Combined oral contraceptives and pharmacokinetic drug interactions: impact on efficacy and safety

Progestins are primarily metabolized through phase I enzymes, especially CYP3A4, whereas estrogen metabolism relies on a combination of both phase I and phase II pathways. Nevertheless, the contribution of phase II enzymes to the clearance of COCs remains underappreciated. Much of the existing studies have focused on characterizing metabolic pathways and pharmacokinetic effects rather than assessing meaningful clinical outcomes. While pharmacokinetic interactions can theoretically predict potential adverse effects, robust DCI studies that incorporate real-world clinical outcomes are still critically needed.