Effect of different insertion regimens on side effects with a combination contraceptive vaginal ring.
The study population included 159 women aged 18 to 37 years requiring contraception (60 in Sydney, 99 in Los Angeles). The design consisted of a 6 month study of a contraceptive vaginal ring (CVR) releasing 20 micrograms ethinyl estradiol and 1 mg of norethindrone acetate daily over two successive cycles with a new ring on each of three different insertion regimens. A total of 831 woman-months of exposure were recorded, and 129 women completed the study. The overall incidence of side effects was similar in the two centers and differences between the insertion regimens were not observed. Transient nausea following insertion of a new ring (mainly lasting 0.5 to 48 h) was the most prominent side effect, with no significant difference between the insertion regimens (although the incidence tended to be highest with bedtime insertion [34%] and lowest with early evening insertion and temporary removal during the first night [27%]). Transient vomiting occurred in about 10% of women in the first 24 h after first insertion of a new ring. The incidence and severity of nausea was greatly reduced in cycle 2 with each regimen (6% to 9% of women). Nausea could be prevented by overnight soaking of the ring in water before use. Other side effects such as headache, dizziness, uterine cramps, breakthrough bleeding, weight gain, and ring expulsion occurred with similarly low frequency in all three insertion groups. One pregnancy occurred with probable ovulation between cycles 5 and 6, the only pregnancy recorded to date in studies with this ring. The study demonstrated that this effective and generally well tolerated CVR causes a relatively high incidence of transient nausea after insertion of a new ring, which is probably due to accumulation of ethinyl estradiol on the ring surface during storage. Acceptability is still high, and this particular CVR merits further development.
Weisberg
E
E
Sydney Centre for Reproductive Health Research, Ashfield, Australia.
Fraser
I S
IS
Lacarra
M
M
Mishell
D R
DR
Jackanicz
T
T
D000328:Adult; D003274:Contraceptive Devices, Female / Q000009:adverse effects* / Q000592:standards; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006261:Headache / Q000139:chemically induced*; D006801:Humans; D009325:Nausea / Q000139:chemically induced*; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced*
D004997:Ethinyl Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone