A concept for a new approach to combined oral contraception from adolescence to perimenopause: Continuous use of the oral <scp>GnRH</scp> antagonist Relugolix and the fetal estrogen Estetrol

The introduction of oral GnRH antagonists has created the possibility to replace progestins in combined oral contraceptives as the suppressor of ovarian function. A concept for this new approach to oral hormonal contraception is the combination of 40 mg relugolix, known to inhibit ovulation, and a low dose of the fetal estrogen estetrol. Major noncontraceptive benefits of this regimen will be the establishment of continuous amenorrhea and a smooth and symptomless perimenopausal transition to the postmenopausal status, creating a life cycle endocrine management approach for women (the RE4Women concept). An additional long-term effect of RE4W is the expected strong reduction of the incidence of breast cancer due to the absence of luteal progesterone and progestins. The dose of estetrol maintaining estrogen function, preventing perimenopausal symptoms, and not causing unacceptable endometrial growth and/or breakthrough bleeding will be assessed in two Phase 2 studies in women aged 18-35 and 36-51 years, respectively.