A comparative study of two contraceptive vaginal rings releasing norethindrone acetate and differing doses of ethinyl estradiol

Two combined contraceptive vaginal rings (CVR) each releasing approximately 1 mg norethindrone acetate (NET-Ac) and either 20 mu g or 15 mu g ethinyl estradiol over 24 h were tested at three clinic sites in Los Angeles, San F rancisco, 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 estrad iol, progesterone, norethindrone (NET), and ethinyl estradiol (EE) levels w ere assayed twice weekly in all four treatment cycles. Both CVR performed well, with no pregnancies occurring and only one cycle o f luteal activity suggestive of ovulation (serum progesterone >32 nmol/L) o ccurring with each ring (0.9% of cycles with the 1/15 ring and 1.2% of cycl es with the 1/20 ring). Although there was significantly more luteal activi ty in women using the 1/15 CVR (5.9% compared with 1.2% of cycles), only th ree 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 ri ngs. 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 signifi cant difference in EE levels between the women in Los Angeles and Sydney us ing the same dose rings. Total cholesterol, HDL, and LDL cholesterol values were not significantly c hanged during treatment. Triglycerides increased but remained within the no rmal range. Overall cycle control was good with both formulations, but ther e was slightly more cycle disturbance with the lower dose ring. There was n o change in mean body weight during the study, and individual weight change s appeared to be idiosyncratic. Side effects were infrequent and similar to those reported with other steroidal contraceptive methods. Three women com plained of vaginal discharge, one with accompanying itch and one with a vag inal 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, E-2, and prog esterone levels and lipids, and on vaginal bleeding patterns. CONTRACEPTION 1999;59:305-310 (C) 1999 Elsevier Science Inc. All rights reserved.