EFFECT OF GRADED ORAL DOSES OF OESTRADIOL ON CIRCULATING HORMONAL LEVELS

Abstract

ABSTRACT A single oral dose of micronized oestradiol (1, 2 or 4 mg) was administered to 10 normally menstruating women on the second day of 3 consecutive menstrual cycles. The order in which the 3 doses were given was chosen randomly for each subject. Samples of peripheral blood were withdrawn on 3 occasions (10, 5 and 1 min) before and on 9 occasions (0.37, 0.75, 1.5, 3.0, 6.0, 12.0, 24.0, 48.0 and 72.0 h) after the ingestion of oestradiol. Oestradiol, oestrone, oestradiol sulphate, oestrone sulphate, testosterone and LH were measured by means of radioimmunoassays in blood plasma on all occasions. The levels of all oestrogens increased significantly following the ingestion of oestradiol, although to a greatly different extent. The largest and most prolonged increase was seen in the case of oestrone sulphate, the levels of which — depending on the dose ingested — were 20–50 times higher than the pre-treatment levels 3 h after the ingestion of the oestradiol capsule. The increase of the levels of oestrone sulphate was still significant (P < 0.001) after 24 h, and following the ingestion of 2 and 4 mg of oestradiol even after 72 h (P < 0.05). The levels of oestrone and oestradiol sulphate exhibited smaller increases 3 h after ingestion, i. e. 4–10 and 2.5–5 times, respectively, and the plasma levels of oestradiol showed a minor increase only (1.4–1.8 times). The concentration of oestradiol metabolites studied increased proportionally with the dose of oestradiol administered. On the other hand, a clear-cut dose — effect relationship could not be observed between the amount of oestradiol administered and the plasma levels of LH and testosterone. The data indicate that the bulk of perorally administered oestradiol is transformed to oestrone sulphate accompanied by smaller quantities of oestrone and oestradiol sulphate and that the ratios of circulating oestrogens seen after the ingestion of oestradiol deviate considerably from those observed in the normal menstrual cycle.