Changing convention in combination oral contraceptives: Estradiol and nomegestrol acetate in a monophasic 24/4 regimen

Initial oral contraceptive regimens were characterised by high doses of ethinylestradiol (EE) and a progestogen in a 21-day regimen that either included seven additional hormone-free tablets or simply the 21 days of combination hormonal tablets. These regimens were developed to ensure high contraceptive effectiveness, regular and predictable withdrawal bleeding episodes to mimic a menstrual cycle, and minimal unscheduled vaginal bleeding. However, these regimens were associated with adverse tolerability and safety issues resulting from the dose and characteristics of their hormonal components. Attempts to ameliorate these adverse issues included the development of lower-dose EE regimens, the incorporation of new progestogens, multiphasic regimens, and reduced hormone-free interval regimens. However, the EE component has remained a constant until the recent approval of combination oral contraceptives with an estrogen component other than EE. The development and introduction of an estradiol-based oral contraceptive regimen is presented in this review.