Abstract

The time course of free oestradiol and oestrone as well as of total (free and conjugated) oestrone was determined in plasma of women after oral ingestion of 3.75 mg conjugated equine oestrogens, or 9.74 micromol of oestrone sulfate, oestrone, and oestradiol, respectively. All these oestrogen preparations led to transiently increased plasma oestrogen levels which fell to normal values after 48 h. The main difference observed between administration of free oestrone or oestradiol and of conjugated oestrogens (oestrone sulfate or equine oestrogens) was a much more protracted influx of oestrogens from the intestine into the plasma compartment, with a tendency to more sustained plasma levels, if conjugated oestrogens were administered. There was a consistent discontinuity in plasma oestrogen levels 10--12 h after oral ingestion of all the preparations examined indicating enterohepatic circulation. Comparison of "areas under the curve" obtained with the present preparations to similar previous studies on ethinyl oestradiol indicated that the bioavailability of the non-ethinyl oestrogens is by more than one order of magnitude less than that of ethinyl oestradiol after oral administration. The ratio of oestrone/oestradiol was the highest with free oestrone and similar among the other three preparations indicating an increased metabolism of sulfoconjugated oestrone to oestradiol after oral application when compared with free oestrone.

PIP:

The time course of free estradiol and estrone as well as of total (free and conjugated) estrone was determined in plasma of women after oral ingestion of 3.75 mg conjugated equine estrogens, or 9.74 mcmol of estrone sulfate, estrone, and estradiol, respectively. All these estrogen preparations led to transiently increased plasma estrogen levels which fell to normal values after 48 hours. The main difference observed between administration of free estrone or estradiol and of conjugated estrogens (estrone sulfate or equine estrogens) was a much more protracted influx of estrogens from the intestines into the plasma compartment, with a tendency to more sustained plasma levels, if conjugated estrogens were administered. There was consistent discontinuity in plasma estrogen levels 10-12 hours after oral ingestion of all preparations examined, indicating enterohepatic circulation. Comparison of areas under the curve obtained with the present preparations similar to previous studies on ethinyl estradiol indicated that the bioavailability of the nonethinyl estrogens is by more than 1 order of magnitude less than that of ethinyl estradiol after oral administration. The ratio of estrone/estradiol was the highest with free estrone and similar among the other 3 preparations. This indicates an increased metabolism of sulfoconjugated estrone to estradiol after oral application when compared to free estrone. (author's modified)