Comparison of the pharmacologic and clinical profiles of new combined oral contraceptives containing estradiol

Abstract

Three estradiol (E2)-containing oral contraceptives, estradiol valerate/cyproterone acetate (E2V/CPA, Femilar®), estradiol valerate/dienogest (E2V/DNG, Qlaira®/Natazia™), and estradiol/nomegestrol acetate (E2/NOMAC; Zoely®), have received approval for use in general practice. Only Finnish women currently have access to all three E2-based formulations. E2/NOMAC is currently approved only in Europe, while E2V/DNG is approved globally. To assist clinicians counseling women considering use of one of these formulations, we conducted a review of the published information about the current E2-containing oral contraceptives. A literature search was conducted using the Ovid interface and a combination of free search terms relevant to estradiol and oral contraception to identify suitable articles for inclusion in this review. The available data show that E2V/DNG, E2/NOMAC, and E2V/CPA are all effective oral contraceptives. While direct comparisons are lacking, indirect evidence suggests that E2V/DNG and E2/NOMAC may have better bleeding profiles than E2V/CPA. E2V/DNG is also approved for the treatment of heavy menstrual bleeding. Both E2V/DNG and E2/NOMAC have minimal influence on hemostatic, lipid, and carbohydrate metabolism parameters, or induce less change in these parameters relative to ethinylestradiol-based oral contraceptives. However, the predictive value of these surrogate parameters is a matter of debate, and whether these differences can be translated into meaningful clinical outcomes needs to be established in large-scale, post-marketing, prospective, Phase IV cohort studies. Future studies are required to determine whether E2-based oral contraceptives confer additional benefits compared with those of ethinylestradiol-based COCs.