ABSTRACT

Fraser, Ian S., Edith Weisberg, Vivian Brache, Francisco Alvarez, Rebeca Massai, Daniel R. Mishell, Jr., Dan Apter, Judi Gale, Yun Yen Tsong, and Irving Sivin. 2005. "Serum Nestorone® and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen–ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen," Contraception 72(1): 40–45. (offsite link)

Objectives
This trial tested the hypothesis that menstrually signaled use of contraceptive vaginal rings (“rings”) releasing low-dose combinations of Nestorone (NES) and ethinyl estradiol (EE) would reliably suppress luteal activity and ovulation, and prevent unintended pregnancy, while controlling the incidence of menstrual bleeding episodes and bleeding days.

Methods
Nestorone/ethinyl estradiol rings releasing 50/10, 50/20 and 150/15 μg/day were studied through six months. A ring was to be used continuously, until its removal was signaled by menstrual bleeding. Reinsertion was required 96 hours after removal. Serum for NES, EE, and progesterone were collected and assayed, and vaginal ultrasound scans were performed in three 5-week periods to examine luteal activity, follicular growth, ovulation, and their correlates. In ten subjects using the 150/15 ring, six samples were drawn in the 24-hour period after ring removal to examine serum levels of NES and EE.

Results
One hundred sixty subjects at three doses provided blood samples. Median serum concentrations of NES and EE demonstrated dose ratios slightly below the nominal dose ratios expected. Serum NES concentrations declined 19–22 percent from weeks 3 to 25. Changes in EE levels depended on dose. Nestorone levels fell 81 percent by 24 hours after ring removal and EE levels fell by 50 percent. Luteal activity was completely suppressed in 94–95 percent of cycles and in 90 percent of subjects. Three pregnancies occurred in subjects participating in this serum sampling study.

Conclusion
Satisfactory serum levels of NES and EE, and a high level of ovulation suppression were achieved. Irregular ring use, however, permitted pregnancies to occur.

Projects

• One-year Contraceptive Vaginal Ring, Phase 2 Study
• One-year Contraceptive Vaginal Ring, Phase 3 Study

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