La statistica descrittiva ha evidenziato come nelle 598 pazienti affette da PCOS il sovrappeso e l’obesità abbiano una prevalenza molto elevata, nel 61% dei casi. Questa osservazione è importante perché è stato descritto in letteratura che gran parte delle donne sovrappeso/obese, presentano una adiposità centrale, nota per essere correlata con uno stato di insulino-resistenza, un aumento dell’incidenza del diabete e di malattie cardiovascolari. Nell’analisi delle caratteristiche metaboliche è stato riscontrato come l’insulino-resistenza, probabilmente in misura maggiore rispetto al sovrappeso e all’obesità, contribuisca a determinare variazioni significative nelle variabili metaboliche e biochimiche. Tuttavia è stato rilevato anche che il sovrappeso e l’obesità riproducano le stesse alterazioni (eccezion fatta per i valori delle LDL). Dunque trattamenti volti a ridurre l’IMC, agirebbero contemporaneamente sull’iper-androgenismo, quindi sugli aspetti estetici e psicologici correlati alla sindrome, e su quelli metabolici.
Nella popolazione presa in esame la maggior parte delle donne è rientrata nel fenotipo 1, che è quello maggiormente associato alle alterazioni metaboliche caratteristiche della sindrome. Si potrebbe sottolineare quindi come, soprattutto in questo gruppo, dovrebbero essere indagate, nell’ambito della gestione clinica, le alterazioni metaboliche associate alla sindrome. In considerazione del fatto nel fenotipo 1 è maggiore la prevalenza delle pazienti sovrappeso e obese, la riduzione dell’IMC dovrebbe rappresentare il primo obiettivo della gestione clinica della PCOS.
In conclusione, in base a queste osservazioni, è ipotizzabile che per sviluppare una PCOS in età fertile una donna debba avere una predisposizione genetica di base a complesso modello di ereditarietà poligenica su cui agiscono fattori ambientali di esposizione prenatale (livelli di LH materni o elevati livelli di AMH in utero) e post-natale (interferenti endocrini) che contribuiscono allo sviluppo della PCOS mantenuta ed esacerbata nelle sue manifestazioni dall’ eventuale presenza di obesità centrale ed insulino-resistenza.
Come evidenziato dai dati dello studio, queste due condizioni contribuiscono a generare un circolo vizioso con l’iper-androgenismo, peggiorando il quadro metabolico, aumentando il rischio
70 cardiovascolare a lungo termine delle pazienti, esacerbando segni e sintomi dell’iper-androgenismo con vari meccanismi noti. È chiaro come la patogenesi sia complessa e questi elementi da soli non possano spiegare la totalità dei casi di PCOS, perché altrimenti non ci sarebbero pazienti magre con PCOS. Sicuramente questi elementi interagiscono tra loro e, per questo motivo, qualsiasi trattamento farmacologico personalizzato sulla base del fenotipo deve essere accompagnato da dieta, attività fisica e modifiche dello stile di vita sia nelle pazienti francamente obese che in quelle sovrappeso con adipe a distribuzione prevalentemente viscerale.
Futuri studi dovranno essere indirizzati alla valutazione del reale aumento del rischio cardiovascolare nelle giovani donne affette da PCOS e alle sue implicazioni terapeutiche. Al fine di colmare le attuali lacune sull’eziopatogenesi della sindrome dell’ovaio micropolicistico, si prevede di ampliare in futuro il gruppo delle pazienti magre insulino-resistenti. Inoltre, verranno analizzate le pazienti in età riproduttiva non PCOS che afferiscono all’ambulatorio obesità del reparto di Endocrinologia dell’AOUP. Questo gruppo fornirebbe una popolazione di controllo che permetterebbe di completare l’analisi delle relazioni intercorrenti tra IMC e HOMA.
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Ringraziamenti
Desidero ringraziare il mio relatore, il Professor Massimo Tonacchera, che si è reso sempre disponibile in questi mesi di lavoro con preziosi insegnamenti e che mi ha permesso di frequentare l’ambulatorio di Endocrinologia ginecologica e dell’adolescenza.
Un sincero ringraziamento va anche alla mia correlatrice, la Dott.ssa Elena Benelli, per i suoi suggerimenti e per avermi consentito di affiancarla nella conduzione dell’ambulatorio.
Desidero ringraziare inoltre il Dottor Angelo Molinaro, per la disponibilità dimostratami durante la scrittura della tesi e per le sue preziose istruzioni in materia di analisi statistica.
Un pensiero affettuoso va infine alla Dott.ssa Roberta Asaro, che ha condiviso con me l’interesse per la ricerca nell’ambito della sindrome dell’ovaio micropolicistico.