Afdeling for Vækst og Reproduktion - Department of Growth and ...
Afdeling for Vækst og Reproduktion - Department of Growth and ...
Afdeling for Vækst og Reproduktion - Department of Growth and ...
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Beretning om<br />
<strong>Afdeling</strong> <strong>for</strong> <strong>Vækst</strong> <strong>og</strong> <strong>Reproduktion</strong><br />
Rigshospitalet 2012
Indholds<strong>for</strong>tegnelse<br />
<strong>Afdeling</strong> <strong>for</strong> <strong>Vækst</strong> <strong>og</strong> <strong>Reproduktion</strong><br />
Rundt om biol<strong>og</strong>ien<br />
Sekretariatet<br />
Ambulatoriet<br />
Hormoner<br />
M<strong>and</strong>lig fertilitet<br />
<strong>Vækst</strong><br />
Pubertet<br />
Sædopbevaring<br />
Disorders <strong>of</strong> Sex Development (DSD)<br />
Testikelsyndromet TDS<br />
Brystudvikling hos drenge <strong>og</strong> mænd<br />
Genetik<br />
<strong>Reproduktion</strong> <strong>og</strong> livsstil<br />
Forstadier til testikelkræft<br />
Hormon<strong>for</strong>styrrende st<strong>of</strong>fer<br />
Populationsstudier<br />
Forskningssamarbejder<br />
Workshops<br />
Fakta om afdelingen<br />
Ansatte<br />
Afh<strong>and</strong>linger <strong>og</strong> specialer 2000 - 2012<br />
Videnskabelige publikationer 2000 - 2012<br />
2<br />
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<strong>Afdeling</strong> <strong>for</strong> <strong>Vækst</strong> <strong>og</strong> <strong>Reproduktion</strong><br />
F o r o rd v e d k l i n i kchef Anders J u u l<br />
Kære læser<br />
Velkommen til en beretning om <strong>Afdeling</strong> <strong>for</strong><br />
<strong>Vækst</strong> <strong>og</strong> <strong>Reproduktion</strong>. I et let<strong>for</strong>døjeligt<br />
spr<strong>og</strong> kan du her læse om afdelingens beh<strong>and</strong>ling<br />
af patienter <strong>og</strong> om vores højt pr<strong>of</strong>ilerede<br />
<strong>for</strong>skning.<br />
I 2012 har vi haft 10.000 ambulante besøg <strong>og</strong><br />
publiceret flere videnskabelige artikler end<br />
n<strong>og</strong>ensinde tidligere. Vores patientbeh<strong>and</strong>ling<br />
<strong>og</strong> <strong>for</strong>skning går hånd i hånd <strong>og</strong> har internationalt<br />
<strong>for</strong>mat. Af samme grund blev<br />
afdelingen i 2010 udvalgt som et Global Excellence<br />
Centre i Region Hovedstaden.<br />
3<br />
Som klinikchef glæder jeg mig hver dag til at<br />
gå på arbejde. Jeg har en masse dygtige kolleger<br />
<strong>og</strong> en spændende <strong>og</strong> alsidig arbejdsdag. Og<br />
jeg <strong>for</strong>nemmer at vi gennem vores arbejde gør<br />
en kæmpe <strong>for</strong>skel <strong>for</strong> patienterne.<br />
Det er jeg stolt af at være en del af.<br />
God læselyst<br />
Anders Juul<br />
Klinikchef <strong>og</strong> pr<strong>of</strong>essor
Rundt om biol<strong>og</strong>ien<br />
Starten på livet er karakteriseret ved hurtig vækst.<br />
Særligt i fosterlivet, men <strong>og</strong>så efter fødslen, i barneårene<br />
<strong>og</strong> gennem puberteten. Samtidig sker<br />
kønsudviklingen, først til drenge- eller pigefoster,<br />
<strong>og</strong> siden fra dreng til m<strong>and</strong> <strong>og</strong> fra pige til kvinde.<br />
Endelig sikrer reproduktionen at m<strong>and</strong> <strong>og</strong> kvinde<br />
sammen skaber et nyt individ.<br />
Vi beskæftiger os i <strong>Afdeling</strong> <strong>for</strong> <strong>Vækst</strong> <strong>og</strong><br />
<strong>Reproduktion</strong> med mange aspekter af<br />
denne udvikling, både i <strong>for</strong>sknings- <strong>og</strong> i<br />
beh<strong>and</strong>lingsøjemed. Neden<strong>for</strong> følger lidt<br />
uddybning af biol<strong>og</strong>ien bag afdelingens<br />
<strong>for</strong>skning <strong>og</strong> eksempler på steder, hvor<br />
den almindelige udvikling kan gå skævt<br />
- <strong>og</strong> mennesket blive patient.<br />
Når sæd- <strong>og</strong> ægcelle smelter sammen, bestemmes<br />
<strong>og</strong>så det kommende fosters køn. Moderens ægcelle<br />
indeholder altid kønskromosomet X, mens faderens<br />
sædcelle indeholder kønskromosomet X eller<br />
Y. Får fosteret et X kromosom fra faderen bliver<br />
det en pige (46,XX) <strong>og</strong> får det et Y kromosom bliver<br />
det en dreng (46,XY).<br />
I n<strong>og</strong>le tilfælde går det galt med <strong>for</strong>delingen<br />
af kønskromosomer, <strong>og</strong> fosteret<br />
kan blive en dreng med Klinefelter syndrom<br />
(47,XXY) eller en pige med Turner<br />
syndrom (45,X). Begge syndromer påvirker<br />
væksten <strong>og</strong> udviklingen af kønsorganerne<br />
<strong>og</strong> medfører som <strong>of</strong>test infertilitet.<br />
Har fosteret et Y kromosom, udvikles de primitive<br />
kønsorganer til testikler med Sertoliceller (der støtter<br />
sædcelledannelsen), Leydigceller (der laver<br />
testosteron) <strong>og</strong> spermat<strong>og</strong>onier (der stammer fra<br />
Turner <strong>og</strong> Klinefelter syndrom AGS <strong>og</strong> øvrige DSD<br />
Hyp<strong>of</strong>yse<br />
insufficiens<br />
Dårlig<br />
testikelfunktion<br />
Infertilitet<br />
Gynækomasti<br />
Pubertet<br />
<strong>Vækst</strong><br />
Cirka 10.000 patienter besøgte i 2012 afdelingens ambulatorium.<br />
Disse <strong>for</strong>deler sig mellem <strong>for</strong>skellige diagnosegrupper som<br />
vist i diagrammet. Patientgrupperne afspejler afdelingens fem<br />
<strong>for</strong>skningsområder: <strong>Vækst</strong>, Pubertet, Testikelfunktion, Testikulært<br />
Dysgenese Syndrom (TDS) <strong>og</strong> Disorders <strong>of</strong> Sex Development<br />
(DSD).<br />
4<br />
germinale celler <strong>og</strong> senere udvikles til sædceller).<br />
Testikulært dysgenese syndrom (TDS)<br />
betegner samlet de symptomer, der kan<br />
følge af at testiklen ikke udvikles hensigtsmæssigt.<br />
For eksempel kan nedsat<br />
testosteronproduktion medføre undervirilisering<br />
af drengefostret <strong>og</strong> dårlig testikelfunktion.<br />
Og hvis den tidlige udvikling<br />
af germinale celler går galt, kan de i<br />
visse tilfælde udvikle sig til testikelkræft,<br />
når drengefostret er blevet en ung m<strong>and</strong>.<br />
DSD (Disorders <strong>of</strong> Sex Development)<br />
betegner samlet de sygdomme, hvor<br />
kønsudviklingen i en eller <strong>and</strong>en grad er<br />
<strong>for</strong>styrret. Et eksempel er adren<strong>og</strong>enitalt<br />
syndrom (AGS), der hos pigefostre kan<br />
medføre, at kønsorganerne viriliseres,<br />
<strong>for</strong>di der dannes <strong>for</strong> mange hormoner<br />
med testosteron-lignende effekter.<br />
I puberteten vokser drengens testikler, spermat<strong>og</strong>onierne<br />
udvikles til sædceller, der dannes mere<br />
testosteron <strong>og</strong> penis <strong>og</strong> skrotum vokser. Hos pigen<br />
udvikles brystvævet, der dannes mere østr<strong>og</strong>en <strong>og</strong><br />
menstruationen starter. Hos begge køn kommer<br />
der kønsbehåring, svedlugt <strong>og</strong> uren hud, <strong>og</strong> efter<br />
n<strong>og</strong>et tid begynder pubertetsvækstspurten - en<br />
vækstacceleration der er drevet af køns- <strong>og</strong> væksthormoner.<br />
Puberteten kan hos n<strong>og</strong>le komme ekstremt<br />
tidligt eller meget sent. Endelig kan<br />
den helt udeblive. Det skyldes <strong>for</strong> eksempel,<br />
at signalerne fra hjernen, der skal<br />
starte puberteten, ikke fungerer hensigtsmæssigt<br />
(hyp<strong>of</strong>yseinsufficiens), eller at<br />
kønsorganerne ikke responderer på de<br />
signaler, der bliver sendt fra hjernen.<br />
Hos den voksne m<strong>and</strong> skal testikelfunktionen<br />
være i orden, <strong>for</strong> at m<strong>and</strong>en kan gøre sin partner<br />
gravid <strong>og</strong> producere tilstrækkeligt testosteron.<br />
Testosteron udøver vigtige funktioner både i <strong>og</strong><br />
uden <strong>for</strong> testiklerne, <strong>og</strong>så i voksenlivet.<br />
En del mænd har svært ved at gøre partneren<br />
gravid (infertilitet) eller har et <strong>for</strong><br />
lavt niveau af testosteron. Sidstnævnte<br />
kan medføre at m<strong>and</strong>en får brystvæv<br />
(gynækomasti). I n<strong>og</strong>le tilfælde skyldes<br />
symptomerne at testiklerne allerede i<br />
fosterlivet ikke blev udviklet normalt, i<br />
<strong>and</strong>re tilfælde er der tale om hyp<strong>of</strong>yseinsufficiens,<br />
men <strong>for</strong> langt de fleste mænd<br />
kender man ikke årsagen til infertilitet <strong>og</strong><br />
lave testosteronniveauer.
S e k r e t a r i a t e t e r a fd e l i n g e n s ke r n e<br />
7 lægesekretærer<br />
1 projektsekretær<br />
2 regnskabsmedarbejdere<br />
<strong>og</strong> en masse uundværlige studentermedhjælpere<br />
tager sig hvert år af:<br />
10.000 ambulante besøg<br />
18.000 journaldiktater<br />
15.000 telefonopkald<br />
16.000 personlige henvendelser<br />
I 2012 blev 2.000 nye patienter henvist til afdelingen.<br />
Af disse blev 98 % indkaldt inden otte hverdage.<br />
5<br />
Sekretariatet<br />
Der er travlt i sekretariatet. Herfra koordineres alle<br />
afdelingens aktiviteter. Telefonerne kimer, patienter,<br />
læger <strong>og</strong> <strong>and</strong>re kolleger stikker hovedet ind <strong>og</strong> får<br />
svar på alverdens spørgsmål. Det kan være svært at<br />
udføre sit arbejde under disse banegårdslignende<br />
<strong>for</strong>hold. Som et nyt tiltag er der der<strong>for</strong> oprettet stillezone<br />
i ambulatoriet, hvor lægesekretærerne på<br />
skift kan få fred <strong>og</strong> ro til at skrive journalnotater.<br />
De to regnskabsmedarbejdere tager sig af al økonomistyring,<br />
f.eks. administration af budgetter til patientbeh<strong>and</strong>ling<br />
<strong>og</strong> fondsbevillinger, personaleadministration<br />
<strong>og</strong> indhentning <strong>og</strong> analyse af aktivitetstal.
6<br />
Ambulatoriet<br />
I ambulatoriet kommer patienterne til ambulante<br />
læge- eller sygeplejebesøg. <strong>Afdeling</strong>en beh<strong>and</strong>ler<br />
patienter med vækstproblemer, hormonelle sygdomme,<br />
pubertets<strong>for</strong>styrrelser, m<strong>and</strong>lig infertilitet<br />
<strong>og</strong> sjældne hormonsygdomme, som kræver ekspertviden<br />
<strong>og</strong> et centraliseret beh<strong>and</strong>lingstilbud.<br />
<strong>Afdeling</strong>ens patienter henvises fra nærområdet, Region<br />
Hovedstaden <strong>og</strong> fra praktiserende læger, speciallæger<br />
<strong>og</strong> <strong>and</strong>re sygehusafdelinger i hele l<strong>and</strong>et.<br />
På en travl dag går op til 100 patienter igennem<br />
ambulatoriet, <strong>og</strong> 4-6 konsultationer er i gang samtidigt.<br />
Patienterne ses af speciallæger i pædiatri eller<br />
medicinsk endokrinol<strong>og</strong>i, som har ekspertfunktion i<br />
børneendokrinol<strong>og</strong>i <strong>og</strong>/eller medicinsk <strong>and</strong>rol<strong>og</strong>i,<br />
eller af læger under ekspertuddannelse med supervision<br />
af erfarne kollegaer.<br />
Fa c t s<br />
Vi samarbejder med mange specialambulatorier<br />
på hele Rigshospitalet <strong>og</strong> holder ugentlige fælleskonferencer<br />
med vores samarbejdspartnere.<br />
Ved den seneste nationale undersøgelse af patienttilfredshed<br />
var mere end 90 % af vores patienter<br />
tilfredse eller meget tilfredse med den beh<strong>and</strong>ling<br />
<strong>og</strong> in<strong>for</strong>mation, de har modtaget.<br />
<strong>Afdeling</strong>en samarbejder med patient<strong>for</strong>eninger,<br />
som Hyp<strong>of</strong>ysenetværket <strong>og</strong> Turner <strong>og</strong> AGS <strong>for</strong>eningen,<br />
omkring rådgivning <strong>og</strong> undervisning.<br />
<strong>Afdeling</strong>en er godkendt til ekspertuddannelse<br />
inden<strong>for</strong> pædiatrisk endokrinol<strong>og</strong>i af Dansk<br />
Pædiatrisk Selskab (DPS) <strong>og</strong> certificeret af European<br />
Academy <strong>of</strong> Androl<strong>og</strong>y til beh<strong>and</strong>ling af<br />
<strong>og</strong> uddannelse inden<strong>for</strong> m<strong>and</strong>lige reproduktionssygdomme.<br />
Følgende læger er eller har<br />
været i ekspertuddannelsesstilling hos os:<br />
Pæd. Endokrinol<strong>og</strong>i<br />
Rune Næraa<br />
Peter Christiansen<br />
Thøger Nielsen<br />
Kirsten Holm<br />
Anne Søe Højbjerg<br />
Eva Mosfeldt<br />
Per Kjærsgaard<br />
Dorte Hansen<br />
Kurt Kristensen<br />
Kirsten Holm<br />
Anders Johansen<br />
Anders Schou<br />
Androl<strong>og</strong>i<br />
Elisabeth Carlsen<br />
Mette Holm<br />
Jens Ingemansen*<br />
Jeanette B<strong>og</strong>stad*<br />
Tine Valentin † *<br />
Mette Petri Lauritsen*<br />
Mikkel Andreassen<br />
Torben Leo Nielsen<br />
Katarina Link<br />
Pia Ekbom<br />
*delestilling med<br />
fertilitetsklinikken
S ygeplejeambulatorium<br />
Vi har gennem de sidste fire år kørt med selvstændige<br />
sygeplejeambulatorier <strong>for</strong> udvalgte patientgrupper.<br />
Det fungerer ved at patienten med familie<br />
introduceres til beh<strong>and</strong>lerteamet (læge <strong>og</strong> sygeplejerske)<br />
ved de første ambulante besøg. Herefter<br />
<strong>for</strong>egår den ambulante kontrol skiftevis hos læge <strong>og</strong><br />
sygeplejerske. Undersøgelse <strong>og</strong> relevante blodprøver<br />
aftales fra gang til gang af beh<strong>and</strong>lerteamet i<br />
Tr a n s i t i o n s k l i n i k<br />
Når de børn <strong>og</strong> unge vi følger i afdelingen bliver<br />
gamle nok, skal de overflyttes fra vores ambulatorium<br />
til videre opfølgning på endokrinol<strong>og</strong>isk<br />
eller gynækol<strong>og</strong>isk afdeling på Rigshospitalet.<br />
Dette <strong>for</strong>egår typisk i 15-20 års alderen, afhængigt<br />
af patientens vækst, pubertets<strong>for</strong>løb <strong>og</strong> behov. For<br />
at gøre overgangen til voksenlægerne så skånsom<br />
som muligt arrangeres fælleskonsultationer med<br />
voksen endokrinol<strong>og</strong>er / gynækol<strong>og</strong>er. En såkaldt<br />
transitionsklinik.<br />
7<br />
fællesskab.<br />
Ordningen har været en stor succes. Beh<strong>and</strong>lingseffektivitet<br />
er uændret god, overfyldte lægeambulatorier<br />
aflastes <strong>og</strong> sygeplejerskens job bliver mere<br />
selvstændigt <strong>og</strong> fagligt ud<strong>for</strong>drende. Vigtigst er<br />
det d<strong>og</strong>, at der er kommet <strong>and</strong>re <strong>og</strong> nye aspekter<br />
frem ved de ambulante sygeplejekontroller end<br />
dem vi så ved de traditionelle lægekonsultationer.<br />
U n g e a m b a s s a d ø r e r<br />
En ungeambassadør er en<br />
sygeplejerske, som har særlige<br />
kvalifikationer, viden<br />
<strong>og</strong> interesse i at arbejde<br />
med, udvikle <strong>og</strong> optimere<br />
sygepleje til unge patienter.<br />
Hensigten er at fokusere på den unge <strong>og</strong> de særlige<br />
ud<strong>for</strong>dringer det giver, at leve med en kronisk<br />
sygdom <strong>og</strong> <strong>for</strong>tsat være ung som alle <strong>and</strong>re.<br />
Sygeplejerske Louise Nøttrup fra afdelingen (til<br />
højre) var en af de første på Rigshospitalet til at<br />
uddanne sig til ungeambassadør. Sygeplejerske<br />
Tanja Rosenberg (til venstre) følger nu i hendes<br />
fodspor.
Hormoner<br />
<strong>Afdeling</strong>ens hormonlaboratorium står <strong>for</strong> analyse<br />
af blod- <strong>og</strong> urinprøver fra patienter såvel som projektdeltagere.<br />
Hormonanalyser er en helt essentiel<br />
del af patientudredningen <strong>og</strong> en vigtig brik i adskillige<br />
af afdelingens <strong>for</strong>skningsprojekter. I figuren<br />
neden<strong>for</strong> listes de hormoner <strong>og</strong> bindingsprote-<br />
HYPOFYSE<br />
GH<br />
FSH<br />
LH<br />
BINYRER<br />
17α-hydroxypr<strong>og</strong>esteron<br />
Androstenedion<br />
DHEA<br />
DHEAS<br />
LEVER<br />
IGF-I<br />
IGFBP-3<br />
SHBG<br />
TESTIKLER<br />
OVARIER<br />
Testosteron<br />
Østradiol<br />
AMH<br />
Inhibin A <strong>og</strong> B<br />
8<br />
iner - alle vigtige <strong>for</strong> kroppens vækst <strong>og</strong> reproduktionsevne<br />
- der analyseres i laboratoriet. Bemærk at<br />
hormonerne DHEA, DHEAS, <strong>and</strong>rostenedion <strong>og</strong><br />
17α-hydroxypr<strong>og</strong>esteron, der her er placeret under<br />
binyrerne, <strong>og</strong>så dannes i mindre mængder i ovarier<br />
<strong>og</strong> testikler.
S e n s i t i v a n a l y s e t i l s t e r o i d h o r m o n e r<br />
Kendskab til niveauet af <strong>for</strong>skellige steroidhormoner<br />
i serum er vigtig i udredning af børn med DSD<br />
<strong>og</strong> pubertetsrelaterede sygdomme. Kvantitative<br />
hormonanalyser <strong>for</strong>etages normalt ved brug af<br />
immunanalyser, der imidlertid er uegnede til bestemmelse<br />
af de lave koncentrationer som <strong>for</strong> eksempel<br />
ses hos børn før puberteten.<br />
Der<strong>for</strong> har afdelingen, med <strong>for</strong>sker Tue Søeborg i<br />
spidsen, indført en avanceret, følsom <strong>og</strong> selektiv<br />
analysemetode, der benytter væskekromat<strong>og</strong>rafi<br />
koblet til t<strong>and</strong>em massespektrometri (LC-MS/MS).<br />
T e s t o s t e r o n o g<br />
m e t a b o l i s k s y n d r o m<br />
Kan <strong>for</strong> lave testosteronniveauer spille en kausal<br />
rolle i udviklingen af metabolisk syndrom <strong>og</strong> dermed<br />
være en risik<strong>of</strong>aktor <strong>for</strong> udvikling af type 2<br />
diabetes <strong>og</strong> hjertekarsygdomme? Eller er <strong>for</strong> lavt<br />
testosteron snarere et tidligt tegn på metaboliske<br />
<strong>for</strong>styrrelser? Det undersøger PhD studerende Stine<br />
Holmboe med afsæt i flere omfattende datasæt<br />
af mænd fra den danske befolkning. Hormondata<br />
inkluderer, udover testosteron målinger, <strong>og</strong>så<br />
SHBG <strong>og</strong> LH målinger.<br />
9<br />
LC-MS/MS<br />
Med denne metode kan vi nu kvantificere fem<br />
steroidhormoner i én analyse i langt størstedelen af<br />
serumprøver fra børn.<br />
Normalområder <strong>for</strong> steroidhormonerne DHEA,<br />
DHEAS, 17α-hydroxypr<strong>og</strong>esteron, <strong>and</strong>rostenedion<br />
<strong>og</strong> testosteron hos de 0-18 årige er nu etableret ved<br />
brug af LC-MS/MS analysen. De skal benyttes til<br />
bedre diagnosticering af afdelingens patienter <strong>og</strong> i<br />
<strong>for</strong>skningsprojekter. Snart vil tilsvarende normalområder<br />
<strong>og</strong>så blive etableret <strong>for</strong> østr<strong>og</strong>enerne.<br />
<strong>Afdeling</strong>ens hormonlaboratorium blev i <strong>for</strong>året<br />
2013 akkrediteret til medicinsk undersøgelse<br />
(Diagnostiske specialer: Biokemi <strong>og</strong> Prøvetagning)<br />
af Den Danske Akkrediterings- <strong>og</strong> Metrol<strong>og</strong>ifond<br />
(DANAK) efter st<strong>and</strong>arden DS/EN ISO 15189. Akkrediteringen<br />
er en anerkendelse af faglig kompetence,<br />
organisatorisk opbygning, uvildighed, faciliteter<br />
<strong>og</strong> udstyr samt af et velfungerende <strong>og</strong> dokumenteret<br />
kvalitetsstyringssystem. <strong>Afdeling</strong>slæge<br />
Trine Holm Johannsen har været tovholder på at få<br />
akkrediteringen i hus
M<strong>and</strong>lig fertilitet<br />
K l i n i k ke n<br />
Vi ser i klinikken stadigt flere<br />
mænd, der bliver henvist grundet<br />
problemer med at gøre deres partner<br />
gravid. Mændene gennemgår<br />
et omfattende udredningspr<strong>og</strong>ram<br />
<strong>for</strong> at finde frem til årsagen til den<br />
nedsatte frugtbarhed. Der kan væ-<br />
S æ d k valiteten b l a n d t d a n s ke m æ n d<br />
<strong>Afdeling</strong> <strong>for</strong> <strong>Vækst</strong> <strong>og</strong> <strong>Reproduktion</strong><br />
har siden 1996 undersøgt sædkvaliteten<br />
bl<strong>and</strong>t unge, normale,<br />
danske mænd. Resultaterne fra<br />
studiet, der er det største af sin<br />
slags, er samlet i en stor artikel,<br />
udgivet i BMJ Open i 2012.<br />
Konklusionerne er som følger:<br />
Den gennemsnitlige sædcellekoncentration<br />
er steget en anelse,<br />
fra 43 millioner/mL i 1996-2000<br />
til 48 millioner/mL i 2006-2010<br />
23 procent af de unge mænd har<br />
en optimal sædkvalitet<br />
E A A<br />
<strong>Afdeling</strong>en er certificeret af European<br />
Academy <strong>of</strong> Androl<strong>og</strong>y (EAA)<br />
til beh<strong>and</strong>ling <strong>og</strong> uddannelse inden<strong>for</strong><br />
m<strong>and</strong>lige reproduktionssygdomme.<br />
I 2012 bestod to af afdelingens<br />
yngre læger (Ulla Nordström<br />
Joensen <strong>og</strong> Martin Blomberg<br />
Jensen) den prestigeprægede EAA<br />
<strong>and</strong>rol<strong>og</strong>ieksamen, <strong>og</strong> kan dermed<br />
kalde sig EAA certificerede kliniske<br />
<strong>and</strong>rol<strong>og</strong>er.<br />
10<br />
re tale om aflukkede sædledere,<br />
manglende produktion af sædceller,<br />
genetiske eller kromosomale<br />
<strong>for</strong><strong>and</strong>ringer, eller ubalance i de<br />
hormoner, der regulerer funktionen<br />
af testiklerne.<br />
27 procent af de unge mænd har<br />
en sædkvalitet, der er så lav, at<br />
mændene s<strong>and</strong>synligvis vil være<br />
længere tid om at gøre deres<br />
partner gravid<br />
Herudover har 15 procent en<br />
sædkvalitet, der gør, at de s<strong>and</strong>synligvis<br />
får brug <strong>for</strong> fertilitetsbeh<strong>and</strong>ling<br />
<strong>for</strong> at få et barn<br />
D A S o g I C A 2 0 1 7<br />
Dansk Androl<strong>og</strong>isk Selskab (DAS),<br />
der har overlæge Niels Jørgensen<br />
fra afdelingen som <strong>for</strong>m<strong>and</strong>, er<br />
blevet udnævnt til at være vært <strong>for</strong><br />
den næste store <strong>og</strong> verdensomspændende<br />
<strong>and</strong>rol<strong>og</strong>ikonference<br />
ICA2017. Begivenheden finder sted<br />
i København i <strong>for</strong>året 2017. Se mere<br />
på www.<strong>and</strong>rol<strong>og</strong>y.dk
En grundig analyse af m<strong>and</strong>ens sædkvalitet er en<br />
helt essentiel del af de undersøgelser, et par med<br />
fertilitetsproblemer gennemgår.<br />
De nuværende metoder er manuelle <strong>og</strong> der<strong>for</strong> arbejdstunge.<br />
<strong>Afdeling</strong>en har der<strong>for</strong>, med senior<strong>for</strong>sker<br />
Kristian Almstrup i spidsen <strong>og</strong> i samarbejde<br />
med bl<strong>and</strong>t <strong>and</strong>et Chemometec A/S, startet et udviklingsprojekt<br />
finansieret af Højteknol<strong>og</strong>ifonden.<br />
N e x t g e n e ra t i o n s æ d a n a l y s e<br />
11<br />
S æ d k v a l i t e t o g<br />
f a m i l i e m ø n s t r e<br />
Er din fertilitet bestemt af din fars fertilitet? Og vil<br />
din søn arve din fertilitet? PhD studerende Lærke<br />
Priskorn undersøger, om der er en sammenhæng<br />
mellem sædkvalitet <strong>og</strong> familiemønstre i fertilitet.<br />
Dette belyses i både tidligere <strong>og</strong> efterfølgende generationer,<br />
ved brug af unikke københavnske databaser.<br />
S æ d k v a l i t e t o g<br />
g e n p o l y m o r f i e r<br />
Sædcelledannelsen styres af hormoner. Små variationer<br />
i de gener, der koder <strong>for</strong> hormonerne kan<br />
betyde, at de virker mindre effektivt. Det kan igen<br />
påvirke sædproduktionen. Disse sammenhænge<br />
undersøges af PhD studerende Anne Kirstine Bang.<br />
A f t a g e r<br />
t e s t i k e l f u n k t i o n e n<br />
m e d a l d e r e n ?<br />
Bliver testikelfunktionen dårligere med stigende<br />
alder hos mænd der har testikulært dysgenese<br />
syndrom (TDS)? Det undersøger PhD studerende<br />
Inge Ahlmann Olesen, bl<strong>and</strong>t <strong>and</strong>et ved kliniske<br />
undersøgelser af mænd, der <strong>for</strong> mange år siden<br />
blev diagnosticeret med et eller flere symptomer<br />
på TDS.<br />
Projektet ønsker at modernisere <strong>og</strong> <strong>for</strong>bedre den<br />
nuværende manuelle analyse, ved at tilføre ny<br />
viden <strong>og</strong> ved delvist at automatisere processen.<br />
Image cytometeret NC-3000, der er udviklet af<br />
Chemometec A/S, er en vigtig brik i denne automatisering.<br />
PhD studerende Dorte Egeberg identificerer<br />
i sit projekt relevante markører <strong>for</strong> sædkvalitet<br />
<strong>og</strong> validerer disse på image cytometeret.
<strong>Vækst</strong><br />
Væ k s t fo r s t y r r e l s e r<br />
Vi undersøger mange børn med <strong>for</strong> lille højde eller<br />
<strong>for</strong> stor højde. Højdemålinger vurderes på baggrund<br />
af kurver <strong>for</strong> danske børn. Vi bestemmer<br />
<strong>og</strong>så den biol<strong>og</strong>iske alder ved at tage et røntgenbillede<br />
af venstre hånd <strong>og</strong> vurdere kn<strong>og</strong>lealderen.<br />
Herved kan vi se hvor meget vækst der er til gode,<br />
<strong>og</strong> dermed komme med et kvalificeret bud på sluthøjden<br />
i voksenlivet. Mange børn med lille eller<br />
stor højde kan <strong>og</strong> skal ikke beh<strong>and</strong>les, men det er<br />
vigtigt at udelukke, at de har en underliggende<br />
sygdom som <strong>for</strong>klaring på vækst<strong>for</strong>styrrelsen.<br />
12<br />
N y e d a n s ke h ø j d e ku r v e r<br />
I Danmark har vi indtil nu anvendt 50 år gamle<br />
højdekurver, eller højdekurver baseret på svenske<br />
børn. Nu har vi udviklet helt nye højdekurver baseret<br />
på vores store kohorteundersøgelser af raske<br />
danske børn <strong>og</strong> unge. Vi er i fuld gang med at udgive<br />
disse data så vi kan sikre at de bliver tilgængelige<br />
<strong>for</strong> alle, der vurderer vækst på børn i Danmark.
B e s t e m m e l s e a f k n o g l e a l d e r<br />
I et samarbejde med det danske firma Visiana,<br />
medvirkede vi til udviklingen <strong>og</strong> valideringen af et<br />
nyt computerbaseret produkt (BoneXpert) til at<br />
bestemme kn<strong>og</strong>lealder. Dette startede som et<br />
<strong>for</strong>skningsprojekt, men BoneXpert er nu en uvurderlig<br />
del af vores kliniske hverdag, <strong>og</strong> pr<strong>og</strong>rammet<br />
anvendes mange steder i verden.<br />
B e h a n d l i n g m e d v æ k s t h o r m o n<br />
<strong>Vækst</strong>hormonmangel kan være genetisk betinget<br />
eller en følge af bestråling af hjernen eller<br />
operation <strong>for</strong> en hjernetumor.<br />
Beh<strong>and</strong>ling med væksthormon har <strong>og</strong>så god<br />
virkning hos <strong>and</strong>re patientkategorier, som piger<br />
med Turner syndrom, børn med lav højde som<br />
er født med lav fødselsvægt (SGA), lav højde på<br />
grund af kronisk nyresygdom <strong>og</strong> børn med Prader<br />
Willi Syndrom.<br />
<strong>Afdeling</strong>en varetager væksthormonbeh<strong>and</strong>ling<br />
af alle ovennævnte patientkategorier.<br />
Beh<strong>and</strong>ling hjælper ikke alle med lav højde. Et<br />
barn med lille højde, normal væksthormondannelse<br />
<strong>og</strong> uden <strong>and</strong>re årsager til væksthæmning<br />
har sjældent gavn af væksthormon.<br />
Beh<strong>and</strong>lingen justeres efter vækstrespons, kn<strong>og</strong>lemodning<br />
<strong>og</strong> vækstfaktoren IGF-I. Sidstnævnte<br />
afspejler gennemsnitsmængden af væksthormon<br />
i kroppen <strong>og</strong> er et godt mål <strong>for</strong>, hvor meget<br />
hormon, man skal dosere. IGF-I <strong>og</strong> dets bindingsprotein<br />
måles i afdelingens hormonlaboratorium,<br />
<strong>og</strong> niveauerne sammenlignes med normalområdet<br />
på >5000 raske individer. Dette<br />
muliggør en skræddersyet beh<strong>and</strong>ling.<br />
F o r s k n i n g i b e h a n d l i n g m e d v æ k s t h o r m o n s e r<br />
Vi <strong>for</strong>sker i, hvordan IGF-I påvirker vækst, sukkerst<strong>of</strong>skifte<br />
<strong>og</strong> kropssammensætning hos børn <strong>og</strong><br />
voksne <strong>og</strong> i betydningen af genetiske variationer i<br />
væksthormonreceptor-genet. Derudover koordinerer<br />
afdelingens læger det nordeuropæiske multicenterstudium<br />
NESGAS (North European Small<br />
13<br />
<strong>for</strong> Gestational Age Study). I NESGAS-projektet<br />
undersøger vi virkningen af <strong>for</strong>skellige doser af<br />
væksthormon på vækst, kn<strong>og</strong>lemodning, kropssammensætning<br />
<strong>og</strong> sukkerst<strong>of</strong>skifte. Undersøgelsen<br />
modtager økonomisk støtte fra Novo Nordisk.
Pubertet<br />
Puberteten er en milepæl i et menneskes udvikling.<br />
Vi <strong>for</strong>sker i hvordan genetiske faktorer styrer<br />
<strong>og</strong> påvirker pubertetsstart <strong>og</strong> -udvikling. Gennem<br />
de sidste 10 år har vi i Danmark set en markant<br />
stigning i antallet af piger, der henvises grundet<br />
mistanke om <strong>for</strong> tidlig pubertet. Vores populationsundersøgelser<br />
af raske skolebørn The COPEN-<br />
HAGEN Puberty Study har entydigt vist, at gennemsnitsalderen<br />
<strong>for</strong> pubertetens start har ændret<br />
sig, idet en gennemsnitlig dansk pige nu får brystudvikling<br />
i 10 års alderen, mens det skete i 11 års<br />
alderen <strong>for</strong> blot 20 år siden. Vi kender ikke årsagerne<br />
til disse markante ændringer, men vi <strong>for</strong>moder<br />
at svaret findes i ændret livsstil, fedme, fysisk<br />
inaktivitet eller faktorer vi udsættes <strong>for</strong> i miljøet.<br />
A M H h o s p i g e r<br />
Hos kvinder er AMH en markør <strong>for</strong> ægreserven.<br />
Hormonet har imidlertid været dårligt undersøgt<br />
bl<strong>and</strong>t piger før <strong>og</strong> under puberteten. PhD studerende<br />
Casper Hagen undersøger, hvordan hormonet<br />
udtrykkes hos normale piger i <strong>for</strong>skellige aldre,<br />
hos børn med <strong>for</strong> tidlig <strong>og</strong> <strong>for</strong> sen pubertet <strong>og</strong><br />
bl<strong>and</strong>t patienter med påvirket kønsdifferentiering.<br />
Eksempel på nyligt udgivet artikel, der viser at<br />
særlige små genetiske variationer har betydning<br />
<strong>for</strong> drenges fedtophobning. Artiklen er baseret på<br />
data fra The COPENHAGEN Puberty Study.<br />
14<br />
P u b e r t a s p ræ c ox<br />
Pubertas præcox (PP) er den kliniske betegnelse<br />
<strong>for</strong> <strong>for</strong> tidlig pubertet.<br />
PP defineres ved pubertetsstart før 8 års alderen<br />
hos piger <strong>og</strong> før 9 års alderen hos drenge.<br />
PP kan skyldes ændringer i hjernen (central PP)<br />
eller hormonpåvirkning fra <strong>and</strong>re organer<br />
(perifer PP). I mange tilfælde er årsagen ukendt.<br />
PP er associeret med lav sluthøjde <strong>og</strong> øget risiko<br />
<strong>for</strong> metabolisk syndrom <strong>og</strong> psykosociale problemer.<br />
Hvis PP opdages i tide, kan puberteten bremses<br />
medicinsk. Herved lettes de psykol<strong>og</strong>iske vanskeligheder<br />
<strong>og</strong> der opnås større sluthøjde. Det er<br />
d<strong>og</strong> langtfra alle, som bør tilbydes beh<strong>and</strong>ling.<br />
<strong>Afdeling</strong>en fik alene i 2012 henvist 172 børn<br />
med diagnosen pubertas præcox.<br />
B i n y r e r o g p u b e r t e t<br />
Binyrerne danner steroidhormoner, som <strong>for</strong> eksempel<br />
DHEAS, der virker lidt som testosteron.<br />
Under puberteten er disse bl<strong>and</strong>t <strong>and</strong>et bestemmende<br />
<strong>for</strong> pubesbehåring <strong>og</strong> svedlugt. PhD studerende<br />
Annette Mouritsen har i sit projekt set på<br />
sammenhænge mellem binyrernes produktion af<br />
steroidhormoner, binyrernes størrelse målt ved MR<br />
skanning <strong>og</strong> udviklingen af pubeshår. Desuden<br />
undersøges ovenstående i <strong>for</strong>hold til udvalgte genetiske<br />
variationer <strong>og</strong> eksponering til hormon<strong>for</strong>styrrende<br />
st<strong>of</strong>fer (phthalater).
H j æ l p t i l p a t i e n t e r i r i s i k o f o r a t f å s k a d e t s æ d p r o d u k t i o n e n<br />
Mænd, der skal igennem en beh<strong>and</strong>ling, der kan<br />
ødelægge deres sædproduktion, har på afdelingen<br />
mulighed <strong>for</strong> at få nedfrosset en sædprøve, før<br />
beh<strong>and</strong>lingen startes. Der er især tale om yngre<br />
gigtpatienter <strong>og</strong> patienter, der skal gennemgå strålebeh<strong>and</strong>ling<br />
eller kemoterapi pga. testikelkræft,<br />
leukæmi, lymfeknudekræft eller kræft i kn<strong>og</strong>ler <strong>og</strong><br />
bindevæv. Disse kræft<strong>for</strong>mer rammer typisk yngre<br />
mænd, <strong>og</strong> der er gode chancer <strong>for</strong>, at de bliver kurerede<br />
<strong>for</strong> sygdommen. Nedfrysning af sæd giver<br />
god mulighed <strong>for</strong>, at mændene senere kan blive<br />
fædre, <strong>og</strong>så selvom deres <strong>for</strong>plantningsevne måske<br />
har taget varig skade på grund af beh<strong>and</strong>lingen.<br />
Heldigvis helbredes de fleste børn med kræft, <strong>og</strong><br />
har således et langt liv at se frem til. Drenge i den<br />
15<br />
Sædopbevaring<br />
tidlige pubertet har <strong>og</strong>så mulighed <strong>for</strong> at lave en<br />
sædprøve, enten selv eller ved hjælp af elektrostimulation.<br />
Derved optimeres <strong>og</strong>så deres chancer <strong>for</strong><br />
senere at kunne blive fædre.<br />
Sædbanken er en udstrakt hånd, ikke kun til patienterne,<br />
men <strong>og</strong>så til de beh<strong>and</strong>lende afdelinger.<br />
Vi har et tæt samarbejde med disse afdelinger, både<br />
<strong>for</strong>di det letter hurtig organisering af en nedfrysning,<br />
inden en akut beh<strong>and</strong>ling, men <strong>og</strong>så <strong>for</strong>di<br />
vi derved sammen kan følge et højt prioriteret<br />
<strong>for</strong>skningsområde: Hvordan kan kræftbeh<strong>and</strong>lingers<br />
skadelige virkning på <strong>for</strong>plantningsevnen<br />
mindskes, uden at man samtidig begrænser beh<strong>and</strong>lingens<br />
effektivitet?
Disorders <strong>of</strong> Sex Development (DSD)<br />
Når vi i fostertilværelsen udvikles til dreng eller<br />
pige, <strong>og</strong> senere i livet til m<strong>and</strong> eller kvinde, skal<br />
mange ydre <strong>og</strong> indre faktorer spille sammen:<br />
udvikling af kønskirtler til ovarier eller testikler<br />
kønskromosomer<br />
funktion af<br />
hormonreceptorer<br />
dannelse af m<strong>and</strong>lige <strong>og</strong> kvindelige<br />
hormoner i binyrer <strong>og</strong> kønskirtler<br />
D S D i d e t a l j e r<br />
dannelse af<br />
overordnede<br />
kønshormoner<br />
i hyp<strong>of</strong>ysen<br />
KØNSKROMOSOMER<br />
DSD kan ses hos mennesker, der ikke har de<br />
'typiske' kromosomer, nemlig 46XX <strong>for</strong> piger/<br />
kvinder <strong>og</strong> 46XY <strong>for</strong> drenge/mænd. De kan have<br />
ekstra kønskromosomer, hvilket ses hos mænd<br />
med Klinefelter syndrom (2 eller flere X kromosomer)<br />
<strong>og</strong> kvinder med Triple X syndrom. De kan<br />
<strong>og</strong>så have <strong>for</strong> få kønskromosomer, eksempelvis<br />
har kvinder med Turner syndrom kun ét X kromosom.<br />
Endelig er der mosaiktilst<strong>and</strong>e, hvor celler i<br />
46XY females<br />
Persistent mullerian duct syndrome<br />
Turner syndrom<br />
Adren<strong>og</strong>enitalt<br />
syndrom<br />
Hyp<strong>og</strong>onadotrop hyp<strong>og</strong>onadisme<br />
Klinefelter syndrom<br />
Andr<strong>og</strong>en insensitivitetssyndrom 45X/46XY<br />
SRY positive XX-males<br />
Vi har diagnosticeret <strong>og</strong> beh<strong>and</strong>let mere end 500 patienter med<br />
<strong>for</strong>skellige <strong>for</strong>mer <strong>for</strong> DSD. Lagkagediagrammet viser den<br />
procentvise <strong>for</strong>deling af de <strong>for</strong>skellige tilst<strong>and</strong>e. Bemærk: Klinefelter<br />
syndrom dækker både over 47XXY, 48XXXY <strong>og</strong> 46XY/<br />
47XXY mosaikker, <strong>and</strong>r<strong>og</strong>en insensitivitetssyndrom inkluderer<br />
både den partielle <strong>og</strong> den komplette <strong>for</strong>m, <strong>og</strong> gruppen af<br />
46XY females dækker dem, der ikke har en kendt ætiol<strong>og</strong>i.<br />
16<br />
Udviklingen kan <strong>for</strong>styrres, hvis én af de i figuren<br />
viste faktorer ikke er til stede, ikke virker eller virker<br />
<strong>for</strong> kraftig. Disse tilst<strong>and</strong>e kaldes samlet disorders<br />
<strong>of</strong> sex development (DSD). DSD dækker bredt<br />
<strong>og</strong> inkluderer således milde <strong>for</strong>mer af hypospadi<br />
såvel som sværere tilst<strong>and</strong>e hvor hormonbeh<strong>and</strong>ling<br />
kan være nødvendigt. I n<strong>og</strong>le tilfælde <strong>for</strong>etages<br />
operation, <strong>for</strong>di de ydre <strong>og</strong> indre kønsorganer<br />
kan være misdannede. Da piger <strong>og</strong> drenge vokser<br />
<strong>for</strong>skelligt, kan ændret vækst<strong>for</strong>løb <strong>og</strong> sluthøjde<br />
<strong>og</strong>så <strong>for</strong>ekomme.<br />
Vores afdeling har ekspertfunktion i disse tilst<strong>and</strong>e,<br />
<strong>og</strong> vi ser mange patienter fra hele l<strong>and</strong>et, Grønl<strong>and</strong><br />
<strong>og</strong> Færøerne.<br />
kroppen har <strong>for</strong>skelligt antal kønskromosomer<br />
(eks. 45X/46XY eller 45X/46XX).<br />
HORMONER<br />
For meget m<strong>and</strong>ligt hormon kan give piger et maskulint<br />
præg med øget behåring, stor klitoris <strong>og</strong><br />
<strong>for</strong>styrret cyklus <strong>og</strong> ægløsning (Adren<strong>og</strong>enitalt<br />
syndrom (AGS) <strong>og</strong> Polycystisk ovariesyndrom,<br />
(PCOS)).<br />
Hos drenge kan <strong>for</strong> lidt effekt af m<strong>and</strong>ligt hormon<br />
eller <strong>for</strong> meget kvindeligt hormon give et mere<br />
feminint præg, med små kønsorganer, brystudvikling<br />
<strong>og</strong> <strong>for</strong>styrret sædproduktion (Partiel <strong>and</strong>r<strong>og</strong>en<br />
insensitivitetssyndrom (PAIS)).<br />
Mangel på overordnede kønshormoner (luteiniserende<br />
hormon (LH) <strong>og</strong> follikelstimulerende hormon<br />
(FSH)) gør, at man ikke selv går i pubertet <strong>og</strong><br />
skal have hjælp til at få børn. Kønskirtler <strong>og</strong> kønsorganer<br />
er i øvrigt helt almindelige. N<strong>og</strong>le af disse<br />
patienter har ingen lugtesans (Kallman syndrom<br />
<strong>og</strong> hyp<strong>og</strong>onadotrop hyp<strong>og</strong>onadisme).<br />
N<strong>og</strong>le teenagepiger eller unge kvinder kan gå<br />
i ekstrem tidlig overgangsalder <strong>og</strong> når der<strong>for</strong> aldrig<br />
at få egne børn (præmatur ovarian failure).<br />
RECEPTORER<br />
Receptorer er vore cellers hormonfølere. N<strong>og</strong>le<br />
mennesker danner testosteron, men kroppen kan<br />
ikke 'aflæse' dette hormon, <strong>for</strong>di receptorerne ikke<br />
virker. Dette kaldes <strong>og</strong>så komplet <strong>and</strong>r<strong>og</strong>en insensitivitetssyndrom<br />
(CAIS) eller Morris syndrom.<br />
Kroppen reagerer således kun på de kvindelige<br />
hormoner, <strong>og</strong> man fødes som pige, der senere udvikler<br />
sig til en kvinde helt uden kønsbehåring.
D S D f o r s k n i n g o g b e h a n d l i n g<br />
Hos en del patienter kan vi ikke finde en egentlig<br />
årsag til deres sygdom. Der<strong>for</strong> er dette et af vores<br />
indsatsområder i <strong>for</strong>skningen. Her interesserer vi<br />
os <strong>for</strong> alt fra den helt tidlige udvikling af reproduktionsorganer<br />
<strong>og</strong> reproduktionsfunktion til betydning<br />
af livsstil <strong>og</strong> udsættelse <strong>for</strong> hormon<strong>for</strong>styrrende<br />
kemikalier fra miljøet.<br />
P e s t i c i d e r f ø r f ø d s l e n<br />
o g s e n e r e u d v i k l i n g<br />
Dyrestudier viser, at hvis man udsættes <strong>for</strong> hormon<strong>for</strong>styrrende<br />
st<strong>of</strong>fer, som <strong>for</strong> eksempel pesticider,<br />
før man bliver født, kan det senere påvirke<br />
både vækst <strong>og</strong> <strong>for</strong>plantningsevne. PhD Christine<br />
Wohlfahrt Veje fulgte i sit nu afsluttede PhD projekt<br />
en kohorte af børn, hvis mødre arbejdede i<br />
gartneri under graviditeten. Hun f<strong>and</strong>t at drenge,<br />
der var blevet udsat <strong>for</strong> pesticider i deres tidlige<br />
fosterliv, havde en lavere fødselsvægt, højere fedtprocent<br />
i skolealderen <strong>og</strong> mindre kønsorganer. For<br />
pigerne f<strong>and</strong>t hun tidligere brystudvikling.<br />
Manglende dannelse af overordnede kønshormoner<br />
(FSH <strong>og</strong> LH) kan være medfødt <strong>og</strong> genetisk<br />
betinget (hyp<strong>og</strong>onadotrop hyp<strong>og</strong>onadisme inkl.<br />
Kallmans syndrom). Det kan <strong>og</strong>så skyldes <strong>and</strong>re<br />
erhvervede hyp<strong>of</strong>ysesygdomme, som <strong>for</strong> eksempel<br />
følge af krani<strong>of</strong>aryngeom eller hæmokromatose.<br />
M a r k ø r e r f o r L e y d i g c e l l e r n e s u d v i k l i n g<br />
Leydig cellerne er ansvarlige <strong>for</strong> at danne testosteron,<br />
både i fostertilværelsen <strong>og</strong> i voksenlivet. Hvis<br />
de ikke udvikles <strong>og</strong> fungerer ordentligt, kan det<br />
betyde manglende testosteronproduktion. Det ses<br />
<strong>for</strong> eksempel hos patienter med Klinefelter syndrom.<br />
Også patienter med adren<strong>og</strong>enitalt syndrom<br />
(AGS) har store områder i testiklerne med<br />
17<br />
M i n i p u b e r t e t e n<br />
Hyp<strong>of</strong>ysens dannelse af FSH <strong>og</strong> LH er ikke aktiv ved<br />
fødslen, men aktiveres voldsomt i 2-3 måneders alderen,<br />
hvilket medfører stigning i serum testosteron <strong>og</strong><br />
<strong>and</strong>re testikelhormoner som inhibin B <strong>og</strong> AMH.<br />
I 6 måneders alderen er denne <strong>for</strong>bigående hormonaktivitet<br />
- som vi kalder minipuberteten – lukket ned igen.<br />
Og hormonerne stiger først 11-12 år senere når puberteten<br />
starter.<br />
Minipuberteten er væsentlig at kende til når man udreder<br />
nyfødte drenge med misdannede kønsorganer,<br />
kønskromosomfejl <strong>og</strong> manglende testikler i pungen.<br />
H y p o g o n a d o t r o p h y p o g o n a d i s m e i n k l u s i v e K a l l m a n s s y n d r o m<br />
<strong>Afdeling</strong>en følger >50 patienter med hyp<strong>og</strong>onadotrop<br />
hyp<strong>og</strong>onadisme, som <strong>of</strong>te fødes med underudviklede<br />
kønsorganer <strong>og</strong> ikke nedsunkne testikler. Beh<strong>and</strong>ling i<br />
pubertet <strong>og</strong> voksenliv søger at normalisere pubertetsudviklingen<br />
<strong>og</strong> testosteronniveauer. Injektioner med<br />
FSH <strong>og</strong> hCG kan sætte sædcelleproduktionen i gang.<br />
Leydig celle lignende celler, de såkaldte adrenal rests<br />
eller Leydig celle noduli (se billedet på denne side).<br />
PhD studerende Grete Lottrup undersøger i sit projekt<br />
en række markører <strong>for</strong> Leydig celle udvikling, både hos<br />
raske mennesker <strong>og</strong> hos mennesker med <strong>for</strong>skellige<br />
<strong>for</strong>mer <strong>for</strong> DSD.
Testikelsyndromet TDS<br />
Ved testikulært dysgenese syndrom (TDS) går<br />
n<strong>og</strong>et galt i testiklernes udvikling, hvorved de<br />
sæddannende <strong>og</strong> hormonproducerende væv påvirkes,<br />
i n<strong>og</strong>le tilfælde med varige konsekvenser.<br />
TDS kan vise sig allerede ved fødslen som kryptorkisme<br />
<strong>og</strong>/eller hypospadi. Kryptorkisme er manglende<br />
nedstigning af den ene eller begge testikler<br />
til pungen, mens hypospadi er en misdannelse af<br />
penis, hvor urinrøret udmunder på siden af penis i<br />
stedet <strong>for</strong> på spidsen. TDS kan <strong>og</strong>så komme til<br />
T D S o g g e n e t i s k d i s p o s i t i o n<br />
I hvor høj grad er mænd genetisk disponerede <strong>for</strong><br />
TDS? <strong>Afdeling</strong>en har, med PhD studerende Marlene<br />
Dalgaard i spidsen <strong>og</strong> i samarbejde med DTUs<br />
Center <strong>for</strong> Biol<strong>og</strong>ical Sequence Analysis (CBS) undersøgt<br />
dette i et såkaldt Genome Wide Association<br />
Study (GWAS) på en kohorte af 926 danske<br />
mænd. Ved at kombinere GWAS analyserne med<br />
18<br />
udtryk i voksenlivet, <strong>for</strong> eksempel i <strong>for</strong>m af en<br />
<strong>for</strong>ringet sædkvalitet eller lave testosteronniveauer.<br />
I n<strong>og</strong>le tilfælde ses <strong>og</strong>så testikelkræft hos yngre<br />
mænd.<br />
Pr<strong>of</strong>essor Niels E Skakkebæk, der grundlagde <strong>og</strong><br />
stadig er <strong>for</strong>sker i afdelingen, står bag hypotesen<br />
om TDS. <strong>Afdeling</strong>en har i mange år <strong>for</strong>sket i syndromets<br />
biol<strong>og</strong>i, årsager <strong>og</strong> udbredelse, ligesom<br />
mange <strong>and</strong>re <strong>for</strong>skningsgrupper nu beskæftiger<br />
sig med området.<br />
systembiol<strong>og</strong>i f<strong>and</strong>t vi n<strong>og</strong>le single nucleotid polymorfier<br />
(SNPs), der var associerede til gener med<br />
betydning <strong>for</strong> den tidlige testikeludvikling, <strong>og</strong> derved<br />
kan være relevante <strong>for</strong> TDS. Specielt viste<br />
SNPs i TGF-beta signalvejen at være højt repræsenteret,<br />
ligesom vi f<strong>and</strong>t associationer mellem variationer<br />
i KITLG genet <strong>og</strong> udvikling af testikelkræft.
B r y s t u d v i k l i n g h o s d r e n g e o g m æ n d<br />
<strong>Afdeling</strong>en har siden 2009 modtaget <strong>og</strong> udredt alle<br />
mænd, der henvises til Rigshospitalet på mistanke<br />
om gynækomasti. Det er ca. 300 mænd årligt. Det<br />
har givet os mulighed <strong>for</strong> at <strong>for</strong>ske i årsager til <strong>og</strong><br />
<strong>for</strong>ekomsten af gynækomasti, der ellers tidligere<br />
har været oversete <strong>for</strong>skningsområder.<br />
Å r s a g e r t i l<br />
g y n æ k o m a s t i<br />
I de fleste tilfælde kender man ikke årsagen til, at<br />
en dreng eller en m<strong>and</strong> udvikler gynækomasti.<br />
PhD studerende Mikkel Mieritz vurderer i sit projekt<br />
betydningen af kropssammensætning, vækst,<br />
udvalgte genetiske variationer samt kønshormoner<br />
<strong>for</strong> udviklingen af gynækomasti i puberteten. Desuden<br />
undersøger han underliggende årsager til<br />
gynækomasti hos cirka 1200 voksne mænd.<br />
19<br />
H v a d e r g y n æ ko m a s t i ?<br />
Gynækomasti er den kliniske betegnelse <strong>for</strong><br />
brystudvikling hos drenge <strong>og</strong> mænd.<br />
Gynækomasti er meget almindelig omkring<br />
puberteten, hvor op til halvdelen af alle drenge<br />
udvikler brystkirtelvæv. Det er helt ufarligt <strong>og</strong><br />
<strong>for</strong>svinder hos langt de fleste igen i løbet af cirka<br />
et år.<br />
Hos voksne mænd kan gynækomasti skyldes<br />
mange <strong>for</strong>skellige sygdomme (<strong>for</strong> eksempel<br />
hormonsygdomme, lever- eller nyresygdom <strong>og</strong> i<br />
sjældne tilfælde testikelkræft). Det kan <strong>og</strong>så ses<br />
som bivirkning til <strong>for</strong>skellig medicin, men i<br />
mange tilfælde kan man d<strong>og</strong> ikke finde årsagen.<br />
Det er vigtigt, at man sikrer sig at brystudviklingen<br />
ikke skyldes en sygdom. Der<strong>for</strong> skal drengene<br />
<strong>og</strong> mændene have undersøgt deres hormoner,<br />
lever <strong>og</strong> nyrer <strong>og</strong> have lavet ultralydsscanning<br />
af testiklerne (se billedet).<br />
Hvis man finder en udløsende årsag til brystudviklingen,<br />
beh<strong>and</strong>les denne. Hvis ikke ser man<br />
<strong>of</strong>te tiden an, men i n<strong>og</strong>le tilfælde kan kirurgi<br />
komme på tale.<br />
<strong>Afdeling</strong>en <strong>for</strong>sker i årsagerne til gynækomasti<br />
både hos drenge <strong>og</strong> voksne mænd. Man ved<br />
ikke præcis, hvor<strong>for</strong> n<strong>og</strong>le udvikler gynækomasti<br />
<strong>og</strong> <strong>and</strong>re ikke gør, men har en mistanke<br />
om det skyldes ubalance i hormonerne, specielt<br />
<strong>for</strong> meget østr<strong>og</strong>en.
Genetik<br />
Der ligger mange årsager bag de sygdomme vi<br />
arbejder med i afdelingen. Hos n<strong>og</strong>le er årsagen<br />
genetisk, <strong>og</strong> kan dermed findes ved at undersøge<br />
kromosomerne eller udvalgte gener. Neden<strong>for</strong> er<br />
givet n<strong>og</strong>le eksempler på afdelingens genetiske<br />
<strong>for</strong>skningsområder <strong>og</strong> diagnostiske værktøjer.<br />
S H O X p å k ø n s k r o m o s o m e r n e<br />
Mænd med Klinefelter syndrom (47,XXY) <strong>og</strong> kvinder<br />
med Turner syndrom (45,X) har et unormalt<br />
antal kønskromosomer. Diagnoserne kan stilles<br />
ved en traditionel karyotyping. Vi har etableret en<br />
supplerende molekylærbiol<strong>og</strong>isk analyse, der måler<br />
antallet af SHOX-gen kopier (der sidder på begge<br />
kønskromosomer). SHOX-genet koder <strong>for</strong> et<br />
protein, der øger kn<strong>og</strong>lernes vækst. Antallet af<br />
aktive SHOX-gen kopier kan således delvist <strong>for</strong>klare,<br />
hvor<strong>for</strong> Klinefelter mænd <strong>of</strong>te har lange ben <strong>og</strong><br />
arme (tre SHOX-gen kopier) <strong>og</strong> hvor<strong>for</strong> Turner<br />
kvinder er karakteriserede ved lav højde (én SHOX<br />
-gen kopi). Vi <strong>for</strong>etager SHOX-analysen hos patienter<br />
med stor eller lille højde, uanset om vi mistænker,<br />
at de har Klinefelter/Turner syndrom. Hos<br />
enkelte mennesker ses der nemlig afvigelser i<br />
SHOX-genet, der kan <strong>for</strong>klare ændret vækst, uden<br />
at disse patienter d<strong>og</strong> har et ændret antal kønskromosomer.<br />
Mulighed <strong>for</strong> screening i fremtiden<br />
SHOX-analysen virker <strong>og</strong>så på DNA oprenset fra<br />
den bloddråbe, der tages fra alle nyfødte til screening<br />
<strong>for</strong> alvorlige sygdomme (PKU blodprøven).<br />
Det åbner mulighed <strong>for</strong>, at man i fremtiden kan<br />
screene nyfødte <strong>for</strong> Klinefelter <strong>og</strong> Turner syndrom.<br />
20<br />
Y k r o m o s o m e t s s k r ø b e l i g h e d<br />
M<strong>and</strong>ens Y kromosom indeholder mange gener<br />
med stor betydning <strong>for</strong> sædcelledannelsen. Især ét<br />
område på Y kromosomet, AZF-regionen, der inddeles<br />
i AZFa, b <strong>og</strong> c, er vist at have stor betydning.<br />
Hele Y kromosomet, inklusiv AZF-regionen, har en<br />
struktur med en høj grad af gentagne identiske<br />
sekvenser. En sådan struktur øger risikoen <strong>for</strong> tab<br />
af DNA (deletioner). For at opspore sådanne afvigelser<br />
hos patienter har vi etableret en molekylærbiol<strong>og</strong>isk<br />
test, der viser tilstedeværelsen af små<br />
genetiske markører, der er spredt over hele Y kromosomet.<br />
Patientens kliniske billede afhænger af<br />
størrelsen <strong>og</strong> typen af afvigelsen. En patient med<br />
en stor deletion (<strong>for</strong> eksempel tab af AZFa eller b)<br />
kan ikke danne sædceller. En mindre deletion i<br />
AZFc kan resultere i alt fra fravær af sædceller til<br />
nedsat eller næsten normalt sædcelledannelse.<br />
Afvigelserne kan ikke beh<strong>and</strong>les, men mænd, der<br />
stadig danner sædceller, kan hjælpes via kunstig<br />
befrugtning. Det er d<strong>og</strong> vigtigt at huske, at sønner<br />
kan arve Y kromosomets afvigelser <strong>og</strong> dermed<br />
have risiko <strong>for</strong> fertilitetsproblemer som voksen.<br />
K l i n e f e l t e r o g g e n e r<br />
p å X k r o m o s o m e t<br />
Mænd med Klinefelter syndrom er <strong>of</strong>test infertile<br />
<strong>for</strong>di sædcelledannelsen ikke fungerer. Man kender<br />
ikke årsagen, men involverede gener må være<br />
placerede på X kromosomet. PhD studerende S<strong>of</strong>ia<br />
Winge karakteriserer i sit projekt mekanismer <strong>og</strong><br />
gener, der er ansvarlige <strong>for</strong> fænomenet.
21<br />
G e n e t i s k va r i a t i o n<br />
Mennesker er <strong>for</strong>skellige, bl<strong>and</strong>t <strong>and</strong>et <strong>for</strong>di der er<br />
små variationer (polymorfier) i <strong>for</strong>skellige menneskers<br />
arvemateriale. Polymorfier kan <strong>og</strong>så medføre,<br />
at n<strong>og</strong>le mennesker er mere disponerede <strong>for</strong> at<br />
udvikle en sygdom end <strong>and</strong>re. I afdelingens molekylærbiol<strong>og</strong>iske<br />
laboratorium undersøger vi gener,<br />
der kan belyse arveligt bestemt variation i reproduktionsorganerne<br />
hos raske børn <strong>og</strong> voksne<br />
mænd samt hos patienter med misdannede kønsorganer,<br />
pubertets<strong>for</strong>styrrelser, infertilitet <strong>og</strong> testikelkræft.<br />
Vores hypotese er, at n<strong>og</strong>le polymorfier,<br />
hvis de kombineres med skadelige udefrakommende<br />
påvirkninger under udviklingen, kan være involverede<br />
i disse problemer. Se eksempel på et<br />
studie af denne slags under afsnittet om TDS.<br />
Illumina MiSeq DNA sekventering<br />
Vi planlægger at udføre en større parallel sekventering<br />
af en lang række (ca. 100 <strong>for</strong>skellige) gener,<br />
som styrer kønsorganernes udvikling, pubertet <strong>og</strong><br />
sædcelledannelse. Relevante genetiske polymorfier<br />
vil blive bestemt i store grupper af patienter <strong>og</strong> i<br />
raske kontroller. Til sekventeringen bruger vi et<br />
helt nyt apparatur, der kan kortlægge hele arvemassen:<br />
Illumina MiSeq DNA sekventeringssystem<br />
<strong>og</strong> DNA præparationsudstyr.
<strong>Reproduktion</strong> <strong>og</strong> livsstil<br />
Sædkvaliteten er ikke kun genetisk bestemt, men<br />
påvirkes <strong>og</strong>så af udefrakommende faktorer som<br />
miljøet omkring os <strong>og</strong> den måde vi lever på. Vi<br />
bruger vores populationsstudier med mange sæd-<br />
<strong>og</strong> hormonanalyser <strong>og</strong> detaljerede spørgeskemadata<br />
til at belyse, om der er en sammenhæng mellem<br />
kost, livsstil <strong>og</strong> <strong>for</strong>ringet sædkvalitet.<br />
Almindelig smertestillende håndkøbsmedicin,<br />
som <strong>for</strong> eksempel Panodil,<br />
viste sig at kunne hæmme virkningen<br />
af testosteron i vores basale celle- <strong>og</strong><br />
dyrestudier. Vi f<strong>and</strong>t desuden i et studie baseret<br />
på afdelingens mor-barn kohorte, at brug af smertestillende<br />
medicin under graviditeten ser ud til at<br />
øge risikoen <strong>for</strong> at få et barn med kryptorkisme<br />
(ikke nedfaldne testikler). Oplysninger om omfang<br />
<strong>og</strong> tidspunkt <strong>for</strong> brug af smertestillende var d<strong>og</strong><br />
ikke særligt detaljerede Studiet blev udgivet i Human<br />
Reproduction i 2011.<br />
Derudover har vi fundet at unge danske<br />
mænd, der drikker mere end 7 liter cola<br />
om ugen, har en signifikant dårligere<br />
Patenter relateret til Vitamin D<br />
Blomberg Jernsen et al. Patent WO number 10161711.6:<br />
”Test <strong>for</strong> male fertility”: Filed 03-05-2010<br />
Blomberg Jensen. Patent WO 2,012,116,699:<br />
”Active vitamin D <strong>and</strong> vitamin D anal<strong>og</strong>s <strong>for</strong> use in in<br />
vivo or invtro fertilization.” Submitted 28-02-2011<br />
22<br />
sædkvalitet end mænd, der ikke drikker cola. Vi<br />
kan d<strong>og</strong> ikke i studiet bevise, at cola er den direkte<br />
årsag til den <strong>for</strong>ringede sædkvalitet. Det kan <strong>og</strong>så<br />
være, at de mænd der drikker meget cola i det hele<br />
taget har en mindre sund livsstil, der påvirker reproduktionsevnen.<br />
Studiet blev udgivet i 2010 i<br />
American Journal <strong>of</strong> Epidemiol<strong>og</strong>y.<br />
S t r e s s o g s æ d k v a l i t e t<br />
Mere end hver tiende danske unge <strong>og</strong> midaldrende<br />
m<strong>and</strong> føler sig <strong>of</strong>te stresset. Hvorvidt stress kan<br />
påvirke sædkvaliteten er stort set uafklaret. PhD<br />
studerende Loa Nordkap undersøger, om kronisk<br />
stress har en betydning <strong>for</strong> sædkvalitet <strong>og</strong> testosteronproduktion<br />
hos danske mænd. Hvis stress påvirker<br />
sædkvaliteten, er det potentielt set en årsag,<br />
som både kan <strong>for</strong>ebygges <strong>og</strong> beh<strong>and</strong>les.<br />
Vitamin D <strong>og</strong> sædkvalitet<br />
Vitamin D dannes i huden af solens ultraviolette<br />
stråler <strong>og</strong> optages via kosten. Vitamin D kan, ifølge<br />
dyrestudier, have en gavnlig effekt på sædkvaliteten.<br />
Vi har der<strong>for</strong> undersøgt vitaminet hos mennesker,<br />
<strong>og</strong> fundet at de vitamin D metaboliserende<br />
enzymer kan anvendes som positiv prædiktiv markør<br />
<strong>for</strong> sædkvalitet. Efterfølgende funktionelle studier<br />
bekræftede vores <strong>for</strong>modning om, at D vitamin<br />
er gavnligt <strong>for</strong> fertiliseringen af ægget.<br />
Foruden de basale cellulære effekter af vitamin D<br />
har vi undersøgt sammenhængen mellem niveauet<br />
af vitamin D i blodet <strong>og</strong> sædkvaliteten hos raske<br />
unge mænd. Tværsnitstudiet antydede, ligesom<br />
dyrestudierne <strong>og</strong> de cellulære studier, at D vitamin<br />
er gavnligt <strong>for</strong> bevægeligheden af sædcellerne, da<br />
mænd med lavt D vitamin niveau havde færre bevægelige<br />
<strong>og</strong> normalt udseende sædceller end<br />
mænd med optimalt D vitamin. På den baggrund<br />
iværksatte vi i 2011 et stort r<strong>and</strong>omiseret interventionstudie,<br />
hvor vi undersøger om vitamin D tilskud<br />
kan <strong>for</strong>bedre sædkvaliteten <strong>for</strong> infertile<br />
mænd. Igangværende basale undersøgelser søger<br />
nu <strong>og</strong>så at afdække betydningen af D vitamin <strong>for</strong><br />
testikelkræfts udvikling <strong>og</strong> pr<strong>og</strong>nose.<br />
Læge Martin Blomberg Jensen (billedet) har været<br />
drivkræften bag afdelingens vitamin D studier.
Forstadier til testikelkræft<br />
H v o r d a n o p s t å r C I S<br />
o g t e s t i k e l k r æ f t ?<br />
Testikelkræft rammer hovedsageligt unge mænd,<br />
<strong>og</strong> <strong>for</strong>ekomsten af denne kræft<strong>for</strong>m har igennem<br />
mange år været stigende. Testikelkræft, der er bestemt<br />
af både genetiske <strong>og</strong> ikke genetiske faktorer,<br />
opstår fra ét fælles <strong>for</strong>stadie, som kaldes carcinoma<br />
in situ (CIS). CIS ses <strong>of</strong>te sammen med TDS (se<br />
afsnit om TDS) <strong>og</strong> i tvetydige kønsorganer. CIS<br />
celler, som ligner germinale celler (de celler, der<br />
hos drengen senere kan udvikle sig til sædceller),<br />
blev første gang identificeret af Niels E Skakkebæk<br />
i 1972. Han fremsatte hypotesen om, at CIS celler<br />
opstår allerede under fosterudviklingen, <strong>og</strong> efterfølgende<br />
undersøgelser har vist, at CIS celler udtrykker<br />
mange gener, som ellers kun ses udtrykt i<br />
embryonale stamceller, <strong>og</strong> som normalt kun findes<br />
i fosterets tidlige udvikling.<br />
D i a g n o s t i c e r i n g a f C I S<br />
I afdelingens ambulatorium diagnosticeres årligt<br />
ca. 10-15 patienter med <strong>for</strong>stadier til testikelkræft<br />
(CIS). Langt de fleste af disse kommer i ambulatoriet<br />
på grund af dårlig sædkvalitet eller tidligere<br />
problemer med manglende nedstigning af testiklerne<br />
(kryptorkisme).<br />
Hos de fleste patienter opspores CIS ved en testisbiopsi,<br />
som udarbejdes <strong>og</strong> farves i afdelingens<br />
histolaboratorium <strong>og</strong> vurderes af afdelingens læger<br />
<strong>og</strong> <strong>for</strong>skere. En testisbiopsi kræver imidlertid<br />
et invasivt kirurgisk indgreb, så afdelingen har<br />
udviklet en metode til detektion af CIS celler i sædprøver.<br />
Stadigt flere af afdelingens patienter undersøges<br />
med denne nye metode. Her anvendes en<br />
23<br />
B a s a l e C I S s t u d i e r<br />
Studier peger på, at en <strong>for</strong>sinket modning af drengefostrets<br />
germinale celler kan være det første trin i<br />
udviklingen af CIS celler. For at <strong>for</strong>stå hvordan CIS<br />
opstår, har vi der<strong>for</strong> <strong>for</strong>sket i germinale cellers normale<br />
udvikling - et område der ellers vides meget<br />
lidt om. Til <strong>for</strong>målet vil vi fremadrettet bruge en ny<br />
model, som <strong>for</strong>sker Anne Jørgensen har udviklet,<br />
hvor de germinale celler dyrkes i et kontrolleret<br />
miljø. Her kan vi undersøge hvilke faktorer, der<br />
hæmmer cellernes modning, <strong>og</strong> dermed blive kl<strong>og</strong>ere<br />
på, hvordan CIS opstår.<br />
Vores hypotese er, at CIS celler er en slags køns<strong>for</strong>virrede<br />
germinale celler, som overlever i den voksne<br />
testikel. Vi har tidligere gennemført en række<br />
såkaldte microarray studier, der underbygger denne<br />
hypotese. Senest har Anne <strong>og</strong>så undersøgt mitose-meiose<br />
skiftet i CIS celler før <strong>og</strong> efter puberteten,<br />
<strong>og</strong> fundet, at dette tilsyneladende reguleres fejlagtigt<br />
i CIS cellerne. Resultaterne er publiceret i The<br />
Journal <strong>of</strong> Pathol<strong>og</strong>y.<br />
cytol<strong>og</strong>isk baseret teknik, hvor CIS cellerne dobbeltfarves<br />
<strong>for</strong> alkalisk fosfatase <strong>og</strong> AP-2γ (se eksempel<br />
på denne sides baggrundsbillede). Metoden<br />
er nu automatiseret, idet farvningen udføres<br />
på autostainer <strong>og</strong> efterfølgende skannes <strong>og</strong> undersøges<br />
med specielt udviklet s<strong>of</strong>tware, som hurtig<br />
finder <strong>og</strong> vurderer de farvede celler.<br />
Opsporing af CIS celler før dette <strong>for</strong>stadie udvikler<br />
sig til ondartet testikelkræft er af stor betydning <strong>for</strong><br />
den enkelte patient. Ved tidlig diagnosticering af<br />
CIS kan invasion <strong>og</strong> metastasering af testikelkræft<br />
<strong>for</strong>hindres. Beh<strong>and</strong>ling af CIS er <strong>og</strong>så mere skånsom<br />
end beh<strong>and</strong>ling af testikelkræft, der har flere<br />
bivirkninger.
Hormon<strong>for</strong>styrrende st<strong>of</strong>fer<br />
H v o r fo r b e k y m r e s i g ?<br />
Vi udsættes hver dag <strong>for</strong> en lang række kemiske<br />
st<strong>of</strong>fer, hvoraf n<strong>og</strong>le er hormon<strong>for</strong>styrrende. De<br />
hormon<strong>for</strong>styrrende st<strong>of</strong>fer optages ved indånding,<br />
gennem huden <strong>og</strong> via vores kost. Der har igennem<br />
de senere år, i Danmark <strong>og</strong> i udl<strong>and</strong>et, været meget<br />
fokus på netop denne gruppe af kemikalier.<br />
<strong>Afdeling</strong> <strong>for</strong> <strong>Vækst</strong> <strong>og</strong> <strong>Reproduktion</strong> har særlig interesse<br />
i hormon<strong>for</strong>styrrende st<strong>of</strong>fer <strong>for</strong>di n<strong>og</strong>le af de<br />
problemer som afdelingens patienter har (tidlig pubertet,<br />
kryptorkisme, nedsat testosteronniveau <strong>og</strong><br />
sædproduktion eller brystudvikling hos mænd), er<br />
de samme som ses hos dyr, når de udsættes <strong>for</strong> disse<br />
kemikalier.<br />
Vi vil <strong>for</strong> eksempel gerne vide:<br />
Hvordan optages <strong>og</strong> udskilles hormon<strong>for</strong>styrrende<br />
st<strong>of</strong>fer hos børn, unge <strong>og</strong> voksne?<br />
Hvad er eksponeringsniveauet i Danmark?<br />
Påvirker hormon<strong>for</strong>styrrende st<strong>of</strong>fer tidspunktet <strong>for</strong><br />
pubertetsstart? Og sædkvaliteten?<br />
<strong>Afdeling</strong>en har via prøveindsamling <strong>og</strong> befolkningsundersøgelser<br />
en enestående mulighed <strong>for</strong> at<br />
bidrage til den <strong>for</strong>skning i området, som pågår verden<br />
over.<br />
24
ng/kg/24 timer<br />
C e n t e r f o r H o r m o n -<br />
f o r s t y r r e n d e S t o f f e r<br />
Det nationale Center <strong>for</strong> Hormon<strong>for</strong>styrrende St<strong>of</strong>fer<br />
under Miljøministeriet, hvor Forskningsleder<br />
Anna-Maria Andersson er leder, har hovedsæde i<br />
afdelingen. Centret er et tværgående fagligt netværk,<br />
der har til <strong>for</strong>mål at opbygge ny viden om<br />
hormon<strong>for</strong>styrrende st<strong>of</strong>fer. Centret igangsætter<br />
<strong>og</strong> koordinerer undersøgelser vedrørende hormon<strong>for</strong>styrrende<br />
st<strong>of</strong>fer, der har særligt fokus på danske<br />
<strong>for</strong>hold, <strong>og</strong> er målrettet myndighedernes <strong>for</strong>ebyggende<br />
arbejde. Desuden afholdes årligt åbne<br />
in<strong>for</strong>mationsmøder, <strong>og</strong> oversigter over ny litteratur<br />
på området udarbejdes.<br />
P h t h a l a t e r o g<br />
p a r a b e n e r<br />
Phthalater er plastblødgørere, der kan findes i plastiklegetøj,<br />
regntøj, neglelak, læbestift, fødevareemballage,<br />
byggematerialer, maling <strong>og</strong> medicinsk<br />
udstyr. I rotte<strong>for</strong>søg har n<strong>og</strong>le af phthalaterne vist<br />
at hæmme hannernes reproduktionsevne.<br />
Parabener, triclosan <strong>og</strong> triclocarban, er antimikrobielle<br />
konserveringsmidler, som især anvendes<br />
i kosmetik, desinfektionsmidler <strong>og</strong> medicinalvareindustrien.<br />
I dyrestudier har st<strong>of</strong>ferne svage<br />
østr<strong>og</strong>ene effekter <strong>og</strong> hæmmer måske dannelsen af<br />
testosteron.<br />
<strong>Afdeling</strong>ens kemiske laboratorium har, i <strong>for</strong>skningsøjemed<br />
<strong>og</strong> med senior<strong>for</strong>sker Hanne Frederiksen<br />
ved roret, analyseret indholdet af phthalater,<br />
parabener <strong>og</strong> phenoler i mange tusinde prøver<br />
fra børn, unge <strong>og</strong> voksne (se graferne herunder).<br />
4000<br />
3000<br />
2000<br />
1000<br />
0<br />
Phthalater<br />
6-10 år<br />
11-16 år<br />
17-21 år<br />
MEP ∑MBPm ∑DEHPm ∑DiNPm<br />
Koncentrationer af <strong>for</strong>skellige phthalatmetabolitter i urinprøver<br />
fra danske børn <strong>og</strong> unge. MEP: metabolit af diethylphthalat;<br />
∑MBPm: sum af metabolitter fra di-isobutyl <strong>og</strong> di-n-butyl<br />
phthalat; ∑DEHPm: sum af de fire mest almindelige metabolitter<br />
af di-(2-ethylhexyl) phthalat; ∑DiNPm: sum af de fire mest<br />
almindelige di-iso-nonyl phthalat metabolitter.<br />
25<br />
P å v i r k e r<br />
s o l f i l t r e h e l b r e d e t ?<br />
Solfiltre er designet til at beskytte mod skadelige<br />
effekter af UV stråling. De bruges især i solcremer,<br />
men efterhånden anvendes de <strong>og</strong>så i <strong>and</strong>re kosmetikprodukter,<br />
mademballage, tøj <strong>og</strong> møbler. En<br />
række UV filtre er vist at være hormon<strong>for</strong>styrrende<br />
i dyrestudier. Hvilke konsekvenser det har <strong>for</strong><br />
mennesker vides ikke endnu. PhD studerende Marianna<br />
Krause undersøger i sit projekt hvor meget<br />
danske børn, mænd <strong>og</strong> gravide kvinder udsættes<br />
<strong>for</strong> UV filtre. Desuden vurderer hun effekten af<br />
eksponeringen i de <strong>for</strong>skellige befolkningsgrupper<br />
på reproduktion, st<strong>of</strong>skifte, vækst <strong>og</strong> udvikling.<br />
P h e n o l e r o g<br />
r e p r o d u k t i o n<br />
Bisphenol A bruges i klare hårde plastikbeholdere<br />
<strong>og</strong> til plastikoverflader på industriprodukter.<br />
Bisphenol A er, sammen med <strong>and</strong>re phenoler, mistænkt<br />
<strong>for</strong> at have hormon<strong>for</strong>styrrende egenskaber i<br />
dyr såvel som hos mennesker. PhD studerende<br />
Tina Harmer Lassen undersøger i sit projekt, om<br />
der er en association mellem phenoler <strong>og</strong> henholdsvis<br />
sædkvalitet <strong>og</strong> kønshormonniveauer hos<br />
unge mænd. Desuden ser hun på eventuelle sammenhænge<br />
mellem phenolkoncentrationen målt hos<br />
gravide kvinder <strong>og</strong> deres børns an<strong>og</strong>enitale afst<strong>and</strong><br />
målt i 3-måneders alderen. An<strong>og</strong>enital afst<strong>and</strong>en,<br />
der er defineret som afst<strong>and</strong>en mellem<br />
anus <strong>og</strong> genitalierne, giver viden om, hvor meget<br />
testosteron barnet er blevet påvirket af i fostertilværelsen.<br />
Desto længere afst<strong>and</strong>, desto mere testosteron.<br />
ng/kg/24 timer<br />
70<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
Phenoler<br />
BPA TCS BP-3<br />
Koncentrationer af phenolerne bisphenol A (BPA), triclosan<br />
(TCS) <strong>og</strong> benzophenon 3 (BP-3) i urinprøver fra danske børn<br />
<strong>og</strong> unge. BP-3 er et af de mest anvendte UV filtre. Farverne<br />
indikerer de samme aldersgrupper, som i phthalat figuren til<br />
venstre.
Populationsstudier<br />
For at indhente mere viden om, hvordan vækst <strong>og</strong><br />
reproduktion fungerer i dagens danske befolkning,<br />
følger vi store grupper af repræsentative<br />
danskere i afdelingens populationskohorter. Vi<br />
startede i 1996 en stor mor-barn kohorte, som stadig<br />
følges, <strong>og</strong> har <strong>og</strong>så siden 1996 undersøgt sædkvaliteten<br />
bl<strong>and</strong>t unge danske mænd. I 2006 påbegyndte<br />
vi en stor pubertetsundersøgelse, hvoraf en<br />
Ko h o r t e r o g u n d e r s ø g e l s e r<br />
Undersøgelsesdeltagerne bidrager med følgende<br />
(afhængig af alder <strong>og</strong> køn):<br />
Undersøgelser af nyfødte inkluderer vægt, længde,<br />
<strong>og</strong> fedtfoldsmål, <strong>og</strong> <strong>for</strong> drengene en vurdering af<br />
testiklernes placering <strong>og</strong> eventuel hypospadi.<br />
Undersøgelser af børn <strong>og</strong> unge inkluderer bl<strong>and</strong>t<br />
<strong>and</strong>et højde, vægt, mave- <strong>og</strong> h<strong>of</strong>teomfang, fedtfoldsmål,<br />
blodtryk, pubertetsvurdering <strong>og</strong> <strong>for</strong> n<strong>og</strong>le<br />
<strong>og</strong>så DEXA <strong>og</strong> MR skanninger (se billede) <strong>og</strong><br />
ultralyd af kønskirtlerne.<br />
Undersøgelser af voksne mænd inkluderer højde,<br />
vægt, vurdering af maskuliniseringsgrad, de ydre<br />
kønsorganer <strong>og</strong> eventuel gynækomasti (brystudvikling),<br />
samt ultralydsundersøgelse af testiklerne.<br />
Biol<strong>og</strong>iske prøver inkluderer blod- <strong>og</strong> urinprøver,<br />
<strong>for</strong> alle, sædprøver <strong>for</strong> voksne mænd, <strong>og</strong> mælkeprøver<br />
<strong>for</strong> nybagte mødre. Blodprøver analyseres<br />
<strong>for</strong> en række hormoner <strong>og</strong> vækstfaktorer samt genetisk<br />
variation, mens urin- <strong>og</strong> mælkeprøver undersøges<br />
<strong>for</strong> <strong>for</strong>skellige kemikalier. Sædprøver<br />
bruges til vurdering af sædparametre som koncentration,<br />
morfol<strong>og</strong>i <strong>og</strong> motilitet.<br />
26<br />
del <strong>og</strong>så stadig følges. Kohorterne er helt centrale<br />
<strong>for</strong> afdelingens <strong>for</strong>skning, <strong>og</strong> bidrager med uvurderlige<br />
biol<strong>og</strong>iske prøver, kliniske data <strong>og</strong> spørgeskemabesvarelser.<br />
Vi er meget opmærksomme på de etiske aspekter<br />
omkring populationsundersøgelser <strong>og</strong> <strong>and</strong>re <strong>for</strong>mer<br />
<strong>for</strong> <strong>for</strong>skning, <strong>og</strong> har i sagens natur etisk godkendelse<br />
til samtlige <strong>for</strong>skningsprojekter.<br />
Spørgeskemaoplysninger bruges til at vurdere sociol<strong>og</strong>iske<br />
faktorer <strong>og</strong> livsstil samt nuværende <strong>og</strong><br />
tidligere vækst, udvikling <strong>og</strong> helbred.<br />
Sædkvalitetsstudier<br />
Forplantning<br />
<strong>Reproduktion</strong><br />
Pubertetskohorten<br />
Mor-barn kohorten<br />
Pubertet<br />
Fosterudvikling<br />
<strong>Vækst</strong> i barndommen<br />
<strong>Afdeling</strong>ens kohorter spreder sig over fostertilværelsen, barndom,<br />
ungdom <strong>og</strong> det tidlige voksenliv.
T h e C O P E N H A G E N<br />
P u b e r t y S t u d y<br />
The COPENHAGEN Puberty Study startede i 2006<br />
<strong>og</strong> omfatter pubertetsundersøgelser af 2.000 raske<br />
skolebørn <strong>og</strong> -unge fra Københavnsområdet.<br />
Knapt 200 af disse børn følges op med undersøgelser<br />
hvert halve år i en 8-årig periode. Undersøgelsen<br />
er støttet økonomisk fra Kirsten <strong>og</strong> Freddy<br />
Johansens Fond, <strong>og</strong> har <strong>for</strong>eløbig resulteret i mere<br />
end 20 videnskabelige publikationer siden 2009.<br />
M o r - b a r n k o h o r t e n<br />
Mor-barn kohorten startede i 1996 med rekruttering<br />
af mere end 2.000 gravide kvinder fra Københavnsområdet.<br />
Deres børn er blevet undersøgt<br />
adskillige gange igennem barndommen <strong>og</strong> er nu i<br />
pubertetalderen. Cirka 1.200 af børnene bliver stadig<br />
fulgt. Data fra denne longitudinelle kohorte<br />
har indtil videre dannet basis <strong>for</strong> mere end 50 videnskabelige<br />
publikationer.<br />
S æ d k v a l i t e t s s t u d i e r<br />
Unge danske mænd er siden 1996 blevet inviteret<br />
til at deltage i afdelingens sædkvalitetsundersøgelser<br />
i <strong>for</strong>bindelse med deres obligatoriske fremmøde<br />
til Forsvarets Dag. Undersøgelserne, der indtil<br />
videre har inkluderet mere end 5.000 mænd,<br />
støttes bl<strong>and</strong>t <strong>and</strong>et af Miljøstyrelsen <strong>og</strong> Sundheds<br />
-ministeriet, <strong>og</strong> har <strong>for</strong>eløbigt dannet basis <strong>for</strong><br />
mere end 30 videnskabelige publikationer<br />
K r o p s s a m m e n s æ t n i n g<br />
<strong>Afdeling</strong>ens mor-barn kohorte giver en unik mulighed<br />
<strong>for</strong> at undersøge, hvordan faktorer, der spiller<br />
ind allerede i fostertilværelsen <strong>og</strong> de tidlige<br />
barneår, påvirker helbredet senere i livet. PhD<br />
studerende Jeanette Tinggaard benytter i sit projekt<br />
data fra mor-barn kohorten til at undersøge,<br />
hvordan bl<strong>and</strong>t <strong>and</strong>et tidlig eksponering <strong>og</strong> tidlig<br />
vækst påvirker kropssammensætning senere i livet.<br />
Kropssammensætning vurderes ved helkrops<br />
DXA skanning (se billede til højre) <strong>og</strong> MR skanning<br />
af maveregionen (se billede på modsatte<br />
side). DXA skanning er egnet til estimering af<br />
børns fedtmasse, mens MR skanning af maveregionen<br />
er den mest præcise metode til vurdering af<br />
<strong>for</strong>skellige <strong>for</strong>mer <strong>for</strong> fedt.<br />
27
Forskningssamarbejder<br />
New York, USA<br />
University <strong>of</strong> Rochester<br />
Mt. Sinai School <strong>of</strong> Medicin<br />
Cali<strong>for</strong>nia, USA<br />
Stan<strong>for</strong>d University<br />
Maryl<strong>and</strong>, USA<br />
Endocrine Society<br />
Philadelphia, USA<br />
University <strong>of</strong> Pennsylvania<br />
Colorado, USA<br />
Colorado State University<br />
University <strong>of</strong> Colorado Denver<br />
Missouri, USA<br />
Washington University<br />
School <strong>of</strong> Medicine<br />
Belgium<br />
University <strong>of</strong> Leuven<br />
United Kingdom<br />
Hammersmith Hospital, London<br />
University <strong>of</strong> London<br />
University <strong>of</strong> Sheffield<br />
University <strong>of</strong> Cambridge<br />
University <strong>of</strong> Ox<strong>for</strong>d<br />
University <strong>of</strong> Brunel<br />
Scotl<strong>and</strong><br />
University <strong>of</strong> Edinburgh<br />
University <strong>of</strong> Glasgow<br />
Irel<strong>and</strong><br />
University <strong>of</strong> Dublin<br />
Spain<br />
University <strong>of</strong> Murcia<br />
University <strong>of</strong> Granada<br />
France<br />
Université de Rennes<br />
L’ecole Nationale Veterinaire de Nantes<br />
Pasteur Institute, Paris<br />
GERM-INSERM, Rennes<br />
INSERM, Creteil<br />
Schwitzerl<strong>and</strong><br />
WHO, Geneve<br />
University <strong>of</strong> Zurich<br />
<strong>Afdeling</strong>en blev i 2010 udnævnt til<br />
Global Excellence Center i sundhed.<br />
Anerkendelsen gives <strong>for</strong> beh<strong>and</strong>ling<br />
<strong>og</strong> <strong>for</strong>skning på internationalt niveau.<br />
28<br />
Germany<br />
University <strong>of</strong> Leipzig<br />
Justus Liebig University Giessen<br />
Caesar Institute, Bonn<br />
Ruhr University, Bochum<br />
FBN Leibniz Institute <strong>of</strong> Farm Biol<strong>og</strong>y<br />
Norway<br />
University <strong>of</strong> Oslo<br />
Doping Laboratory, Oslo<br />
Sweden<br />
University <strong>of</strong> Uppsala<br />
Malmö Medical Center<br />
Karolinska Institute<br />
University <strong>of</strong> Lund<br />
Astrid Lindgrens Hospital, Stockholm<br />
Finl<strong>and</strong><br />
University <strong>of</strong> Turku<br />
University <strong>of</strong> Helsinki<br />
Estonia<br />
Tartu University Hospital<br />
Latvia<br />
Riga University Hospital<br />
Lithuania<br />
Kaunas University Hospital<br />
Bulgaria<br />
Bulgarian Academy <strong>of</strong> Sciences<br />
Rumania<br />
University <strong>of</strong> Bukarest<br />
Pol<strong>and</strong><br />
University <strong>of</strong> Lodz<br />
Italy<br />
University <strong>of</strong> Florence<br />
Singapore<br />
Singapore University<br />
Australia<br />
Monash University, Victoria<br />
University <strong>of</strong> Western Australia<br />
University <strong>of</strong> Queensl<strong>and</strong>, Brisbane<br />
China<br />
National Research Institute <strong>for</strong><br />
Family Planning, Beijing<br />
Japan<br />
Marianna University Hospital, Tokyo<br />
International University <strong>of</strong> Health <strong>and</strong> Welfare Hospital, Nasushiobara
Workshops<br />
Workshops <strong>og</strong> konferencer giver gode muligheder <strong>for</strong> udveksling<br />
af nye ideer <strong>og</strong> tanker, <strong>og</strong> danner grobund <strong>for</strong> samarbejder<br />
med internationale <strong>for</strong>skningsgrupper. <strong>Afdeling</strong>ens <strong>for</strong>skere<br />
deltager der<strong>for</strong> så vidt muligt i relevante konferencer<br />
rundt omkring i verden. Derudover arrangerer vi selv workshops,<br />
hvor <strong>for</strong>skere fra hele verden kommer til Danmark, <strong>for</strong><br />
at blive inspirerede. Disse er listet neden<strong>for</strong>.<br />
Vores internationale Copenhagen Workshop<br />
on Endocrine Disrupters (COW) er<br />
blevet afholdt hvert <strong>and</strong>et år siden 2000. I<br />
<strong>for</strong>året 2013 afholdes den syvende i rækken.<br />
<strong>Afdeling</strong>en arrangerer den internationale<br />
CIS workshop hvert fjerde<br />
år. I 2014 afholdes den ottende i<br />
rækken.<br />
I 2010 arrangerede vi en international<br />
konference om Klinefelter<br />
Syndrom.<br />
Vi har tradition <strong>for</strong> at udgive<br />
proceedings fra de afholdte<br />
konferencer i peer-reviewed<br />
internationale videnskabelige<br />
tidsskrifter.<br />
F o r m i d l i n g o g ko m m u n i k a t i o n<br />
Formidling af vores <strong>for</strong>skningsresultater <strong>og</strong> ekspertise til den<br />
danske befolkning er vigtig. Formidlingen sker via interviews<br />
til aviser, ugeblade, TV <strong>og</strong> radio, <strong>og</strong> debatindlæg <strong>og</strong> kronikker<br />
i de store dagblade. Derudover holder vi møder <strong>for</strong> <strong>of</strong>fentligheden.<br />
Eksempelvis afholder Center <strong>for</strong> Hormon<strong>for</strong>styrrende<br />
St<strong>of</strong>fer årligt et in<strong>for</strong>mationsmøde ligesom afdelingen i december<br />
2012 var medarrangører af debatmødet ”Tager vi vores<br />
reproduktion alvorligt?” med efterfølgende politisk paneldebat.<br />
For at styrke <strong>for</strong>midling af afdelingens arbejde,<br />
tager <strong>for</strong>sker Katrine Bay sideløbende med sit<br />
arbejde i afdelingen en journalistisk diplomuddannelse<br />
ved Danmarks Medie- <strong>og</strong> Journalisthøjskole.<br />
29
Fakta om afdelingen<br />
Organisation<br />
Fonds- <strong>og</strong> virksomhedsstøtte<br />
<strong>Afdeling</strong>en har modtaget støtte fra følgende fonde<br />
<strong>og</strong> virksomheder i perioden 2000-2012:<br />
Anti-doping Danmark<br />
AP Møller Fonden<br />
Augustinus Fonden<br />
Axel Muusfeldts Fond<br />
Brødrene Hartmanns Fond<br />
Børnecancerfonden<br />
Cancer<strong>for</strong>skningsfonden<br />
Dagmar Marshalls Fond<br />
Dansk Kræft<strong>for</strong>skningsfond<br />
Det Fri Forskningsråd<br />
Det Strategiske Forskningsråd<br />
Dr. Louises Børnehospitals Forskningsfond<br />
Ejner Willumsens Mindelegat<br />
Erhvervsfremmestyrelsen<br />
EU<br />
Forskningsstyrelsen<br />
Fødevaredirektoratet<br />
Glash<strong>of</strong>s Legat<br />
H:S Forskningspulje<br />
Hertz’ Fond<br />
Højteknol<strong>og</strong>ifonden<br />
Indenrigs- <strong>og</strong> Sundhedsministeriets<br />
Miljømedicinske Forskningscenter<br />
Japan Science <strong>and</strong> Technol<strong>og</strong>y<br />
John <strong>og</strong> Birthe Meyers Fond<br />
Kirsten <strong>og</strong> Freddy Johansens Fond<br />
Knudsens Fond<br />
Klinikledelse<br />
Sekretariat Ambulatorium Molekylærlab Histolab <strong>og</strong> sædbank Hormon- <strong>og</strong> kemilab<br />
30<br />
Økonomi, personale, fundraising,<br />
kommunikation, IT, statistik<br />
Kræftens Bekæmpelse<br />
Københavns Universitet<br />
Lundbeckfonden<br />
Miljøstyrelsen<br />
NorFA<br />
Novartis<br />
Novo Nordisk Fonden<br />
Novo Nordisk<br />
Pharmacia<br />
Pro<strong>of</strong> <strong>of</strong> Concept v/ Forsknings- <strong>og</strong><br />
Innovationsstyrelsen<br />
Region Hovedstaden<br />
Rigshospitalets Apparaturfond<br />
Rigshospitalets Forskningsfond<br />
Savværksejer J Juhl & Hustru O Juhls Mindelegat<br />
Statens Strat. Miljø<strong>for</strong>skningspr<strong>og</strong>ram<br />
Statens Sundhedsvidensk. Forskningsråd<br />
Sundhedsministeriet<br />
Svend Andersens Fond<br />
Sygekassernes Helsefond<br />
Toyota Fonden<br />
Tømmerh<strong>and</strong>ler Vilhelm Bangs Fond<br />
Velux / VKR Fonden<br />
Ville Heises Legat<br />
Vissing Fonden<br />
Aase <strong>og</strong> Ejnar Danielsens Fond<br />
Den økonomiske støtte fra medicinalindustrien<br />
overstiger ikke 5% af afdelingens samlede årlige<br />
<strong>for</strong>skningsbudget.
Sociale arrangementer<br />
Julefrokoster, sommerfester, receptioner, strategiweekender<br />
<strong>og</strong> DHL stafetter. Imellem al arbejdet<br />
får vi <strong>og</strong>så tid til sociale arrangementer. Mange af<br />
disse er endt som solide traditioner, der vender<br />
tilbage år efter år. Ved afdelingens julefrokost holdes<br />
der hvert år tour de lab, hvor de enkelte laboratoriers<br />
medarbejdere, <strong>of</strong>te udklædte til ugenkendelighed,<br />
arrangerer konkurrencer <strong>og</strong> lege <strong>for</strong> hinan-<br />
I n t e r n a t i o n a l e o g d a n s k e t i l l i d s p o s t e r<br />
Internationale<br />
Co-Editor-in-Chief Androl<strong>og</strong>y (Ewa Rajpert-De Meyts)<br />
Associate Editor Human Reproduction (Anna-Maria Andersson)<br />
Associate Editor International Journal <strong>of</strong> Androl<strong>og</strong>y (2007-2012) (Niels Jørgensen)<br />
Editorial Board Member Best Practice & Research Clinical Endocrinol<strong>og</strong>y <strong>and</strong> Metabolism (Anders Juul)<br />
Editorial Board Member Basic <strong>and</strong> clinical <strong>and</strong>rol<strong>og</strong>y (Katharina M Main)<br />
Advisory Board Member Asian Journal <strong>of</strong> Androl<strong>og</strong>y (2005-2012) (Niels Jørgensen)<br />
Advisory Editorial Board Member Asian pacific Journal <strong>of</strong> Reproduction, The Open Reproduction Science Journal,<br />
ISRN Molecular Biol<strong>og</strong>y <strong>and</strong> The Open Biomarkers Journal (Kristian Almstrup)<br />
Editorial Board Member ISRN Urol<strong>og</strong>y (Niels Jørgensen)<br />
Editorial Committee Member Acta Paediatrica Sc<strong>and</strong> (Katharina M Main)<br />
ESPE Research Fellowship Grant Committee Member (1999-2012) (Anders Juul)<br />
Principal Investigator <strong>for</strong> NESGAS (Nordeuropæisk multicenterstudium) (Anders Juul)<br />
Member <strong>of</strong> Scientific Board <strong>of</strong> Royan International Research Award (Kristian Almstrup)<br />
Member <strong>of</strong> the Scientific Committee <strong>for</strong> The European Testis Workshops (Ewa Rajpert-De Meyts)<br />
Member <strong>of</strong> Executive Council <strong>of</strong> the European Academy <strong>of</strong> Androl<strong>og</strong>y (since 2009) (Ewa Rajpert-De Meyts)<br />
EU COST consortium on GnRH deficiency - National representative (Anders Juul)<br />
Danske<br />
Leder af Center <strong>for</strong> Hormon<strong>for</strong>styrrende St<strong>of</strong>fer (Anna-Maria Andersson)<br />
Form<strong>and</strong> <strong>for</strong> Dansk Androl<strong>og</strong>isk Selskab (Niels Jørgensen)<br />
Form<strong>and</strong> <strong>for</strong> det Nationale RADS udvalg vedrørende væksthormon (Anders Juul)<br />
Medlem af Sundhedsstyrelsens Rådgivende Videnskabelige Udvalg <strong>for</strong> Miljø <strong>og</strong> Sundhed (Tina Kold Jensen)<br />
Medlem af Rigshospitalets <strong>for</strong>skningsudvalg, herunder biblioteksudvalg (Anders Juul)<br />
Form<strong>and</strong> <strong>for</strong> PhD bedømmelsesudvalg (Anders Juul)<br />
Medlem af Endokrinol<strong>og</strong>iudvalg under Sundhedsfagligt Råd i RegionH (Anders Juul)<br />
Delkursusleder postgraduat uddannelse i Pædiatrisk Endokrinol<strong>og</strong>i (Katharina M Main)<br />
Form<strong>and</strong> <strong>for</strong> Mødeudvalget i Den Danske Studiegruppe <strong>for</strong> Børne- <strong>og</strong> Ungdomsdiabetes (Anders Johansen)<br />
Medlem af Forskningsudvalget i Den Danske Studiegruppe <strong>for</strong> Børne- <strong>og</strong> Ungdomsdiabetes (Anders Johansen)<br />
Medlem af Adipositasudvalget under DPS (Dansk Pædiatrisk Selskab) (Anders Johansen)<br />
Associeret senior<strong>for</strong>sker (MODY <strong>og</strong> T2DM), Centre <strong>of</strong> Excellence <strong>for</strong> Diabetes in Childhood <strong>and</strong> Adolescence,<br />
Herlev Universitetshospital (Anders Johansen)<br />
Bestyrelsesmedlem i Yngre Pædiatere (Christine Wohlfahrt Veje)<br />
Form<strong>and</strong> <strong>for</strong> bestyrelsen af FYF (Foreningen af Yngre Forskere på RH) (Casper Hagen)<br />
31<br />
den. Sommerfesterne har så vidt muligt et element<br />
af natur i sig, mens afdelingens strategiweekender<br />
er en god bl<strong>and</strong>ing af fagligt indhold <strong>og</strong> fysiske<br />
aktiviteter. I anledning af jubilæer <strong>og</strong> runde fødselsdage,<br />
PhD- <strong>og</strong> disputats<strong>for</strong>svar afholdes receptioner<br />
under trange <strong>for</strong>hold på afdelingens gang,<br />
hvor kummefrysere omdannes til receptionsborde,<br />
<strong>og</strong> folk står som sild i en tønde.
Ansatte<br />
Ansatte i afdelingen pr. 1. marts 2013<br />
Klinikledelse<br />
Anders Juul<br />
Anna-Maria Andersson<br />
Katharina M. Main<br />
Speciallæger <strong>og</strong> Senior<strong>for</strong>skere<br />
Anders Johansen<br />
Anders Jørgen Schou<br />
Ewa Rajpert-De Meyts<br />
Niels Erik Skakkebæk<br />
Niels Jørgensen<br />
Peter Christiansen<br />
Pia Ekbom<br />
Tina Kold Jensen<br />
Trine Holm Johannsen<br />
Anne Jørgensen<br />
Hanne Frederiksen<br />
John Erik Nielsen<br />
Jorma Toppari<br />
Jørgen Holm Petersen<br />
Katrine Bay<br />
Kristian Almstrup<br />
Terje Svingen<br />
Tue B. Søeborg<br />
Lægelige specialkonsulenter<br />
(1-2 gange månedligt)<br />
Claus Thøger Nielsen<br />
Per Kjærsgaard<br />
Yngre læger <strong>og</strong> Forskere<br />
Annette K. Mouritsen<br />
Casper Hagen<br />
Christine Veje<br />
Inge A. Olesen<br />
Jacob G. Lawaetz<br />
Jeanette Tinggaard<br />
Katrine Tefre de Renzy-Martin<br />
Loa Nordkap<br />
Marianna Krause<br />
Martin B. Jensen<br />
Marie L. Johansen<br />
Mikkel G. Mieritz<br />
Rosanna H. Cetti<br />
Dorte L. Egeberg<br />
Grete Lottrup Poulsen<br />
Lærke Priskorn<br />
Marlene D. Dalgaard<br />
S<strong>of</strong>ia B. Winge<br />
Stine A. Holmboe<br />
Tina H. Lassen<br />
Sekretariat<br />
Tina Tronier, ledende lægesekretær<br />
Birgitte B. S. Havmøller<br />
Hanne Lyhne<br />
Kathrine D. Hurtigkarl<br />
Nini N. Makris<br />
Trine Schwaner<br />
Vibeke L. Nielsen<br />
Økonomi<br />
Anette M. Pedersen<br />
Britt Stricker<br />
IT<br />
Jørgen Riis Christensen<br />
Bioanalytikere <strong>og</strong> laboranter<br />
Hormonlab<br />
Jannie H. Hennings, afd. bioanalytiker<br />
Eva Br<strong>and</strong>orff<br />
Irina Safonenko<br />
Kristine Harild<br />
Maiken Probst<br />
Marianne Falck<br />
Marianne Seilund<br />
Tuba Kütük<br />
Kemilab<br />
Ole Nielsen<br />
Stine E. Andersen (hormon/kemilab)<br />
Histolab<br />
Lene D. Andersen, afd. bioanalytiker<br />
Ana R. Nielsen<br />
Beathe M. M. Christiansen<br />
Bonnie S. Håkansson (histo/mol. lab)<br />
32<br />
Camilla B. Campen<br />
Ina Lund<br />
Maiken S. Simonsen<br />
Sabina E. Sultanova<br />
Molekylærlab<br />
Inger D. Garn, afd. bioanalytiker<br />
Betina F. Nielsen<br />
Brian V. Hansen<br />
Dijana Maslovaric<br />
Hanh Hansen<br />
Ambulatoriets <strong>og</strong><br />
Forskningssygeplejersker<br />
Camilla F. Asmussen<br />
Helle Kelkel<strong>and</strong><br />
Louise N. Monnerup<br />
Tanja Rosenberg<br />
Blodprøvetagning<br />
Elisabeth K. Kr<strong>og</strong>h<br />
Karen R. Jølving<br />
Morten Petersen<br />
Studentermedhjælpere<br />
Frederikke R. Wigen<br />
Steffen S. Hansen<br />
Tine B. Olsen<br />
Herudover er der en række studentermedhjælpere,<br />
der assisterer i afdelingen<br />
på timebasis.
Afh<strong>and</strong>linger <strong>og</strong> specialer 2000-2012<br />
P h D a f h a n d l i n g e r<br />
Anne-Grethe Andersen 2001<br />
Semen quality <strong>and</strong> reproductive hormones<br />
in normal young men <strong>and</strong> in<br />
partners <strong>of</strong> pregnant women.<br />
Rasmus Damsgaard 2001<br />
Children in competitive sports.<br />
Lone Frydelund-Larsen 2004<br />
Microdeletions on the Y chromosome<br />
<strong>and</strong> male infertility<br />
Anne Marie Ottesen 2004<br />
Investigations <strong>of</strong> chromosomal aberrations<br />
<strong>and</strong> DNA content in early<br />
stages <strong>of</strong> testicular germ cell cancer:<br />
Implications <strong>for</strong> the path<strong>og</strong>enesis<br />
Kristian Almstrup 2005<br />
Gene expression pr<strong>of</strong>iling <strong>of</strong> developing<br />
mouse testes <strong>and</strong> human testicular<br />
germ cell neoplasms<br />
Kirsten Arndt Boisen 2005<br />
Prevalence <strong>of</strong> cryptorchidism <strong>and</strong><br />
hypospadias in 1072 Danish boys followed<br />
from birth to three years <strong>of</strong> age<br />
Marla Chellakooty 2005<br />
The function <strong>of</strong> the placental GH <strong>and</strong><br />
IGF-I axis in the regulation <strong>of</strong> normal<br />
fetal <strong>and</strong> early postnatal growth<br />
Ida Maria Schmidt 2005<br />
Determinants <strong>of</strong> kidney size in young<br />
children: 1270 Danish children followed<br />
from birth to 18 months <strong>of</strong> age<br />
Martin Asser Hansen 2006<br />
Bioin<strong>for</strong>matic analysis <strong>of</strong> gene families<br />
in mouse <strong>and</strong> human spermat<strong>og</strong>enesis<br />
S p e c i a l e r<br />
Maja Bévort 2000.<br />
Changes in gene expression during<br />
neuronal differentiation <strong>of</strong> human<br />
NTERA2 cells.<br />
Si Brask Sonne 2004.<br />
Uptake <strong>and</strong> Metabolisation <strong>of</strong> Dibutyl<br />
Phthalate (DBP) in MCF-7 <strong>and</strong> TM<br />
-3 cells: Correlation with Gene Expression.<br />
Fozia Jabeen Shah 2005.<br />
Re-initiation <strong>of</strong> spermat<strong>og</strong>enesis in<br />
adult C3H/He strain mice by radiation.<br />
Grete Lottrup Poulsen 2007.<br />
In vitro effects <strong>of</strong> phthalates on steroid<br />
producing cells.<br />
Marlene Dalgaard 2008.<br />
Gene expression changes in testis<br />
after perinatal exposure to anti<strong>and</strong>r<strong>og</strong>enic<br />
mixtures.<br />
Trine Holm Johannsen 2006<br />
Long-term outcomes <strong>of</strong> intersex-like<br />
conditions. A Danish follow-up<br />
study <strong>of</strong> seventy adult women<br />
Ida Norgil Damgaard 2007<br />
Risk factors <strong>for</strong> congenital cryptorchidism<br />
Rikke Beck Jensen 2007<br />
Long-term effects <strong>of</strong> fetal growth on<br />
postnatal growth, bone mass <strong>and</strong> pituitary-gonadal<br />
function in adolescence<br />
Claudia Mau Kai 2007<br />
<strong>Growth</strong> <strong>and</strong> reproductive function <strong>of</strong><br />
children conceived by intracytoplasmic<br />
sperm injection (ICSI)<br />
Grete Teilmann 2007<br />
Pubertal development in internationally<br />
adopted girls<br />
Camilla Asklund 2008<br />
Hypospadias, semen quality <strong>and</strong><br />
fertility. Studies <strong>of</strong> male reproductive<br />
health <strong>and</strong> inter-generational effects<br />
in three different populations<br />
Si Brask Sonne 2008<br />
Origin <strong>of</strong> carcinoma in situ <strong>of</strong> the<br />
testis: insight from comparative gene<br />
expression pr<strong>of</strong>iling <strong>of</strong> microdissected<br />
embryonic cell populations <strong>and</strong> studies<br />
<strong>of</strong> selected putative CIS markers<br />
Guy Wayne Novotny 2009<br />
Small RNA molecules: potential regulators<br />
<strong>of</strong> carcin<strong>og</strong>enesis <strong>and</strong> a novel<br />
tool in molecular biol<strong>og</strong>y research<br />
Maria Skalkam 2009.<br />
Screening <strong>of</strong> putative endocrine disruptors<br />
<strong>for</strong> prostagl<strong>and</strong>in synthesis<br />
inhibition.<br />
Maria Scheel 2009.<br />
Possible association <strong>of</strong> RLN1 gene<br />
copy number with testicular cancer<br />
<strong>and</strong> the biol<strong>og</strong>ical role <strong>of</strong> Relaxins 1<br />
<strong>and</strong> 2 in male reproduction.<br />
Stine Holmboe & Lærke Priskorn 2011.<br />
Fertility Trends among Danish Men -<br />
Is fecundity Declining?<br />
Tine H Bentsen 2012.<br />
The biol<strong>og</strong>ical role <strong>of</strong> mononuclear<br />
infiltrates in testicular neoplasia.<br />
Olga M Culbreth 2012.<br />
Epigenetic plasticity <strong>of</strong> Testicular<br />
Seminomas.<br />
Dina Kristensen 2013.<br />
Epigenetics in the Path<strong>og</strong>enesis <strong>of</strong><br />
Testicular Germ Cell Cancer.<br />
33<br />
Katrine Bay 2009<br />
Human testicular insulin-like factor<br />
3: in relation to development, reproductive<br />
hormones, <strong>and</strong> <strong>and</strong>rol<strong>og</strong>ical<br />
disorders<br />
Lise Aksglæde 2010<br />
Secular changes in pubertal development<br />
Malene Boas 2010<br />
Thyroid function in pregnant women<br />
<strong>and</strong> in children: associations with<br />
growth <strong>and</strong> phthalate exposure.<br />
David Møbjerg Kristensen 2010<br />
On the origin <strong>of</strong> testicular dysgenesis<br />
<strong>and</strong> non-invasive detection <strong>of</strong> CIS:<br />
Hitting TDS<br />
Kaspar Sørensen 2011<br />
Sex hormone-binding globulin <strong>and</strong><br />
body composition in normal <strong>and</strong><br />
precocious puberty<br />
Christine Wohlfahrt Veje 2012<br />
Prenatal exposure to modern pesticides<br />
<strong>and</strong> possible effects on childhood<br />
growth <strong>and</strong> reproductive development<br />
Ulla Nordström Joensen 2012<br />
Environmental endocrine disrupters<br />
<strong>and</strong> testicular function<br />
D o k t o r -<br />
a f h a n d l i n g e r<br />
Anders Juul 2003<br />
Serum levels <strong>of</strong> insulin-like growth<br />
factor I <strong>and</strong> its binding proteins in<br />
health <strong>and</strong> disease.<br />
Ewa Rajpert-De Meyts 2006<br />
Developmental model <strong>for</strong> the path<strong>og</strong>enesis<br />
<strong>of</strong> testicular carcinoma in situ:<br />
genetic <strong>and</strong> environmental aspects.<br />
Christina Engel Høi-Hansen 2008<br />
Application <strong>of</strong> stem cell markers in<br />
search <strong>for</strong> neoplastic germ cells in dysgenetic<br />
gonads, extragonadal tumours,<br />
<strong>and</strong> in semen <strong>of</strong> infertile men.
Videnskabelige publikationer 2000-2012<br />
2012<br />
1. Aksglæde L, Garn ID, Hollegaard MV, Hougaard DM,<br />
Rajpert-De Meyts E, Juul A: Detection <strong>of</strong> increased gene<br />
copy number in DNA from dried blood spot samples<br />
allows efficient screening <strong>for</strong> Klinefelter syndrome. Acta<br />
Paediatr 2012;101:e561-e563.<br />
2. Almstrup K, Rajpert-De Meyts E, Skakkebæk NE: Perinatal<br />
origin <strong>of</strong> testicular germ cell cancer: Possible involvement<br />
<strong>of</strong> developmental repr<strong>og</strong>ramming; in Plagemann<br />
A (ed): Perinatal Pr<strong>og</strong>ramming. The State <strong>of</strong> the Art.<br />
Berlin, De Gruyter, 2012, pp 219-228.<br />
3. Amaral A, Wahlgren A, Tuttelmann F, De GK, Blomberg<br />
Jensen M, Nurmio M, Welsh M, Stukenborg JB:<br />
Minutes <strong>of</strong> the 5th meeting <strong>of</strong> the International Network<br />
<strong>for</strong> Young Researchers in Male Fertility. Asian J Androl<br />
2012;14:796.<br />
4. Andersen HR, Wohlfahrt-Veje C, Dalgard C, Christiansen<br />
L, Main KM, Nellemann C, Murata K, Jensen TK,<br />
Skakkebæk NE, Gr<strong>and</strong>jean P: Paraoxonase 1 polymorphism<br />
<strong>and</strong> prenatal pesticide exposure associated<br />
with adverse cardiovascular risk pr<strong>of</strong>iles at school age.<br />
PLoS ONE 2012;7:e36830.<br />
5. Andersson AM, Bay K, Grigor KM, Rajpert-De Meyts<br />
E, Skakkebæk NE: Special issue on the impact <strong>of</strong> endocrine<br />
disrupters on reproductive health. Int J Androl<br />
2012;35:215.<br />
6. Bentzen JG, Forman JL, Pinborg A, Lidegaard O, Larsen<br />
EC, Friis-Hansen L, Johannsen TH, Nyboe AA: Ovarian<br />
reserve parameters: a comparison between users <strong>and</strong><br />
non-users <strong>of</strong> hormonal contraception. Reprod Biomed<br />
Online 2012;25:612-619.<br />
7. Blomberg Jensen M, Publicover SJ: Pr<strong>og</strong>esterone <strong>and</strong><br />
CatSper dependency. Int J Androl 2012;35:631-632.<br />
8. Blomberg Jensen M, Jørgensen A, Nielsen JE, Bjerrum<br />
PJ, Skalkam M, Petersen JH, Egeberg DL, Bangsbøll S,<br />
Andersen AN, Skakkebæk NE, Juul A, Rajpert-De Meyts<br />
E, Dissing S, Leffers H, Jørgensen N: Expression <strong>of</strong> the<br />
vitamin D metabolizing enzyme CYP24A1 at the annulus<br />
<strong>of</strong> human spermatozoa may serve as a novel marker <strong>of</strong><br />
semen quality. Int J Androl 2012;35:499-510.<br />
9. Blomberg Jensen M, Dissing S: Non-genomic effects <strong>of</strong><br />
vitamin D in human spermatozoa. Steroids 2012;77:903-<br />
909.<br />
10. Blomberg Jensen M, Jørgensen A, Nielsen JE, Steinmeyer<br />
A, Leffers H, Juul A, Rajpert-De Meyts E: Vitamin<br />
D metabolism <strong>and</strong> effects on pluripotency genes <strong>and</strong> cell<br />
differentiation in testicular germ cell tumors in vitro <strong>and</strong><br />
in vivo. Neoplasia 2012;14:952-963.<br />
11. Blomberg Jensen M: Vitamin D metabolism, sex hormones,<br />
<strong>and</strong> male reproductive function. Reproduction<br />
2012;144:135-152.<br />
12. Boas M, Feldt-Rasmussen U, Main KM: Thyroid effects<br />
<strong>of</strong> endocrine disrupting chemicals. Mol Cell<br />
Endocrinol 2012;355:240-248.<br />
13. Bonefeld K, Hobolth L, Juul A, Møller S: The insulin<br />
like growth factor system in cirrhosis. Relation to changes<br />
in body composition following adrenoreceptor<br />
blockade. <strong>Growth</strong> Horm IGF Res 2012;22:212-218.<br />
14. Bourguignon JP, Juul A: Normal female puberty in a<br />
developmental perspective. Endocr Dev 2012;22:11-23.<br />
15. Brokken LJ, Lundberg-Giwercman Y, Rajpert De-<br />
Meyts E, Eberhard J, Stahl O, Cohn-Cedermark G, Dau-<br />
34<br />
gaard G, Arver S, Giwercman A: Association <strong>of</strong> polymorphisms<br />
in genes encoding hormone receptors ESR1,<br />
ESR2 <strong>and</strong> LHCGR with the risk <strong>and</strong> clinical features <strong>of</strong><br />
testicular germ cell cancer. Mol Cell Endocrinol<br />
2012;351:279-285.<br />
16. Dalgaard MD, Weinhold N, Edsgärd D, Silver JD, Pers<br />
TH, Nielsen JE, Jørgensen N, Juul A, Gerds TA, Giwercman<br />
A, Giwercman YL, Cedermark GC, Virtanen<br />
HE, Toppari J, Daugaard G, Jensen TS, Brunak S, Rajpert-<br />
De Meyts E, Skakkebæk NE, Leffers H, Gupta R: A genome-wide<br />
association study <strong>of</strong> men with symptoms <strong>of</strong><br />
testicular dysgenesis syndrome <strong>and</strong> its network biol<strong>og</strong>y<br />
interpretation. J Med Genet 2012;49:58-65.<br />
17. Eisenberg ML, Jensen TK, Walters RC, Skakkebæk<br />
NE, Lipshultz LI: The relationship between an<strong>og</strong>enital<br />
distance <strong>and</strong> reproductive hormone levels in adult men. J<br />
Urol 2012;187:594-598.<br />
18. Fern<strong>and</strong>ez MF, Duran I, Olea N, Avivar C, Vierula M,<br />
Toppari J, Skakkebæk NE, Jørgensen N: Semen quality<br />
<strong>and</strong> reproductive hormone levels in men from southern<br />
Spain. Int J Androl 2012;35:1-10.<br />
19. Frederiksen H, Sørensen K, Mouritsen A, Aksglæde L,<br />
Hagen CP, Petersen JH, Skakkebæk NE, Andersson AM,<br />
Juul A: High urinary phthalate concentration associated<br />
with delayed pubarche in girls. Int J Androl 2012;35:216-<br />
226.<br />
20. Friedrich N, Jørgensen T, Juul A, Spielhagen C, Nauck<br />
M, Wallasch<strong>of</strong>ski H, Linneberg A: Insulin-like growth<br />
factor I <strong>and</strong> anthropometric parameters in a Danish population.<br />
Exp Clin Endocrinol Diabetes 2012;120:171-174.<br />
21. Friedrich N, Thuesen B, Jørgensen T, Juul A, Spielhagen<br />
C, Wallasch<strong>of</strong>ksi H, Linneberg A: The association<br />
between IGF-I <strong>and</strong> insulin resistance: a general population<br />
study in Danish adults. Diabetes Care 2012;35:768-773.<br />
22. Gr<strong>and</strong>jean P, Grønlund C, Kjær IM, Jensen TK, Sørensen<br />
N, Andersson AM, Juul A, Skakkebæk NE, Budtz-<br />
Jorgensen E, Weihe P: Reproductive hormone pr<strong>of</strong>ile <strong>and</strong><br />
pubertal development in 14-year-old boys prenatally<br />
exposed to polychlorinated biphenyls. Reprod Toxicol<br />
2012;34:498-503.<br />
23. Gueler B, Sonne SB, Zimmer J, Hilscher B, Hilscher W,<br />
Græm N, Rajpert-De Meyts E, V<strong>og</strong>t PH: AZFa protein<br />
DDX3Y is differentially expressed in human male germ<br />
cells during development <strong>and</strong> in testicular tumours: new<br />
evidence <strong>for</strong> phenotypic plasticity <strong>of</strong> germ cells. Hum<br />
Reprod 2012;27:1547-1555.<br />
24. Hagen CP, Aksglæde L, Sørensen K, Mouritsen A,<br />
Andersson AM, Petersen JH, Main KM, Juul A: Individual<br />
serum levels <strong>of</strong> Anti-Müllerian hormone in healthy<br />
girls persist through childhood adolescence: a longitudinal<br />
cohort study. Hum Reprod 2012;27:861-866.<br />
25. Hagen CP, Vestergaard S, Juul A, Skakkebæk NE,<br />
Andersson AM, Main KM, Hjollund NH, Ernst E, Bonde<br />
JP, Anderson RA, Jensen TK: Low concentration <strong>of</strong> circulating<br />
antimullerian hormone is not predictive <strong>of</strong> reduced<br />
fecundability in young healthy women: a prospective<br />
cohort study. Fertil Steril 2012;98:1602-1608.<br />
26. Hagen CP, Sørensen K, Anderson RA, Juul A: Serum<br />
levels <strong>of</strong> antimullerian hormone in early maturing girls<br />
be<strong>for</strong>e, during, <strong>and</strong> after suppression with GnRH agonist.<br />
Fertil Steril 2012;98:1326-1330.<br />
27. Hellmann P, Christiansen P, Johannsen TH, Main KM,<br />
Duno M, Juul A: Male patients with partial <strong>and</strong>r<strong>og</strong>en<br />
insensitivity syndrome: a longitudinal follow-up <strong>of</strong>
growth, reproductive hormones <strong>and</strong> the development <strong>of</strong><br />
gynaecomastia. Arch Dis Child 2012;97:403-409.<br />
28. Joensen UN, Frederiksen H, Blomberg Jensen M.,<br />
Lauritsen MP, Olesen IA, Lassen TH, Andersson AM,<br />
Jørgensen N: Phthalate excretion pattern <strong>and</strong> testicular<br />
function: a study <strong>of</strong> 881 healthy Danish men. Environ<br />
Health Perspect 2012;120:1397-1403.<br />
29. Johannsen TH, Søeborg T, Frederiksen H, Andersson<br />
A-M, Juul A: Andr<strong>og</strong>enstatus. DSKB-NYT 2012;8-12.<br />
30. Johannsen TH, Søeborg T, Frederiksen H, Andersson<br />
A-M, Juul A: Andr<strong>og</strong>enstatus - metode <strong>og</strong> klinisk anvendelse.<br />
Klinisk Biokemi i Norden 2012;3:10-17.<br />
31. Juul A, Hagen CP, Aksglæde L, Sørensen K, Mouritsen<br />
A, Frederiksen H, Main KM, M<strong>og</strong>ensen SS, Pedersen<br />
AT: Endocrine evaluation <strong>of</strong> reproductive function in<br />
girls during infancy, childhood <strong>and</strong> adolescence. Endocr<br />
Dev 2012;22:24-39.<br />
32. Jørgensen A, Nielsen JE, Blomberg Jensen M, Græm<br />
N, Rajpert-De Meyts E: Analysis <strong>of</strong> meiosis regulators in<br />
human gonads: a sexually dimorphic spatio-temporal<br />
expression pattern suggests involvement <strong>of</strong> DMRT1 in<br />
meiotic entry. Mol Hum Reprod 2012;18:523-534.<br />
33. Jørgensen A, Blomberg Jensen M., Nielsen JE, Juul A,<br />
Rajpert-De Meyts E: Influence <strong>of</strong> vitamin D on cisplatin<br />
sensitivity in testicular germ cell cancer-derived cell lines<br />
<strong>and</strong> in a NTera2 xen<strong>og</strong>raft model. J Steroid Biochem Mol<br />
Biol. 2012. Epub ahead <strong>of</strong> print<br />
34. Jørgensen N, Joensen UN, Jensen TK, Blomberg Jensen<br />
M, Almstrup K, Olesen IA, Juul A, Andersson AM, Carlsen<br />
E, Petersen JH, Toppari J, Skakkebæk NE: Human<br />
semen quality in the new millennium: a prospective cross<br />
-sectional population-based study <strong>of</strong> 4867 men. BMJ<br />
Open 2012;2:e000990.<br />
35. Krause M, Klit A, Blomberg Jensen M, Søeborg T,<br />
Frederiksen H, Schlumpf M, Lichtensteiger W, Skakkebæk<br />
NE, Drzewiecki KT: Sunscreens: are they beneficial<br />
<strong>for</strong> health? An overview <strong>of</strong> endocrine disrupting properties<br />
<strong>of</strong> UV-filters. Int J Androl 2012;35:424-436.<br />
36. Kristensen DG, Mlynarska O, Nielsen JE, Jacobsen<br />
GK, Rajpert-De Meyts E, Almstrup K: Heter<strong>og</strong>eneity <strong>of</strong><br />
chromatin modifications in testicular spermatocytic seminoma<br />
point toward an epigenetically unstable phenotype.<br />
Cancer Genet 2012;205:425-431.<br />
37. Krysiak-Baltyn K, Toppari J, Skakkebæk NE, Jensen<br />
TS, Virtanen HE, Schramm KW, Shen H, Vartiainen T,<br />
Kiviranta H, Taboureau O, Audouze K, Brunak S, Main<br />
KM: Association between chemical pattern in breast milk<br />
<strong>and</strong> congenital cryptorchidism: modelling <strong>of</strong> complex<br />
human exposures. Int J Androl 2012;35:294-302.<br />
38. Lassen TH, Sobotka T, Jensen TK, Jacobsen R, Erb K,<br />
Skakkebæk NE: Trends in rates <strong>of</strong> natural conceptions<br />
among Danish women born during 1960-1984. Hum Reprod<br />
2012;27:2815-2822.<br />
39. Lim J, Maher GJ, Turner GDH, Dudka-Ruszkowska<br />
W, Taylor S, Rajpert-De Meyts E, Goriely A, Wilkie AOM:<br />
Selfish spermat<strong>og</strong>onial selection: Evidence from an immunohistochemical<br />
screen in testes <strong>of</strong> elderly men. PLoS<br />
ONE 2012;7:e42382.<br />
40. Lindhardt Johansen M., Hagen CP, Rajpert-De Meyts<br />
E, Kjærgaard S, Petersen BL, Skakkebæk NE, Main KM,<br />
Juul A: 45,X/46,XY mosaicism: phenotypic characteristics,<br />
growth, <strong>and</strong> reproductive function--a retrospective longitudinal<br />
study. J Clin Endocrinol Metab 2012;97:E1540-<br />
E1549.<br />
41. Mendiola J, Meeker JD, Jørgensen N, Andersson AM,<br />
Liu F, Calafat AM, Redmon JB, Drobnis EZ, Sparks AE,<br />
Wang C, Hauser R, Swan SH: Urinary concentrations <strong>of</strong><br />
di(2-ethylhexyl) phthalate metabolites <strong>and</strong> serum repro-<br />
35<br />
ductive hormones: pooled analysis <strong>of</strong> fertile <strong>and</strong> infertile<br />
men. J Androl 2012;33:488-498.<br />
42. Mieritz MG, Frederiksen H, Sørensen K, Aksglæde L,<br />
Mouritsen A, Hagen CP, Skakkebæk NE, Andersson AM,<br />
Juul A: Urinary phthalate excretion in 555 healthy Danish<br />
boys with <strong>and</strong> without pubertal gynaecomastia. Int J<br />
Androl 2012;35:227-235.<br />
43. Min JL, Nicholson G, Halgrimsdottir I, Almstrup K,<br />
Petri A, Barrett A, Travers M, Rayner NW, Magi R, Pettersson<br />
FH, Broxholme J, Neville MJ, Wills QF, Cheeseman<br />
J, Allen M, Holmes CC, Spector TD, Fleckner J,<br />
McCarthy MI, Karpe F, Lindgren CM, Zondervan KT:<br />
Coexpression Network Analysis in Abdominal <strong>and</strong> Gluteal<br />
Adipose Tissue Reveals Regulatory Genetic Loci <strong>for</strong><br />
Metabolic Syndrome <strong>and</strong> Related Phenotypes. PLoS Genet<br />
2012;8:e1002505.<br />
44. M<strong>og</strong>ensen SS, Aksglæde L, Mouritsen A, Sørensen K,<br />
Main KM, Gideon P, Juul A: Pathol<strong>og</strong>ical <strong>and</strong> incidental<br />
findings on brain MRI in a single-center study <strong>of</strong> 229<br />
consecutive girls with early or precocious puberty. PLoS<br />
ONE 2012;7:e29829.<br />
45. Mouritsen A, Aksglæde L, Sørensen K, Hagen CP,<br />
Petersen JH, Main KM, Juul A.: The Pubertal Transition in<br />
179 Healthy Danish Children: Associations between<br />
Pubarche, Adrenarche, Gonadarche <strong>and</strong> Body Composition.<br />
Eur J Endocrinol 2012;168:129-136.<br />
46. Nielsen JE, Kristensen DM, Almstrup K, Jørgensen A,<br />
Olesen IA, Jacobsen GK, Horn T, Skakkebæk NE, Leffers<br />
H, Rajpert-De Meyts E: A novel double staining strategy<br />
<strong>for</strong> improved detection <strong>of</strong> testicular carcinoma in situ<br />
cells in human semen samples. Androl<strong>og</strong>ia 2012;44:78-85.<br />
47. Nordkap L, Carlsen E, Fedder J, Jørgensen N: M<strong>and</strong>lig<br />
infertilitet. Ugeskr Læger 2012;174:2444-2448.<br />
48. Nordkap L, Joensen UN, Blomberg Jensen M, Jørgensen<br />
N: Regional differences <strong>and</strong> temporal trends in male<br />
reproductive health disorders: semen quality may be a<br />
sensitive marker <strong>of</strong> environmental exposures. Mol Cell<br />
Endocrinol 2012;355:221-230.<br />
49. Novotny GW, Belling K, Bramsen JB, Nielsen JE, Bork-<br />
Jensen J, Almstrup K, Sonne SB, Kjems J, Rajpert-De<br />
Meyts E, Leffers H: MicroRNA expression pr<strong>of</strong>iling <strong>of</strong><br />
carcinoma in situ cells <strong>of</strong> the testis. Endocr Relat Cancer<br />
2012;19:365-379.<br />
50. Priskorn L, Holmboe SA, Jørgensen N, Andersson<br />
AM, Almstrup K, Toppari J, Skakkebæk NE: Adverse<br />
trends in male reproductive health <strong>and</strong> decreasing fertility<br />
rates. Anim Reprod 2012;9:760-771.<br />
51. Priskorn L, Holmboe SA, Jacobsen R, Jensen TK, Lassen<br />
TH, Skakkebæk NE: Increasing trends in childlessness<br />
in recent birth cohorts - a registry-based study <strong>of</strong><br />
the total Danish male population born from 1945 to 1980.<br />
Int J Androl 2012;35:449-455.<br />
52. Rajpert-De Meyts E, Eliasson R, Comhaire FH, Skakkebæk<br />
NE, Sharpe RM, Toppari J: Goodbye International<br />
Journal <strong>of</strong> Androl<strong>og</strong>y, welcome Androl<strong>og</strong>y. Int J Androl<br />
2012;35:769-774.<br />
53. Rajpert-De Meyts E, Almstrup K, Skakkebæk NE:<br />
Testicular Dysgenesis Syndrome <strong>and</strong> Carcinoma in situ<br />
Testis; in Jezek D (ed): Atlas on the Human Testis. London,<br />
Springer Verlag, 2012, pp 159-178.<br />
54. Rajpert-De Meyts E, Almstrup K, Nielsen JE, Skakkebæk<br />
NE: The testis in childhood between birth <strong>and</strong> puberty;<br />
in Jezek (ed): Atlas on the human testis. London,<br />
Springer Verlag, 2012, pp 69-75.<br />
55. Søeborg T, Frederiksen H, Andersson AM: Cumulative<br />
risk assessment <strong>of</strong> phthalate exposure <strong>of</strong> Danish children<br />
<strong>and</strong> adolescents using the hazard index approach.<br />
Int J Androl 2012;35:245-252.
56. Sørensen K, Mouritsen A, Aksglæde L, Hagen CP,<br />
M<strong>og</strong>ensen SS, Juul A: Recent secular trends in pubertal<br />
timing: implications <strong>for</strong> evaluation <strong>and</strong> diagnosis <strong>of</strong> precocious<br />
puberty. Horm Res Paediatr 2012;77:137-145.<br />
57. Sørensen K, Aksglæde L, Petersen JH, Andersson<br />
AM, Juul A: Serum IGF1 <strong>and</strong> insulin levels in girls with<br />
normal <strong>and</strong> precocious puberty. Eur J Endocrinol<br />
2012;166:903-910.<br />
58. Tinggaard J, Mieritz MG, Sørensen K, Mouritsen A,<br />
Hagen CP, Aksglæde L, Wohlfahrt-Veje C, Juul A: The<br />
physiol<strong>og</strong>y <strong>and</strong> timing <strong>of</strong> male puberty. Curr Opin<br />
Endocrinol Diabetes Obes 2012;19:197-203.<br />
59. Toppari J, Adamsson A, Boas M, Juul A, Main KM,<br />
Skakkebæk NE, Virtanen HE: Possible developmental<br />
early effects <strong>of</strong> endocrine disrupters on child health.<br />
WHO report 2012. 2012.<br />
60. Tuttelmann F, De GK, Amaral A, Giachini CC, Welsh<br />
M, Blomberg Jensen M, Nurmio M, Wahlgren A, Stukenborg<br />
JB: The future <strong>of</strong> testis research is turning 6! Six<br />
years <strong>of</strong> International Network <strong>for</strong> Young Researchers in<br />
Male Fertility. Int J Androl 2012;35:211-213.<br />
61. Vestergaard S, Nielsen F, Andersson AM, Hjollund<br />
NH, Gr<strong>and</strong>jean P, Andersen HR, Jensen TK: Association<br />
between perfluorinated compounds <strong>and</strong> time to pregnancy<br />
in a prospective cohort <strong>of</strong> Danish couples attempting<br />
to conceive. Hum Reprod 2012;27:873-880.<br />
62. Virtanen HE, Koskenniemi JJ, Sundqvist E, Main KM,<br />
Kiviranta H, Tuomisto JT, Tuomisto J, Viluksela M, Vartiainen<br />
T, Skakkebæk NE, Toppari J: Associations between<br />
congenital cryptorchidism in newborn boys <strong>and</strong> levels <strong>of</strong><br />
dioxins <strong>and</strong> PCBs in placenta. Int J Androl 2012;35:283-<br />
293.<br />
63. Wohlfahrt-Veje C, Andersen HR, Schmidt IM, Aksglæde<br />
L, Sørensen K, Juul A, Jensen TK, Gr<strong>and</strong>jean P,<br />
Skakkebæk NE, Main KM: Early breast development in<br />
girls after prenatal exposure to non-persistent pesticides.<br />
Int J Androl 2012;35:273-282.<br />
64. Wohlfahrt-Veje C, Andersen HR, Jensen TK, Gr<strong>and</strong>jean<br />
P, Skakkebæk NE, Main KM: Smaller genitals at<br />
school age in boys whose mothers were exposed to nonpersistent<br />
pesticides in early pregnancy. Int J Androl<br />
2012;35:265-272.<br />
65. Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebæk<br />
NE, Soto AM, Woodruff TJ, vom Saal FS: Endocrinedisrupting<br />
chemicals <strong>and</strong> public health protection: a<br />
statement <strong>of</strong> principles from The Endocrine Society.<br />
Endocrinol<strong>og</strong>y 2012;153:4097-4110.<br />
2011<br />
1. Aksglæde L, Skakkebæk NE, Almstrup K, Juul A: Clinical<br />
<strong>and</strong> biol<strong>og</strong>ical parameters in 166 boys, adolescents<br />
<strong>and</strong> adults with nonmosaic Klinefelter syndrome: a Copenhagen<br />
experience. Acta Paediatr 2011;100:793-806.<br />
2. Aksglæde L, Christiansen P, Sørensen K, Boas M,<br />
Linneberg A, Main KM, Andersson AM, Skakkebæk NE,<br />
Juul A: Serum concentrations <strong>of</strong> Anti-Mullerian Hormone<br />
(AMH) in 95 patients with Klinefelter syndrome<br />
with or without cryptorchidism. Acta Paediatr<br />
2011;100:839-845.<br />
3. Aksglæde L, Skakkebæk NE, Juul A: Sex chromosome<br />
aneuploidy <strong>and</strong> anthropometry; in Preedy VY (ed):<br />
H<strong>and</strong>book <strong>of</strong> Anthropometry: Physical measures <strong>of</strong> human<br />
<strong>for</strong>m in health <strong>and</strong> disease. Springer Verlag, 2011.<br />
4. Almstrup K, Mlynarska O, Rajpert-de-Meyts E: Germ<br />
cell cancer, testicular dysgenesis <strong>and</strong> epigenetics; in<br />
Rousseaux S, Khochbin S (eds): Epigenetics <strong>and</strong> Human<br />
Reproduction, Epigenetics <strong>and</strong> Human Health. Berlin<br />
Heidelberg, Springer-Verlag, 2011, pp 19-44.<br />
36<br />
5. Almstrup K, Lippert M, M<strong>og</strong>ensen HO, Nielsen JE,<br />
Hansen JD, Daugaard G, Jørgensen N, F<strong>og</strong>ed NT,<br />
Skakkebæk NE, Rajpert-De Meyts E: Screening <strong>of</strong> subfertile<br />
men <strong>for</strong> testicular carcinoma in situ by an automated<br />
image analysis-based cytol<strong>og</strong>ical test <strong>of</strong> the ejaculate. Int J<br />
Androl 2011;34:e21-e30.<br />
6. B<strong>and</strong>ak M, Aksglæde L, Juul A, Rørth M, Daugaard G:<br />
The pituitary-Leydig cell axis be<strong>for</strong>e <strong>and</strong> after orchiectomy<br />
in patients with stage I testicular cancer. Eur J Cancer<br />
2011;47:2585-2591.<br />
7. Bang P, Bjerknes R, Dahlgren J, Dunkel L, Gustafsson J,<br />
Juul A, Kristrom B, Tapanainen P, Aberg V: A comparison<br />
<strong>of</strong> different definitions <strong>of</strong> growth response in short<br />
prepubertal children treated with growth hormone.<br />
Horm Res Paediatr 2011;75:335-345.<br />
8. Bartkova J, Moudry P, Hodny Z, Lukas J, Rajpert-De<br />
Meyts E, Bartek J: Heterochromatin marks HP1gamma,<br />
HP1alpha <strong>and</strong> H3K9me3, <strong>and</strong> DNA damage response<br />
activation in human testis development <strong>and</strong> germ cell<br />
tumours. Int J Androl 2011;34:e103-e113.<br />
9. Bay K, Andersson AM: Human testicular insulin-like<br />
factor 3: in relation to development, reproductive hormones<br />
<strong>and</strong> <strong>and</strong>rol<strong>og</strong>ical disorders. Int J Androl 2011;34:97<br />
-109.<br />
10. Bay K, Main KM, Toppari J, Skakkebæk NE: Testicular<br />
descent: INSL 3, testosterone, genes <strong>and</strong> the intrauterine<br />
milieu. Nature Reviews Urol<strong>og</strong>y 2011;8:187-196.<br />
11. Beck JR, Vielwerth S, Larsen T, Hilsted L, Cohen A,<br />
Hougaard DM, Jensen LT, Greisen G, Juul A: Influence <strong>of</strong><br />
fetal growth velocity <strong>and</strong> smallness at birth on adrenal<br />
function in adolescence. Horm Res Paediatr 2011;75:2-7.<br />
12. Blomberg JM, Bjerrum PJ, Jessen TE, Nielsen JE, Joensen<br />
UN, Olesen IA, Petersen JH, Juul A, Dissing S, Jørgensen<br />
N: Vitamin D is positively associated with sperm<br />
motility <strong>and</strong> increases intracellular calcium in human<br />
spermatozoa. Hum Reprod 2011;26:1307-1317.<br />
13. Boas M, Feldt-Rasmussen U, Main KM: Thyroid effects<br />
<strong>of</strong> endocrine disrupting chemicals. Mol Cell Endocrinol<br />
2011;355:240-248.<br />
14. Bush JM, Gardiner DW, Palmer JS, Rajpert-De Meyts<br />
E, Veeramachaneni DN: Testicular germ cell tumours in<br />
d<strong>og</strong>s are predominantly <strong>of</strong> spermatocytic seminoma type<br />
<strong>and</strong> are frequently associated with somatic cell tumours.<br />
Int J Androl 2011;34:e288-e295.<br />
15. Cleemann L, Holm K, Kobbernagel H, Skouby SO,<br />
Kristensen B, Smedegaard H, Andersson AM, Cohen A,<br />
Gravholt CH: Normal Tempo <strong>of</strong> Bone Formation in<br />
Turner Syndrome despite Signs <strong>of</strong> Accelerated Bone Resorption.<br />
Horm Res Paediatr 2011;76:193-201.<br />
16. Cleemann L, Holm K, Fallentin E, Skouby SO, Smedegaard<br />
H, Møller N, Borch-Christensen H, Jeppesen EM,<br />
Wiesl<strong>and</strong>er SB, Andersson A-M, Cohen A, Gravholt CH:<br />
Uterus <strong>and</strong> ovaries in girls <strong>and</strong> young women with<br />
Turner syndrome evaluated by ultrasound <strong>and</strong> magnetic<br />
resonance imaging. Clin Endocrinol (Oxf) 2011;74:756-<br />
761.<br />
17. Edsgärd D, Scheel M, Hansen NT, Ralfkiaer U, Jensen<br />
TS, Skakkebæk NE, Brunak S, Gupta R, Rajpert-De Meyts<br />
E, Ottesen AM: Heterozygous deletion at the RLN1 locus<br />
in a family with testicular germ cell cancer identified by<br />
integrating copy number variation data with phenome<br />
<strong>and</strong> interactome in<strong>for</strong>mation. Int J Androl 2011;34:e122e132.<br />
18. Ewen K, Boag P: Meiotic crossover: what controls the<br />
breaks? Asian J Androl 2011;13:191-192.<br />
19. Flanagan KL, Klein SL, Skakkebæk NE, Marriott I,<br />
Marchant A, Selin L, Fish EN, Prentice AM, Whittle H,<br />
Benn CS, Aaby P: Sex differences in the vaccine-specific
<strong>and</strong> non-targeted effects <strong>of</strong> vaccines. Vaccine 2011;29:2349<br />
-2354.<br />
20. Frederiksen H, Jørgensen N, Andersson AM: Parabens<br />
in urine, serum <strong>and</strong> seminal plasma from healthy Danish<br />
men determined by liquid chromat<strong>og</strong>raphy-t<strong>and</strong>em mass<br />
spectrometry (LC-MS/MS). J Expo Sci Environ Epidemiol<br />
2011;21:262-271.<br />
21. Frederiksen H, Aksglæde L, Sørensen K, Skakkebæk<br />
NE, Juul A, Andersson AM: Urinary excretion <strong>of</strong><br />
phthalate metabolites in 129 healthy Danish children <strong>and</strong><br />
adolescents: Estimation <strong>of</strong> daily phthalate intake. Environ<br />
Res 2011;111:656-663.<br />
22. Grigorova M, Punab M, Zilaitiene B, Erenpreiss J,<br />
Ausmees K, Matulevicius V, Tsarev I, Jørgensen N, Laan<br />
M: Genetically determined dosage <strong>of</strong> follicle-stimulating<br />
hormone (FSH) affects male reproductive parameters. J<br />
Clin Endocrinol Metab 2011;96:E1534-E1541.<br />
23. Hagen CP, Aksglæde L, Sørensen K, Mouritsen A,<br />
Juul A: Clinical use <strong>of</strong> Anti-müllerian hormone (AMH)<br />
determinations in patients with disorders <strong>of</strong> sex development:<br />
importance <strong>of</strong> sex- <strong>and</strong> age-specific reference ranges.<br />
Pediatr Endokrinol Rev 2011;9(suppl):525-527.<br />
24. Juul A, Main KM, Skakkebæk NE: Development: disorders<br />
<strong>of</strong> sex development-the tip <strong>of</strong> the iceberg? Nat Rev<br />
Endocrinol 2011;7:504-505.<br />
25. Juul A: In utero pr<strong>og</strong>ramming <strong>of</strong> pubertal development?<br />
Arch Dis Child 2011;96:703.<br />
26. Juul A, Aksglæde L, Bay K, Grigor KM, Skakkebæk<br />
NE: Klinefelter syndrome: the <strong>for</strong>gotten syndrome: basic<br />
<strong>and</strong> clinical questions posed to an international group <strong>of</strong><br />
scientists. Acta Paediatr 2011;100:791-792.<br />
27. Jørgensen A, Dalgaard MD, Sonne SB: Microdissection<br />
<strong>of</strong> gonadal tissues <strong>for</strong> gene expression analyses. Methods<br />
Mol Biol 2011;755:307-313.<br />
28. Jørgensen N, Vierula M, Jacobsen R, Pukkala E, Perheentupa<br />
A, Virtanen HE, Skakkebæk NE, Toppari J:<br />
Recent adverse trends in semen quality <strong>and</strong> testis cancer<br />
incidence among Finnish men. Int J Androl 2011;34:e37e48.<br />
29. Kristensen DM, Hass U, Lesne L, Lottrup G, Jacobsen<br />
PR, Desdoits-Lethimonier C, Boberg J, Petersen JH, Toppari<br />
J, Jensen TK, Brunak S, Skakkebæk NE, Nellemann<br />
C, Main KM, Jegou B, Leffers H: Intrauterine exposure to<br />
mild analgesics is a risk factor <strong>for</strong> development <strong>of</strong> male<br />
reproductive disorders in human <strong>and</strong> rat. Hum Reprod<br />
2011;26:235-244.<br />
30. Kristensen DM, Skalkam ML, Audouze K, Lesne L,<br />
Desdoits-Lethimonier C, Frederiksen H, Brunak S,<br />
Skakkebæk NE, Jegou B, Hansen JB, Junker S, Leffers H:<br />
Many Putative Endocrine Disruptors Inhibit Prostagl<strong>and</strong>in<br />
Synthesis. Environ Health Perspect 2011;119:534-541.<br />
31. Kusk KO, Krüger T, Long M, Taxvig C, Lykkesfeldt<br />
AE, Frederiksen H, Andersson A-M, Andersen HR, Hansen<br />
KM, Nellemann C, Bonefeld-Jørgensen EC: Endocrine<br />
potency <strong>of</strong> wastewater: Contents <strong>of</strong> endocrine disrupting<br />
chemicals <strong>and</strong> effects measured by in vivo <strong>and</strong> in vitro<br />
assays. Environ Toxicol Chem 2011;30:413-426.<br />
32. Lim J, Goriely A, Turner GD, Ewen KA, Jacobsen GK,<br />
Graem N, Wilkie AO, Rajpert-De Meyts E: OCT2, SSX<br />
<strong>and</strong> SAGE1 reveal the phenotypic heter<strong>og</strong>eneity <strong>of</strong> spermatocytic<br />
seminoma reflecting distinct subpopulations <strong>of</strong><br />
spermat<strong>og</strong>onia. J Pathol 2011;224:473-483.<br />
33. Mendiola J, Jørgensen N, Andersson AM, Calafat AM,<br />
Silva MJ, Redmon JB, Sparks A, Drobnis EZ, Wang C, Liu<br />
F, Swan SH: Associations between urinary metabolites <strong>of</strong><br />
di(2-ethylhexyl) phthalate <strong>and</strong> reproductive hormones in<br />
fertile men. Int J Androl 2011;34:369-378.<br />
34. Mendiola J, Stahlhut RW, Jørgensen N, Liu F, Swan<br />
SH: Shorter an<strong>og</strong>enital distance predicts poorer semen<br />
37<br />
quality in young men in Rochester, New York. Environ<br />
Health Perspect 2011;119:958-963.<br />
35. M<strong>og</strong>ensen SS, Aksglæde L, Mouritsen A, Sørensen K,<br />
Main KM, Gideon P, Juul A: Diagnostic work-up <strong>of</strong> 449<br />
consecutive girls who were referred to be evaluated <strong>for</strong><br />
precocious puberty. J Clin Endocrinol Metab 2011;96:1393<br />
-1401.<br />
36. Rajpert-De Meyts E, Ottesen AM, Garn ID, Aksglæde<br />
L, Juul A: Deletions <strong>of</strong> the Y chromosome are associated<br />
with sex chromosome aneuploidy but not with Klinefelter<br />
syndrome. Acta Paediatr 2011;100:900-902.<br />
37. Rajpert-De Meyts E, Toppari J: European Academy <strong>of</strong><br />
Androl<strong>og</strong>y revives the International Journal <strong>of</strong> Androl<strong>og</strong>y<br />
Award <strong>and</strong> Lecture. Int J Androl 2011;34:1.<br />
38. Rajpert-De Meyts E, Skakkebæk NE: Path<strong>og</strong>enesis <strong>of</strong><br />
testicular carcinoma in situ <strong>and</strong> germ cell cancer: still<br />
more questions than answers. Int J Androl 2011;34:e2-e6.<br />
39. Rajpert-De Meyts E, Grigor KM, Skakkebæk NE: Proceedings<br />
<strong>of</strong> the 7th Copenhagen Workshop on Testicular<br />
Carcinoma in situ <strong>and</strong> Germ Cell Cancer, 13-15 October<br />
2010. Int J Androl 2011;34:e1.<br />
40. Rasmussen MH, Juul A, Main KM, Hilsted J: Normal<br />
sweat secretion despite impaired growth hormoneinsulin-like<br />
growth factor-I axis in obese subjects. Int J<br />
Endocrinol 2011:493840. doi: 10.1155/2011/493840.<br />
41. Ravnborg TL, Jensen TK, Andersson AM, Toppari J,<br />
Skakkebæk NE, Jørgensen N: Prenatal <strong>and</strong> adult exposures<br />
to smoking are associated with adverse effects on<br />
reproductive hormones, semen quality, final height <strong>and</strong><br />
body mass index. Hum Reprod 2011;26:1000-1011.<br />
42. Ringholm L, Vestgaard M, Laugesen CS, Juul A,<br />
Damm P, Mathiesen ER: Pregnancy-induced increase in<br />
circulating IGF-I is associated with pr<strong>og</strong>ression <strong>of</strong> diabetic<br />
retinopathy in women with type 1 diabetes. <strong>Growth</strong><br />
Horm IGF Res 2011;21:25-30.<br />
43. Roque FS, Jensen PB, Schmock H, Dalgaard M, Andreatta<br />
M, Hansen T, Soeby K, Bredkjaer S, Juul A, Werge T,<br />
Jensen LJ, Brunak S: Using electronic patient records to<br />
discover disease correlations <strong>and</strong> stratify patient cohorts.<br />
PLoS Comput Biol 2011;7:e1002141.<br />
44. Skakkebæk NE, Andersson AM, Juul A, Jensen TK,<br />
Almstrup K, Toppari J, Jørgensen N: Commentary: sperm<br />
counts, data responsibility, <strong>and</strong> good scientific practice.<br />
Epidemiol<strong>og</strong>y 2011;22:620-621.<br />
45. Skakkebæk NE, Andersson AM, Juul A, Jensen TK,<br />
Almstrup K, Toppari J, Jørgensen N: Sperm counts, data<br />
responsibility, <strong>and</strong> good scientific practice. Epidemiol<strong>og</strong>y<br />
2011;22:620-621.<br />
46. Skakkebæk NE, Toppari J, Söder O, Gordon CM, Divall<br />
S, Draznin M: The exposure <strong>of</strong> fetuses <strong>and</strong> children to<br />
endocrine disrupting chemicals: a European Society <strong>for</strong><br />
Paediatric Endocrinol<strong>og</strong>y (ESPE) <strong>and</strong> Pediatric Endocrine<br />
Society (PES) call to action statement. J Clin Endocrinol .<br />
Metab 2011;96:3056-3058.<br />
47. Tommiska J, Sorensen K, Aksglaede L, Koivu R, Puhakka<br />
L, Juul A, Raivio T: LIN28B, LIN28A, KISS1, <strong>and</strong><br />
KISS1R in idiopathic central precocious puberty. BMC<br />
Res Notes 2011;4:363.<br />
48. Vestergaard TR, Juul A, Lausten-Thomsen U, Lausen<br />
B, Hjalgrim H, Kvist TK, Andersen EW, Schmiegelow K:<br />
Duration <strong>of</strong> adrenal insufficiency during treatment <strong>for</strong><br />
childhood acute lymphoblastic leukemia. J Pediatr Hematol<br />
Oncol 2011;33:442-449.<br />
49. Västermark A, Giwercman YL, Hagstromer O, Rajpert<br />
-De Meyts E, Eberhard J, Stahl O, Cedermark GC,<br />
Rastkhani H, Daugaard G, Arver S, Giwercman A: Polymorphic<br />
variation in the <strong>and</strong>r<strong>og</strong>en receptor gene: association<br />
with risk <strong>of</strong> testicular germ cell cancer <strong>and</strong> metastatic<br />
disease. Eur J Cancer 2011;47:413-419.
50. Wesolowska A, Dalgaard MD, Borst L, Gautier L, Bak<br />
M, Weinhold N, Nielsen BF, Helt LR, Audouze K,<br />
Nersting J, Tommerup N, Brunak S, Sicheritz-Ponten T,<br />
Leffers H, Schmiegelow K, Gupta R: Cost-effective multiplexing<br />
be<strong>for</strong>e capture allows screening <strong>of</strong> 25 000 clinically<br />
relevant SNPs in childhood acute lymphoblastic leukemia.<br />
Leukemia 2011;25:1001-1006.<br />
51. Wohlfahrt-Veje C, Main KM, Schmidt IM, Boas M,<br />
Jensen TK, Gr<strong>and</strong>jean P, Skakkebæk NE, Andersen HR:<br />
Lower birth weight <strong>and</strong> increased body fat at school age<br />
in children prenatally exposed to modern pesticides: a<br />
prospective study. Environ Health 2011;10:79.<br />
52. Wright A, Andrews N, Bardsley K, Nielsen JE, Avery<br />
K, Pewsey E, jones M, Harley D, Nielsen AR, Moore H,<br />
Gokhale P, Rajpert-De Meyts E, Andrews PW, Walsh J,<br />
Harrison NJ: Mapping the stem cell state: eight novel<br />
human embryonic stem <strong>and</strong> embryonal carcinoma cell<br />
antibodies. Int J Androl 2011;34:e175-e187.<br />
2010<br />
1. Aksglæde L, Sørensen K, Boas M, Mouritsen A, Hagen<br />
CP, Jensen RB, Petersen JH, Linneberg A, Andersson AM,<br />
Main KM, Skakkebæk NE, Juul A: Changes in anti-<br />
Mullerian hormone (AMH) throughout the life span: a<br />
population-based study <strong>of</strong> 1027 healthy males from birth<br />
(cord blood) to the age <strong>of</strong> 69 years. J Clin Endocrinol<br />
Metab 2010;95:5357-5364.<br />
2. Almstrup K, Nielsen JE, Mlynarska O, Jansen MT,<br />
Jørgensen A, Skakkebæk NE, Rajpert-De Meyts E: Carcinoma<br />
in situ testis displays permissive chromatin modifications<br />
similar to immature foetal germ cells. Br J Cancer<br />
2010;103:1269-1276.<br />
3. Andersson AM, Bay K, Grigor KM, Toppari J,<br />
Skakkebæk NE: Proceedings <strong>of</strong> the 5th Copenhagen<br />
Workshop on endocrine disrupters: ubiquitous endocrine<br />
disrupters <strong>and</strong> possible human health effects. Preface. Int<br />
J Androl 2010;33:251.<br />
4. Asklund C, Jensen TK, Main KM, Sobotka T,<br />
Skakkebæk NE, Jørgensen N: Semen quality, reproductive<br />
hormones <strong>and</strong> fertility <strong>of</strong> men operated <strong>for</strong> hypospadias.<br />
Int J Androl 2010;33:80-87.<br />
5. Bentsen AH, Ansel L, Simonneaux V, Tena-Sempere<br />
M, Juul A, Mikkelsen JD: Maturation <strong>of</strong> kisspeptinergic<br />
neurons coincides with puberty onset in male rats. Peptides<br />
2010;31:275-283.<br />
6. Blomberg Jensen M, Andersen CB, Nielsen JE, Bagi P,<br />
Jørgensen A, Juul A, Leffers H: Expression <strong>of</strong> the vitamin<br />
D receptor, 25-hydroxylases, 1alpha-hydroxylase <strong>and</strong> 24hydroxylase<br />
in the human kidney <strong>and</strong> renal clear cell<br />
cancer. J Steroid Biochem Mol Biol 2010;121:376-382.<br />
7. Blomberg Jensen M, Nielsen JE, Jørgensen A, Rajpert-<br />
De Meyts E, Kristensen DM, Jørgensen N, Skakkebæk<br />
NE, Juul A, Leffers H: Vitamin D receptor <strong>and</strong> vitamin D<br />
metabolizing enzymes are expressed in the human male<br />
reproductive tract. Hum Reprod 2010;25:1303-1311.<br />
8. Blomberg M, Blomberg Jensen M, Henry A, Singh ST,<br />
Banipal RP, da Cunha-Bang C, Bygbjerg IC: Antimicrobial<br />
drug use in a small Indian community hospital. Trop<br />
Doct 2010;40:194-198.<br />
9. Boas M, Frederiksen H, Feldt-Rasmussen U,<br />
Skakkebæk NE, Hegedüs L, Hilsted L, Juul A, Main KM:<br />
Childhood exposure to phthalates - associations with<br />
thyroid function, insulinlike growth factor I (IGF-I) <strong>and</strong><br />
growth. Environ Health Perspect 2010;118:1458-1464.<br />
10. Courant F, Aksglæde L, Antignac JP, Monteau F,<br />
Sørensen K, Andersson AM, Skakkebæk NE, Juul A, Le<br />
Bizec B: Assessment <strong>of</strong> Circulating Sex Steroid Levels in<br />
Prepubertal <strong>and</strong> Pubertal Boys <strong>and</strong> Girls by a Novel Ultrasensitive<br />
Gas Chromat<strong>og</strong>raphy-T<strong>and</strong>em Mass Spectrometry<br />
Method. J Clin Endocrinol Metab 2010;95:82-92.<br />
38<br />
11. Frederiksen H, Jørgensen N, Andersson A-M: Correlations<br />
between phthalate metabolites in urine, serum <strong>and</strong><br />
seminal plasma from young danish men determined by<br />
isotope dilution liquid chromat<strong>og</strong>raphy t<strong>and</strong>em mass<br />
spectrometry. J Anal Toxicol 2010;34:400-410.<br />
12. Frokjaer VG, Erritzoe D, Juul A, Nielsen FA, Holst K,<br />
Svarer C, Madsen J, Paulson OB, Knudsen GM: End<strong>og</strong>enous<br />
plasma estradiol in healthy men is positively correlated<br />
with cerebral cortical serotonin 2A receptor binding.<br />
Psychoneuroendocrinol<strong>og</strong>y 2010;35:1311-1320.<br />
13. Haak CS, Nymann P, Pedersen AT, Clausen HV, Feldt<br />
RU, Rasmussen AK, Main KM, Haedersdal M: Hair removal<br />
in hirsute women with normal testosterone levels:<br />
a r<strong>and</strong>omized controlled trial <strong>of</strong> long-pulsed diode laser<br />
vs. intense pulsed light. Br J Dermatol 2010;163:1007-1013.<br />
14. Hagen CP, Main KM, Kjaergaard S, Juul A: FSH, LH,<br />
inhibin B <strong>and</strong> estradiol levels in Turner syndrome depend<br />
on age <strong>and</strong> karyotype: longitudinal study <strong>of</strong> 70 Turner<br />
girls with or without spontaneous puberty. Hum Reprod<br />
2010;25:3134-3141.<br />
15. Hagen CP, Aksglæde L, Sørensen K, Main KM, Boas<br />
M, Cleemann L, Holm K, Gravholt CH, Andersson AM,<br />
Pedersen AT, Petersen JH, Linneberg A, Kjaergaard S,<br />
Juul A: Serum levels <strong>of</strong> anti-Mullerian hormone as a<br />
marker <strong>of</strong> ovarian function in 926 healthy females from<br />
birth to adulthood <strong>and</strong> in 172 Turner syndrome patients. J<br />
Clin Endocrinol Metab 2010;95:5003-5010.<br />
16. Hagenäs I, Jørgensen N, Rechnitzer C, Sommer P,<br />
Holm M, Schmiegelow K, Daugaard G, Jacobsen N, Juul<br />
A: Clinical <strong>and</strong> biochemical correlates <strong>of</strong> successful semen<br />
collection <strong>for</strong> cryopreservation from 12-18-year-old patients:<br />
a single-center study <strong>of</strong> 86 adolescents. Hum Reprod<br />
2010;25:2031-2038.<br />
17. Jensen TK, Swan SH, Skakkebæk NE, Rasmussen S,<br />
Jørgensen N: Caffeine intake <strong>and</strong> semen quality in a population<br />
<strong>of</strong> 2,554 young Danish men. Am J Epidemiol<br />
2010;171:883-891.<br />
18 Johannsen TH, Ripa CP, Carlsen E, Starup J, Nielsen<br />
OH, Schwartz M, Drzewiecki KT, Mortensen EL, Main<br />
KM: Long-Term Gynecol<strong>og</strong>ical Outcomes in Women with<br />
Congenital Adrenal Hyperplasia due to 21-Hydroxylase<br />
Deficiency. Int J Pediatr Endocrinol. 2010:784297. doi:<br />
10.1155/2010/784297.<br />
19. Juul A, Hagen CP, Aksglæde L, Sørensen K, Mouritsen<br />
A, Frederiksen H, Main KM, M<strong>og</strong>ensen SS,P edersen<br />
AT: Endocrine evaluation <strong>of</strong> reproductive function in<br />
girls during infancy, childhood <strong>and</strong> adolescence; in Sultan<br />
C (ed): Paediatric <strong>and</strong> Adolescent Gynaecol<strong>og</strong>y.<br />
Karger AG, 2010.<br />
20. Jørgensen A, Nielsen JE, Nielsen BF, Morthorst JE,<br />
Bjerregaard P, Leffers H: Expression <strong>of</strong> prostagl<strong>and</strong>in<br />
synthases (pgds <strong>and</strong> pges) during zebrafish gonadal differentiation.<br />
Comp Biochem Physiol A Mol Integr Physiol<br />
2010;157:102-108.<br />
21. Jørgensen N, Liu F, Andersson AM, Vierula M, Irvine<br />
DS, Auger J, Brazil CK, Drobnis EZ, Jensen TK, Jouannet<br />
P, Overstreet JW, Redmon JB, Sparks A, Toppari J, Wang<br />
C, Skakkebæk NE, Swan SH: Serum inhibin-b in fertile<br />
men is strongly correlated with low but not high sperm<br />
counts: a coordinated study <strong>of</strong> 1,797 European <strong>and</strong> US<br />
men. Fertil Steril 2010;94:2128-2134.<br />
22. Jørgensen N, Rajpert-De Meyts E, Main KM,<br />
Skakkebæk NE: Testicular dysgenesis syndrome comprises<br />
some but not all cases <strong>of</strong> hypospadias <strong>and</strong> impaired<br />
spermat<strong>og</strong>enesis. Int J Androl 2010;33:298-303.<br />
23. Kristensen DM, Nielsen JE, Kalisz M, Dalgaard MD,<br />
Audouze K, Larsen ME, Jacobsen GK, Horn T, Brunak S,<br />
Skakkebæk NE, Leffers H: OCT4 <strong>and</strong> downstream factors<br />
are expressed in human somatic ur<strong>og</strong>enital epithelia <strong>and</strong>
in culture <strong>of</strong> epididymal spheres. Mol Hum Reprod<br />
2010;16:835-845.<br />
24. Krysiak-Baltyn K, Toppari J, Skakkebæk NE, Jensen<br />
TS, Virtanen HE, Schramm KW, Shen H, Vartiainen T,<br />
Kiviranta H, Taboureau O, Brunak S, Main KM: Countryspecific<br />
chemical signatures <strong>of</strong> persistent environmental<br />
compounds in breast milk. Int J Androl 2010;33:270-278.<br />
25. Lovel<strong>and</strong> KL, Rajpert-De Meyts E, Veeramachaneni<br />
DNR: Testicular cancer; in McQueen CA (ed): Comprehensive<br />
Toxicol<strong>og</strong>y. Ox<strong>for</strong>d, Academic Press, 2010, pp<br />
247-263.<br />
26. Main KM, Skakkebæk NE, Virtanen HE, Toppari J:<br />
Genital anomalies in boys <strong>and</strong> the environment. Best<br />
Pract Res Clin Endocrinol Metab 2010;24:279-289.<br />
27. Mendiola J, Jørgensen N, Andersson AM, Calafat AM,<br />
Ye X, Redmon JB, Drobnis EZ, Wang C, Sparks A,<br />
Thurston SW, Liu F, Swan SH: Are Environmental Levels<br />
<strong>of</strong> Bisphenol A Associated with Reproductive Function in<br />
Fertile Men? Environ Health Perspect 2010;118:1286-1291.<br />
28. Mouritsen A, Aksglæde L, Sørensen K, M<strong>og</strong>ensen SS,<br />
Leffers H, Main KM, Frederiksen H, Andersson AM,<br />
Skakkebæk NE, Juul A: Hypothesis: exposure to endocrine-disrupting<br />
chemicals may interfere with timing <strong>of</strong><br />
puberty. Int J Androl 2010;33:346-359.<br />
29. Mouritsen A, Juul A, Jørgensen N: Improvement <strong>of</strong><br />
semen quality in an infertile man with 21-hydroxylase<br />
deficiency, suppressed serum gonadotropins <strong>and</strong> testicular<br />
adrenal rest tumours. Int J Androl 2010;33:518-520.<br />
30. Mouritsen A, Jørgensen N, Main KM, Schwartz M,<br />
Juul A: Testicular adrenal rest tumours in boys, adolescents<br />
<strong>and</strong> adult men with congenital adrenal hyperplasia<br />
may be associated with the CYP21A2 mutation. Int J<br />
Androl 2010;33:521-527.<br />
31. Nielsen AM, Olsen EM, Juul A: New Danish reference<br />
values <strong>for</strong> height, weight <strong>and</strong> body mass index <strong>of</strong> children<br />
aged 0-5 years. Acta Paediatr 2010;99:268-278.<br />
32. Nielsen JE, Lindegaard ML, Friis-Hansen L, Almstrup<br />
K, Leffers H, Nielsen LB, Rajpert-De Meyts E: Lipoprotein<br />
lipase <strong>and</strong> endothelial lipase in human testis <strong>and</strong> in<br />
germ cell neoplasms. Int J Androl 2010;33:e207-e215.<br />
33. Ottesen AM, Aksglæde L, Garn I, Tartaglia N, Tassone<br />
F, Gravholt CH, Bojesen A, Sørensen K, Jørgensen<br />
N, Rajpert-De Meyts E, Gerdes T, Lind AM, Kjaergaard S,<br />
Juul A: Increased number <strong>of</strong> sex chromosomes affects<br />
height in a nonlinear fashion: a study <strong>of</strong> 305 patients with<br />
sex chromosome aneuploidy. Am J Med Genet A<br />
2010;152A:1206-1212.<br />
34. Pedersen NG, Juul A, Christiansen M, Wojdemann<br />
KR, Tabor A: Maternal serum placental growth hormone,<br />
but not human placental lact<strong>og</strong>en or insulin growth factor-1,<br />
is positively associated with fetal growth in the first<br />
half <strong>of</strong> pregnancy. Ultrasound Obstet Gynecol<br />
2010;36:534-541.<br />
35. Rajpert-De Meyts E, Main KM, Toppari J, Skakkebæk<br />
NE: Cryptorchidism, hypospadias, testicular tumours<br />
<strong>and</strong> testicular dysgenesis syndrome; in De Groot LJ,<br />
Jameson JL (eds): Endocrinol<strong>og</strong>y. Philadelphia, Elsevier<br />
Saunders, 2010, pp 2499-2513.<br />
36. Rajpert-De Meyts E: International Journal <strong>of</strong> Androl<strong>og</strong>y:<br />
new editorial team. Int J Androl 2010;33:1.<br />
37. Rosendahl M, Andersen CY, la Cour FN, Juul A, Løssl<br />
K, Andersen AN: Dynamics <strong>and</strong> mechanisms <strong>of</strong> chemotherapy-induced<br />
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38. Salonen J, Rajpert-De Meyts E, Mannisto S, Nielsen JE,<br />
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39<br />
genes in testicular carcinoma in situ <strong>and</strong> germ cell tumours.<br />
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42. Skakkebæk NE: Normal reference ranges <strong>for</strong> semen<br />
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43. Sonne SB, Perrett RM, Nielsen JE, Baxter MA, Kristensen<br />
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44. Storr HL, Metherell LA, Dias R, Savage MO, Rasmussen<br />
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45. Sørensen K, Mouritsen A, M<strong>og</strong>ensen SS, Aksglæde L,<br />
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22. Krausz C, Giachini C, Xue Y, O'Bryan MK, Gromoll J,<br />
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Juul A, Pinchera A: Thyroid autoantibodies <strong>and</strong> thyroid<br />
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pulsatile secretion <strong>of</strong> FSH <strong>and</strong> LH in young men with<br />
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levels <strong>of</strong> insulin-like growth factor(IGF)-I, IGF binding<br />
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6. Andersen HR, Schmidt IM, Gr<strong>and</strong>jean P, Jensen TK,<br />
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10. Bay K, Cohen AS, Jørgensen FS, Jørgensen C, Lind<br />
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13. Crain DA, Janssen SJ, Edwards TM, Heindel J, Ho SM,<br />
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Skakkebæk NE, Soto AM, Swan S, Walker C, Woodruff<br />
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17. Euling SY, Selevan SG, Pescovitz OH, Skakkebæk NE:<br />
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18. Euling SY, Herman-Giddens ME, Lee PA, Selevan SG,<br />
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1. Aksglæde L, Andersson A-M, Jørgensen N, Jensen TK,<br />
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ma in situ in subfertile danish men. Int J Androl 30:406-<br />
412, 2007<br />
40. Olesen IA, Sonne SB, Høi-Hansen CE, Rajpert-<br />
DeMeyts E, Skakkebæk NE: Environment, testicular dysgenesis<br />
<strong>and</strong> carcinoma in situ testis. Best Pract Res Clin<br />
Endocrinol Metab 21:462-478, 2007<br />
41. Ottesen AM, Garn ID, Aksglæde L, Juul A, Rajpert-De<br />
Meyts E: A simple screening method <strong>for</strong> detection <strong>of</strong><br />
Klinefelter syndrome <strong>and</strong> other X-chromosome aneuploidies<br />
based on copy number <strong>of</strong> the <strong>and</strong>r<strong>og</strong>en receptor<br />
gene. Mol Hum Reprod 13:745-750, 2007<br />
42. Rajpert-De Meyts E: Recent advances <strong>and</strong> future directions<br />
in research on testicular germ cell cancer. Int J<br />
Androl 30:192-197, 2007<br />
43. Rajpert-De Meyts E, Graem N: The Reproductive<br />
System. In: Fetal <strong>and</strong> Neonatal Pathol<strong>og</strong>y. Keeling JW,<br />
Khong TY, eds. London: Springer-Verlag, pp. 651-661,<br />
2007<br />
44. Rajpert-De Meyts E, Poll SN, Goukasian I, Jeanneau C,<br />
Herlihy AS, Bennett EP, Skakkebæk NE, Clausen H, Giwercman<br />
A, M<strong>and</strong>el U: Changes in the pr<strong>of</strong>ile <strong>of</strong> simple<br />
mucin-type O-glycans <strong>and</strong> polypeptide GalNActransferases<br />
in human testis <strong>and</strong> testicular neoplasms are<br />
associated with germ cell maturation <strong>and</strong> tumour differentiation.<br />
Virchows Arch 451:805-814, 2007<br />
45. Rajpert-De Meyts E, Høi-Hansen CE: From Gonocytes<br />
to Testicular Cancer: The Role <strong>of</strong> Impaired Gonadal Development.<br />
Ann N Y Acad Sci 1120: 168-180, 2007<br />
46. Rajpert-De Meyts E, Ottesen AM, Høi-Hansen CE,<br />
Sonne SB, Leffers H, Skakkebæk NE: Origin <strong>of</strong> testicular<br />
germ cell neoplasia:The role <strong>of</strong> sex chromosomes. In: The<br />
chromosome <strong>and</strong> male germ cell biol<strong>og</strong>y in health <strong>and</strong><br />
diseases. Lau YFC, Chan WY, eds. World Scientific, pp.<br />
289-308, 2007<br />
47. Rasmussen MH, Juul A, Hilsted J: Effect <strong>of</strong> weight loss<br />
on free insulin-like growth factor-I in obese women with<br />
hyposomatotropism. Obesity 15:879-886, 2007<br />
48. Ritzen EM, Bergh A, Bjerknes R, Christiansen P, Cortes<br />
D, Haugen S, Jørgensen N, Kollin C, Lindahl S, Läckgren<br />
G, Main KM, Nordenskjöld A, Rajpert-De Meyts E,<br />
Söder O, Taskinen S, Thorsson A, Thorup J, Toppari J,<br />
Virtanen H: Nordic consensus on treatment <strong>of</strong> undescended<br />
testes. Acta Paediatr 96:638-643, 2007<br />
49. Shen H, Main KM, Virtanen HE, Damgaard IN, Haavisto<br />
A-M, Kaleva M, Boisen KA, Schmidt IM,<br />
Chellakooty M, Skakkebæk NE, Toppari J, Schramm KW:<br />
From mother to child: Investigation <strong>of</strong> prenatal <strong>and</strong> postnatal<br />
exposure to persistent bioaccumulationg toxicants<br />
using breast milk <strong>and</strong> placenta biomonitoring. Chemosphere<br />
67:256-262, 2007<br />
50. Skakkebæk NE, Jørgensen N, Rajpert-De Meyts E, et<br />
al: Environment, lifestyle <strong>and</strong> male fertility: a review. In:<br />
Advances in fertility studies <strong>and</strong> reproductive medicine -<br />
IFFS 2007. Kruger TF, van der Spuy Z, Kempers RD, eds.<br />
Cape Town: pp. 374-384, 2007<br />
51. Skakkebæk NE, Rajpert-De Meyts E, Jørgensen N,<br />
Main KM, Leffers H, Andersson A-M, Juul A, Jensen TK,<br />
Toppari J: Testicular cancer trends as "whistle blowers" <strong>of</strong><br />
testicular developmental problems in populations. Int J<br />
Androl 30:198-205, 2007<br />
52. Swan SH, Liu F, Overstreet JW, Brazil C, Skakkebæk<br />
NE: Semen quality <strong>of</strong> fertile US males in relation to their<br />
mothers' beef consumption during pregnancy. Hum Reprod<br />
22:1497-1502, 2007<br />
53. Sørensen K, Andersson AM, Skakkebæk NE, Juul A:<br />
Serum sex hormone-binding globulin levels in healthy<br />
children <strong>and</strong> girls with precocious puberty be<strong>for</strong>e <strong>and</strong><br />
during gonadotropin-releasing hormone agonist treatment.<br />
J Clin Endocrinol Metab 92: 3189-3196, 2007
54. Teilmann G, Boas M, Petersen JH, Main KM, Gormsen<br />
M, Damgaard K, Brocks V, Skakkebæk NE, Jensen TK:<br />
Early pituitary-gonadal activation in 5-8 years old adopted<br />
girls be<strong>for</strong>e clinical signs <strong>of</strong> puberty: A study <strong>of</strong> 99<br />
<strong>for</strong>eign adopted girls <strong>and</strong> 93 controls. J Clin Endocrinol<br />
Metab 2538:2544, 2007<br />
55. Toppari J, Kaleva M, Virtanen HE, Main KM,<br />
Skakkebæk NE: Luteinizing hormone in testicular descent.<br />
Mol Cell Endocrinol 269:34-37, 2007<br />
56. Tüttelmann F, Rajpert-De Meyts E, Nieschlag E, Simoni<br />
M: Gene polymorphisms <strong>and</strong> male infertility - a metaanalysis<br />
<strong>and</strong> literature review. RBM Online 15:643-658,<br />
2007<br />
57. Vielwerth SE, Jensen RB, Larsen T, Greisen G: The<br />
impact <strong>of</strong> maternal smoking on fetal <strong>and</strong> infant growth.<br />
Early Hum Dev 83:491-495, 2007<br />
58. Virtanen HE, Cortes D, Rajpert-De Meyts E, Ritzen<br />
EM, Nordenskjöld A, Skakkebæk NE, Toppari J: Development<br />
<strong>and</strong> descent <strong>of</strong> the testis in relation to cryptorchidism.<br />
Acta Paediatr 96:622-627, 2007<br />
59. Virtanen HE, Bjerknes R, Cortes D, Jørgensen N, Rajpert-De<br />
Meyts E, Thorsson AV, Thorup J, Main KM:<br />
Cryptorchidism: classification, prevalence <strong>and</strong> long-term<br />
consequences. Acta Paediatr 96:611-616, 2007<br />
60. Wikström AM, Høi-Hansen CE, Dunkel L, Rajpert-De<br />
Meyts E: Immuno-expression <strong>of</strong> <strong>and</strong>r<strong>og</strong>en receptor <strong>and</strong><br />
nine markers <strong>of</strong> maturation in the testes <strong>of</strong> adolescent<br />
boys with Klinefelter Syndrome: evidence <strong>for</strong> degeneration<br />
<strong>of</strong> germ cells at the onset <strong>of</strong> meiosis. J Clin Endocrinol<br />
Metab 92:714-719, 2007<br />
2006<br />
1. Aitken RJ, Skakkebæk NE, Roman SD: Male reproductive<br />
health <strong>and</strong> the environment. Med J Aust 185:414-415,<br />
2006<br />
2. Aksglæde L, Wikstrom AM, Rajpert-De Meyts E, Dunkel<br />
L, Skakkebæk NE, Juul A: Natural history <strong>of</strong> seminiferous<br />
tubule degeneration in Klinefelter syndrome. Hum<br />
Reprod Update 12:39-48, 2006<br />
3. Aksglæde L, Juul A, Leffers H, Skakkebæk NE, Andersson<br />
AM: The sensitivity <strong>of</strong> the child to sex steroids: possible<br />
impact <strong>of</strong> ex<strong>og</strong>enous estr<strong>og</strong>ens. Hum Reprod Update<br />
12:341-349, 2006<br />
4. Almstrup K, Sonne SB, Høi-Hansen CE, Ottesen AM,<br />
Nielsen JE, Skakkebæk NE, Leffers H, Rajpert-De Meyts<br />
E: From embryonic stem cells to testicular germ cell cancer<br />
- should we be concerned? Int J Androl 29:211-218,<br />
2006<br />
5. Bay K, Matthiesson KL, McLachlan RI, Andersson AM:<br />
Brief report: The Effects <strong>of</strong> Gonadotropin Suppression<br />
<strong>and</strong> Selective Replacement on INSL3 Secretion in Normal<br />
Adult Men. J Clin Endocrinol Metab 91(3):1108-1111, 2006<br />
6. Bay K, Asklund C, Skakkebæk NE, Andersson AM:<br />
Testicular dysgenesis syndrome: possible role <strong>of</strong> endocrine<br />
disrupters. Best Pract Res Clin Endocrinol Metab<br />
20:77-90, 2006<br />
7. Boas M, Boisen KA, Virtanen HE, Kaleva M, Suomi A-<br />
M, Schmidt IM, Damgaard IN, Kai CM, Chellakooty M,<br />
Skakkebæk NE, Toppari J, Main KM: Postnatal penile<br />
length <strong>and</strong> growth rate correlate to serum testosterone<br />
levels: a longitudinal study <strong>of</strong> 1962 normal boys. Eur J<br />
Endocrinol 154:125-129, 2006<br />
8. Boas M, Feldt-Rasmussen U, Skakkebæk NE, Main KM:<br />
Environmental chemicals <strong>and</strong> thyroid function. Eur J<br />
Endocrinol 154:599-611, 2006<br />
9. Buhl AM, Jurl<strong>and</strong>er J, Geisler CH, Pedersen LB, Andersen<br />
MK, Josefs-son P, Petersen JH, Leffers H: CLLU1<br />
expression levels predict time to initiation <strong>of</strong> therapy <strong>and</strong><br />
45<br />
overall survival in chronic lymphocytic leukemia. Eur J<br />
Haematol 76:455-464, 2006<br />
10. Buhl AM, Jurl<strong>and</strong>er J, Jorgensen FS, Ottesen AM,<br />
Cowl<strong>and</strong> JB, Gjerdrum LM, Hansen BV, Leffers H: Identification<br />
<strong>of</strong> a gene on chromosome 12q22 uniquely overexpressed<br />
in chronic lymphocytic leukemia. Blood 107:2904-<br />
2911, 2006<br />
11. Chellakooty M, Juul A, Boisen KA, Damgaard IN, Kai<br />
CM, Schmidt IM, Petersen JH, Skakkebæk NE, Main KM:<br />
A prospective study <strong>of</strong> serum insulin-like growth factor I<br />
(IGF-I) <strong>and</strong> IGF-binding protein-3 in 942 healthy infants:<br />
associations with birth weight, gender, growth velocity,<br />
<strong>and</strong> breastfeeding. J Clin Endocrinol Metab 91:820-826,<br />
2006<br />
12. Christesen HBT, Jensen RB, Birkebæk NH, Hertel NT,<br />
Main KM, Mortensen HB, Næraa RW, Juul A: <strong>Vækst</strong>hormonbeh<strong>and</strong>ling<br />
af korte børn født small <strong>for</strong> gestational<br />
age. Ugeskr Læger 168:889-895, 2006<br />
13. Damgaard IN, Skakkebæk NE, Toppari J, Virtanen<br />
HE, Shen H, Schramm KW, Petersen JH, Jensen TK, The<br />
Nordic Cryptorchidism Study Group, Main KM: Persistent<br />
pesticides in human breast milk <strong>and</strong> cryptorchidism.<br />
Environ Health Perspect 114: 1133-1138, 2006<br />
14. Ekbom P, Damm P, Andersson AM, Skakkebæk NE,<br />
Feldt-Rasmussen U, Mathiesen ER: Serum levels <strong>of</strong> activin<br />
A <strong>and</strong> inhibin A are not related to the increased susceptibility<br />
to pre-eclampsia in type I diabetic pregnancies.<br />
Acta Obstet Gynecol Sc<strong>and</strong> 85: 143-147, 2006<br />
15. Hannema SE, Scott IS, Rajpert-De Meyts E,<br />
Skakkebæk NE, Coleman N, Hughes IA: Testicular development<br />
in the complete <strong>and</strong>r<strong>og</strong>en insensitivity syndrome.<br />
J Pathol 208:518-527, 2006<br />
16. Hansen MA, Nielsen JE, Tanaka M, Almstrup K,<br />
Skakkebæk NE, Leffers H: Identification <strong>and</strong> expression<br />
pr<strong>of</strong>iling <strong>of</strong> 10 novel spermatid expressed CYPT genes.<br />
Mol Reprod Dev 73:568-579, 2006<br />
17. Høi-Hansen CE, Sehested A, Juhler M, Lau YF,<br />
Skakkebæk NE, Laursen H, Rajpert-De Meyts E: New<br />
evidence <strong>for</strong> the origin <strong>of</strong> intracranial germ cell tumours<br />
from primordial germ cells: expression <strong>of</strong> pluripotency<br />
<strong>and</strong> cell differentiation markers. J Pathol 209:25-33, 2006<br />
18. Iwamoto T, Hoshino T, Nishida T, Baaba K, Matsusita<br />
T, Kaneko S, Tanaka N, Naka M, Yoshiike M, Nozawa S,<br />
Skakkebæk NE, Jørgensen N: Semen quality <strong>of</strong> 324 fertile<br />
Japanese men. Hum Reprod 21:760-765, 2006<br />
19. Johannsen TH, Ripa CP, Morten-sen EL, Main KM:<br />
Quality <strong>of</strong> life in 70 women with disorders <strong>of</strong> sex development.<br />
Eur J Endocrinol 155:877-885, 2006<br />
20. Johannsen TH, Ripa CP, Reinisch JM, Schwartz M,<br />
Mortensen EL, Main KM: Impaired c<strong>og</strong>nitive function in<br />
women with congenital adrenal hyperplasia. J Clin Endocrinol<br />
Metab 91: 1376-1381, 2006<br />
21. Juul A, Teilmann G, Scheike T, Hertel NT, Holm K,<br />
Laursen EM, Main KM, Skakkebæk NE: Pubertal development<br />
in Danish children: comparison <strong>of</strong> recent European<br />
<strong>and</strong> US data. Int J Androl 29:247-255, 2006<br />
22. Jørgensen N, Asklund C, Bay K, Skakkebæk NE: Testicular<br />
dysgenesis syndrome: biol<strong>og</strong>ical <strong>and</strong> clinical significance.<br />
In: Male Infertility. Diagnosis <strong>and</strong> treatment.<br />
Oehninger SC, Kruger TF, eds. Hampshire: Thomson<br />
Publishing Services, pp. 105-113, 2006<br />
23. Jørgensen N, Asklund C, Carlsen E, Skakkebæk NE:<br />
Coordinated European investigations <strong>of</strong> semen quality:<br />
results from studies <strong>of</strong> Sc<strong>and</strong>inavian young men is a matter<br />
<strong>of</strong> concern. Int J Androl 29:54-61, 2006<br />
24. Kai CM, Main KM, Andersen AN, L<strong>of</strong>t A, Chellakooty<br />
M, Skakkebæk NE, Juul A: Serum insulin-like growth<br />
factor-I (IGF-I) <strong>and</strong> growth in children born after assisted<br />
reproduction. J Clin Endocrinol Metab 91:4352-4360, 2006
25. Leffers H, Navarro VM, Nielsen JE, Mayen A, Pinilla<br />
L, Dalgaard M, Malagon MM, Castano JP, Skakkebæk<br />
NE, Aguilar E, Tena-Sempere M: Increased expression <strong>of</strong><br />
alpha- <strong>and</strong> beta-globin mRNAs at the pituitary following<br />
