Two combined contraceptive vaginal rings (CVR) each releasing approximately 1 mg norethindrone acetate (NET-Ac) and either 20 micrograms or 15 micrograms ethinyl estradiol over 24 h were tested at three clinic sites in Los Angeles, San Francisco, and Sydney. A total of 61 women were enrolled to use the ring on a schedule of 3 weeks in/1 week out for four treatment cycles. Serum estradiol, progesterone, norethindrone (NET), and ethinyl estradiol (EE) levels were assayed twice weekly in all four treatment cycles. Both CVR performed well, with no pregnancies occurring and only one cycle of luteal activity suggestive of ovulation (serum progesterone > 32 nmol/L) occurring with each ring (0.9% of cycles with the 1/15 ring and 1.2% of cycles with the 1/20 ring). Although there was significantly more luteal activity in women using the 1/15 CVR (5.9% compared with 1.2% of cycles), only three cycles with a marked degree of luteal activity (progesterone > 10 nmol/L) occurred among compliant women. Serum levels of NET and EE were consistently elevated during use of both rings. There was no significant difference between serum levels with the two rings because of wide interindividual variations, although both NET and EE levels tended to be higher with the 1/20 ring. However, there was a significant difference in EE levels between the women in Los Angeles and Sydney using the same dose rings. Total cholesterol, HDL, and LDL cholesterol values were not significantly changed during treatment. Triglycerides increased but remained within the normal range. Overall cycle control was good with both formulations, but there was slightly more cycle disturbance with the lower dose ring. There was no change in mean body weight during the study, and individual weight changes appeared to be idiosyncratic. Side effects were infrequent and similar to those reported with other steroidal contraceptive methods. Three women complained of vaginal discharge, one with accompanying itch and one with a vaginal Candida infection in cycle 1. Overall, both of these EE/NET-Ac rings performed well, with only minor and mainly nonsignificant differences in effect on serum EE, NET, E2, and progesterone levels and lipids, and on vaginal bleeding patterns.
PIP: This study compares the performance of 2 combined contraceptive vaginal rings (CVRs) releasing 1 mg norethindrone acetate (NET-Ac) and either 20 or 15 mcg ethinyl estradiol (EE) over 24 hours. 61 women selected at 3 clinic sites in Los Angeles, San Francisco and Sydney were included. The performance of the 2 CVRs was determined by luteal activity, menstrual bleeding patterns, sum levels of EE and NET-Ac, and effects on serum lipoproteins. Results showed that both CVRs worked effectively: no pregnancies occurred, and there was only 1 cycle of luteal activity suggestive of ovulation (serum progesterone 32 nmol/l) with each ring (0.9% of cycles with the 1/15 ring and 1.2% of cycles with the 1/20 ring). Although there was more luteal activity in 1/15 CVR users, only 3 cycles with a significant level of luteal activity (progesterone 10 nmol/l) occurred among compliant users. Consistent elevation in serum levels of NET and EE was observed during use of both rings. A significant difference in EE levels was observed between women in Los Angeles and Sydney using the same dose of rings. There were no significant changes in the total cholesterol, HDL and LDL cholesterol values during treatment. The increase in triglycerides remained within the normal range while mean body weight showed no change. Side effects were infrequent and were similar to those associated with other steroidal contraceptives. Overall, both CVRs performed well, showing only minor and mainly nonsignificant differences in effect on serum EE, NET, E2, on progesterone levels and lipids, and on vaginal bleeding patterns.