Meer dan gewichtsverlies: Mounjaro en de vergeten vraag rond eicelkwaliteit
Silke Roofthooft
Na de hype rond Ozempic verovert Mounjaro nu in sneltempo de Belgische markt. Het geneesmiddel laat de kilo’s smelten als sneeuw voor de zon. Toch duiken er nieuwe vragen op: wat betekent dit voor de gezondheid van de eicel?
Obesitas zet vrouwelijke vruchtbaarheid op het spel
Obesitas is uitgegroeid tot één van de grootste gezondheidsproblemen van onze tijd. In 2022 was wereldwijd al één op de acht volwassenen obees. Het gaat daarbij om meer dan alleen wat kilo’s te veel. Het is een ernstige vorm van overgewicht die de stofwisseling in ons lichaam uit balans brengt en gepaard gaat met gezondheidsrisico’s, gaande van hart-en vaatziekten tot nierfalen. Minder bekend is dat obesitas ook de vruchtbaarheid aantast. Niet alleen bij mannen, maar ook bij vrouwen. In mijn thesis focuste ik mij specifiek op de impact op de eicel. Bij obesitas verandert de samenstelling van het bloed: er circuleren meer vrije vetzuren, die ook de eicel bereiken. Het gevolg is schade die de kwaliteit van de eicel vermindert en de kans op een natuurlijke zwangerschap verkleint. Vooral de mitochondriën, de energieleveranciers van de cel en cruciaal voor een goede werking van de eicel, blijken zwaar getroffen.
Preconceptiezorg: de eicelkwaliteit herstellen vóór de zwangerschap
Een gezonde eicel is de basis voor een succesvolle zwangerschap en voor een gezonde baby. Preconceptiezorg, letterlijk “zorg vóór de bevruchting”, omvat maatregelen die de gezondheid van toekomstige ouders verbeteren, en dus ook die van de eicel. Vandaag ligt de nadruk vooral op gewichtsverlies via een gezonder dieet, maar onderzoek met obese muizen toont aan dat dit niet altijd volstaat. Zelfs na gewichtsverlies via dieet normalisatie blijft schade in de eicel zichtbaar, vooral in de mitochondriën. Dat roept een belangrijke vraag op: hoe zorgen we ervoor dat de eicel écht volledig herstelt? Is dat eigenlijk wel mogelijk? Misschien ligt de oplossing in een combinatie van levensstijlaanpassingen met medicatie die gewichtsverlies promoot. Precies dat vraagstuk stond centraal in mijn masteronderzoek.
Ozempic was nog maar het begin: Mounjaro in opmars
Een groep geneesmiddelen die hier voor in aanmerking komt zijn de incretine-agonisten, beter bekend als obesitas medicatie. Tot voor kort ging alle aandacht naar Ozempic, maar sinds de officiële toelating op de Belgische markt (november 2024) wint Mounjaro vliegensvlug terrein. Het succes is eenvoudig te verklaren: Mounjaro, met tirzepatide als actief bestanddeel, blijkt nog effectiever in het bevorderen van gewichtsverlies dan Ozempic, waarbij semaglutide als actief bestanddeel optreedt. Het verschil zit in het werkingsmechanisme van de actieve stoffen. Beide bootsen incretinehormonen na. Deze lichaamseigen stoffen komen na een maaltijd vrij vanuit de darmen en zorgen voor onder meer een stabiele bloedsuikerspiegel en verminderde eetlust. Ozempic is enkel instaat GLP-1 na te bootsen, terwijl Mounjaro daarnaast ook in staat is GIP na te bootsen. Dat dubbele effect zorgt doorgaans voor sterker en consistenter gewichtsverlies.
Vrouwen van vruchtbare leeftijd en Mounjaro: veel vragen
Vrouwen van vruchtbare leeftijd die een zwangerschap plannen, krijgen vandaag het advies om minstens één maand voor de bevruchting te stoppen met Mounjaro, een zogenaamde “washout-periode”. Opmerkelijk genoeg, bestaan er nauwelijks gegevens over het effect van dit geneesmiddel op de eicel tijdens de preconceptieperiode. Deze inzichten zijn urgenter dan ooit. Vrouwen in de vruchtbare leeftijd vormen immers de snelst groeiende groep met obesitas. Ik wilde daarom in mijn thesis nagaan of tirzepatide, de actieve stof in Mounjaro, invloed heeft op de eicel in de periode vóór de zwangerschap, en of het geneesmiddel misschien zelfs kan bijdragen aan een beter herstel van de eicel als onderdeel van preconceptiezorg.
Muizenonderzoek biedt eerste inzichten
Om die eerste resultaten te verkrijgen, voerden mijn collega’s en ik een studie uit met een dieet-geïnduceerd obees muismodel. Deze muizen ontwikkelen obesitas door een suiker- en vetrijk rantsoen dat onze moderne levensstijl nabootst, een model dat vaak wordt gebruikt binnen het Gamete Research Centre aan de Universiteit Antwerpen. In dit specifieke experiment werden obese muizen verdeeld in drie groepen; een eerste groep bleef obees, een tweede schakelde over op een gezond dieet en een derde kreeg naast dat dieet ook tirzepatide-injecties. Na twee weken werd bij de helft van de muizen de eicellen verzameld. De rest van de muizen volgde de interventie nog twee weken langer, met als enige aanpassing dat in de derde groep de tirzepatide-injecties stopgezet werden om zo een “wahsout-periode” na te bootsen zoals ook bij vrouwen wordt aangeraden. De verzamelde eicellen werden vervolgens onderzocht op drie parameters die samen een eerste inzicht geven over de gezondheid van de eicel: de hoeveelheid vetdruppels in de eicel, de activiteit van de mitochondriën en de aanwezigheid van reactieve zuurstof. Dat laatste zijn kleine, agressieve deeltjes die vrijkomen wanneer cellen energie produceren, een soort afvalproduct van de mitochondriën.
Dus..?
Net als bij mensen verloren de obese muizen met het nemen van tirzepatide aanzienlijk meer gewicht dan met enkel een gezond dieet. Uit mijn thesis bleek echter dat dit snelle gewichtsverlies acute stress veroorzaakt op het niveau van de eicel tijdens de preconceptieperiode. Dit komt doordat bij obesitas een overmaat aan vet wordt opgeslagen in het lichaam. Tijdens een periode van snel gewichtsverlies komt dit vet plots in grote hoeveelheiden in de bloedbaan terecht. Ook de eicel wordt eraan blootgesteld, met schade als gevolg. Gelukkig vertoonden de eicellen gecollecteerd na de "washout-periode", waarin de behandeling met het geneesmiddel twee weken werd stopgezet, minder effecten van deze stress periode. Dat komt omdat de muizen toen minder snel afvielen en zelfs wat bijkwamen, waardoor de eicel minder werd belast door vrije vetzuren. Het is belangrijk om te benadrukken dat deze resultaten voortvloeien uit een eerste verkennend onderzoek, uitgevoerd op muizen, gebaseerd op slechts drie parameters die indicatief zijn voor de gezondheid van de eicel. Meer onderzoek is nodig om de volledige impact van tirzepatide op eicelniveau bij de mens te begrijpen. Mijn thesis was slechts een klein onderdeel van een groter doctoraatonderzoek waarin verdere analyse van meerdere parameters gaande is! Eén ding is duidelijk: tirzepatide mag dan spectaculair gewichtsverlies opleveren, het verhaal is complexer dan een simpele “wonderspuit”, toch als het over de eicel gaat.
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