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 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.
Weisberg
E
E
Sydney Centre for Reproductive Health Research, Family Planning NSW, Australia. eweisberg@s055.aone.net.au
Fraser
I S
IS
Mishell
D R
DR
Lacarra
M
M
Darney
P
P
Jackanicz
T M
TM
D000293:Adolescent; D000328:Adult; D001672:Biocompatible Materials; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003274:Contraceptive Devices, Female; D003338:Corpus Luteum / Q000187:drug effects; D003692:Delayed-Action Preparations; D020724:Elastomers; D004958:Estradiol / Q000097:blood; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000077563:Norethindrone Acetate; D006080:Ovarian Follicle / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D012828:Silicones; D014621:Vagina
D001672:Biocompatible Materials; D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D020724:Elastomers; D012828:Silicones; D004997:Ethinyl Estradiol; D011374:Progesterone; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone