Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans.
BACKGROUND
The oxidative metabolism of estrogens in humans is mediated primarily by cytochrome P450, many isoenzymes of which are inducible by dietary and pharmacologic agents. One major pathway, 2-hydroxylation, is induced by dietary indole-3-carbinol (I3C), which is present in cruciferous vegetables (e.g., cabbage and broccoli).


OBJECTIVE
Because the pool of available estrogen substrates for all pathways is limited, we hypothesized that increased 2-hydroxylation of estrogens would lead to decreased activity in competing metabolic pathways.


METHODS
Urine samples were collected from subjects before and after oral ingestion of I3C (6-7 mg/kg per day). In the first study, seven men received I3C for 1 week; in the second study, 10 women received I3C for 2 months. A profile of 13 estrogens was measured in each sample by gas chromatography-mass spectrometry.


RESULTS
In both men and women, I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16alpha-hydroxyestrone, were lower after I3C treatment.


CONCLUSIONS
These findings support the hypothesis that I3C-induced estrogen 2-hydroxylation results in decreased concentrations of several metabolites known to activate the estrogen receptor. This effect may lower estrogenic stimulation in women.


CONCLUSIONS
I3C may have chemopreventive activity against breast cancer in humans, although the long-term effects of higher catechol estrogen levels in women require further investigation.
Michnovicz
J J
JJ
Rockefeller University Hospital and The Institute for Hormone Research, New York, NY 10016, USA.
Adlercreutz
H
H
Bradlow
H L
HL
D000328:Adult; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004967:Estrogens / Q000652:urine*; D002393:Estrogens, Catechol / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D004967:Estrogens; D002393:Estrogens, Catechol; D007211:Indoles; D003577:Cytochrome P-450 Enzyme System; C016517:indole-3-carbinol