Chen MJ, Creinin MD, Turok DK, et al. - Via performing a multicenter dose-finding study in healthy, reproductive-aged women with regular cycles with sequential enrollment to increasing E2 dose groups, researchers here evaluated serum estradiol (E2) concentrations during use of 90-day contraceptive vaginal rings releasing E2 75, 100, or 200 mcg/day and segesterone acetate (SA) 200 mcg/day to determine a dose that avoids hypoestrogenism. Serum E2 concentrations were determined twice weekly for the primary outcome of median E2 concentrations throughout initial 30-day use (target ≥ 40 pg/mL). In an optional 2-cycle extension substudy, participants were randomized to 2- or 4-day ring-free intervals per 30-day cycle to determine bleeding and spotting based on daily diary information. They enrolled 65 participants who received CVRs releasing E2 75 mcg/day (n = 22), E2 100 mcg/day (n = 21), or E2 200 mcg/day (n = 22) along with SA 200 mcg/day; 35 participated in the substudy. Per findings, the CVR releasing E2 200 mcg/day and SA 200 mcg/day may allow attainment of adequate E2 concentrations to avoid hypoestrogenism over 30-day use.