Pharmacokinetic and pharmacodynamic studies of vaginal rings releasing low-dose levonorgestrel.

Pharmacokinetic and pharmacodynamic effects of a vaginal ring releasing 20 micrograms/day levonorgestrel (L-NOG) have been studied in 15 women. Serum levels of L-NOG, estradiol and progesterone were measured three times a week in a control menstrual cycle and a treatment period of 3 months after the insertion of the first vaginal ring. All control cycles were normal ovulatory. Among the 36 treatment cycles 13 were ovulatory (36%), 5 ovulatory with inadequate luteal function (14%), 14 anovulatory but with marked follicle activity (39%) and 4 anovulatory (11%). In the groups with ovulatory reaction the serum levels of L-NOG showed a decline of 54% of the initial level at the end of the treatment period, calculated according to the linear regression equation of Y = 0.903-0.0142X, while in the groups without ovulation the L-NOG levels were higher and the decline was 24% of the initial level (Y = 1.034-0.0086X). There were distinct individual differences in the levels of L-NOG and ovarian reactions. Marked follicle activity with very high estradiol levels were found in correlation with high L-NOG in 7 treatment cycles, particularly in the B type of reaction (B = anovulatory cycle with marked follicle activity). More intermenstrual bleeding and spotting occurred in the second treatment cycles, particularly in those with anovulatory reactions.