Vaginal administration of ethinylestradiol: effects on ovulation and hepatic transcortin synthesis

Ethinylestradiol (EE) was given vaginally to circumvent the intestinal metabolism and initial liver passage which follow oral intake. This route of administration was chosen in an effort to enhance the antiovulatory potency of EE, while decreasing adverse hepatic reactions. Vaginal tablets containing 20-30 micrograms of EE were taken daily by 7 ovulating volunteers from day 5 to day 25 of the menstrual cycle. The regimen resulted in serum EE levels of 62 +/- 27 pg/ml (mean +/- S.D.) 8-10 hours after insertion. Ovulation was inhibited in 5 women (monophasic basal body temperature curves, serum progesterone levels of 0.9 +/- 1.1 ng/ml during the second half of the treatment cycle). The cortisol-binding capacity of transcortin was significantly elevated in all subjects (52.3 +/- 6.4 micrograms/100 ml; controls 25.7 +/- 2.2 micrograms/100 ml). These findings indicate that intravaginal EE is twice as potent as oral EE in regard to inhibition of ovulation as well as stimulation of the hepatic transcortin synthesis. Vaginal administration apparently increases the bioavailability of EE; it does not facilitate a selective reduction of estrogenic effects upon the liver.