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Estradiol metabolism in cirrhosis

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PMC
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  • Biology
  • Medicine
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Abstract

Abnormal estrogen metabolism has been found in cirrhosis after administration of intravenous tracers of estradiol-3H to 6 patients and 23 healthy controls. The major abnormalities observed involved estrogen metabolites other than the 3 “classic” ones, i.e., estrone (E1), estradiol (E2), and estriol (E3). Urinary recovery of radioactivity was regularly elevated in the patients, to an average of 71% of the dose compared to 51% in normals. This is considered to reflect the component of intrahepatic cholestasis in cirrhosis. The per cent dose recovered as urinary glucosiduronates (42%) was normal in cirrhotics in contrast to impaired glucuronidation of cortisol metabolites in this disease. E1 and E2 were present in normal amounts, and E3 was slightly elevated to 21% of the extract compared to 14% in controls. There were strikingly decreased excretion of 2-hydroxyestrone (3% compared with normal 20%) and 2-methoxyestrone (2% compared with 5%) and increased excretion of 16α-hydroxyestrone (12% compared with normal 6%). Thus cirrhosis, too, is characterized by the reciprocal relationship between decreased 2-hydroxylation and increased 16α-hydroxylation previously described in hypothyroidism and male breast cancer. However, unlike these latter, the increase of 16α-hydroxy metabolites was less than the decrease of 2-hydroxy metabolites. The data indicate clearcut impairment of 2-hydroxylation, suggestive impairment of 16α-hydroxylation, and a definite depression of the reaction 16α-hydroxyestrone→estriol, the latter finding so far unique to cirrhosis. Demonstration of abnormal peripheral metabolism of estrogen in cirrhosis provides a new approach to the origin of the hyperestrogenic syndrome in this disease.

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