The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 4 1779-1787
Copyright © 2004 by The Endocrine Society

Phytoestrogens Are Potent Inhibitors of Estrogen Sulfation: Implications for
Breast Cancer Risk and Treatment
R. M. Harris, D. M. Wood, L. Bottomley, S. Blagg, K. Owen, P. J. Hughes, R.
H. Waring and C. J. Kirk
School of Biosciences and Medical School, University of Birmingham,
Edgbaston, Birmingham B15 2TT, United Kingdom

Address all correspondence and requests for reprints to: C. J. Kirk, School
of Biosciences and Medical School, University of Birmingham, Edgbaston,
Birmingham B15 2TT, United Kingdom. E-mail: .

We investigated the ability of 37 flavonoids and flavonoid sulfoconjugates,
including some abundant dietary constituents, to act as substrates and/or
inhibitors of the sulfotransferase and sulfatase enzymes that interconvert
active estrogens and inactive estrogen sulfates in human tissues. The
enzymes studied include estrogen sulfotransferase, the thermostable
phenolsulfotransferase that acts on a range of substrates including
estrogens; steroid sulfatase; and two related enzymes, monoamine
phenolsulfotransferase and arylsulfatase A. Several dietary flavonoids,
including the soy isoflavones genistein and daidzein, were sulfated by these
human sulfotransferases. Many flavonoids were potent inhibitors of
thermostable phenolsulfotransferase. Genistein and equol were potent mixed
inhibitors of hepatic estrogen sulfotransferase, with inhibitory constant
values of 500 nM and 400 nM, respectively. Monoamine phenolsulfotransferase
activity was relatively unaffected by flavonoids, but this enzyme was mainly
responsible for the sulfation of flavonoids at concentrations greater than 1
µM. Of the compounds tested, only daidzein 4,7-bisulfate, a trace metabolite
in humans, significantly inhibited steroid sulfatase in the micromolar
concentration range. Hence, dietary flavonoids may be able to influence the
bioavailability of endogenous estrogens, and disrupt endocrine balance, by
increasing the ratio of active estrogens to inactive estrogen sulfates in
human tissues.