Comparative bioavailability of orally and vaginally administered progesterone.

Abstract

To study the pharmacokinetics of progesterone (P) in healthy premenopausal female volunteers to compare the bioavailability of orally or vaginally administered hormone.Subjects were randomly allocated to receive either oral P or a vaginal pessary then crossed over to the alternate preparation 1 month later.The study was conducted in outpatient setting.All subjects were healthy, normal female volunteers who underwent a physical and gynecological examination before the study. None were using oral contraceptives. Ten subjects (mean age 32.6 +/- 7.3 years) entered the study and all completed it.Progesterone was administered as 200 mg of micronized hormone or as a pessary containing 400 mg.Plasma levels of P were measured by radioimmunoassay to test the apriori hypothesis of similar bioavailability.Peak plasma P concentrations attained within 4 hours after oral administration ranged from 8.5 to 70.6 ng/mL, whereas after vaginal administration the peak levels were attained within 8 hours and ranged from 4.4 to 181.1 ng/mL. Considerable interindividual variation was noted. Area under the plasma concentration-time curve for the two formulations was not significantly different (F = 1.09; P greater than 0.1; ANOVA).The two formulations had similar bioavailability.