the study
This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.
Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).
The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.
Study strengths and weaknesses
This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.
However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.
In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.
Based on these current data, there is insufficient evidence to suggest the use of low-dose aspirin for chemoprophylaxis of ovarian cancer. In order to suggest the use of a drug for prophylaxis the benefits must outweigh the risks, and in the case of NSAIDs, this has yet to be confirmed.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
EXPERT COMMENTARY
Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.
Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.2-6
_
Details of the study
This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.
Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).
The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.
Study strengths and weaknesses
This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.
However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.
In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.
Based on these current data, there is insufficient evidence to suggest the use of low-dose aspirin for chemoprophylaxis of ovarian cancer. In order to suggest the use of a drug for prophylaxis the benefits must outweigh the risks, and in the case of NSAIDs, this has yet to be confirmed.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Poole EM, Lee IM, Ridker PM, et al. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol. 2013;178:1256-1264.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.
- Peres LC, Camacho F, Abbott SE, et al. Analgesic medication use and risk of epithelial ovarian cancer in African American women. Br J Cancer. 2016;114(7):819-825.
- Murphy MA, Trabert B, Yang HP, et al. Non-steroidal antiinflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control. 2012;23:1839-1852.
- Brasky TM, Liu J, White E, et al. Non-steroidal antiinflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer. 2014;135:1869-1883.
- Lacey JV Jr, Sherman ME, Hartge P, et al. Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer. 2004;108:281-286.
- Poole EM, Lee IM, Ridker PM, et al. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol. 2013;178:1256-1264.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.
- Peres LC, Camacho F, Abbott SE, et al. Analgesic medication use and risk of epithelial ovarian cancer in African American women. Br J Cancer. 2016;114(7):819-825.
- Murphy MA, Trabert B, Yang HP, et al. Non-steroidal antiinflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control. 2012;23:1839-1852.
- Brasky TM, Liu J, White E, et al. Non-steroidal antiinflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer. 2014;135:1869-1883.
- Lacey JV Jr, Sherman ME, Hartge P, et al. Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer. 2004;108:281-286.
2018 Update on bone health
As ObGyns, we are the first-line health care providers for our menopausal patients in terms of identifying, preventing, and initiating treatment for women at risk for fragility fractures. Osteoporosis is probably the most important risk factor for bone health, although sarcopenia, frailty, poor eyesight, and falls also play a significant role in bone health and fragility fracture.
In 2005, more than 2 million incident fractures were reported in the United States, with a total cost of $17 billion.1 By 2025, annual fractures and costs are expected to rise by almost 50%. People who are 65 to 74 years of age will likely experience the largest increase in fracture—greater than 87%.1
Findings from the Women’s Health Initiative study showed that the number of women who had a clinical fracture in 1 year exceeded all the cases of myocardial infarction, stroke, and breast cancer combined.2 Furthermore, the morbidity and mortality rates for fractures are staggering. Thirty percent of women with a hip fracture will be dead within 1 year.3 So, although many patients fear developing breast cancer, and cardiovascular disease remains the number 1 cause of death, the impact of maintaining and protecting bone health cannot be emphasized enough.
_
WHI incidental findings: Hormone-treated menopausal women had decreased hip fracture rate
Manson JE, Aragaki AK, Rossouw JE, et al; WHI Investigators. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials. JAMA. 2017;318:927-938.
Manson and colleagues examined the total and cause-specific cumulative mortality of the 2 Women’s Health Initiative (WHI) hormone therapy trials. This was an observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years (mean age at baseline, 63.4 years) enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. A total of 27,347 women were randomly assigned to treatment.
Treatment groups
Depending on the presence or absence of a uterus, women received conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8,506) or placebo (n = 8,102) for a median of 5.6 years or CEE alone (n = 5,310) versus placebo (n = 5,429) for a median of 7.2 years. All-cause mortality (the primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) were analyzed in the 2 trials pooled and in each trial individually.
All-cause and cause-specific mortality findings
Mortality follow-up was available for more than 98% of participants. During the cumulative 18-year follow-up, 7,489 deaths occurred. In the overall pooled cohort, all-cause mortality in the hormone therapy group was 27.1% compared with 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.94–1.03]). In the CEE plus MPA group, the HR was 1.02 (95% CI, 0.96–1.08). For those in the CEE-alone group, the HR was 0.94 (95% CI, 0.88–1.01).
In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92–1.08 [8.9% with hormone therapy vs 9.0% with placebo]). For total cancer mortality, the HR was 1.03 (95% CI, 0.95–1.12 [8.2% with hormone therapy vs 8.0% with placebo]). For other causes, the HR was 0.95 (95% CI, 0.88–1.02 [10.0% with hormone therapy vs 10.7% with placebo]). Results did not differ significantly between trials.
Key takeaway
The study authors concluded that among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.
Postmenopausal hormone therapy is arguably the most effective “bone drug” available. While all other antiresorptive agents show hip fracture efficacy only in subgroup analyses of the highest-risk patients (women with established osteoporosis, who often already have pre-existing vertebral fractures), the hormone-treated women in the WHI—who were not chosen for having low bone mass (in fact, dual-energy x-ray absorptiometry [DXA] scores were not even recorded)—still had a statistically significant decrease in hip fracture as an adverse event when compared with placebo-treated women. Increasing data on the long-term safety of hormone therapy in menopausal patients will perhaps encourage its greater use from a bone health perspective.
Continue to: Appropriate to defer DXA testing to age 65...
Appropriate to defer DXA testing to age 65 when baseline FRAX score is below treatment level
Gourlay ML, Overman RA, Fine JP, et al; Women’s Health Initiative Investigators. Time to clinically relevant fracture risk scores in postmenopausal women. Am J Med. 2017;130:862.e15-862.e23.
Gourlay ML, Fine JP, Preisser JS, et al; Study of Osteoporotic Fractures Research Group. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225-233.
Many clinicians used to (and still do) order bone mineral density (BMD) testing at 23-month intervals because that was what insurance would allow. Gourlay and colleagues previously published a study on BMD testing intervals and the time it takes to develop osteoporosis. I covered that information in previous Updates.4,5
To recap, Gourlay and colleagues studied 4,957 women, 67 years of age or older, with normal BMD or osteopenia and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis; the women were followed prospectively for up to 15 years. The estimated time for 10% of women to make the transition to osteoporosis was 16.8 years for those with normal BMD, 4.7 years for those with moderate osteopenia, and 1.1 years for women with advanced osteopenia.
Today, FRAX is recommended to assess need for treatment
Older treatment recommendations involved determining various osteopenic BMD levels and the presence or absence of certain risk factors. More recently, the National Osteoporosis Foundation and many medical societies, including the American College of Obstetricians and Gynecologists, have recommended using the FRAX fracture prediction algorithm (available at https://www.sheffield.ac.uk/FRAX/) instead of T-scores to consider initiating pharmacotherapy.
The FRAX calculation tool uses information such as the country where the patient lives, age, sex, height, weight, history of previous fracture, parental fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, alcohol use of 3 or more units per day, and, if available, BMD determination at the femoral neck. It then yields the 10-year absolute risk of hip fracture and any major osteoporotic fracture for that individual or, more precisely, for an individual like that.
In the United States, accepted levels for cost-effective pharmacotherapy are a 10-year absolute risk of hip fracture of 3% or major osteoporotic fracture of 20%.
Continue to: Age also is a key factor in fracture risk assessment
Age also is a key factor in fracture risk assessment
Gourlay and colleagues more recently conducted a retrospective analysis of new occurrence of treatment-level fracture risk scores in postmenopausal women (50 years of age and older) before they received pharmacologic treatment and before they experienced a first hip or clinical vertebral fracture.
In 54,280 postmenopausal women aged 50 to 64 without a BMD test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of the rarity of treatment-level scores. In 6,096 women who had FRAX scores calculated with their BMD score, the estimated time to treatment-level FRAX was 7.6 years for those 65 to 69 and 5.1 years for 75 to 79 year olds. Furthermore, of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, only 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65.
The investigators concluded that, “Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.”
Many health care providers begin BMD testing early in menopause. Bone mass results may motivate patients to initiate healthy lifestyle choices, such as adequate dietary calcium, vitamin D supplementation, exercise, moderate alcohol use, smoking cessation, and fall prevention strategies. However, providers and their patients should be aware that if the fracture risk is beneath the threshold score at baseline, the risk of experiencing an osteoporotic fracture prior to age 65 is extremely low, and this should be taken into account before prescribing pharmacotherapy. Furthermore, as stated, FRAX can be performed without a DXA score. When the result is beneath a treatment level in a woman under 65, DXA testing may be deferred until age 65.
Continue to: USPSTF offers updated recommendations for osteoporosis screening
USPSTF offers updated recommendations for osteoporosis screening
US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:2521-2531.
The 2018 updated osteoporosis screening recommendations from the United States Preventative Services Task Force (USPSTF) may seem contradictory to the conclusions of Gourlay and colleagues discussed above. They are not.
The USPSTF authors point out that by 2020, about 12.3 million US individuals older than 50 years are expected to have osteoporosis. Osteoporotic fractures (especially hip fractures) are associated with limitations in ambulation, chronic pain and disability, loss of independence, and decreased quality of life. In fact, 21% to 30% of people who sustain a hip fracture die within 1 year. As the US population continues to age, the potential preventable burden will likely increase.
_
Evidence on bone measurement tests, risk assessment tools, and drug therapy efficacy
The USPSTF conducted an evidence review on screening for and treatment of osteoporotic fractures in women as well as risk assessment tools. The task force found the evidence convincing that bone measurement tests are accurate for detecting osteoporosis and predicting osteoporotic fractures. In addition, there is adequate evidence that clinical risk assessment tools are moderately accurate in identifying risk of osteoporosis and osteoporotic fractures. Furthermore, there is convincing evidence that drug therapies reduce subsequent fracture rates in postmenopausal women.
The USPSTF recommends the following:
- For women aged 65 and older, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.
- For women younger than 65 who are at increased risk for osteoporosis based on formal clinical risk assessment tools, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.
We all agree that women older than 65 years of age should be screened with DXA measurements of bone mass. The USPSTF says that in women under 65, a fracture assessment tool like FRAX, which does not require bone density testing to yield an individual’s absolute 10-year fracture risk, should be used to determine if bone mass measurement by DXA is, in fact, warranted. This recommendation is further supported by the article by Gourlay and colleagues, in which women aged 50 to 64 with subthreshold FRAX scores had a very low risk of fracture prior to age 65.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22:465-475.
- Cauley JA, Wampler NS, Barnhart JM, et al; Women’s Health Initiative Observational Study. Incidence of fractures compared to cardiovascular disease and breast cancer: the Women’s Health Initiative Observational Study. Osteoporos Int. 2008;19:1717-1723.
- Brauer CA, Coca-Perraillon M, Cutler DM, et al. Incidence and mortality of hip fractures in the United States. JAMA. 2009;302:1573-1579.
- Goldstein SR. Update on osteoporosis. OBG Manag. 2012;24:16-21.
- Goldstein SR. 2017 update on bone health. OBG Manag. 2017;29-32, 48.
As ObGyns, we are the first-line health care providers for our menopausal patients in terms of identifying, preventing, and initiating treatment for women at risk for fragility fractures. Osteoporosis is probably the most important risk factor for bone health, although sarcopenia, frailty, poor eyesight, and falls also play a significant role in bone health and fragility fracture.
In 2005, more than 2 million incident fractures were reported in the United States, with a total cost of $17 billion.1 By 2025, annual fractures and costs are expected to rise by almost 50%. People who are 65 to 74 years of age will likely experience the largest increase in fracture—greater than 87%.1
Findings from the Women’s Health Initiative study showed that the number of women who had a clinical fracture in 1 year exceeded all the cases of myocardial infarction, stroke, and breast cancer combined.2 Furthermore, the morbidity and mortality rates for fractures are staggering. Thirty percent of women with a hip fracture will be dead within 1 year.3 So, although many patients fear developing breast cancer, and cardiovascular disease remains the number 1 cause of death, the impact of maintaining and protecting bone health cannot be emphasized enough.
_
WHI incidental findings: Hormone-treated menopausal women had decreased hip fracture rate
Manson JE, Aragaki AK, Rossouw JE, et al; WHI Investigators. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials. JAMA. 2017;318:927-938.
Manson and colleagues examined the total and cause-specific cumulative mortality of the 2 Women’s Health Initiative (WHI) hormone therapy trials. This was an observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years (mean age at baseline, 63.4 years) enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. A total of 27,347 women were randomly assigned to treatment.
Treatment groups
Depending on the presence or absence of a uterus, women received conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8,506) or placebo (n = 8,102) for a median of 5.6 years or CEE alone (n = 5,310) versus placebo (n = 5,429) for a median of 7.2 years. All-cause mortality (the primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) were analyzed in the 2 trials pooled and in each trial individually.
All-cause and cause-specific mortality findings
Mortality follow-up was available for more than 98% of participants. During the cumulative 18-year follow-up, 7,489 deaths occurred. In the overall pooled cohort, all-cause mortality in the hormone therapy group was 27.1% compared with 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.94–1.03]). In the CEE plus MPA group, the HR was 1.02 (95% CI, 0.96–1.08). For those in the CEE-alone group, the HR was 0.94 (95% CI, 0.88–1.01).
In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92–1.08 [8.9% with hormone therapy vs 9.0% with placebo]). For total cancer mortality, the HR was 1.03 (95% CI, 0.95–1.12 [8.2% with hormone therapy vs 8.0% with placebo]). For other causes, the HR was 0.95 (95% CI, 0.88–1.02 [10.0% with hormone therapy vs 10.7% with placebo]). Results did not differ significantly between trials.
Key takeaway
The study authors concluded that among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.
Postmenopausal hormone therapy is arguably the most effective “bone drug” available. While all other antiresorptive agents show hip fracture efficacy only in subgroup analyses of the highest-risk patients (women with established osteoporosis, who often already have pre-existing vertebral fractures), the hormone-treated women in the WHI—who were not chosen for having low bone mass (in fact, dual-energy x-ray absorptiometry [DXA] scores were not even recorded)—still had a statistically significant decrease in hip fracture as an adverse event when compared with placebo-treated women. Increasing data on the long-term safety of hormone therapy in menopausal patients will perhaps encourage its greater use from a bone health perspective.
Continue to: Appropriate to defer DXA testing to age 65...
Appropriate to defer DXA testing to age 65 when baseline FRAX score is below treatment level
Gourlay ML, Overman RA, Fine JP, et al; Women’s Health Initiative Investigators. Time to clinically relevant fracture risk scores in postmenopausal women. Am J Med. 2017;130:862.e15-862.e23.
Gourlay ML, Fine JP, Preisser JS, et al; Study of Osteoporotic Fractures Research Group. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225-233.
Many clinicians used to (and still do) order bone mineral density (BMD) testing at 23-month intervals because that was what insurance would allow. Gourlay and colleagues previously published a study on BMD testing intervals and the time it takes to develop osteoporosis. I covered that information in previous Updates.4,5
To recap, Gourlay and colleagues studied 4,957 women, 67 years of age or older, with normal BMD or osteopenia and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis; the women were followed prospectively for up to 15 years. The estimated time for 10% of women to make the transition to osteoporosis was 16.8 years for those with normal BMD, 4.7 years for those with moderate osteopenia, and 1.1 years for women with advanced osteopenia.
Today, FRAX is recommended to assess need for treatment
Older treatment recommendations involved determining various osteopenic BMD levels and the presence or absence of certain risk factors. More recently, the National Osteoporosis Foundation and many medical societies, including the American College of Obstetricians and Gynecologists, have recommended using the FRAX fracture prediction algorithm (available at https://www.sheffield.ac.uk/FRAX/) instead of T-scores to consider initiating pharmacotherapy.
The FRAX calculation tool uses information such as the country where the patient lives, age, sex, height, weight, history of previous fracture, parental fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, alcohol use of 3 or more units per day, and, if available, BMD determination at the femoral neck. It then yields the 10-year absolute risk of hip fracture and any major osteoporotic fracture for that individual or, more precisely, for an individual like that.
In the United States, accepted levels for cost-effective pharmacotherapy are a 10-year absolute risk of hip fracture of 3% or major osteoporotic fracture of 20%.
Continue to: Age also is a key factor in fracture risk assessment
Age also is a key factor in fracture risk assessment
Gourlay and colleagues more recently conducted a retrospective analysis of new occurrence of treatment-level fracture risk scores in postmenopausal women (50 years of age and older) before they received pharmacologic treatment and before they experienced a first hip or clinical vertebral fracture.
