Updated project metadata. Ethinylestradiol (EE)-based combined oral contraceptives (COC) have multiple beneficial effects besides contraception, but they also cause certain unfavorable health outcomes. They interfere, for example, with metabolism, inflammation, hepatic protein synthesis, and blood coagulation. COCs containing natural estrogens have recently been developed, yet little is known about their non-contraceptive effects compared to conventional EE-based COCs. The aim of the study was to analyze the serum proteome during three different treatments: EE+dienogest (DNG), estradiol valerate (EV)+DNG, and DNG only.