Long-Term Follow-Up of Transsexual Persons Undergoing Sex Reassignment Surgery Cohort Study in Sweden (2).docx

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043071/

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PMC3043071

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P*o ne. 011 2: e1 5.

P$blishe, online 011 6eb . ,oi:10.1371/ o$rnal.pone.001 5PMCI8: PMC3043071

Long-Term Follow-Up of TranssexualPersons Undergoing Sex ReassignmentSurgery: Cohort Study in SwedenCecilia 8he ne91 Pa$l *ichtenstein9 Marc$s Boman9 'nna *. . -ohansson 9 Ni!las

*;ngstr

-ames cott9 ?,itor '$thor in+ormation @ 'rticle notes @ Cop(right an, *icense in+ormation @&his article has beencite, b( other articles in PMC.Ao to:

!stra"t

Context

&he treatment +or transse $alism is se reassignment9 incl$,ing hormonal treatment an, s$rger(aime, at ma!ing the person s bo,( as congr$ent with the opposite se as possible. &here is a,earth o+ long term9 +ollowD$p st$,ies a+ter se reassignment.

#!$e"ti%e

&o estimate mortalit(9 morbi,it(9 an, criminal rate a+ter s$rgical se reassignment o+ transse $al persons.

&esign

' pop$lationDbase, matche, cohort st$,(.

Setting

we,en9 1E73D 003.

Parti"ipants

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'll 3 4 se Dreassigne, persons 1E1 maleDtoD+emales9 133 +emaleDtoDmales2 in we,en9 1E7003. #an,om pop$lation controls 10 12 were matche, b( birth (ear an, birth se or reassigne,+inal2 se 9 respectivel(.

Main #ut"ome Measures

%aGar, ratios %#2 with E5H con+i,ence intervals CI2 +or mortalit( an, ps(chiatric morbi,it(were obtaine, with Co regression mo,els9 which were a, $ste, +or immigrant stat$s an, ps(chiatric morbi,it( prior to se reassignment a, $ste, %# a%#J2.

Results

&he overall mortalit( +or se Dreassigne, persons was higher ,$ring +ollowD$p a%# . E5H C1. F4.32 than +or controls o+ the same birth se 9 partic$larl( ,eath +rom s$ici,e a%# 1E.1 E5HCI 5. F .E2. e Dreassigne, persons also ha, an increase, ris! +or s$ici,e attempts a%# 4.EE5H CI .EF .52 an, ps(chiatric inpatient care a%# . E5H CI .0F3.E2. Comparisons with

controls matche, on reassigne, se (iel,e, similar res$lts. 6emaleDtoDmales9 b$t not maleDtoD+emales9 ha, a higher ris! +or criminal convictions than their respective birth se controls.

Con"lusions

Persons with transse $alism9 a+ter se reassignment9 have consi,erabl( higher ris!s +or mortalit(9s$ici,al behavio$r9 an, ps(chiatric morbi,it( than the general pop$lation. $r +in,ings s$ggestthat se reassignment9 altho$gh alleviating gen,er ,(sphoria9 ma( not s$++ice as treatment +ortransse $alism9 an, sho$l, inspire improve, ps(chiatric an, somatic care a+ter se reassignment+or this patient gro$p.

Ao to:

'ntrodu"tion

&ransse $alism IC8D1029 1J or gen,er i,entit( ,isor,er 8 MDI 29 J is a con,ition in which a person s gen,er i,entit( D the sense o+ being a man or a woman D contra,icts his or her bo,il( secharacteristics. &he in,ivi,$al e periences gen,er ,(sphoria an, ,esires to live an, be accepte,as a member o+ the opposite se .

&he treatment +or transse $alism incl$,es removal o+ bo,( hair9 vocal training9 an, crossDsehormonal treatment aime, at ma!ing the person s bo,( as congr$ent with the opposite se as possible to alleviate the gen,er ,(sphoria. e reassignment also involves the s$rgical removalo+ bo,( parts to ma!e e ternal se $al characteristics resemble those o+ the opposite se 9 so calle,se reassignment/con+irmation s$rger( # 2. &his is a $niK$e intervention not onl( in ps(chiatr( b$t in all o+ me,icine. &he present +orm o+ se reassignment has been practise, +ormore than hal+ a cent$r( an, is the internationall( recogniGe, treatment to ease gen,er ,(sphoriain transse $al persons.3J9 4J

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8espite the long histor( o+ this treatment9 however9 o$tcome ,ata regar,ing mortalit( an, ps(chiatric morbi,it( are scant. Lith respect to s$ici,e an, ,eaths +rom other ca$ses a+ter sereassignment9 an earl( we,ish st$,( +ollowe, 4 transse $al persons +or an average o+ si (earsan, reporte, one s$ici,e . 5J ' s$bseK$ent we,ish st$,( recor,e, three s$ici,es a+ter sereassignment s$rger( o+ 175 patients. J ' recent we,ish +ollowD$p st$,( reporte, no s$ici,es

in 0 transse $al patients9 b$t one ,eath ,$e to complications a+ter the se reassignment s$rger(.7J ' 8anish st$,( reporte, ,eath b( s$ici,e in 3 o$t o+ E operate, maleDtoD+emale transse $al persons +ollowe, +or an average o+ si (ears.J B( contrast9 a Belgian st$,( o+ 107 transse $al persons +ollowe, +or 4F (ears +o$n, no s$ici,es or ,eaths +rom other ca$ses.EJ ' large 8$tchsingleDcentre st$,( N 1910E29 +oc$sing on a,verse events +ollowing hormonal treatment9compare, the o$tcome a+ter crossDse hormone treatment with national 8$tch stan,ar,iGe,mortalit( an, morbi,it( rates an, +o$n, no increase, mortalit(9 with the e ception o+ ,eath +roms$ici,e an, 'I8 in maleDtoD+emales 5F3E (ears o+ age.10J &he same research gro$pconcl$,e, in a recent report that treatment with crossDse hormones seems acceptabl( sa+e9 b$twith the reservation that soli, clinical ,ata are missing.11J ' limitation with respect to the8$tch cohort is that the proportion o+ patients treate, with crossDse hormones who also ha,

