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In vivo and in vitro studies have reported that EE itself is biotransformed for excretion mainly by glucuronidation (85%) and sulfation (12%) and that hydroxylation (mainly by CYP3A4 and CYP2A9 on C2) occurs only at low levels 22

It is worth to note that both Arx -/- mice and HNF-3 -/- mice were neonatal lethal 4,13

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