Estradiol valerate versus ethinylestradiol in combined contraceptives: effects on blood proteome, lipids, inflammation, and steroid hormones.

Marika Kangasniemi, MD, will defend her doctoral thesis on Friday, 2.12.2022, at the University of Oulu. Thesis project aimed to investigate the differences between ethinylestradiol (EE)- and estradiol valerate (EV)- based combined oral contraceptives (COCs) in the serum proteome, inflammation, lipids, and ovarian and adrenal hormones. The thesis is based on a randomized, controlled clinical trial SYLVI.

Millions of women globally use COCs for contraception and the treatment of various conditions, even for decades. Traditionally COCs have contained very potent EE, but recently COCs containing natural estrogens have been introduced to the market. These more natural combinations seem to have a milder impact, for example, on hepatic proteins and metabolism than EE combinations, but knowledge is still lacking.

In the trial, healthy young women used either EE+dienogest (DNG), EV+DNG, or DNG only for nine weeks. The number of affected proteins in the circulation during EE+DNG use was multifold compared with the natural-estrogen-based EV+DNG and DNG-only preparations. These proteins were related, for example, to inflammation and the coagulation system. A natural-estrogen-based COC also had significantly milder effects on low-grade inflammation, lipid profile, ovarian & adrenal steroids, and steroid-binding proteins than synthetic EE+DNG preparation.

This thesis highlights the neutral effects of natural estrogen in a COC compared with the synthetic and highly potent EE. To date, the choice of COC is based mainly on the properties of progestin components. However, emerging data suggesting the milder metabolic impact of natural estrogens promote the consideration of estrogen when prescribing COCs. The results encourage further research and development of natural-estrogen-based COCs.