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

Jeffrey T Jensen,¹ Johannes Bitzer,² Marco Serrani<sup>3

1</sup>Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; ²Department of Social Medicine and Psychosomatics, Women’s Hospital, University Hospital of Basel, Basel, Switzerland; ³Global Medical Affairs, Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany

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.

Keywords: estradiol valerate, dienogest, nomegestrol acetate, cyproterone acetate