Estrogen and the metabolism of progesterone in vivo

Abstract

The effect of estrogen administration on the metabolism of progesterone was studied in ovariectomized, hysterectomized women. Estrogen was withheld from each subject for at least 4 weeks, then 200 μg of ethinyl estradiol were administered orally each day for 3 weeks and then no estrogen was given for 3 weeks. The subjects were studied before estrogen was started, on the third day of estrogen, after 3 weeks of daily estrogen and after the estrogen was withdrawn for 3 weeks. In 5 women plasma transcortin concentrations, measured by equilibrium dialysis, were 0.82 ± 0.06, 1.5 ± 0.16, 2.1 ± 0.13, and 0.90 ± 0.09 (S.E.) μM before starting estrogen (control), on the third day of estrogen treatment, after 3 weeks of estrogen, and after having stopped estrogen for 3 weeks, respectively. Corresponding values for the metabolic clearance rates (MCR) of cortisol (by the continuous infusion method) were 306 ± 33, 172 ± 18, 136 ± 14, and 258 ± 23 (S.E.) L. per day. Although estrogen administration caused a significant elevation of the plasma transcortin concentrations and a significant decrease in the MCR of cortisol, it had no significant effect on the MCR of progesterone or of cortisone. The estrogen administration did cause a decrease in the peripheral conversion of progesterone to 20α-hydroxy-pregn-4-en-3-one (20α-OHP) and of cortisol to cortisone but an increase in the conversion of 20α-OHP to progesterone and of cortisone to cortisol.