In 54,280 postmenopausal women aged 50 to 64 without a BMD test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of the rarity of treatment-level scores. In 6,096 women who had FRAX scores calculated with their BMD score, the estimated time to treatment-level FRAX was 7.6 years for those 65 to 69 and 5.1 years for 75 to 79 year olds. Furthermore, of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, only 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65.
The investigators concluded that, “Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.”
Many health care providers begin BMD testing early in menopause. Bone mass results may motivate patients to initiate healthy lifestyle choices, such as adequate dietary calcium, vitamin D supplementation, exercise, moderate alcohol use, smoking cessation, and fall prevention strategies. However, providers and their patients should be aware that if the fracture risk is beneath the threshold score at baseline, the risk of experiencing an osteoporotic fracture prior to age 65 is extremely low, and this should be taken into account before prescribing pharmacotherapy. Furthermore, as stated, FRAX can be performed without a DXA score. When the result is beneath a treatment level in a woman under 65, DXA testing may be deferred until age 65.
Continue to: USPSTF offers updated recommendations for osteoporosis screening
USPSTF offers updated recommendations for osteoporosis screening
US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:2521-2531.
The 2018 updated osteoporosis screening recommendations from the United States Preventative Services Task Force (USPSTF) may seem contradictory to the conclusions of Gourlay and colleagues discussed above. They are not.
The USPSTF authors point out that by 2020, about 12.3 million US individuals older than 50 years are expected to have osteoporosis. Osteoporotic fractures (especially hip fractures) are associated with limitations in ambulation, chronic pain and disability, loss of independence, and decreased quality of life. In fact, 21% to 30% of people who sustain a hip fracture die within 1 year. As the US population continues to age, the potential preventable burden will likely increase.
_
Evidence on bone measurement tests, risk assessment tools, and drug therapy efficacy
The USPSTF conducted an evidence review on screening for and treatment of osteoporotic fractures in women as well as risk assessment tools. The task force found the evidence convincing that bone measurement tests are accurate for detecting osteoporosis and predicting osteoporotic fractures. In addition, there is adequate evidence that clinical risk assessment tools are moderately accurate in identifying risk of osteoporosis and osteoporotic fractures. Furthermore, there is convincing evidence that drug therapies reduce subsequent fracture rates in postmenopausal women.
The USPSTF recommends the following:
- For women aged 65 and older, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.
- For women younger than 65 who are at increased risk for osteoporosis based on formal clinical risk assessment tools, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.
We all agree that women older than 65 years of age should be screened with DXA measurements of bone mass. The USPSTF says that in women under 65, a fracture assessment tool like FRAX, which does not require bone density testing to yield an individual’s absolute 10-year fracture risk, should be used to determine if bone mass measurement by DXA is, in fact, warranted. This recommendation is further supported by the article by Gourlay and colleagues, in which women aged 50 to 64 with subthreshold FRAX scores had a very low risk of fracture prior to age 65.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
As ObGyns, we are the first-line health care providers for our menopausal patients in terms of identifying, preventing, and initiating treatment for women at risk for fragility fractures. Osteoporosis is probably the most important risk factor for bone health, although sarcopenia, frailty, poor eyesight, and falls also play a significant role in bone health and fragility fracture.
In 2005, more than 2 million incident fractures were reported in the United States, with a total cost of $17 billion.1 By 2025, annual fractures and costs are expected to rise by almost 50%. People who are 65 to 74 years of age will likely experience the largest increase in fracture—greater than 87%.1
Findings from the Women’s Health Initiative study showed that the number of women who had a clinical fracture in 1 year exceeded all the cases of myocardial infarction, stroke, and breast cancer combined.2 Furthermore, the morbidity and mortality rates for fractures are staggering. Thirty percent of women with a hip fracture will be dead within 1 year.3 So, although many patients fear developing breast cancer, and cardiovascular disease remains the number 1 cause of death, the impact of maintaining and protecting bone health cannot be emphasized enough.
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WHI incidental findings: Hormone-treated menopausal women had decreased hip fracture rate
Manson JE, Aragaki AK, Rossouw JE, et al; WHI Investigators. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials. JAMA. 2017;318:927-938.
Manson and colleagues examined the total and cause-specific cumulative mortality of the 2 Women’s Health Initiative (WHI) hormone therapy trials. This was an observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years (mean age at baseline, 63.4 years) enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. A total of 27,347 women were randomly assigned to treatment.
Treatment groups
Depending on the presence or absence of a uterus, women received conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8,506) or placebo (n = 8,102) for a median of 5.6 years or CEE alone (n = 5,310) versus placebo (n = 5,429) for a median of 7.2 years. All-cause mortality (the primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) were analyzed in the 2 trials pooled and in each trial individually.
All-cause and cause-specific mortality findings
Mortality follow-up was available for more than 98% of participants. During the cumulative 18-year follow-up, 7,489 deaths occurred. In the overall pooled cohort, all-cause mortality in the hormone therapy group was 27.1% compared with 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.94–1.03]). In the CEE plus MPA group, the HR was 1.02 (95% CI, 0.96–1.08). For those in the CEE-alone group, the HR was 0.94 (95% CI, 0.88–1.01).
In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92–1.08 [8.9% with hormone therapy vs 9.0% with placebo]). For total cancer mortality, the HR was 1.03 (95% CI, 0.95–1.12 [8.2% with hormone therapy vs 8.0% with placebo]). For other causes, the HR was 0.95 (95% CI, 0.88–1.02 [10.0% with hormone therapy vs 10.7% with placebo]). Results did not differ significantly between trials.
Key takeaway
The study authors concluded that among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.
Postmenopausal hormone therapy is arguably the most effective “bone drug” available. While all other antiresorptive agents show hip fracture efficacy only in subgroup analyses of the highest-risk patients (women with established osteoporosis, who often already have pre-existing vertebral fractures), the hormone-treated women in the WHI—who were not chosen for having low bone mass (in fact, dual-energy x-ray absorptiometry [DXA] scores were not even recorded)—still had a statistically significant decrease in hip fracture as an adverse event when compared with placebo-treated women. Increasing data on the long-term safety of hormone therapy in menopausal patients will perhaps encourage its greater use from a bone health perspective.
Continue to: Appropriate to defer DXA testing to age 65...
Appropriate to defer DXA testing to age 65 when baseline FRAX score is below treatment level
Gourlay ML, Overman RA, Fine JP, et al; Women’s Health Initiative Investigators. Time to clinically relevant fracture risk scores in postmenopausal women. Am J Med. 2017;130:862.e15-862.e23.
Gourlay ML, Fine JP, Preisser JS, et al; Study of Osteoporotic Fractures Research Group. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225-233.
Many clinicians used to (and still do) order bone mineral density (BMD) testing at 23-month intervals because that was what insurance would allow. Gourlay and colleagues previously published a study on BMD testing intervals and the time it takes to develop osteoporosis. I covered that information in previous Updates.4,5
To recap, Gourlay and colleagues studied 4,957 women, 67 years of age or older, with normal BMD or osteopenia and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis; the women were followed prospectively for up to 15 years. The estimated time for 10% of women to make the transition to osteoporosis was 16.8 years for those with normal BMD, 4.7 years for those with moderate osteopenia, and 1.1 years for women with advanced osteopenia.
Today, FRAX is recommended to assess need for treatment
Older treatment recommendations involved determining various osteopenic BMD levels and the presence or absence of certain risk factors. More recently, the National Osteoporosis Foundation and many medical societies, including the American College of Obstetricians and Gynecologists, have recommended using the FRAX fracture prediction algorithm (available at https://www.sheffield.ac.uk/FRAX/) instead of T-scores to consider initiating pharmacotherapy.
The FRAX calculation tool uses information such as the country where the patient lives, age, sex, height, weight, history of previous fracture, parental fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, alcohol use of 3 or more units per day, and, if available, BMD determination at the femoral neck. It then yields the 10-year absolute risk of hip fracture and any major osteoporotic fracture for that individual or, more precisely, for an individual like that.
In the United States, accepted levels for cost-effective pharmacotherapy are a 10-year absolute risk of hip fracture of 3% or major osteoporotic fracture of 20%.
Continue to: Age also is a key factor in fracture risk assessment
Age also is a key factor in fracture risk assessment
Gourlay and colleagues more recently conducted a retrospective analysis of new occurrence of treatment-level fracture risk scores in postmenopausal women (50 years of age and older) before they received pharmacologic treatment and before they experienced a first hip or clinical vertebral fracture.
In 54,280 postmenopausal women aged 50 to 64 without a BMD test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of the rarity of treatment-level scores. In 6,096 women who had FRAX scores calculated with their BMD score, the estimated time to treatment-level FRAX was 7.6 years for those 65 to 69 and 5.1 years for 75 to 79 year olds. Furthermore, of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, only 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65.
The investigators concluded that, “Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.”
Many health care providers begin BMD testing early in menopause. Bone mass results may motivate patients to initiate healthy lifestyle choices, such as adequate dietary calcium, vitamin D supplementation, exercise, moderate alcohol use, smoking cessation, and fall prevention strategies. However, providers and their patients should be aware that if the fracture risk is beneath the threshold score at baseline, the risk of experiencing an osteoporotic fracture prior to age 65 is extremely low, and this should be taken into account before prescribing pharmacotherapy. Furthermore, as stated, FRAX can be performed without a DXA score. When the result is beneath a treatment level in a woman under 65, DXA testing may be deferred until age 65.
Continue to: USPSTF offers updated recommendations for osteoporosis screening
USPSTF offers updated recommendations for osteoporosis screening
US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:2521-2531.
The 2018 updated osteoporosis screening recommendations from the United States Preventative Services Task Force (USPSTF) may seem contradictory to the conclusions of Gourlay and colleagues discussed above. They are not.
The USPSTF authors point out that by 2020, about 12.3 million US individuals older than 50 years are expected to have osteoporosis. Osteoporotic fractures (especially hip fractures) are associated with limitations in ambulation, chronic pain and disability, loss of independence, and decreased quality of life. In fact, 21% to 30% of people who sustain a hip fracture die within 1 year. As the US population continues to age, the potential preventable burden will likely increase.
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Evidence on bone measurement tests, risk assessment tools, and drug therapy efficacy
The USPSTF conducted an evidence review on screening for and treatment of osteoporotic fractures in women as well as risk assessment tools. The task force found the evidence convincing that bone measurement tests are accurate for detecting osteoporosis and predicting osteoporotic fractures. In addition, there is adequate evidence that clinical risk assessment tools are moderately accurate in identifying risk of osteoporosis and osteoporotic fractures. Furthermore, there is convincing evidence that drug therapies reduce subsequent fracture rates in postmenopausal women.
The USPSTF recommends the following:
- For women aged 65 and older, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.
- For women younger than 65 who are at increased risk for osteoporosis based on formal clinical risk assessment tools, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.
We all agree that women older than 65 years of age should be screened with DXA measurements of bone mass. The USPSTF says that in women under 65, a fracture assessment tool like FRAX, which does not require bone density testing to yield an individual’s absolute 10-year fracture risk, should be used to determine if bone mass measurement by DXA is, in fact, warranted. This recommendation is further supported by the article by Gourlay and colleagues, in which women aged 50 to 64 with subthreshold FRAX scores had a very low risk of fracture prior to age 65.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22:465-475.
- Cauley JA, Wampler NS, Barnhart JM, et al; Women’s Health Initiative Observational Study. Incidence of fractures compared to cardiovascular disease and breast cancer: the Women’s Health Initiative Observational Study. Osteoporos Int. 2008;19:1717-1723.
- Brauer CA, Coca-Perraillon M, Cutler DM, et al. Incidence and mortality of hip fractures in the United States. JAMA. 2009;302:1573-1579.
- Goldstein SR. Update on osteoporosis. OBG Manag. 2012;24:16-21.
- Goldstein SR. 2017 update on bone health. OBG Manag. 2017;29-32, 48.
- Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22:465-475.
- Cauley JA, Wampler NS, Barnhart JM, et al; Women’s Health Initiative Observational Study. Incidence of fractures compared to cardiovascular disease and breast cancer: the Women’s Health Initiative Observational Study. Osteoporos Int. 2008;19:1717-1723.
- Brauer CA, Coca-Perraillon M, Cutler DM, et al. Incidence and mortality of hip fractures in the United States. JAMA. 2009;302:1573-1579.
- Goldstein SR. Update on osteoporosis. OBG Manag. 2012;24:16-21.
- Goldstein SR. 2017 update on bone health. OBG Manag. 2017;29-32, 48.