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

Three estradiol (E 2 )-containing oral contraceptives, estradiol valerate/cyproterone acetate (E 2 V/CPA, Femilar ® ), estradiol valerate/dienogest (E 2 V/DNG, Qlaira ® /Natazia™), and estradiol/nomegestrol acetate (E 2 /NOMAC; Zoely ® ), have received approval for use in general practice. Only Finnish women currently have access to all three E 2 -based formulations. E 2 /NOMAC is currently approved only in Europe, while E 2 V/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 E 2 -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 E 2 V/DNG, E 2 /NOMAC, and E 2 V/CPA are all effec- tive oral contraceptives. While direct comparisons are lacking, indirect evidence suggests that E 2 V/DNG and E 2 /NOMAC may have better bleeding profiles than E 2 V/CPA. E 2 V/DNG is also approved for the treatment of heavy menstrual bleeding. Both E 2 V/DNG and E 2 /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 E 2 -based oral contraceptives confer additional benefits compared with those of ethinylestradiol-based COCs.