Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen.
OBJECTIVE
This trial tested the hypothesis that menstrually signaled use of contraceptive vaginal rings ("rings") releasing low-dose combinations of Nestorone (NES) and ethinyl estradiol (EE) would reliably suppress luteal activity and ovulation, and prevent unintended pregnancy, while controlling the incidence of menstrual bleeding episodes and bleeding days.


METHODS
Nestorone/ethinyl estradiol rings releasing 50/10, 50/20 and 150/15 mug/day were studied through 6 months. A ring was to be used continuously, until its removal was signaled by menstrual bleeding. Reinsertion was required 96 h after removal. Serum for NES, EE and progesterone were collected and assayed, and vaginal ultrasound scans were performed in three 5-week periods to examine luteal activity, follicular growth, ovulation and their correlates. In 10 subjects using the 150/15 ring, six samples were drawn in the 24-h period after ring removal to examine serum levels of NES and EE.


RESULTS
One hundred sixty subjects at three doses provided blood samples. Median serum concentrations of NES and EE demonstrated dose ratios slightly below the nominal dose ratios expected. Serum NES concentrations declined 19-22% from weeks 3 to 25. Changes in EE levels depended on dose. Nestorone levels fell 81% by 24 h after ring removal and EE levels fell by 50%. Luteal activity was completely suppressed in 94-95% of cycles and in 90% of subjects. Three pregnancies occurred in subjects participating in this serum sampling study.


CONCLUSIONS
Satisfactory serum levels of NES and EE, and a high level of ovulation suppression were achieved. Irregular ring use, however, permitted pregnancies to occur.
Fraser
Ian S
IS
Department of Obstetrics and Gynaecology, University of Sydney, Sydney NSW 2006, Australia. helena@med.usyd.edu.au
Weisberg
Edith
E
Brache
Vivian
V
Alvarez
Francisco
F
Massai
Rebeca
R
Mishell
Daniel R
DR
Apter
Dan
D
Gale
Judi
J
Tsong
Yun Yen
YY
Sivin
Irving
I
D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D003274:Contraceptive Devices, Female; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006801:Humans; D008598:Menstruation; D009653:Norprogesterones / Q000008:administration & dosage / Q000097:blood*; D006080:Ovarian Follicle / Q000033:anatomy & histology; D034445:Ovulation Inhibition; D011247:Pregnancy; D011374:Progesterone / Q000097:blood
D003271:Contraceptive Agents, Female; D009653:Norprogesterones; D004997:Ethinyl Estradiol; D011374:Progesterone; C029167:ST 1435