s$rgical se Dreassignment is not acco$nte, +or . 10J8ata is inconsistent with respect to ps(chiatric morbi,it( post se reassignment. 'ltho$gh man(st$,ies have reporte, ps(chiatric an, ps(chological improvement a+ter hormonal an,/or s$rgicaltreatment9 7J9 1 J9 13J9 14J9 15J9 1 J other have reporte, on regrets917J ps(chiatricmorbi,it(9 an, s$ici,e attempts a+ter # . EJ9 1 J ' recent s(stematic review an, metaDanal(sisconcl$,e, that appro imatel( 0H reporte, s$b ective improvement in terms o+ gen,er,(sphoria9 K$alit( o+ li+e9 an, ps(chological s(mptoms9 b$t also that there are st$,ies reportinghigh ps(chiatric morbi,it( an, s$ici,e rates a+ter se reassignment.1EJ &he a$thors concl$,e,tho$gh that the evi,ence base +or se reassignment is o+ ver( low K$alit( ,$e to the serio$smetho,ological limitations o+ incl$,e, st$,ies.O

&he metho,ological shortcomings have man( reasons. 6irst9 the nat$re o+ se reassignment precl$,es ,o$ble blin, ran,omiGe, controlle, st$,ies o+ the res$lt. econ,9 transse $alism israre 0J an, man( +ollowD$ps are hampere, b( small n$mbers o+ s$b ects. 5J9 J9 1J9 J9

3J9 4J9 5J9 J9 7J9 J &hir,9 man( se reassigne, persons ,ecline to participate in+ollowD$p st$,ies9 or relocate a+ter s$rger(9 res$lting in high ,ropDo$t rates an, conseK$entselection bias. J9 EJ9 1 J9 1J9 4J9 J9 EJ9 30J 6orth9 several +ollowD$p st$,ies arehampere, b( limite, +ollowD$p perio,s.7J9 EJ9 1J9 J9 J9 30J &a!en together9 theselimitations precl$,e soli, an, generalisable concl$sions. ' longDterm pop$lationDbase,controlle, st$,( is one wa( to a,,ress these metho,ological shortcomings.

%ere9 we assesse, mortalit(9 ps(chiatric morbi,it(9 an, ps(chosocial integration e presse, incriminal behavio$r a+ter se reassignment in transse $al persons9 in a total pop$lation cohortst$,( with longDterm +ollowD$p in+ormation obtaine, +rom we,ish registers. &he cohort wascompare, with ran,oml( selecte, pop$lation controls matche, +or age an, gen,er. Le a, $ste,+or premorbi, ,i++erences regar,ing ps(chiatric morbi,it( an, immigrant stat$s. &his st$,(,esign she,s new light on transse $al persons health a+ter se reassignment. It ,oes not9however9 a,,ress whether se reassignment is an e++ective treatment or not.

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Ao to:

Methods

(ational registers

&he st$,( pop$lation was i,enti+ie, b( the lin!age o+ several we,ish national registers9 whichcontaine, a total o+ 13. million $niK$e in,ivi,$als. &he %ospital 8ischarge #egister %8#9 hel, b( the National Boar, o+ %ealth an, Lel+are2 contains ,ischarge ,iagnoses9 $p to sevencontrib$tor( ,iagnoses9 e ternal ca$ses o+ morbi,it( or mortalit(9 s$rgical proce,$re co,es9 an,,ischarge ,ate. 8ischarge ,iagnoses are co,e, accor,ing to the th 1E ED1E 29 Eth 1E 7F1EE 29an, 10 th e,itions 1EE7D2 o+ the International Classi+ication o+ 8iseases IC82. &he registercovers virt$all( all ps(chiatric inpatient episo,es in we,en since 1E73. 8ischarges that occ$rre,$p to 31 8ecember 003 were incl$,e,. $rgical proce,$re co,es co$l, not be $se, +or thisst$,( ,$e to the lac! o+ a speci+ic co,e +or se reassignment s$rger(. &he &otal Pop$lation#egister &P#9 hel, b( tatistics we,en2 is comprise, o+ ,ata abo$t the entire we,ish pop$lation. &hro$gh lin!age with the &otal Pop$lation #egister it was possible to i,enti+( birth,ate an, birth gen,er +or all st$,( s$b ects. &he register is $p,ate, ever( (ear an, gen,erin+ormation was available $p to 004/ 005. &he Me,ical Birth #egister MB#2 was establishe,in 1E73 an, contains birth ,ata9 incl$,ing gen,er o+ the chil, at birth. National cens$ses base, onman,ator( sel+Dreport K$estionnaires complete, b( all a,$lt citiGens in 1E 09 1E709 1E 09 an,1EE0 provi,e, in+ormation on in,ivi,$als9 ho$sehol,s9 an, ,wellings9 incl$,ing gen,er9 livingarea9 an, highest e,$cational level. Complete migration ,ata9 incl$,ing co$ntr( o+ birth +orimmigrants +or 1E EF 0039 were obtaine, +rom the &P#. In a,,ition to e,$cational in+ormation+rom the cens$ses9 we also obtaine, highest e,$cational level ,ata +or 1EE0 an, 000 +rom the#egister o+ ?,$cation. &he Ca$se o+ 8eath #egister C8#9 tatistics we,en2 recor,s all ,eathsin we,en since 1E5 an, provi,e, in+ormation on ,ate o+ ,eath an, ca$ses o+ ,eath. 8eathevents occ$rring $p to 31 8ecember 003 are incl$,e, in the st$,(. &he Crime #egister hel, b(the National Co$ncil o+ Crime Prevention2 provi,e, in+ormation regar,ing crime t(pe an, ,ateon all criminal convictions in we,en ,$ring the perio, 1E73F 004. 'ttempte, an, aggravate,+orms o+ all o++ences were also incl$,e,. 'll crimes in we,en are registere, regar,less o+insanit( at the time o+ perpetration +or e ample9 +or in,ivi,$als who s$++ere, +rom ps(chosis atthe time o+ the o++ence. Moreover9 conviction ,ata incl$,e in,ivi,$als who receive, c$sto,ial ornonDc$sto,ial sentences an, cases where the prosec$tor ,eci,e, to ca$tion or +ine witho$t co$rt procee,ings. 6inall(9 we,en ,oes not ,i++er consi,erabl( +rom other members o+ the ?$ropean)nion regar,ing rates o+ violent crime an, their resol$tion. 31J

Study population) identifi"ation of sex-reassigned persons *exposure assessment+

&he st$,( was ,esigne, as a pop$lationDbase, matche, cohort st$,(. Le $se, the in,ivi,$alnational registration n$mber9 assigne, to all we,ish resi,ents9 incl$,ing immigrants on arrival9as the primar( !e( thro$gh all lin!ages. &he registration n$mber consists o+ 10 ,igits the +irst si provi,e in+ormation o+ the birth ,ate9 whereas the ninth ,igit in,icates the gen,er. In we,en9 a person presenting with gen,er ,(sphoria is re+erre, to one o+ si specialise, gen,er teams thateval$ate an, treat patients principall( accor,ing to international consens$s g$i,elines: tan,ar,so+ Care. 3J Lith a me,ical certi+icate9 the person applies to the National Boar, o+ %ealth an,

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Lel+are to receive permission +or se reassignment s$rger( an, a change o+ legal se stat$s. 'new national registration n$mber signi+(ing the new gen,er is assigne, a+ter se reassignments$rger(. &he National Boar, o+ %ealth an, Lel+are maintains a lin! between ol, an, newnational registration n$mbers9 ma!ing it possible to +ollow in,ivi,$als $n,ergoing sereassignment across registers an, over time. %ence9 se reassignment s$rger( in we,en reK$ires

i2 a transse $alism ,iagnosis an, ii2 permission +rom the National Boar, o+ %ealth an,Lel+are.

' person was ,e+ine, as e pose, to se reassignment s$rger( i+ two criteria were met: i2 at leastone inpatient ,iagnosis o+ gen,er i,entit( ,isor,er ,iagnosis witho$t concomitant ps(chiatric,iagnoses in the %ospital 8ischarge #egister9 an, ii2 at least one ,iscrepanc( between gen,ervariables in the Me,ical Birth #egister +rom 1E73 an, onwar,s2 or the National Cens$ses +rom1E 09 1E709 1E 09 or 1EE0 an, the latest gen,er ,esignation in the &otal Pop$lation #egister. &he+irst criterion was emplo(e, to capt$re the hospitaliGation +or se reassignment s$rger( thatserves to sec$re the ,iagnosis an, provi,e a time point +or se reassignment s$rger( the plastics$rgeons namel( recor, the reason +or se reassignment s$rger(9 i.e.9 transse $alism9 b$t not an(

coDocc$rring ps(chiatric morbi,it(. &he secon, criterion was $se, to ens$re that the person wentthro$gh all steps in se Dreassignment an, also change, se legall(.

&he ,ate o+ se reassignment start o+ +ollowD$p2 was ,e+ine, as the +irst occ$rrence o+ a gen,eri,entit( ,isor,er ,iagnosis9 witho$t an( other concomitant ps(chiatric ,isor,er9 in the %ospital8ischarge #egister a+ter the patient change, se stat$s an( ,iscor,ance in se ,esignationacross the Cens$ses9 Me,ical Birth9 an, &otal Pop$lation registers2. I+ this in+ormation wasmissing9 we $se, instea, the closest ,ate in the %ospital 8ischarge #egister on which the patientwas ,iagnose, with gen,er i,entit( ,isor,er witho$t concomitant ps(chiatric ,isor,er prior tochange in se stat$s. &he reason +or prioritiGing the $se o+ a gen,er i,entit( ,isor,er ,iagnosisafter change, se stat$s overbefore was to avoi, overestimating personD(ears at ris! o+ se D

reassigne, person.)sing these criteria9 a total o+ 04 patients with gen,er i,entit( ,isor,er were i,enti+ie,9 whereo+ 3 4 ,ispla(e, a shi+t in the gen,er variable ,$ring the perio, 1E73F 003. &he 4 0 persons that,i, not shi+t gen,er variable comprise persons who either ,i, not appl(9 or were not approve,9+or se reassignment s$rger(. Moreover9 the IC8 E co,e 30 is a non speci+ic co,e +or se $al,isor,ers. %ence9 this gro$p might also comprise persons that were hospitaliGe, +or se $al,isor,ers other than transse $alism. &here+ore9 the( were omitte, +rom +$rther anal(ses. + theremaining 3 4 persons9 were i,enti+ie, with the gen,er i,entit( ,iagnosisafter an, 3before change o+ se stat$s. $t o+ the persons i,enti+ie,after change, se stat$s9 1 5 co$l,also be i,enti+ie, before change in se stat$s. &he me,ian time lag between the hospitaliGationbefore an, after se change +or these 1 5 persons was 0.E (ears mean . (ears9 8 3.32.

Aen,er i,entit( ,isor,er was co,e, accor,ing to IC8D : 30 .3 transse $alism2 an, 30 .Ese $al ,eviation N 2 IC8DE: 30 overall co,e +or se $al ,eviations an, ,isor,ers9 more

speci+ic co,es were not available in IC8DE2 an, IC8D10: 6 4.0 transse $alism29 6 4.1 ,$alDrole transvestism29 6 4. other gen,er i,entit( ,isor,er29 an, 6 4.E gen,er i,entit( ,isor,er N 2. ther ps(chiatric ,isor,ers were co,e, as IC8D : E0D301 an, 303D315 IC8DE: E0D301an, 303D31E an, IC8D10: 600D6 3 as well as 6 5D6EE.

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'dentifi"ation of population-!ased "ontrols *unexposed group+

6or each e pose, person N 3 429 we ran,oml( selecte, 10 $ne pose, controls. ' person was,e+ine, as $ne pose, i+ there were no ,iscrepancies in se ,esignation across the Cens$ses9Me,ical Birth9 an, &otal Pop$lation registersand no gen,er i,entit( ,isor,er ,iagnosis

accor,ing to the %ospital 8ischarge #egister. Control persons were matche, b( se an, birth(ear an, ha, to be alive an, resi,ing in we,en at the estimate, se reassignment ,ate o+ thecase person. &o st$,( possible gen,erDspeci+ic e++ects on o$tcomes o+ interest9 we $se, two,i++erent control gro$ps: one with the same se as the case in,ivi,$al at birth birth sematching2 an, the other with the se that the case in,ivi,$al ha, been reassigne, to +inal sematching2.

#ut"ome measures

Le st$,ie, mortalit(9 ps(chiatric morbi,it(9 acci,ents9 an, crime +ollowing se reassignment.More speci+icall(9 we investigate,: 12 allDca$se mortalit(9 2 ,eath b( ,e+inite/$ncertain

s$ici,e9 32 ,eath b( car,iovasc$lar ,isease9 an, 42 ,eath b( t$mo$r. Morbi,it( incl$,e, 52 an( ps(chiatric ,isor,er gen,er i,entit( ,isor,ers e cl$,e,29 2 alcohol/,r$g mis$se an,,epen,ence9 72 ,e+inite/$ncertain s$ici,e attempt9 an, 2 acci,ents. 6inall(9 we a,,resse, co$rtconvictions +or E2 an( criminal o++ence an, 102 an( violent o++ence. ?ach in,ivi,$al co$l,contrib$te with several o$tcomes9 b$t onl( one event per o$tcome. Ca$ses o+ ,eath Ca$se o+8eath #egistr( +rom 1E5 an, onwar,s2 were ,e+ine, accor,ing to IC8 as s$ici,e IC8D an,IC8DE co,es ?E50D?E5E an, ?E 0D?E E9 IC8D10 co,es 0D 4 an, Q10DQ342 car,iovasc$l,isease IC8D co,es 3E0D45 9 IC8DE co,es 3E0D45E9 IC8D10 co,es I00DIEE2 neoplasms Ian, IC8DE co,es 140D 3E9 IC8D10 co,es C00D84 29 an( ps(chiatric ,isor,er gen,er i,entit(,isor,ers e cl$,e,2 IC8D co,es E0D301 an, 303D3159 IC8DE co,es E0D301 an, 303D31E9IC8D10 co,es 600D6 3 an, 6 5D6EE2 alcohol/,r$g ab$se an, ,epen,ence IC8D co,es 303D

3049 IC8DE co,es 303D305 tobacco $se ,isor,er e cl$,e,29 IC8D10 co,es 610D61 an, 61 D61E5 e cl$,e,2 an, acci,ents IC8D an, IC8DE co,es ? 00D?E E9 IC8D10 co,es 01D 5E2.

'n( criminal conviction ,$ring +ollowD$p was co$nte, speci+icall(9 violent crime was ,e+ine,as homici,e an, attempte, homici,e9 aggravate, assa$lt an, assa$lt9 robber(9 threatening behavio$r9 harassment9 arson9 or an( se $al o++ense. 3 J

Co%ariates

evere ps(chiatric morbi,it( was ,e+ine, as inpatient care accor,ing to IC8D co,es E19 E5D3019 303D3049 an, 307 IC8DE co,es E1D E 9 E5D E 9 300D3019 303D305 tobacco $se

e cl$,e,29 307.19 307.59 30 D30E9 an, 311 IC8D10 co,es 610D61 9 61 D6 59 6 D6459 64an, 6 0D6 . Immigrant stat$s9 ,e+ine, as in,ivi,$als born abroa,9 was obtaine, +rom the &otalPop$lation #egister. 'll o$tcome/covariate variables were ,ichotomiGe, i.e.9 a++ecte, or$na++ecte,2 an, witho$t missing val$es.

Statisti"al analyses

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?ach in,ivi,$al contrib$te, personDtime +rom st$,( entr( +or e pose,: ,ate o+ se reassignment+or $ne pose,: ,ate o+ se reassignment o+ matche, case2 $ntil ,ate o+ o$tcome event9 ,eath9emigration9 or en, o+ st$,( perio, 31 8ecember 00329 whichever came +irst. &he association between e pos$re se reassignment2 an, o$tcome mortalit(9 morbi,it(9 crime2 was meas$re, b( haGar, ratios %#2 with E5H CIs9 ta!ing +ollowD$p time into acco$nt. %#s were estimate,

+rom Co proportional haGar, regression mo,els9 strati+ie, on matche, sets 1 102 to acco$nt +orthe matching b( se 9 age9 an, calen,ar time birth (ear2. Le present cr$,e %#s tho$gh a, $ste,+or se an, age thro$gh matching2 an, con+o$n,erDa, $ste, %#s a%#sJ +or all o$tcomes. &hetwo potential con+o$n,ers9 immigrant stat$s (es/no2 an, histor( o+ severe ps(chiatric morbi,it(

(es/no2 prior to se reassignment9 were chosen base, on previo$s research1 J9 33J an,,i++erent prevalence across cases an, controls &able 12.

&able 1,aseline "hara"teristi"s among sex-reassigned su!$e"ts in Sweden *( ./0+ and population"ontrols mat"hed for !irth year and sex1

Aen,erDseparate, anal(ses were per+orme, an, a RaplanDMeier s$rvival plot graphicall(ill$strates the s$rvival o+ the se reassigne, cohort an, matche, controls allDca$se mortalit(2over time. &he signi+icance level was set at 0.05 all tests were twoDsi,e,2. 'll o$tcome/covariatevariables were witho$t missing val$es9 since the( are generate, +rom register ,ata9 which are

either present a++ecte,2 or missing $na++ecte,2. &he ,ata were anal(se, $sing ' version E.1' Instit$te Inc.9 Car(9 NC9 ) '2.

2thi"s

&he ,ata lin!ing o+ national registers reK$ire, +or this st$,( was approve, b( the I#B atRarolins!a Instit$tet9 toc!holm. 'll ,ata were anal(Ge, anon(mo$sl( there+ore9 in+orme,consent +or each in,ivi,$al was neither necessar( nor possible.

Ao to:

ResultsLe i,enti+ie, 3 4 transse $al persons e pose, cohort2 who $n,erwent se reassignment s$rger(an, were assigne, a new legal se between 1E73 an, 003. &hese constit$te, the se Dreassigne,

e pose,2 gro$p. 6i+t(Dnine percent N 1E12 o+ se Dreassigne, persons were maleDtoD+emalan, 41H N 1332 +emaleDtoDmales9 (iel,ing a se ratio o+ 1.4 1 &able 12.

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&he average +ollowD$p time +or allDca$se mortalit( was 11.4 me,ian E.12 (ears. &he average+ollowD$p time +or the ris! o+ being hospitaliGe, +or an( ps(chiatric ,isor,er was 10.4 me,ian

.12.

Chara"teristi"s prior to sex reassignment

&able 1 ,ispla(s ,emographic characteristics o+ se Dreassigne, an, control persons prior to st$,(entr( se reassignment2. &here were no s$bstantial ,i++erences between +emaleDtoDmales an,maleDtoD+emales regar,ing meas$re, baseline characteristics. Immigrant stat$s was twice ascommon among transse $al in,ivi,$als compare, to controls9 living in an $rban area somewhatmore common9 an, higher e,$cation abo$t eK$all( prevalent. &ransse $al in,ivi,$als ha, beenhospitaliGe, +or ps(chiatric morbi,it( other than gen,er i,entit( ,isor,er prior to sereassignment abo$t +o$r times more o+ten than controls. &o a, $st +or these baseline,iscrepancies9 haGar, ratios a, $ste, +or immigrant stat$s an, ps(chiatric morbi,it( prior to baseline are presente, +or all o$tcomes a%#sJ.

Mortality

&able ,escribes the ris!s +or selecte, o$tcomes ,$ring +ollowD$p among se Dreassigne, persons9 compare, to sameDage controls o+ the same birth se . e Dreassigne, transse $al persons o+ both gen,ers ha, appro imatel( a three times higher ris! o+ allDca$se mortalit( thancontrols9 also a+ter a, $stment +or covariates.&able separatel( lists the o$tcomes ,epen,ing onwhen se reassignment was per+orme,: ,$ring the perio, 1E73D1E or 1E EF 003. ?ven tho$ghthe overall mortalit( was increase, across both time perio,s9 it ,i, not reach statisticalsigni+icance +or the perio, 1E EF 003. &he RaplanDMeier c$rve 6ig$re 12 s$ggests that s$rvivalo+ transse $al persons starte, to ,iverge +rom that o+ matche, controls a+ter abo$t 10 (ears o++ollowD$p. &he ca$seDspeci+ic mortalit( +rom s$ici,e was m$ch higher in se Dreassigne, person

compare, to matche, controls. Mortalit( ,$e to car,iovasc$lar ,isease was mo,eratel( increase,among the se Dreassigne,9 whereas the n$mericall( increase, ris! +or malignancies was bor,erline statisticall( signi+icant. &he malignancies were l$ng cancer N 329 tong$e cancer N

129 phar(ngeal cancer N 129 pancreas cancer N 129 liver cancer N 129 an, $n!nownorigin N 12.

6ig$re 1

&eath from any "ause as a fun"tion of time after sex reassignment among ./0 transsexualpersons in Sweden *male-to-female: ( 343) female-to-male: ( 3..+) and population"ontrols mat"hed on !irth year1 111

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&able Ris5 of %arious out"omes among sex-reassigned su!$e"ts in Sweden *( ./0+ "ompared topopulation "ontrols mat"hed for !irth year and !irth sex1

Psy"hiatri" mor!idity) su!stan"e misuse) and a""idents

e Dreassigne, persons ha, a higher ris! o+ inpatient care +or a ps(chiatric ,isor,er other thangen,er i,entit( ,isor,er than controls matche, on birth (ear an, birth se &able 2. &his hel,a+ter a, $stment +or prior ps(chiatric morbi,it(9 an, was tr$e regar,less o+ whether se

reassignment occ$rre, be+ore or a+ter 1E E. In line with the increase, mortalit( +rom s$ici,e9se Dreassigne, in,ivi,$als were also at a higher ris! +or s$ici,e attempts9 tho$gh this was notstatisticall( signi+icant +or the time perio, 1E EF 003. &he ris!s o+ being hospitalise, +ors$bstance mis$se or acci,ents were not signi+icantl( increase, a+ter a, $sting +or covariates&able 2.

Crime rate

&ransse $al in,ivi,$als were at increase, ris! o+ being convicte, +or an( crime or violent crimea+ter se reassignment &able 2 this was9 however9 onl( signi+icant in the gro$p who $n,erwentse reassignment be+ore 1E E.

6ender differen"es

Comparisons o+ +emaleDtoDmales an, maleDtoD+emales9 altho$gh hampere, b( low statistical power an, associate, wi,e con+i,ence intervals9 s$ggeste, mostl( similar ris!s +or a,verseo$tcomes &ables 1 an, 2. %owever9 violence against sel+ s$ici,al behavio$r2 an, others

violentJ crime2 constit$te, important e ceptions. 6irst9 maleDtoD+emales ha, signi+icantl(increase, ris!s +or s$ici,e attempts compare, to both +emale a%# E.3 E5H CI 4.4F1E.E2 an,male a%# 10.4 E5H CI 4.EF .12 controls. B( contrast9 +emaleDtoDmales ha, signi+icantl(increase, ris! o+ s$ici,e attempts onl( compare, to male controls a%# . E5H CI .1F 1. 2 b$t not compare, to +emale controls a%# 1.E E5H CI 0.7F4. 2. &his s$ggests that maleDtoD+emales are at higher ris! +or s$ici,e attempts a+ter se reassignment9 whereas +emaleDtoDmalesmaintain a +emale pattern o+ s$ici,e attempts a+ter se reassignment &ables 1 an, 2.

econ,9 regar,ing an( crime9 maleDtoD+emales ha, a signi+icantl( increase, ris! +or crimecompare, to +emale controls a%# . E5H CI 4.1F10. 2 b$t not compare, to males a%# 0.E5H CI 0.5F1. 2. &his in,icates that the( retaine, a male pattern regar,ing criminalit(. &he samewas tr$e regar,ing violent crime. B( contrast9 +emaleDtoDmales ha, higher crime rates than+emale controls a%# 4.1 E5H CI .5F .E2 b$t ,i, not ,i++er +rom male controls. &his in,icates

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shi+t to a male pattern regar,ing criminalit( an, that se reassignment is co$ple, to increase,crime rate in +emaleDtoDmales. &he same was tr$e regar,ing violent crime.

Ao to:

&is"ussionPrin"ipal findings and "omparison with pre%ious resear"h

Le report on the +irst nationwi,e pop$lationDbase,9 longDterm +ollowD$p o+ se Dreassigne,transse $al persons. Le compare, o$r cohort with ran,oml( selecte, pop$lation controlsmatche, +or age an, gen,er. &he most stri!ing res$lt was the high mortalit( rate in both maleDtoD+emales an, +emaleDto males9 compare, to the general pop$lation. &his contrasts with previo$sreports with one e ception J2 that ,i, not +in, an increase, mortalit( rate a+ter sereassignment9 or onl( note, an increase, ris! in certain s$bgro$ps.7J9 EJ9 10J9 11J Previo$sclinical st$,ies might have been biase, since people who regar, their se reassignment as a+ail$re are more li!el( to be lost to +ollowD$p. *i!ewise9 it is c$mbersome to trac! ,ecease, persons in clinical +ollowD$p st$,ies. %ence9 pop$lationDbase, register st$,ies li!e the presentare nee,e, to improve representativit(. 1EJ9 34J

&he poorer o$tcome in the present st$,( might also be e plaine, b( longer +ollowD$p perio,me,ian S10 (ears2 compare, to previo$s st$,ies. In s$pport o+ this notion9 the s$rvival c$rve

6ig$re 12 s$ggests increase, mortalit( +rom ten (ears a+ter se reassignment an, onwar,s. Inaccor,ance9 the overall mortalit( rate was onl( signi+icantl( increase, +or the gro$p operate, be+ore 1E E. %owever9 the latter might also be e plaine, b( improve, health care +or transse $al persons ,$ring 1EE0s9 along with altere, societal attit$,es towar,s persons with ,i++erent gen,ere pressions. 35J

Mortalit( ,$e to car,iovasc$lar ,isease was signi+icantl( increase, among se reassigne,in,ivi,$als9 albeit these res$lts sho$l, be interprete, with ca$tion ,$e to the low n$mber o+events. &his contrasts9 however9 a 8$tch +ollowD$p st$,( that reporte, no increase, ris! +orcar,iovasc$lar events. 10J9 11J ' recent metaDanal(sis concl$,e,9 however9 that ,ata oncar,iovasc$lar o$tcome a+ter crossDse steroi, $se are sparse9 inconcl$sive9 an, o+ ver( lowK$alit(. 34J

Lith respect to neoplasms9 prolonge, hormonal treatment might increase the ris! +ormalignancies93 J b$t no previo$s st$,( has teste, this possibilit(. $r ,ata s$ggeste, that theca$seDspeci+ic ris! o+ ,eath +rom neoplasms was increase, abo$t twice bor,erline statisticalsigni+icance2. &hese malignancies see#es$lts29 however9 are $nli!el( to be relate, to crossDhormonal treatment.

&here might be other e planations to increase, car,iovasc$lar ,eath an, malignancies. mo!ingwas in one st$,( reporte, in almost 50H b( the maleDto +emales an, almost 0H b( +emaleDtoDmales. EJ It is also possible that transse $al persons avoi, the health care s(stem ,$e to a pres$me, ris! o+ being ,iscriminate,.

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Mortalit( +rom s$ici,e was stri!ingl( high among se Dreassigne, persons9 also a+ter a, $stment+or prior ps(chiatric morbi,it(. In line with this9 se Dreassigne, persons were at increase, ris! +or s$ici,e attempts. Previo$s reports J9 J9 10J9 11J s$ggest that transse $alism is a strong ris!+actor +or s$ici,e9 also a+ter se reassignment9 an, o$r longDterm +in,ings s$pport the nee, +orcontin$e, ps(chiatric +ollowD$p +or persons at ris! to prevent this.

Inpatient care +or ps(chiatric ,isor,ers was signi+icantl( more common among se Dreassigne, persons than among matche, controls9 both be+ore an, a+ter se reassignment. It is generall(accepte, that transse $als have more ps(chiatric illDhealth than the general pop$lation prior tothe se reassignment.1 J9 1J9 J9 33J It sho$l, there+ore come as no s$rprise that st$,ieshave +o$n, high rates o+ ,epression9EJ an, low K$alit( o+ li+e1 J9 5J also a+ter sereassignment. Notabl(9 however9 in this st$,( the increase, ris! +or ps(chiatric hospitalisation persiste, even a+ter a, $sting +or ps(chiatric hospitalisation prior to se reassignment. &hiss$ggests that even tho$gh se reassignment alleviates gen,er ,(sphoria9 there is a nee, toi,enti+( an, treat coDocc$rring ps(chiatric morbi,it( in transse $al persons not onl( be+ore b$talso a+ter se reassignment.

Criminal activit(9 partic$larl( violent crime9 is m$ch more common among men than women inthe general pop$lation. ' previo$s st$,( o+ all applications +or se reassignment in we,en $p to1EE +o$n, that E.7H o+ maleDtoD+emale an, .1H o+ +emaleDtoDmale applicants ha, been prosec$te, +or a crime. 33J Crime a+ter se reassignment9 however9 has not previo$sl( beenst$,ie,. In this st$,(9 maleDtoD+emale in,ivi,$als ha, a higher ris! +or criminal convictionscompare, to +emale controls b$t not compare, to male controls. &his s$ggests that the sereassignment proce,$re neither increase, nor ,ecrease, the ris! +or criminal o++en,ing in maleDtoD+emales. B( contrast9 +emaleDtoDmales were at a higher ris! +or criminal convictions compareto +emale controls an, ,i, not ,i++er +rom male controls9 which s$ggests increase, crime proneness in +emaleDtoDmales a+ter se reassignment.

Strengths and limitations of the study

trengths o+ this st$,( incl$,e nationwi,e representativit( over more than 30 (ears9 e tensive+ollowD$p time9 an, minimal loss to +ollowD$p. Man( previo$s st$,ies s$++er +rom low o$tcomeascertainment9 J9 EJ9 1J9 EJ whereas this st$,( has capt$re, almost the entire pop$lation o+se Dreassigne, transse $al in,ivi,$als in we,en +rom 1E73F 003. Moreover9 previo$s o$tcomest$,ies have mi e, preDoperative an, postDoperative transse $al persons9 J9 37J while weincl$,e, onl( postDoperative transse $al persons that also legall( change, se . 6inall(9 whereas previo$s st$,ies either lac! a control gro$p or $se stan,ar,ise, mortalit( rates or stan,ar,ise,inci,ence rates as comparisons9EJ9 10J9 11J we selecte, ran,om pop$lation controls matche,

b( birth (ear9 an, either birth or +inal se .Aiven the nat$re o+ se reassignment9 a ,o$ble blin, ran,omiGe, controlle, st$,( o+ the res$lta+ter se reassignment is not +easible. Le there+ore have to rel( on other st$,( ,esigns. 6or the p$rpose o+ eval$ating whether se reassignment is an e++ective treatment +or gen,er ,(sphoria9 itis reasonable to compare reporte, gen,er ,(sphoria pre an, post treatment. $ch st$,ies have been con,$cte, either prospectivel( 7J9 1 J or retrospectivel(9 5J9 J9 EJ9 J9 5J9 J9 EJ9

3 J an, s$ggest that se reassignment o+ transse $al persons improves K$alit( o+ li+e an, gen,er

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,(sphoria. &he limitation is o+ co$rse that the treatment has not been assigne, ran,oml( an, hasnot been carrie, o$t blin,l(.

6or the p$rpose o+ eval$ating the sa+et( o+ se reassignment in terms o+ morbi,it( an, mortalit(9however9 it is reasonable to compare se reassigne, persons with matche, pop$lation controls.

&he caveat with this ,esign is that transse $al persons be+ore se reassignment might ,i++er +romhealth( controls altho$gh this bias can be statisticall( correcte, +or b( a, $sting +or baseline,i++erences2. It is there+ore important to note that the c$rrent st$,( is onl( in+ormative withrespect to transse $als persons health a+ter se reassignment no in+erences can be ,rawn as tothe e++ectiveness o+ se reassignment as a treatment +or transse $alism. In other wor,s9 theres$lts sho$l, not be interprete, s$ch as se reassignment per se increases morbi,it( an,mortalit(. &hings might have been even worse witho$t se reassignment. 's an analog(9 similarst$,ies have +o$n, increase, somatic morbi,it(9 s$ici,e rate9 an, overall mortalit( +or patientstreate, +or bipolar ,isor,er an, schiGophrenia. 3EJ9 40J &his is important in+ormation9 b$t it,oes not +ollow that moo, stabiliGing treatment or antips(chotic treatment is the c$lprit.

ther +acets to consi,er are +irst that this st$,( re+lects the o$tcome o+ ps(chiatric an, somatictreatment +or transse $alism provi,e, in we,en ,$ring the 1E70s an, 1E 0s. ince then9treatment has evolve, with improve, se reassignment s$rger(9 re+ine, hormonal treatment911J9

41J an, more attention to ps(chosocial care that might have improve, the o$tcome. econ,9transse $alism is a rare con,ition an, we,en is a small co$ntr( E. million inhabitants in

00 2. %ence9 ,espite being base, on a comparativel( large national cohort an, longDterm+ollowD$p9 the statistical power was limite,. &hir,9 regar,ing ps(chiatric morbi,it( a+ter sereassignment9 we assesse, inpatient ps(chiatric care. ince most ps(chiatric care is provi,e, ino$tpatient settings +or which no reliable ,ata were available29 $n,erestimation o+ theabsolute prevalences was inevitable. %owever9 there is no reason to believe that this wo$l, change therelative risks +or ps(chiatric morbi,it( $nless se Dreassigne, transse $al in,ivi,$als were more

li!el( than matche, controls to be a,mitte, to hospital +or an( given ps(chiatric con,ition.6inall(9 to estimate start o+ +ollowD$p9 we prioritiGe, $sing the ,ate o+ a gen,er i,entit( ,isor,er,iagnosis after change, se stat$s overbefore change, se stat$s9 in or,er to avoi,overestimating personD(ears at ris! a+ter se Dreassignment. &his means that a,verse o$tcomesmight have been $n,erestimate,. %owever9 given that the me,ian time lag between thehospitaliGation be+ore an, a+ter change o+ se stat$s was less than a (ear seeMetho,s29 thismane$ver is $nli!el( to have in+l$ence, the res$lts signi+icantl(. Moreover9 all ,eaths will berecor,e, regar,less o+ this e ercise an, mortalit( hence correctl( estimate,.

Con"lusion

&his st$,( +o$n, s$bstantiall( higher rates o+ overall mortalit(9 ,eath +rom car,iovasc$lar,isease an, s$ici,e9 s$ici,e attempts9 an, ps(chiatric hospitalisations in se Dreassigne,transse $al in,ivi,$als compare, to a health( control pop$lation. &his highlights that posts$rgical transse $als are a ris! gro$p that nee, longDterm ps(chiatric an, somatic +ollowD$p.?ven tho$gh s$rger( an, hormonal therap( alleviates gen,er ,(sphoria9 it is apparentl( nots$++icient to reme,( the high rates o+ morbi,it( an, mortalit( +o$n, among transse $al persons.

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Improve, care +or the transse $al gro$p a+ter the se reassignment sho$l, there+ore beconsi,ere,.

Ao to:

Supporting 'nformationTa!le S3

Ris5 of %arious out"omes in sex-reassigned persons in Sweden "ompared to population"ontrols mat"hed for !irth year and birth sex 1

8 C 2

Clic! here +or a,,itional ,ata +ile. R9 ,oc 2

Ta!le S/

Ris5 of %arious out"omes in sex-reassigned persons in Sweden "ompared to "ontrolsmat"hed for !irth year and final sex 1

8 C 2

Clic! here +or a,,itional ,ata +ile. R9 ,oc 2Ao to:

FootnotesCompeting 'nterests: &he a$thors have ,eclare, that no competing interests e ist.

Funding: 6inancial s$pport was provi,e, thro$gh the regional agreement on me,ical trainingan, clinical research '*62 between toc!holm Co$nt( Co$ncil an, the Rarolins!a Instit$tet9an, thro$gh grants +rom the we,ish Me,ical #esearch Co$ncil R 00 D D14 47D0 D32 an,the #o(al we,ish 'ca,em( o+ ciences &orsten 'm$n,son s 6o$n,ation2. &he sponsors o+ thest$,( ha, no role in st$,( ,esign9 ,ata collection9 ,ata anal(sis9 ,ata interpretation9 or writing o+the report. 'll a$thors ha, +$ll access to the ,ata in the st$,( an, the +inal responsibilit( +or the,ecision to s$bmit +or p$blication was ma,e b( the correspon,ing a$thor.

Ao to:

Referen"es

1. Lorl, %ealth rganiGation. 8iagnostic criteria +or research. Aeneva: L% 1EE3. &he IC8D10 Classi+ication o+ Mental an, Behavio$ral 8isor,ers.

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. 'merican Ps(chiatric 'ssociation9 e,itor. Lashington9 8C: 'P' 1EE4. 8iagnostic an,tatistical Man$al o+ Mental 8isor,ers.

3. Me(er L9 Boc!ting L9 CohenDRettenis P9 Coleman ?9 8iCeglie 89 et al. &he %arr( Ben aminInternational Aen,er 8(sphoria 'ssociation s tan,ar,s o+ Care +or Aen,er I,entit( 8isor,ers9

i th ersion. -o$rnal o+ Ps(cholog( T %$man e $alit(. 00 13:1F30.

4. CohenDRettenis P&9 Aooren *-A. &ransse $alism: ' review o+ etiolog(9 ,iagnosis an,treatment. - Ps(chosom #es. 1EEE 4 :315F333. P$bMe,J5. L;lin,er -9 &h$we I. A

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. Bo,l$n, 9 R$llgren A. &ransse $alismDAeneral o$tcome an, prognostic +actors. ' +ive (ear +ollowD$p st$,( o+ 1E transse $als in the process o+ changing se . 'rch e Behav.1EE 5:303F31 . P$bMe,J

3. *in,emalm A9 R

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41. &oorians 'L9 &homassen MC9 Wweegman 9 Mag,ele(ns ?-9 &ans A9 et al. eno$sthrombosis an, changes o+ hemostatic variables ,$ring crossDse hormone treatment intransse $al people. - Clin ?n,ocrinol Metab. 003 :57 3F57 E. P$bMe,J

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