Abstract
Background: As part of a program to develop a novel estradiol-releasing contraceptive vaginal ring (CVR), we evaluated the pharmacokinetic (PK) profile of CVRs releasing segesterone acetate (Nestorone® (NES)) combined with one of three different estradiol (E 2 ) doses. Study design: A prospective, double-blind, randomized, multi-centered study to evaluate a 90-day CVR releasing NES [200 mcg/day] plus E 2 , either 10 mcg/day, 20 mcg/day, or 40 mcg/day in healthy reproductive-age women with regular cycles. Participants provided blood samples twice weekly for NES and E 2 levels during the first 60 days (ring 1) and the last 30 days (ring 2) of use. A subset underwent formal PK assessments at ring initiation, ring exchange (limited PK), and study completion. Results: The main study enrolled 197 women; 22 participated in the PK substudy. Baseline characteristics between the main and PK participants were comparable, with an average BMI of 25.8 kg/m 2 (SD 4.3). In the PK substudy, all three rings showed similar NES PK: mean area under the curve (AUC (0–72) ) 34,181 pg*day/mL; concentration maximum (C max ) 918 pg/mL; time to maximum concentration (T max ) 3.5 h. For E 2, the C max occurred at 2 h, and was significantly higher with the 20 mcg/day ring (mean 390 pg/mL); 10 mcg/day, 189 pg/mL, p=.003; 40 mcg/day, 189 pg/mL, p<.001), and declined rapidly to≤50 pg/mL for all doses by 24 h. For all subjects, the median E 2 levels remained under 35 pg/mL during treatment. Conclusion: PK parameters of NES were not affected when paired with different doses of E 2 , but E 2 levels from all three doses were lower than anticipated and no dose response was observed. Implications: While these novel estradiol-releasing combination contraceptive vaginal rings provided sustained release of contraceptive levels of Nestorone over 90 days, the E 2 levels achieved were not consistent with bone protection, and a dose–response was not observed.
Original language | English (US) |
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Pages (from-to) | 422-427 |
Number of pages | 6 |
Journal | Contraception |
Volume | 97 |
Issue number | 5 |
DOIs | |
State | Published - May 2018 |
Keywords
- Continuous cycling
- Contraception
- Contraceptive vaginal ring
- Estradiol
- Nestorone
- Pharmacokinetics
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology