Dose-finding study of a 90-day contraceptive vaginal ring releasing estradiol and segesterone acetate.

ObjectiveTo evaluate 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 identify a dose that avoids hypoestrogenism.Study designWe conducted a multicenter dose-finding study in healthy, reproductive-aged women with regular cycles with sequential enrollment to increasing E2 dose groups. We evaluated serum E2 concentrations 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, we randomized participants to 2- or 4-day ring-free intervals per 30-day cycle to evaluate bleeding and spotting based on daily diary information.ResultsSixty-five participants enrolled in E2 75 (n = 22), 100 (n = 21), and 200 (n = 22) mcg/day groups; 35 participated in the substudy. Median serum E2 concentrations in 75 and 100 mcg/day groups were <40 pg/mL. In the 200 mcg/day group, median E2 concentrations peaked on days 4-5 of CVR use at 194 pg/mL (range 114-312 pg/mL) and remained >40 pg/mL throughout 30 days; E2 concentrations were 37 pg/mL (range 28-62 pg/mL) on days 88-90 (n = 11). Among the E2 200 mcg/day substudy participants, all had withdrawal bleeding following ring removal. The 2-day ring-free interval group reported zero median unscheduled bleeding and two (range 0-16) and three (range 0-19) unscheduled spotting days in extension cycles 1 and 2, respectively. The 4-day ring-free interval group reported zero median unscheduled bleeding or spotting days.ConclusionsEstradiol concentrations with rings releasing E2 200 mcg/day and SA 200 mcg/day avoid hypoestrogenism over 30-day use.ImplicationsA 90-day contraceptive vaginal ring releasing estradiol 200 mcg/day and segesterone acetate 200 mcg/day achieves estradiol concentrations that should avoid hypoestrogenism and effectively suppresses ovulation

Contraceptive Efficacy and Comparative Side Effects of a Mini Copper Intrauterine Device.

BackgroundIntrauterine devices (IUDs) are highly effective, yet acceptability and continuation differ by user and device characteristics. We evaluated the efficacy of the NTCu380 Mini, a 380-mm2 copper IUD available in Europe and Canada, and compared safety and continuation with the TCu380A IUD, the 380-mm2 copper IUD available in the United States.MethodsWe randomly assigned participants between 16 and 40 years of age in a 4:1 ratio to the NTCu380 Mini or TCu380A and assessed over 37 months. The primary outcome was NTCu380 Mini efficacy measured by the Pearl Index (defined as the number of pregnancies per 100 woman-years) in participants 35 years of age and under. Additional outcomes included NTCu380 Mini time to pregnancy by survival analysis, and comparative adverse events (AEs) and continuation rates of NTCu380 Mini versus TCu380A.ResultsWe randomly assigned 887 participants to NTCu380 Mini (744 [83.9%] nulliparous) and 218 to TCu380A (183 [83.9%] nulliparous), of whom 875 (98.6%) and 213 (97.7%), respectively, had successful placement. The NTCu380 Mini IUD 3-year cumulative Pearl Index was 1.86 (95% confidence interval [CI], 1.20 to 2.74) pregnancies per 100 women-years; the cumulative rate of pregnancy through year 3 was 4.8% (95% CI, 2.8 to 6.9%). Serious AEs occurred in 31 (3.5%) NTCu380 Mini and 4 (1.9%) TCu380A users (P=0.28). Discontinuation occurred in 449 (51.3%) NTCu380 Mini and 122 (57.3%) TCu380A users (P=0.07). AEs led to discontinuation less frequently among NTCu380 Mini (152 [20.8%]) than TCu380A users (57 [33.2%]) (P=0.001), particularly bleeding or pelvic pain AEs (103 [14.5%] vs. 46 [27.3%], respectively; P<0.001).ConclusionsIn this predominantly nulliparous population, the NTCu380 Mini IUD had an approximate 5% pregnancy rate over 3 years, with fewer side effects leading to discontinuation than observed among TCu380A users. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03124160.) The findings and conclusions in this article are those of the authors and do not necessarily reflect the views of the Planned Parenthood Federation of America, Inc