Dose-finding study of a contraceptive ring releasing norethindrone acetate/ethinyl estradiol.
A core design contraceptive vaginal ring (CVR) with average daily release of 650 mcg of norethindrone acetate (NA) and 30 mcg of ethinyl estradiol (EE) inhibited ovulation and controlled vaginal bleeding well, but caused some nausea. This study was designed to minimally alter the dose of steroid to see if nausea could be reduced without loss of contraceptive efficacy. This 30/650 CVR was compared to a CVR releasing 20 mcg of EE and 1000 mcg of NA (20/1000) and another releasing 25 mcg of EE and 650 mcg of NA (25/650) in 69 subjects. Twenty-three subjects using an oral contraceptive containing NA/EE served as controls. Ovulation inhibition was excellent and comparable to the OC for all formulations. The CVR provided better control of vaginal bleeding than did the OC. Side effects were equivalent to the OC with the exception of a slight increase in nausea in CVR users. Lipid changes and globulin increases were comparable to oral contraceptive users. The 20/1000 CVR increased sex hormone binding globulin-binding capacity less than the other two CVRs. The performance of the three CVRs was not significantly different, but the 25/650 showed a trend of reduced performance relative to the other two formulations.
Ballagh
S A
SA
University of Southern California School of Medicine, Department of Obstetrics and Gynecology, Los Angeles.
Mishell
D R
DR
Jackanicz
T M
TM
Lacarra
M
M
Eggena
P
P
D000282:Administration, Intravaginal; D000328:Adult; D003274:Contraceptive Devices, Female / Q000009:adverse effects / Q000592:standards*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000592:standards*; D005260:Female; D006801:Humans; D008183:Luteal Phase / Q000187:drug effects / Q000502:physiology; D008597:Menstrual Cycle / Q000187:drug effects / Q000502:physiology; D009325:Nausea / Q000139:chemically induced; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000592:standards; D000077563:Norethindrone Acetate; D010060:Ovulation / Q000187:drug effects; D012738:Sex Hormone-Binding Globulin / Q000032:analysis
D003692:Delayed-Action Preparations; D012738:Sex Hormone-Binding Globulin; D004997:Ethinyl Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone