Studies on Phenolic Steroids in Human Subjects. II. The Metabolic Fate and Hepato-Biliary-Enteric Circulation of C14-Estrone and C14-Estradiol in Women1

Abstract

C14-Estrone and C14-estradiol were injected intravenously into 22 women. A little over 80% of the administered radioactivity were excreted in the urine during the 96 to 120 hours following injection. On the average, 72% of the counts in the urine were extractable following various hydrolytic procedures, with the preponderant part being present in the glucuroni-date form. About 50% of the radioactivity administered appeared in the bile, collected through T-tube drainage, mostly as conjugates released by hydrolysis at pH 1 or by hot acid. Approximately 7% of the radio-activity appeared in the stools of non-fistula patients, indicating gastrointestinal reabsorption of metabolites excreted in the bile. The radioactive steroids were cleared from the plasma rapidly with at least two separate rates having half-lives of approximately 20 and 70 minutes, respectively. The conjugated metabolites of C14-estrone and C14-estradiol reached their peak in the plasma within 15-30 minutes following the injection of the steroids and retained high levels for as long as 3 days. The levels of the conjugated steroids in the plasma of patients with T-tube drainage of bile were the lowest of the group. The significance of the hepato-biliary-enteric circulation of estrogens in relation to the slow urinary excretion of the radioactivity is discussed.