Journal of Clinical Endocrinology & Metabolism, Vol 43, 497-505, Copyright © 1976 by Endocrine Society

ARTICLES

Intestinal metabolism of estrogens

H Adlercreutz, F Martin, M Pulkkinen, H Dencker, U Rimer, NO Sjoberg and MJ Tikkanen

Estrogen metabolism in the human intestine was studied in two ways. Firstly, by measuring the excretion of 12 estrogens in pooled human late pregnancy feces before and during the administration of ampicillin (2 g/day). Secondly, by administering 5.4 and 20 mg of 16alpha- hydroxyestrone orally to two postmenopausal women and analyzing the estrogens in simultaneously drawn portal and peripheral venous blood samples at time intervals from 0 to 150 min after steroid administration. The majority of the estrogens in normal pregnancy feces were unconjugated. The amounts of estradiol, estreon and 16-epiestriol excreted, relative to the principal estrogen estriol, were greater than in pregnancy bile or urine and 16alpha-hydroxyestrone, an important biliary estrogen, was only present in trace amounts. Considerable quantities of 15alpha-hydroxyestradiol-17beta were also found. Ampicillin administration, which decreases intestinal bacterial steroid metabolism, caused a huge increase in the fecal excretion of conjugated estrogens. In particular it caused very striking increases in the excretion of both unconjugated and conjugated, estriol, 15alpha- hydroxyestrone, 15alpha-hydroxyestradiol and 2-methoxyestrone. These findings emphasize the active role played by the intestinal microflora in estrogen metabolism under normal conditions. Administration of 16alpha-hydroxyestrone resulted in increases in portal venous unconjugated and conjugated 16alpha-hydroxyestrone, 16-oxoestradiol- 17beta, 15alpha-hydroxyestrone, 16-epiestriol and conjugated estriol levels. The most significant finding in both subjects was the large increase in portal venous unconjugated 15alpha-hydroxyestrone. This would suggest that the human intestine (or intestinal contents) has the ability to carry out the transformation, 16alpha-hydroxyestrone leads to 15alpha-hydroxyestrone. Increases in the same estrogens were found in peripheral plasma, with the increase in conjugated estriol occurring in peripheral blood before it was seen in portal blood. The largest elevations in peripheral plasma values were seen in unconjugated estriol and conjugated 16alpha-hydroxyestrone in the subject who received the 20 mg dose and in unconjugated 16alpha-hydroxyestrone and 16-oxoestradiol-17beta in the subject who had the 5.4 mg dose. The intestinal and enterohepatic metabolism of estrogens is discussed in relation to these findings.

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