exposure to estr<strong>og</strong>en during the critical period <strong>of</strong> neonatal<br />
sex differentiation in the rat. J Steroid Biochem Mol<br />
Biol 99: 33-43, 2006<br />
26. Lottrup G, Andersson A-M, Leffers H, Mortensen GK,<br />
Toppari J, Skakkebæk NE, Main KM: Possible impact <strong>of</strong><br />
phthalates on infant reproductive health. Int J Androl<br />
29:172-180, 2006<br />
27. Main KM, Sehested A, Feldt-Rasmussen U: Pegvisomant<br />
treatment in a 4-year-old girl with neur<strong>of</strong>ibromatosis<br />
type I. Horm Res 65:1-5, 2006<br />
28. Main KM, Jensen RB, Asklund C, Høi-Hansen CE,<br />
Skakkebæk NE: Low birth weight <strong>and</strong> male reproductive<br />
function. Horm Res 65 Suppl 3:116-122, 2006<br />
29. Main KM, Mortensen GK, Kaleva M, Boisen K, Damgaard<br />
I, Chellakooty M, Schmidt IM, Suomi A-M, Virtanen<br />
H, Petersen JH, Andersson A-M, Toppari J,<br />
Skakkebæk NE: Human Breast Milk Contamination with<br />
Phthalates <strong>and</strong> Alterations <strong>of</strong> End<strong>og</strong>enous Reproductive<br />
Hormones in Three Months Old Infants. Environmental<br />
Health Perspectives 114:270-276, 2006<br />
30. Main KM, Toppari J, Skakkebæk NE: Gonadal development<br />
<strong>and</strong> reproductive hormones in infant boys. Eur J<br />
Endocrinol 155:S51-S57 2006<br />
31. Main KM, Toppari J, Suomi A-M, Kaleva M,<br />
Chellakooty M, Schmidt IM, Virtanen HE, Boisen KA,<br />
Kai CM, Damgaard IN, Skakkebæk NE: Larger Testes<br />
<strong>and</strong> higher inhibin B levels in Finnish than in Danish<br />
newborn boys. J Clin Endocrinol Metab 91:2732-2737,<br />
2006<br />
32. Rajpert-De Meyts E, Toppari J, Skakkebæk NE: Testicular<br />
tumours with endocrine manifestations. In: Endocrinol<strong>og</strong>y.<br />
DeGroot LJ, Jameson JL, eds. Philadelphia: Elsevier<br />
Saunders, pp. 3257-3264, 2006<br />
33. Rajpert-De Meyts E: Developmental model <strong>for</strong> the<br />
path<strong>og</strong>enesis <strong>of</strong> testicular carcinoma in situ: genetic <strong>and</strong><br />
environmental aspects. Hum Reprod Update 12:303-323,<br />
2006<br />
34. Rasmussen MH, Juul A, Kjems LL, Hilsted J: Effects <strong>of</strong><br />
short-term caloric restriction on circulating free IGF-I,<br />
acid-labile subunit, IGF-binding proteins (IGFBPs)-1-4,<br />
<strong>and</strong> IGFBPs-1-3 protease activity in obese subjects. Eur J<br />
Endocrinol 155:575-581, 2006<br />
35. Shen H, Virtanen HE, Main KM, Kaleva M, Andersson<br />
AM, Skakkebæk NE, Toppari J, Schramm KW: Enantiomeric<br />
ratios as an indicator <strong>of</strong> exposure processes <strong>for</strong><br />
persistent pollutants in human placentas. Chemosphere<br />
62: 390-395, 2006<br />
36. Skakkebæk NE, Jørgensen N, Main KM, Rajpert-De<br />
Meyts E, Leffers H, Andersson A-M, Juul A, Carlsen E,<br />
Mortensen GK, Jensen TK, Toppari J: Is human fecundity<br />
declining? Int J Androl 29:2-11, 2006<br />
37. Sonne SB, Herlihy AS, Høi-Hansen CE, Nielsen JE,<br />
Almstrup K, Skakkebæk NE, Marks A, Leffers H, Rajpert<br />
-De Meyts E: Identity <strong>of</strong> M2A (D2-40) antigen <strong>and</strong> gp36<br />
(Aggrus, T1A-2, podoplanin) in human developing testis,<br />
testicular carcinoma in situ <strong>and</strong> germ-cell tumours. Virchows<br />
Arch 449:200-206, 2006<br />
38. Sonne SB, Høi-Hansen CE, Nielsen JE, Herlihy AS,<br />
Andersson AM, Almstrup K, Daugaard G, Skakkebæk<br />
NE, Leffers H, Rajpert-De Meyts E: CDH1 (E-cadherin) in<br />
testicular germ cell neoplasia: suppressed translation <strong>of</strong><br />
mRNA in pre-invasive carcinoma in situ but increased<br />
protein levels in advanced tumours. APMIS 114:549-558,<br />
2006<br />
39. Suomi A-M, Main KM, Kaleva M, Schmidt IM,<br />
46<br />
Chellakooty M, Virtanen HE, Boisen KA, Damgaard IN,<br />
Kai CM, Skakkebæk NE, Toppari: Hormonal changes in 3<br />
-month-old cryptorchid boys. J Clin Endocrinol Metab<br />
91:953-958, 2006<br />
40. Tanaka M, Nakaya S, Katayama M, Leffers H, Nozawa<br />
S, Nakazawa R, Iwamoto T, Kobayashi S: Effect <strong>of</strong><br />
prenatal exposure to bisphenol A on the serum testosterone<br />
concentration <strong>of</strong> rats at birth. Hum Exp Toxicol<br />
25:369-373, 2006<br />
41. Teilmann G, Pedersen CB, Skakkebæk NE, Jensen TK:<br />
Increased risk <strong>of</strong> precocious puberty in internationally<br />
adopted children in Denmark. Pediatrics 118:391-399,<br />
2006<br />
42. Thomsen AR, Almstrup K, Nielsen JE, Sorensen IK,<br />
Petersen OW, Leffers H, Breinholt VM: Estr<strong>og</strong>enic effect<br />
<strong>of</strong> soy is<strong>of</strong>lavones on mammary gl<strong>and</strong> morph<strong>og</strong>enesis<br />
<strong>and</strong> gene expression pr<strong>of</strong>ile. Toxicol Sci 93:357-368, 2006<br />
43. Toppari J, Virtanen H, Skakkebæk NE, Main KM:<br />
Environmental effects on hormonal regulation <strong>of</strong> testicular<br />
descent. J Steroid Biochem Mol Biol 102:184-186, 2006<br />
44. Virtanen HE, Tapanainen AE, Kaleva MM, Suomi<br />
AM, Main KM, Skakkebæk NE, Toppari J: Mild gestational<br />
diabetes as a risk factor <strong>for</strong> congenital cryptorchidism. J<br />
Clin Endocrinol Metab 91:4862-4865, 2006<br />
45. Wennerholm UB, Bonduelle M, Sutcliffe A, Bergh C,<br />
Niklasson A, Tarlatzis B, Kai CM, Peters C, Cederqvist<br />
AV, L<strong>of</strong>t A: Paternal sperm concentration <strong>and</strong> growth<br />
<strong>and</strong> c<strong>og</strong>nitive development in children born with a gestational<br />
age more than 32 weeks after assisted reproductive<br />
therapy. Hum Reprod 21: 1514-1520, 2006<br />
46. Wikstrom AM, Bay K, Hero M, Andersson AM, Dunkel<br />
L: Serum insulin-like factor 3 levels during puberty in<br />
healthy boys <strong>and</strong> boys with Klinefelter syndrome. J Clin<br />
Endocrinol Metab 91:4705-4708, 2006<br />
2005<br />
1. Almstrup K, Høi-Hansen CE, Nielsen JE, Wirkner U,<br />
Ansorge W, Skakkebæk NE, Rajpert-De Meyts E, Leffers<br />
H: Genome-wide gene expression pr<strong>of</strong>iling <strong>of</strong> testicular<br />
carcinoma in situ pr<strong>og</strong>ression into overt tumours. Br J<br />
Cancer 92:1934-1941, 2005<br />
2. Almstrup K, Ottesen AM, Sonne SB, Høi-Hansen CE,<br />
Leffers H, Rajpert-De Meyts E, Skakkebæk NE: Genomic<br />
<strong>and</strong> gene expression signature <strong>of</strong> the pre-invasive testicular<br />
carcinoma in situ. Cell Tissue Res 322:159-165, 2005<br />
3. Bang AK, Carlsen E, Holm M, Petersen JH, Skakkebæk<br />
NE, Jørgensen N: A study <strong>of</strong> finger lengths,semen quality<br />
<strong>and</strong> sex hormones in 360 young men from the general<br />
Danish population. Hum Reprod 20:3109-3113, 2005<br />
4. Bartkova J, Bakkenist CJ, Rajpert-De Meyts E,<br />
Skakkebæk NE, Sehested M, Lukas J, Kastan MB, Bartek<br />
J: ATM activation in normal human tissues <strong>and</strong> testicular<br />
cancer. Cell Cycle 4:838-845, 2005<br />
5. Bay K, Hartung S, Ivell R, Schumacher M, Jurgensen D,<br />
Jorgensen N, Holm M, Skakkebæk NE, Andersson A-M:<br />
Insulin-like factor 3 serum levels in 135 normal men <strong>and</strong><br />
85 men with testicular disorders: relationship to the luteinizing<br />
hormone-testosterone axis. J Clin Endocrinol<br />
Metab 90:3410-3418, 2005<br />
6. Boisen KA, Chellakooty M, Schmidt IM, Kai CM, Damgaard<br />
IN, Suomi AM, Toppari J, Skakkebæk NE, Main<br />
KM: Hypospadias in a cohort <strong>of</strong> 1072 Danish newborn<br />
boys: Prevalence <strong>and</strong> relationship to placental weight,<br />
anthropometrical measurements at birth, <strong>and</strong> reproductive<br />
hormone levels at 3 months <strong>of</strong> age. J Clin Endocrinol<br />
Metab 90:4041-4046, 2005<br />
7. Bonduelle M, Wennerholm UB, L<strong>of</strong>t A, Tarlatzis BC,<br />
Peters C, Henriet S, Mau C, Victorin-Cederquist A, van<br />
Steirteghem A, Balaska A, Emberson JR, Sutcliffe AG: A
multi-centre cohort study <strong>of</strong> the physical health <strong>of</strong> 5-yearold<br />
children conceived after intracytoplasmic sperm injection,<br />
in vitro fertilization <strong>and</strong> natural conception. Hum<br />
Reprod 20:413-419, 2005<br />
8. Carlsen E, Swan SH, Holm PJ, Skakkebæk NE: Longitudinal<br />
changes in semen parameters in young Danish men<br />
from the Copenhagen area. Hum Reprod 20:942-949, 2005<br />
9. Carlsen E, Jørgensen N, Juul A, Skakkebæk NE: Udredning<br />
<strong>og</strong> beh<strong>and</strong>ling af m<strong>and</strong>lig infertilitet <strong>og</strong> hyp<strong>og</strong>onadisme.<br />
Månedsskr Prakt Lægegern 83:1239-1250, 2005<br />
10. Clayton PE, Cuneo RC, Juul A, Monson JP, Shalet SM,<br />
Tauber M: Consensus statement on the management <strong>of</strong><br />
the GH-treated adolescent in the transition to adult care.<br />
Eur J Endocrinol 152:165-170, 2005<br />
11. Hammer NA, Hansen TVO, Byskov AG, Rajpert-De<br />
Meyts E, Grøndahl ML, Bredkjær HE, Wewer UM, Christiansen<br />
J, Nielsen FC: Expression <strong>of</strong> IGF-II mRNAbinding<br />
proteins (IMPs) in gonads <strong>and</strong> testicular cancer.<br />
Reproduction 130:203-212, 2005<br />
12. Høi-Hansen CE, Almstrup K, Nielsen JE, Sonne SB,<br />
Graem N, Skakkebæk NE, Leffers H, Rajpert-De Meyts E:<br />
Stem cell pluripotency factor NANOG is expressed in<br />
human fetal gonocytes, testicular carcinoma in situ <strong>and</strong><br />
germ cell tumours. Histopathol<strong>og</strong>y 47:48-56, 2005<br />
13. Høi-Hansen CE, Rajpert-De Meyts E, Carlsen E,<br />
Almstrup K, Leffers H, Skakkebæk NE: Fast-track Article:<br />
A subfertile patient diagnosed with testicular carcinoma<br />
in situ by immunocytol<strong>og</strong>ical staining <strong>for</strong> AP-2 in semen<br />
samples: Case report. Hum Reprod 20:579-582, 2005<br />
14. Høi-Hansen CE, Rajpert-De Meyts E, Daugaard G,<br />
Skakkebæk NE: Carcinoma in situ testis, the pr<strong>og</strong>enitor <strong>of</strong><br />
testicular germ cell tumours: a clinical review. Ann Oncol<br />
16:863-868, 2005<br />
15. Jensen RB, Jeppesen KA, Vielwerth S, Michaelsen KF,<br />
Main KM, Skakkebæk NE, Juul A: Insulin-Like <strong>Growth</strong><br />
Factor I (IGF-I) <strong>and</strong> IGF-Binding Protein 3 as Diagnostic<br />
Markers <strong>of</strong> <strong>Growth</strong> Hormone Deficiency in Infancy.<br />
Horm Res 63:15-21, 2005<br />
16. Johannsen TH, Mallet D, Dige-Petersen H, Müller JR,<br />
Main KM, Morel Y, Forest MG: Delayed Diagnosis <strong>of</strong><br />
Congenital Adrenal Hyperplasia with Salt Wasting due to<br />
Type II 3{beta}-Hydroxysteroid Dehydr<strong>og</strong>enase Deficiency.<br />
J Clin Endocrinol Metab 90: 2076-2080, 2005<br />
Juul A: IGF-I measurements. Epidemiol<strong>og</strong>ical <strong>and</strong> clinical<br />
aspects. Front Horm Res 33:45-67, 2005<br />
17. Kaleva M, Virtanen H, Haavisto AM, Main K,<br />
Skakkebæk NE, Huhtaniemi I, Irjala K, Toppari J: Does<br />
Variant Luteinizing Hormone (V-LH) Predispose to Improper<br />
Testicular Position in Late Pregnancy? Pediatr Res<br />
58: 447-450, 2005<br />
18. Kaleva M, Virtanen HE, Haavisto AM, Main KM,<br />
Reunanen M, Skakkebæk NE, Toppari J: Circannual<br />
rhythm in the incidence <strong>of</strong> cryptorchidism in Finl<strong>and</strong>. Int<br />
J Androl 28:53-57, 2005<br />
19. Lange M, Müller J, Svendsen OL, Kastrup KW, Juul A,<br />
Feldt-Rasmussen U: The impact <strong>of</strong> idiopathic childhoodonset<br />
growth hormone deficiency (GHD) on bone mass in<br />
subjects without adult GHD. Clin Endocrinol (Oxf) 62:18-<br />
23, 2005<br />
20. Lindegaard MLS, Nielsen JE, Hannibal J, Nielsen LB:<br />
Expression <strong>of</strong> the endothelial lipase gene in murine embryos<br />
<strong>and</strong> reproductive organs. J Lipid Research 46:439-<br />
444, 2005<br />
21. Mabeck LM, Jensen MS, T<strong>of</strong>t G, Thulstrup M, Andersson<br />
A-M, Jensen TK, Giwercman A, Olsen J, Bonde JP:<br />
Fecundability according to male serum inhibin B - a prospective<br />
study among first pregnancy planners. Hum<br />
Reprod 20:2909-2915, 2005<br />
47<br />
22. Mortensen GK, Main KM, Andersson A-M, Leffers H,<br />
Skakkebæk NE: Determination <strong>of</strong> phthalate monoesters<br />
in human breast milk, consumer milk <strong>and</strong> infant <strong>for</strong>mula<br />
by t<strong>and</strong>em mass spectrometry(LC/MC/MS). Analytical<br />
Bioanalytical Chemistry 382:1084-1092, 2005<br />
23. Preiksa RT, Zilaitiene B, Matulevicius V, Skakkebæk<br />
NE, Petersen JH, Jørgensen N, Toppari J: Higher than<br />
expected prevalence <strong>of</strong> congenital cryptorchidism in Lithuania:<br />
a study <strong>of</strong> 1204 boys at birth <strong>and</strong> 1 year follow-up.<br />
Hum Reprod 20:1928-1932, 2005<br />
24. Schmidt IM, Chellakooty M, Boisen KA, Damgaard<br />
IN, Mau KC, Olgaard K, Main KM: Impaired kidney<br />
growth in low-birth-weight children: distinct effects <strong>of</strong><br />
maturity <strong>and</strong> weight <strong>for</strong> gestational age. Kidney Int<br />
68:731-740, 2005<br />
25. Shen H, Main KM, Kaleva M, Virtanen HE, Haavisto<br />
A-M, Skakkebæk NE, Toppari J, Schramm KW: Prenatal<br />
organochlorine pesticides in placentas from Finl<strong>and</strong>:<br />
exposure <strong>of</strong> male infants born during 1997-2001. Placenta<br />
26: 512-514, 2005<br />
26. Skakkebæk NE, Jørgensen N: Testicular dysgenesis<br />
<strong>and</strong> fertility. Androl<strong>og</strong>ia 37:217-218, 2005<br />
27. Swan SH, Main KM, Liu F, Stewart SL, Kruse RL,<br />
Calafat AM, Mao CS, Redmon JB, Tern<strong>and</strong> CL, Sullivan S,<br />
Teague JL: Decrease in an<strong>og</strong>enital distance among male<br />
infants with prenatal phthalate exposure. Environmental<br />
Health Perspectives 113:1056-1061, 2005<br />
28. Teilmann G, Pedersen CB, Jensen TK, Skakkebæk NE,<br />
Juul A: Prevalence <strong>and</strong> incidence <strong>of</strong> precocious pubertal<br />
development in Denmark: an epidemiol<strong>og</strong>ic study based<br />
on national registries. Pediatrics 116:1323-1328, 2005<br />
29. Virtanen HE, Rajpert-De Meyts E, Main KM,<br />
Skakkebæk NE, Toppari J: Testicular dysgenesis syndrome<br />
<strong>and</strong> the development <strong>and</strong> occurrence <strong>of</strong> male reproductive<br />
disorders. Toxicol Appl Pharmacol 207:501-<br />
505, 2005<br />
30. Øverlie I, Mørkrid L, Andersson AM, Skakkebæk NE,<br />
Moen MH, Holte A: Inhibin A <strong>and</strong> B as markers <strong>of</strong> menopause:<br />
a five-year prospective longitudinal study <strong>of</strong> hormonal<br />
changes during the menopausal transition. Acta<br />
Obstet Gynecol Sc<strong>and</strong> 84:281-285, 2005<br />
2004<br />
1. Almstrup K, Høi-Hansen CE, Wirkner U, Blake J,<br />
Schwager C, Ansorge W, Nielsen JE, Skakkebæk NE,<br />
Rajpert-De Meyts E, Leffers H: Embryonic stem cell-like<br />
features <strong>of</strong> testicular carcinoma in situ revealed by genome-wide<br />
gene expression pr<strong>of</strong>iling. Cancer Res 64:4736-<br />
4743, 2004<br />
2. Almstrup K, Nielsen JE, Hansen MA, Tanaka M,<br />
Skakkebæk NE, Leffers H: Analysis <strong>of</strong> cell-type-specific<br />
gene expression during mouse spermat<strong>og</strong>enesis. Biol<br />
Reprod 70:1751-1761, 2004<br />
3. Andersson A-M, Petersen JH, Jørgensen N, Jensen TK,<br />
Skakkebæk NE: Serum inhibin B <strong>and</strong> follicle-stimulating<br />
hormone levels as tools in the evaluation <strong>of</strong> infertile men:<br />
significance <strong>of</strong> adequate reference values from proven<br />
fertile men. J Clin Endocrinol Metab 89:2873-2879, 2004<br />
4. Andersson AM, Jørgensen N, Larsen LF, Rajpert-De<br />
Meyts E, Skakkebæk NE: Impaired Leydig cell function in<br />
infertile men: a study <strong>of</strong> 357 idiopathic infertile men <strong>and</strong><br />
318 proven fertile controls. J Clin Endocrinol Metab<br />
89:3161-3167, 2004<br />
5. Asklund C, Jørgensen N, Jensen TK, Skakkebæk NE:<br />
Biol<strong>og</strong>y <strong>and</strong> epidemiol<strong>og</strong>y <strong>of</strong> testicular dysgenesis syndrome.<br />
BJU Int 93:6-11, 2004<br />
6. Bay K, Andersson A-M, Skakkebæk NE: Estradiol levels<br />
in prepubertal boys <strong>and</strong> girls - analytical challenges.<br />
Int J Androl 27:266-273, 2004
7. Boisen KA, Kaleva M, Main KM, Virtanen HE, Haavisto<br />
A-M, Schmidt IM, Chellakooty M, Damgaard IN, Mau<br />
C, Reunanen M, Skakkebæk NE, Toppari J: Difference in<br />
prevalence <strong>of</strong> congenital cryptorchidism in infants between<br />
two Nordic countries. Lancet 363:1264-1269, 2004<br />
8. Boisen KA, Kaleva M, Main KM, Virtanen H, Haavisto<br />
AM, Schmidt IM, Chellakooty M, Damgaard IN, Mau C,<br />
Reunanen M, Skakkebæk NE, Toppari J: [High <strong>and</strong> increasing<br />
prevalence <strong>of</strong> cryptorchidism in Denmark].<br />
Ugeskr Læger 166:4372-4375, 2004<br />
9. Carlsen E, Petersen JH, Andersson A-M, Skakkebæk<br />
NE: Effects <strong>of</strong> ejaculatory frequency <strong>and</strong> season on variations<br />
in semen quality. Fertil Steril 82:358-366, 2004<br />
10. Chellakooty M, Vangsgaard K, Larsen T, Scheike T,<br />
Falck-Larsen J, Legarth J, Andersson AM, Main KM,<br />
Skakkebæk NE, Juul A: A longitudinal study <strong>of</strong> intrauterine<br />
growth <strong>and</strong> the placental growth hormone (GH)insulin-like<br />
growth factor I axis in maternal circulation:association<br />
between placental GH <strong>and</strong> fetal growth. J<br />
Clin Endocrinol Metab 89:384-391, 2004<br />
11. Christiansen P, Mølgaard C, Mûller J: Normal Bone<br />
Mineral Content in Young Adults with Congenital Adrenal<br />
Hyperplasia due to 21-Hydroxylase Deficiency.<br />
Horm Res 61:133-136, 2004<br />
12. Dalsgaard MK, Ott P, Dela F, Juul A, Pedersen BK,<br />
Warberg J, Fahrenkrug J, Secher NH: The CSF <strong>and</strong> arterial<br />
to internal jugular venous hormonal differences during<br />
exercise in humans. Exp Physiol 89:271-277, 2004<br />
13. Ditton HJ, Zimmer J, Kamp C, Rajpert-De Meyts E,<br />
V<strong>og</strong>t PH: The AZFa gene DBY(DDX3Y) is widely transcribed<br />
but the protein is limited to the male germ cells<br />
by translation control. Hum Mol Genet 13:2333-2341,<br />
2004<br />
14. Henriksen TB, Hjollund NH, Jensen TK, Bonde JP,<br />
Andersson A-M, Kolstad H, Ernst E, Giwercman A,<br />
Skakkebæk NE, Olsen J: Alcohol consumption at the time<br />
<strong>of</strong> conception <strong>and</strong> spontaneous abortion. Am J Epidemiol<br />
160:661-667, 2004<br />
15. Hjollund NH, Bonde JP, Henriksen TB, Giwercman A,<br />
Olsen J: Reproductive effects <strong>of</strong> male psychol<strong>og</strong>ic stress.<br />
Epidemiol<strong>og</strong>y 15:21-27, 2004<br />
16. Hoppe C, Udam TR, Lauritzen L, Mølgaard C, Juul A,<br />
Michaelsen KF: Animal protein intake, serum insulin-like<br />
growth factor I, <strong>and</strong> growth in healthy 2.5-y-old Danish<br />
children. Am J Clin Nutr 80:447-452, 2004<br />
17. Hoppe C, Mølgaard C, Thomsen BL, Juul A, Michaelsen<br />
KF: Protein intake at 9 mo <strong>of</strong> age is associated with<br />
body size but not with body fat in 10-y-old Danish children.<br />
Am J Clin Nutr 79:494-501, 2004<br />
18. Hoppe C, Mølgaard C, Juul A, Michaelsen KF: High<br />
intakes <strong>of</strong> skimmed milk, but not meat, increase serum<br />
IGF-I <strong>and</strong> IGFBP-3 in eight-year-old boys. Eur J Clin Nutr<br />
58:1211-1216, 2004<br />
19. Hubina E, Mersebach H, Rasmussen AK, Juul A,<br />
Sneppen SB, Goth MI, Feldt-Rasmussen U: Effect <strong>of</strong><br />
growth hormone replacement therapy on pituitary hormone<br />
secretion <strong>and</strong> hormone replacement therapies in<br />
GHD adults. Horm Res 61:211-217, 2004<br />
20. Høi-Hansen CE, Nielsen JE, Almstrup K, Hansen MA,<br />
Skakkebæk NE, Rajpert-DeMeyts E, Leffers H: Identification<br />
<strong>of</strong> genes differentially expressed in testes containing<br />
carcinoma in situ. Mol Hum Reprod 10:423-431, 2004<br />
21. Høi-Hansen CE, Nielsen JE, Almstrup K, Sonne SB,<br />
Graem N, Skakkebæk NE, Leffers H, Rajpert-De Meyts E:<br />
Transcription factor AP-2g is a developmentally regulated<br />
marker <strong>of</strong> testicular carcinoma in situ <strong>and</strong> germ cell<br />
tumors. Clin Can Res 10:8521-8530, 2004<br />
22. Janjua NR, M<strong>og</strong>ensen B, Andersson A-M, Petersen JH,<br />
Henriksen M, Skakkebæk NE, Wulf HC: Systemic Ab-<br />
48<br />
sorption <strong>of</strong> the Sunscreens Benzophenone-3, Octyl-<br />
Methoxycinnamate, <strong>and</strong> 3-(4-Methyl-Benzylidene) Camphor<br />
After Whole-Body Topical Application <strong>and</strong> Reproductive<br />
Hormone Levels in Humans. J Invest Dermatol 123:57-<br />
61, 2004<br />
23. Jensen M, Leffers H, Petersen JH, Andersen AN,<br />
Jørgensen N, Carlsen E, Jensen TK, Skakkebæk NE, Rajpert-De<br />
Meyts E: Frequent polymorphism <strong>of</strong> the mitochondrial<br />
DNA polymerase gamma gene (POLG) in patients<br />
with normal spermi<strong>og</strong>rams <strong>and</strong> unexplained subfertility.<br />
Hum Reprod 19:65-70, 2004<br />
24. Jensen TK, Andersson A-M, Jørgensen N, Andersen A-<br />
G, Carlsen E, Petersen JH, Skakkebæk NE: Body mass index<br />
in relation to semen quality <strong>and</strong> reproductive hormones<br />
among 1,558 Danish men. Fertil Steril 82:863-870,<br />
2004<br />
25. Jensen TK, Jørgensen N, Punab M, Haugen TB, Suominen<br />
J, Zilaitiene B, Horte A, Andersen A-G, Carlsen E,<br />
Magnus Ø, Matulevicius V, Nermoen I, Vierula M,<br />
Keiding N, Toppari J, Skakkebæk NE: Association <strong>of</strong> in<br />
utero exposure to maternal smoking with reduced semen<br />
quality <strong>and</strong> testis size in adulthood: a cross-sectional<br />
study <strong>of</strong> 1,770 young men from the general population in<br />
five European countries. Am J Epidemiol 159:49-58, 2004<br />
26. Larsen EC, Schmiegelow K, Rechnitzer C, L<strong>of</strong>t A,<br />
Müller J, Nyboe AA: Radiotherapy at a young age reduces<br />
uterine volume <strong>of</strong> childhood cancer survivors. Acta<br />
Obstet Gynecol Sc<strong>and</strong> 83:96-102, 2004<br />
27. Main KM, Rajpert-De Meyts E, Toppari J, Skakkebæk<br />
NE: Endocrine disrupters <strong>and</strong> development <strong>of</strong> the reproductive<br />
system: a paediatric perspective. In: Pediatric<br />
Endocrinol<strong>og</strong>y: Mechanisms. Pescovitz OH, Eugster EA,<br />
eds. Philadelphia: Lippincott, Williams & Wilkins, pp. 376-<br />
390, 2004<br />
28. Mau C, Juul A, Main KM, L<strong>of</strong>t A: Children conceived<br />
after intracytoplasmic sperm injection (ICSI): is there a<br />
role <strong>for</strong> the paediatrician? Acta Paediatr 93:1238-1244,<br />
2004<br />
29. Ottesen AM, Rajpert-De Meyts E, Holm M, Andersen<br />
I-LF, V<strong>og</strong>t PH, Lundsteen C, Skakkebæk NE: Cyt<strong>og</strong>enetic<br />
<strong>and</strong> molecular analysis <strong>of</strong> a family with three brothers<br />
afflicted with germ-cell cancer. Clin Genet 65:32-39, 2004<br />
30. Ottesen AM, Larsen J, Gerdes T, Larsen JK, Lundsteen<br />
C, Skakkebæk NE, Rajpert-De Meyts E: Cyt<strong>og</strong>enetic investigation<br />
<strong>of</strong> testicular carcinoma in situ <strong>and</strong> early seminoma<br />
by high-resolution comparative genomic hybridization<br />
analysis <strong>of</strong> subpopulations flow sorted according to<br />
DNA content. Cancer Genet Cyt<strong>og</strong>enet 149:89-97, 2004<br />
31. Rajpert-De Meyts E, Hanstein R, Jørgensen N, Græm<br />
N, V<strong>og</strong>t PH, Skakkebæk NE: Developmental expression<br />
<strong>of</strong> POU5F1( OCT-3/4 ) in normal <strong>and</strong> dysgenetic human<br />
gonads. Hum Reprod 19:1338-1344, 2004<br />
32. Samson M, Peale FV, Jr., Frantz G, Rioux-Leclercq N,<br />
Rajpert-De Meyts E, Ferrara N: Human Endocrine Gl<strong>and</strong>derived<br />
Vascular Endothelial <strong>Growth</strong> Factor: expression<br />
early in development <strong>and</strong> in Leydig cell tumors suggests<br />
roles in normal <strong>and</strong> pathol<strong>og</strong>ical testis angi<strong>og</strong>enesis. J<br />
Clin Endocrinol Metab 89:4078-4088, 2004<br />
33. Scheike TH, Juul A: Maximum likelihood estimation<br />
<strong>for</strong> Cox's regression model under nested case-control<br />
sampling. Biostatistics 5:193-206, 2004<br />
34. Schmidt IM, Damgaard IN, Boisen KA, Mau C,<br />
Chellakooty M, Olgaard K, Main KM: Increased kidney<br />
growth in <strong>for</strong>mula-fed versus breast-fed healthy infants.<br />
Pediatr Nephrol 19:1137-1144, 2004<br />
35. Schmidt IM, Main KM, Damgaard IN, Mau C, Haavisto<br />
AM, Chellakooty M, Boisen KA, Petersen JH, Scheike T,<br />
Ølgaard K: Kidney growth in 717 healthy children aged 0-<br />
18 months: a longitudinal cohort study. Pediatr Nephrol<br />
19:992-1003, 2004
36. Schmidt KLT, Larsen E, Bangsbøll S, Meinertz H,<br />
Carlsen E, Andersen AN: Assisted reproduction in male<br />
cancer survivors: fertility treatment <strong>and</strong> outcome in 67<br />
couples. Hum Reprod 19:2806-2810, 2004<br />
37. Schmoll HJ, Souchon R, Krege S, Albers P, Beyer J,<br />
Kollmannsberger C, Fossa SD, Skakkebæk NE, De Wit R,<br />
Fizazi K, Droz JP, Pizzocaro G, Daugaard G, De Mulder<br />
PHM, Horwich A, Oliver T, Huddart R, Rosti G, Paz Ares<br />
L, Pont O, Hartmann JT, Aass N, Algaba F, Bamberg M,<br />
Bodr<strong>og</strong>i I, Bokemeyer C, Classen J, Clemm S, Culine S, De<br />
Wit M, Derigs HG, Dieckmann KP, Flasshove M, Del<br />
Muro XG, Gerl A, Germa-Lluch JR, Hartmann M, Heidenreich<br />
A, Hoeltl W, J<strong>of</strong>fe J, Jones W, Kaiser G, Klepp O,<br />
Kliesch S, Kisbenedek L, Koehrmann KU, Kuczyk M,<br />
Laguna MP, Leiva O, Loy V, Mason MD, Mead GM,<br />
Mueller RP, Nicolai N, Oosterh<strong>of</strong> GO, Pottek T, Rick O,<br />
Schmidberger H, Sedlmayer F, Siegert W, Studer U,<br />
Tjul<strong>and</strong>in S, von der Maase H, Walz P, Weinknecht S,<br />
Weissbach L, Winter E, Wittekind C: European consensus<br />
on diagnosis <strong>and</strong> treatment <strong>of</strong> germ cell cancer: a report<br />
<strong>of</strong> the European Germ Cell Cancer Consensus Group<br />
(EGCCCG). Ann Oncol 15:1377-1399, 2004<br />
38. Skakkebæk NE: Testicular dysgenesis syndrome: new<br />
epidemiol<strong>og</strong>ical evidence. Int J Androl 27:189-191, 2004<br />
39. Skakkebæk NE, Juul A, Jørgensen N, Rajpert-De<br />
Meyts E: Androl<strong>og</strong>isk endokrinol<strong>og</strong>i. In: Medicinsk Kompendium.<br />
Hansen NE, Haunsø S, Schaffalitzky de Muckadell<br />
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Busck, pp. 2188-2213, 2004<br />
40. Sonne SB, Høi-Hansen CE, Fisher JS, Leffers H, Rajpert-De<br />
Meyts E, Skakkebæk NE: Do environmental factors<br />
play a role in the aetiol<strong>og</strong>y <strong>of</strong> carsinoma in situ testis<br />
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41. Storr HL, Mitchell H, Swords FM, Main KM, Hindmarsh<br />
PC, Betts PR, Shaw NJ, Johnston DI, Clark AJ,<br />
Reznek RH, Grossman AB, Savage MO: Clinical features,<br />
diagnosis, treatment <strong>and</strong> molecular studies in paediatric<br />
Cushing's syndrome due to primary nodular adrenocortical<br />
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42. Zimmermann-Belsing T, Juul A, Juul HJ, Feldt-<br />
Rasmussen U: The insulin-like growth axis in patients<br />
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drug treatment. <strong>Growth</strong> Horm IGF Res 14:235-244, 2004<br />
2003<br />
1. Andersson A-M, Carlsen E, Petersen JH, Skakkebæk<br />
NE: Variation in levels <strong>of</strong> serum inhibin B, testosterone,<br />
estradiol, luteinizing hormone, follicle-stimulating hormone,<br />
<strong>and</strong> sex hormone- binding globulin in monthly<br />
samples from healthy men during a 17-month period:<br />
possible effects <strong>of</strong> seasons. J Clin Endocrinol Metab 88:932<br />
-937, 2003<br />
2. Bartkova J, Rajpert-De Meyts E, Skakkebæk NE, Lukas J,<br />
Bartek J: Deregulation <strong>of</strong> the G1/S-phase control in human<br />
testicular germ cell tumours. APMIS 111:252-266, 2003<br />
3. Bartkova J, Lukas C, Sørensen CS, Rajpert-De Meyts E,<br />
Skakkebæk NE, Lukas J, Bartek J: Deregulation <strong>of</strong> the RB<br />
pathway in human testicular germ cell tumours. J Pathol<br />
200:149-156, 2003<br />
4. Bonde JP, Hjollund HI, Henriksen TB, Jensen TK,<br />
Spano M, Kolstad H, Giwercman A, Storgaard L, Ernst E,<br />
Olsen J: Epidemiol<strong>og</strong>ic evidence on biol<strong>og</strong>ical <strong>and</strong> environmental<br />
male factors in embryonic loss. Adv Exp Med<br />
Biol 518:25-35, 2003<br />
5. Bouloux PM, Nieschlag E, Burger HG, Skakkebæk NE,<br />
Wu FC, H<strong>and</strong>elsman DJ, Baker GH, Ochsenkuehn R,<br />
Syska A, McLachlan RI, Giwercman A, Conway AJ, Turner<br />
L, van Kuijk JH, Voortman G: Induction <strong>of</strong> spermat<strong>og</strong>enesis<br />
by recombinant follicle-stimulating hormone<br />
49<br />
(puregon) in hyp<strong>og</strong>onadotropic azoospermic men who<br />
failed to respond to human chorionic gonadotropin alone.<br />
J Androl 24:604-611, 2003<br />
6. Carlsen E, Andersson A-M, Petersen JH, Skakkebæk<br />
NE: History <strong>of</strong> febrile illness <strong>and</strong> variation in semen quality.<br />
Hum Reprod 18:2089-2092, 2003<br />
7. Chellakooty M, Schmidt IM, Haavisto A-M, Boisen KA,<br />
Damgaard IN, Mau C, Petersen JH, Juul A, Skakkebæk<br />
NE, Main KM: Inhibin A, Inhibin B, follicle-stimulating<br />
hormone, luteinizing hormone, estradiol, <strong>and</strong> sex hormone-binding<br />
globulin levels in 473 healthy infant girls. J<br />
Clin Endocrinol Metab 88: 3515-3520, 2003<br />
8. Christiansen P, Andersson A-M, Skakkebæk NE: Longitudinal<br />
studies <strong>of</strong> inhibin B levels in boys <strong>and</strong> young<br />
adults with Klinefelter syndrome. J Clin Endocrinol<br />
Metab 88:888-891, 2003<br />
9. Fosså SD, Aass N, Heilo A, Daugaard G, Skakkebæk<br />
NE, Stenwig AE, Nesl<strong>and</strong> JM, Looijenga LHJ, Oosterhuis<br />
JW: Testicular carcinoma in situ in patients with extragonadal<br />
germ cell tumours: the clinical role <strong>of</strong> pretreatment<br />
biopsy. Ann Oncol 14:1412-1418, 2003<br />
10. Frydelund-Larsen L, V<strong>og</strong>t PH, Leffers H, Schadwinkel<br />
A, Daugaard G, Skakkebæk NE, Rajpert-De Meyts E: No<br />
AZF deletion in 160 patients with testicular germ cell<br />
neoplasia. Mol Hum Reprod 9:517-521, 2003<br />
11. Holm M, Rajpert-De Meyts E, Andersson A-M,<br />
Skakkebæk NE: Leydig cell micronodules are a common<br />
finding in testicular biopsies from men with impaired<br />
spermat<strong>og</strong>enesis <strong>and</strong> are associated with decreases testosterone/LH<br />
ratio. J Pathol 199:378-386, 2003<br />
12. Holm M, Høi-Hansen CE, Rajpert-De Meyts E,<br />
Skakkebæk NE: Increased risk <strong>of</strong> carcinoma in situ in<br />
patients with testicular germ cell cancer with ultrasonic<br />
microlithiasis in the contralateral testicle. J Urol 170:1163-<br />
1167, 2003<br />
13. Høi-Hansen CE, Holm M, Rajpert-De Meyts E,<br />
Skakkebæk NE: Histol<strong>og</strong>ical evidence <strong>of</strong> testicular dysgenesis<br />
in contralateral biopsies from 218 patients with<br />
testicular germ cell cancer. J Pathol 200:370-374, 2003<br />
14. Jensen RB, Chellakooty M, Vielwerth S, Vaag A,<br />
Larsen T, Greisen G, Skakkebæk NE, Scheike T, Juul A:<br />
Intrauterine growth retardation <strong>and</strong> consequences <strong>for</strong><br />
endocrine <strong>and</strong> cardiovascular diseases in adult life: does<br />
insulin-like growth factor-I play a role? Horm Res 60<br />
Suppl 3:136-148, 2003<br />
15. Johannsen TH, Lundsteen C, Visfeldt J, Schwartz M,<br />
Petersen BL, Byskov AG, Müller J: Erroneous genetic sex<br />
determination <strong>of</strong> a newborn twin girl due to chimerism<br />
caused by foetal blood transfusion. A case report. Horm<br />
Res 60:148-151, 2003<br />
16. Juul A: Serum levels <strong>of</strong> insulin-like growth factor I<br />
<strong>and</strong> its binding proteins in health <strong>and</strong> disease. <strong>Growth</strong><br />
Hormone <strong>and</strong> IGF Research 13:113-170, 2003<br />
17. Juul A, Bernasconi S, Carel J-C, Clayton PE, Kiess W,<br />
Schrama SDK: <strong>Growth</strong> hormone treatment <strong>and</strong> risk <strong>of</strong><br />
solid tumours. Horm Res 60:103-104, 2003<br />
18. Jørgensen MH, Ott P, Juul A, Skakkebæk NE, Michaelsen<br />
KF: Does breast feeding influence liver biochemistry?<br />
J Pediatr Gastroenterol Nutr 37:559-565, 2003<br />
19. Jørgensen N, Skakkebæk NE: Dårlig sædkvalitet hos<br />
unge danske mænd. Månedsskr Prakt Lægegern 81:169-<br />
175, 2003<br />
20. L<strong>and</strong>o A, Holm K, Nysom K, Rasmussen ÅK, Høier<br />
MM, Feldt-Rasmussen U, Müller J: Serum thyr<strong>og</strong>lobulin<br />
as a marker <strong>of</strong> thyroid neoplasms after childhood cancer.<br />
Acta Paediatr 92:1284-1290, 2003<br />
21. Lange M, Feldt-Rasmussen U, Svendsen OL, Kastrup<br />
KW, Juul A, Müller J: High risk <strong>of</strong> adrenal insufficiency in
adults previously treated <strong>for</strong> idiopathic childhood onset<br />
growth hormone deficiency. J Clin Endocrinol Metab<br />
88:5784-5789, 2003<br />
22. Larsen EC, Müller J, Rechnitzer C, Schmiegelow K,<br />
Andersen AN: Diminished ovarian reserve in female<br />
childhood cancer survivors with regular menstrual cycles<br />
<strong>and</strong> basal FSH
8. Fern<strong>and</strong>es S, Huellen K, Goncalves J, Dukal H, Zeisler<br />
J, Rajpert-De Meyts E, Skakkebæk NE, Habermann B,<br />
Krause W, Sousa M, Barros A, V<strong>og</strong>t PH: High frequency<br />
<strong>of</strong> DAZ1/DAZ2 gene deletions in patients with severe<br />
oligozoospermia. Mol Hum Reprod 8:286-298, 2002<br />
9. Frydelund-Larsen L, Krausz C, Leffers H, Andersson A<br />
-M, Carlsen E, Bangsbøll S, McElreavey K, Skakkebæk<br />
NE, Rajpert-De Meyts E: Inhibin B: a marker <strong>for</strong> the functional<br />
state <strong>of</strong> the seminiferous epithelium in patients<br />
with azoospermia factor c microdeletions. J Clin Endocrinol<br />
Metab 87:5618-5624, 2002<br />
10. Gravholt CH, Naeraa RW, Andersson A-M, Christiansen<br />
JS, Skakkebæk NE: Inhibin A <strong>and</strong> B in adolescents<br />
<strong>and</strong> young adults with Turner syndrome <strong>and</strong> no sign <strong>of</strong><br />
spontaneous puberty. Hum Reprod 17:2049-2053, 2002<br />
11. Holm M, Rajpert-De Meyts E, Daugaard G,<br />
Skakkebæk NE: Re: The prevalence <strong>of</strong> testicular microlithiasis<br />
in a asymptomatic population <strong>of</strong> men 18 to 35<br />
years old (letter). J Urol 168:1108-1109, 2002<br />
12. Høi-Hansen CE, Rajpert-De Meyts E, Skakkebæk NE:<br />
Germ cell tumours <strong>of</strong> the testis:how do they start? Histopathol<strong>og</strong>y<br />
41 suppl. 2:382-388, 2002<br />
13. Jensen TK, Carlsen E, Jørgensen N, Berthelsen JG,<br />
Keiding N, Christensen K, Petersen JH, Knudsen LB,<br />
Skakkebæk NE: Poor semen quality may contribute to<br />
recent decline in fertility rates. Hum Reprod 17:1437-<br />
1440, 2002<br />
14. Jung A, Main KM, Scheibel E, Peitersen B, Clausen N,<br />
Erichsen G, Schmiegelow K, Illum N: Beta-thalassaemia<br />
major hos børn <strong>og</strong> unge i Danmark. Ugeskr Læger<br />
164:5803-5806, 2002<br />
15. Juul A, Bernasconi S, Clayton PE, Kiess W, DeMuinck-<br />
Keizer SS: European audit <strong>of</strong> current practice in diagnosis<br />
<strong>and</strong> treatment <strong>of</strong> childhood growth hormone deficiency.<br />
Horm Res 58:233-241, 2002<br />
16. Juul A, Scheike T, Davidsen M, Gyllenborg J, Jørgensen<br />
T: Low serum insulin-like growth factor I is associated<br />
with increased risk <strong>of</strong> ischemic heart disease: a population-based<br />
case-control study. Circulation 106:939-944,<br />
2002<br />
17. Juul A, Skakkebæk NE: Testosteronbeh<strong>and</strong>ling af<br />
ældre mænd. Ugeskr Læger 42:4941-4942, 2002<br />
18. Juul A, Skakkebæk NE: Andr<strong>og</strong>ens <strong>and</strong> the ageing<br />
male. Human Reproduction Update 8:423-433, 2002<br />
19. Jørgensen JOL, Nørrelund H, Vahl N, Juul A,<br />
Skakkebæk NE, Christiansen JS: Continuation <strong>of</strong> growth<br />
hormone therapy versus placebo in transition-phase patients<br />
with growth hormone deficiency: impact on body<br />
composition, insulin sensitivity <strong>and</strong> thyroid function. J<br />
Pediatr Endocrinol Metab 15:1355-1360, 2002<br />
20. Jørgensen N, Carlsen E, Nermoen I, Punab M, Suominen<br />
J, Andersen A-G, Andersson A-M, Haugen TB, Horte<br />
A, Jensen TK, Magnus Ø, Petersen JH, Vierula M, Toppari<br />
J, Skakkebæk NE: East-West gradient in semen quality<br />
in the Nordic-Baltic area: a study <strong>of</strong> men from the general<br />
population in Denmark, Norway, Estonia <strong>and</strong> Finl<strong>and</strong>.<br />
Hum Reprod 17:2199-2208, 2002<br />
21. Kiess W, Conway G, Ritzen M, Rosenfield R, Bernasconi<br />
S, Juul A, Van Pareren Y, de Muinck Keizer-Schrama<br />
SM, Bourguignon JP: Induction <strong>of</strong> puberty in the hyp<strong>og</strong>onadal<br />
girl - practices <strong>and</strong> attitudes <strong>of</strong> pediatric endocrinol<strong>og</strong>ists<br />
in Europe. Horm Res 57:66-71, 2002<br />
22. Lajer H, Daugaard G, Andersson A-M, Skakkebæk<br />
NE: Clinical use <strong>of</strong> serum TRA-1-60 as tumor marker in<br />
patients with germ cell cancer. Int J Cancer 100:244-246,<br />
2002<br />
23. Lange IG, Daxenberger A, Meyer HHD, Rajpert-De<br />
Meyts E, Skakkebæk NE, Veeramachaneni DNR: Quantitative<br />
assessment <strong>of</strong> foetal exposure to trenbolone acetate,<br />
51<br />
zeranol <strong>and</strong> melengestrol acetate, following maternal<br />
dosing in rabbits. Xenobiotica 32: 641-651, 2002<br />
24. Lange M, Svendsen OL, Skakkebæk NE, Müller J, Juul<br />
A, Schmiegelow M, Feldt-Rasmussen U: An audit <strong>of</strong> the<br />
insulin-tolerance test in 255 patients with pituitary disease.<br />
Eur J Endocrinol 147:41-47, 2002<br />
25. Larsen J, Ottesen AM, Kirchh<strong>of</strong>f M, Lundsteen C,<br />
Larsen JK: High resolution comparative genomic hybridization<br />
detects 7-8 megabasepair deletion in PCR amplified<br />
DNA. Anal Cell Pathol 23:61-64, 2002<br />
26. Main KM, Skov M, Sillesen IB, Lanng S, Dige-Petersen<br />
H, Müller J, Koch C: Cushing's syndrome due to pharmacol<strong>og</strong>ical<br />
interaction in a cystic fibrosis patient. Acta Paediatr<br />
91:1008-1011, 2002<br />
27. Mol NM, Sørensen N, Weihe P, Andersson A-M,<br />
Jørgensen N, Skakkebæk NE, Keiding N, Gr<strong>and</strong>jean P:<br />
Spermaturia <strong>and</strong> serum hormone concentrations at the<br />
age <strong>of</strong> puberty in boys prenatally exposed to polychlorinated<br />
biphenyls. Eur J Endocrinol 146: 357-363, 2002<br />
28. Müller J: Disturbance <strong>of</strong> pubertal development after<br />
cancer treatment. Best practice & research clinical endocrinol<strong>og</strong>y<br />
<strong>and</strong> metabolism 1:91-103, 2002<br />
29. Punab M, Zilaitiene B, Jørgensen N, Horte A, Matulevicius<br />
V, Peetsalu A, Skakkebæk NE: Regional differences<br />
in semen qualities in the Baltic region. Int J Androl<br />
25:243-252, 2002<br />
30. Rajpert-De Meyts E, Leffers H, Daugaard G, Andersen<br />
CB, Petersen PM, Hinrichsen J, Pedersen LG, Skakkebæk<br />
NE: Analysis <strong>of</strong> the polymorphic CAG repeat length in<br />
the <strong>and</strong>r<strong>og</strong>en receptor gene in patients with testicular<br />
germ cell cancer. Int J Cancer 102:201-204, 2002<br />
31. Rajpert-De Meyts E, Høi-Hansen CE, Ottesen AM,<br />
Frydelund-Larsen L, Holm M, Skakkebæk NE: Le cancer<br />
à cellules germinales du testicule, élément constitutif du<br />
syndrome de dysgénésie testiculaire: rôle des facteurs<br />
environnementaux et de la susceptibilité génétique. Androl<strong>og</strong>ie<br />
12:262-268, 2002<br />
32. Rajpert-De Meyts E, Leffers H, Petersen HJ, Andersen<br />
A-G, Carlsen E, Jørgensen N, Skakkebæk NE: CAG repeat<br />
length in <strong>and</strong>r<strong>og</strong>en-receptor gene <strong>and</strong> reproductive<br />
variables in fertile <strong>and</strong> infertile men. Lancet 359:44-46,<br />
2002<br />
33. Satie AP, Rajpert-De Meyts E, Spagnoli GC, Henno S,<br />
Olivo L, Jacobsen GK, Rioux-Leclercq N, Jégou B, Samson<br />
M: The cancer-testis gene, NY-ESO-1, is expressed in<br />
normal fetal <strong>and</strong> adult testes <strong>and</strong> in spermatocytic seminomas<br />
<strong>and</strong> testicular carcinoma in situ. Lab Invest 82:775-<br />
780, 2002<br />
34. Schmidt IM, Chellakooty M, Haavisto A-M, Boisen<br />
KA, Damgaard IN, Steendahl U, Toppari J, Skakkebæk<br />
NE, Main KM: Gender difference in breast tissue size in<br />
infancy: correlation with serum estradiol. Pediatr Res<br />
52:682-686, 2002<br />
35. Skakkebæk NE: Carcinoma in situ <strong>of</strong> the testis: frequency<br />
<strong>and</strong> relationship to invasive germ cell tumours in<br />
fertile men. N.E.Skakkebæk. Histopathol<strong>og</strong>y 1978;2;157-<br />
170 Author commentary. Histopathol<strong>og</strong>y 41:2-4, 2002<br />
36. Skakkebæk NE: Carcinoma in situ <strong>of</strong> the testis: frequency<br />
<strong>and</strong> relationship to invasive germ cell tumours in<br />
fertile men. Histopathol<strong>og</strong>y 41:5-18, 2002<br />
37. Skakkebæk NE, Rajpert-De Meyts E: Testicular dysgenesis<br />
syndrome: a common link between human male<br />
reproductive disorders? Clin Pediatr Endocrinol 11:77-79,<br />
2002<br />
38. Skov M, Main KM, Sillesen IB, Müller J, Koch C,<br />
Lanng S: Iatr<strong>og</strong>enic adrenal insufficiency as a side-effect<br />
<strong>of</strong> combined treatment <strong>of</strong> itraconazole <strong>and</strong> budesonide.<br />
Eur Respir J 20:127-133, 2002
39. Slama R, Eustache F, Ducot B, Jensen TK, Jørgensen<br />
N, Horte A, Irvine S, Suominen J, Andersen AG, Auger J,<br />
Vierula M, Toppari J, Andersen AN, Keiding N,<br />
Skakkebæk NE, Spira A, Jouannet P: Time to pregnancy<br />
<strong>and</strong> semen parameters: a cross-sectional study among<br />
fertile couples from four European cities. Hum Reprod<br />
17:503-515, 2002<br />
40. Teilmann G, Juul A, Skakkebæk NE, Toppari J: Putative<br />
effects <strong>of</strong> endocrine disrupters on pubertal development<br />
in the human. Best Practice & Research Clinical<br />
Endocrinol<strong>og</strong>y <strong>and</strong> Metabolism 16:105-121, 2002<br />
2001<br />
1. Andersson A-M, Skakkebæk NE: Serum inhibin B<br />
levels during male childhood <strong>and</strong> puberty. Mol Cell Endocrinol<br />
180:103-107, 2001<br />
2. Aubry F, Satie AP, Rioux-Leclercq N, Rajpert-De Meyts<br />
E, Spagnoli GC, Chomez P, De Backer O, Jegou B, Samson<br />
M: MAGE-A4, a germ cell specific marker, is expressed<br />
differentially in testicular tumors. Cancer 92:<br />
2778-2785, 2001<br />
3. Auger J, Eustache F, Andersen AG, Irvine DS, Jørgensen<br />
N, Skakkebæk NE, Suominen J, Toppari J, Vierula M,<br />
Jouannet P: Sperm morphol<strong>og</strong>ical defects related to environment,<br />
lifestyle <strong>and</strong> medical history <strong>of</strong> 1001 male partners<br />
<strong>of</strong> pregnant women from four European cities. Hum<br />
Reprod 16: 2710-2717, 2001<br />
4. Bartkova J, Falck J, Rajpert-De Meyts E, Skakkebæk<br />
NE, Lukas J, Bartek J: Chk2 tumour suppressor protein in<br />
human spermat<strong>og</strong>enesis <strong>and</strong> testicular germ-cell tumours.<br />
Onc<strong>og</strong>ene 20:5897-5902, 2001<br />
5. Boisen KA, Main KM, Rajpert-De Meyts E, Skakkebæk<br />
NE: Are male reproductive disorders a common entity?<br />
The testicular dysgenesis syndrome. Ann N Y Acad Sci<br />
948:90-99, 2001<br />
6. Chang A, Yousef GM, Jung K, Rajpert-De Meyts E,<br />
Diam<strong>and</strong>is EP: Identification <strong>and</strong> molecular characterization<br />
<strong>of</strong> five novel kallikrein gene 13 (KLK13; KLK-L4)<br />
splice variants: differential expression in the human testis<br />
<strong>and</strong> testicular cancer. Anticancer Res 21:3147-3152, 2001<br />
7. Fisker S, Nørrelund H, Juul A, Skakkebæk NE, Christiansen<br />
JS, Jørgensen JOL: The growth hormone (GH)-<br />
insulin-like growth factor axis during testosterone replacement<br />
therapy in GH-treated hypopituitary males.<br />
<strong>Growth</strong> Horm IGF Res 11:104-109, 2001<br />
8. Gyllenborg J, Rasmussen SL, Borch-Johnsen K, Heitmann<br />
BL, Skakkebæk NE, Juul A: Cardiovascular risk<br />
factors in men: The role <strong>of</strong> gonadal steroids <strong>and</strong> sex hormone-binding<br />
globulin. Metabolism 50:882-888, 2001<br />
9. Holm M, Lenz S, Rajpert-De Meyts E, Skakkebæk NE:<br />
Microcalcifications <strong>and</strong> carcinoma in situ <strong>of</strong> the testis.<br />
BJU Int 87:144-149, 2001<br />
10. Ishøy T, Suadicani P, Andersson A-M, Guldager B,<br />
Appleyard M, Skakkebæk NE, Gyntelberg F: Prevalence<br />
<strong>of</strong> male sexual problems in the Danish Gulf war study.<br />
Sc<strong>and</strong> J Sexol<strong>og</strong>y 4:43-55, 2001<br />
11. Jensen TK, Slama R, Ducot B, Suominen J, Cawood<br />
EH, Andersen AG, Eustache F, Irvine S, Auger S, Jouannet<br />
P, Vierula M, Jørgensen N, Toppari J, Skakkebæk NE,<br />
Keiding N, Spira A: Regional differences in waiting time<br />
to pregnancy among fertile couples from four European<br />
cities. Hum Reprod 16:2697-2704, 2001<br />
12. Juul A: Determination <strong>of</strong> insulin-like growth factor I<br />
in children: normal values <strong>and</strong> clinical use. Horm Res<br />
55:94-99, 2001<br />
13. Juul A: The effects <strong>of</strong> oestr<strong>og</strong>ens on linear bone<br />
growth. Hum Reprod Update 7:303-313, 2001<br />
14. Jørgensen N, Andersen A-G, Eustache F, Irvine DS,<br />
52<br />
Suominen J, Petersen JH, Andersen AN, Auger J, Cawood<br />
EHH, Horte A, Jensen TK, Jouannet P, Keiding N, Vierula<br />
M, Toppari J, Skakkebæk NE: Regional differences in<br />
semen quality in Europe. Hum Reprod 16:1012-1019, 2001<br />
15. Kaleva M, Virtanen H, Haavisto AM, Main K,<br />
Skakkebæk NE, Toppari J: Incidence <strong>of</strong> cryptorchidism in<br />
finnish boys. Horm Res 55:54 2001<br />
16. Krausz C, Quintana-Murci L, Rajpert-De Meyts E,<br />
Jørgensen N, Jobling MA, Rosser ZH, Skakkebæk NE,<br />
McElreavey K: Identification <strong>of</strong> a Y chromosome hapl<strong>og</strong>roup<br />
associated with reduced sperm counts. Hum Mol<br />
Genet 10:1873-1877, 2001<br />
17. Krausz C, Rajpert-De Meyts E, Frydelund-Larsen L,<br />
Quintana-Murci L, McElreavey K, Skakkebæk NE: Double-blind<br />
Y chromosome microdeletion analysis in men<br />
with known sperm parameters <strong>and</strong> reproductive hormone<br />
pr<strong>of</strong>iles:microdeletions are specific <strong>for</strong> spermat<strong>og</strong>enetic<br />
failure. J Clin Endocrinol Metab 86:2638-2642, 2001<br />
18. Lange M, Thulesen J, Feldt-Rasmussen U, Skakkebæk<br />
NE, Vahl N, Jørgensen JO, Christiansen JS, Poulsen SS,<br />
Sneppen SB, Juul A: Skin morphol<strong>og</strong>ical changes in<br />
growth hormone deficiency <strong>and</strong> acromegaly. Eur J Endocrinol<br />
145:147-153, 2001<br />
19. Larsen J, Ottesen AM, Lundsteen C, Leffers H, Larsen<br />
JK: Optimization <strong>of</strong> DOP-PCR amplification <strong>of</strong> DNA <strong>for</strong><br />
high-resolution comparative genomic hybridization analysis.<br />
Cytometry 44: 317-325, 2001<br />
20. Larsen LF, Skakkebæk NE: Genetiske årsager til dårlig<br />
sædkvalitet. Mdskr prakt lægeg 9:1033-1040, 2001<br />
21. Leffers H, Næsby M, Vendelbo B, Skakkebæk NE,<br />
Jørgensen M: Oestr<strong>og</strong>enic potencies <strong>of</strong> Zeranol, oestradiol,<br />
diethylstilboestrol, Bisphenol-A <strong>and</strong> genistein: implications<br />
<strong>for</strong> exposure assessment <strong>of</strong> potential endocrine<br />
disrupters. Hum Reprod 16:1037-1045, 2001<br />
22. Lim HN, Rajpert-De Meyts E, Skakkebæk NE, Hawkins<br />
JR, Hughes IA: Genetic analysis <strong>of</strong> the INSL3 gene in<br />
patients with maldescent <strong>of</strong> the testis. Eur J Endocrinol<br />
144:129-137, 2001<br />
23. Luo LY, Rajpert-De Meyts E, Jung K, Diam<strong>and</strong>is EP:<br />
Expression <strong>of</strong> the normal epithelial cell-specific 1 (NES1;<br />
KLK10) c<strong>and</strong>idate tumour suppressor gene in normal <strong>and</strong><br />
malignant testicular tissue. Br J Cancer 85:220-224, 2001<br />
24. Mikkelsen AL, Andersson A-M, Skakkebæk NE, Lindenberg<br />
S: Basal concentrations <strong>of</strong> oestradiol may predict<br />
the outcome <strong>of</strong> in-vitro maturation in regularly menstruating<br />
women. Hum Reprod 16:862-867, 2001<br />
25. Ono Y, Rajpert-De Meyts E, Guellaën G, Bulle F: Sporadic<br />
testicular germ cell cancers do not exhibit specific<br />
alteration in CAG/CTG repeats containing genes expressed<br />
in human testis. Onc<strong>og</strong>ene 20:5548-5553, 2001<br />
26. Quintana-Murci L, Krausz C, Heyer E, Gromoll J,<br />
Seifer I, Barton DE, Barrett T, Skakkebæk NE, Rajpert-De<br />
Meyts E, Mitchell M, Lee AC, Jobling MA, McElreavey K:<br />
The relationship between Y chromosome DNA haplotypes<br />
<strong>and</strong> Y chromosome deletions leading to male infertility.<br />
Hum Genet 108:55-58, 2001<br />
27. Rajpert-De Meyts E, Skakkebæk NE: Biol<strong>og</strong>y <strong>of</strong> testicular<br />
carcinoma in situ,the stem cell-like precursor <strong>of</strong> germ<br />
cell cancer. In: Androl<strong>og</strong>y in the 21st century. Robaire B,<br />
Chemes H, Morales CR, eds. New York: Medimond, pp.<br />
409-417, 2001<br />
28. Rajpert-De Meyts E, Toppari J, Skakkebæk NE: Testicular<br />
tumours with endocrine manifestations. In: Endocrinol<strong>og</strong>y.<br />
DeGroot LJ, Jameson JL, eds. Philadelphia: Saunders,<br />
pp. 2351-2356, 2001<br />
29. Ranke MB, Feldt-Rasmussen U, Bang P, Baxter RC,<br />
Camacho-Hubner C, Clemmons DR, Juul A, Ørskov H,<br />
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31. Schmiegelow M, Lassen S, Poulsen HS, Schmiegelow<br />
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32. Scorilas A, Yousef GM, Jung K, Rajpert-De Meyts E,<br />
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38. Virtanen HE, Kaleva M, Haavisto A-M, Schmidt IM,<br />
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1. Andersen A-G, Jørgensen N, Andersson A-M, Carlsen<br />
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3. Andersson A-M: Inhibin B in the assessment <strong>of</strong> seminiferous<br />
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10. Giwercman A, Kledal T, Schwartz M, Giwercman YL,<br />
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13. Hjollund NHI, Jensen TK, Bonde JPE, Henriksen TB,<br />
Andersson A-M, Kolstad HA, Ernst E, Giwercman A,<br />
Skakkebæk NE, Olsen J: Spontaneous abortion <strong>and</strong> physical<br />
strain around implantation: a follow-up study <strong>of</strong> firstpregnancy<br />
planners. Epidemiol<strong>og</strong>y 11: 18-23, 2000<br />
14. Hjollund NHI, Bonde JPE, Jensen TK, Henriksen TB,<br />
Andersson A-M, Kolstad HA, Ernst E, Giwercman A,<br />
Skakkebæk NE, Olsen J: Male-mediated spontaneous<br />
abortion among spouses <strong>of</strong> stainless steel welders. Scan J<br />
Work Environ Health 26:187-192, 2000<br />
15. Jacobsen R, Bost<strong>of</strong>te E, Skakkebæk NE, Hansen J,<br />
Møller H: Offspring sex ratio <strong>of</strong> subfertile men <strong>and</strong> men<br />
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15:2369-2370, 2000<br />
16. Jacobsen R, Bost<strong>of</strong>te E, Engholm G, Hansen J,<br />
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study. Hum Reprod 15: 1958-1961, 2000<br />
17. Jacobsen R, Bost<strong>of</strong>te E, Engholm G, Hansen J, Olsen<br />
JH, Skakkebæk NE, Møller H: Risk <strong>of</strong> testicular cancer in<br />
men with abnormal semen characteristics: cohort study.<br />
Br Med J 321: 789-792, 2000<br />
18. Jensen TK, Vierula M, Hjollund NHI, Saaranen M,<br />
Scheike T, Saarikoski S, Suominen J, Keiski A, Toppari J,<br />
Skakkebæk NE, The Danish First Pregnancy Planner<br />
Study Team: Semen quality among Danish <strong>and</strong> Finnish<br />
men attempting to conceive. Eur J Endocrinol 142:47-52,<br />
2000<br />
19. Juul A, Fisker S, Scheike T, Hertel T, Müller J, Ørskov<br />
H, Skakkebæk NE: Serum levels <strong>of</strong> growth hormone<br />
binding protein in children with normal <strong>and</strong> precocious<br />
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gonadal steroids. Clin Endocrinol 52:165-172, 2000<br />
20. Jørgensen M, Vendelbo B, Skakkebæk NE, Leffers H:<br />
Assaying estr<strong>og</strong>enicity by quantitating the expression<br />
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21. Kledal TJS, Rajpert-De Meyts E, Skakkebæk NE,<br />
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22. Kledal TJS, Jørgensen M, Mengarda F, Skakkebæk NE,
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23. Lacroix L, Liénard H, Labourier E, Djavaheri MM,<br />
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24. Larsen EC, L<strong>of</strong>t A, Holm K, Müller J, Brocks V, Andersen<br />
AN: Oocyte donation in women cured <strong>of</strong> cancer<br />
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25. Larsen L, Scheike T, Jensen TK, Bonde JP, Ernst E,<br />
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26. Main KM, Schmidt IM, Skakkebæk NE: A Possible<br />
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27. Müller J, Juul A, Andersson A-M, Sehested A,<br />
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28. Müller J, Sønksen J, Sommer P, Schmiegelow M, Petersen<br />
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30. Nysom K, Holm K, Michaelsen KF, Hertz H, Jacobsen<br />
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31. Nørrelund H, Vahl N, Juul A, Møller N, Alberti<br />
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33. Rajpert-De Meyts E, Skakkebæk NE: Origin <strong>of</strong> germ<br />
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34. Rajpert-De Meyts E, Giwercman A, Skakkebæk NE:<br />
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36. Schmiegelow M, Lassen S, Poulsen HS, Feldt-<br />
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girls <strong>and</strong> adult womem: relation to age, stage <strong>of</strong> puberty,<br />
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