A method for estimating catechol estrogen metabolism from excretion of noncatechol estrogens

The relationship of catechol estrogen metabolism to disease has seldom been investigated because of analytic difficulties. Estradiol (E2) and estrone (E1) are oxidized simultaneously at either ring A or ring D, and the rate of catechol estrogen formation (r 2 ) is reciprocally related to the rate of 16α‐hydroxylation (r 3 ). The rate of ovarian estrogen production (X 10 ) can be summarized as to metabolic outcome: X 10 = r 10 + r 2 + r 3 + r u , where r 10 is the loss of E1 and E2 in urine, and r u is the fecal and urinary loss of unknown oxidative products. Assuming a constant r u between subjects: X 10 – r 10 = r 2 + r 3 . The value r 10 is only a very small fraction of X 10 and does not affect the constancy of the X 10 concentration between subjects during similar menstrual cycle phases. In the absence of xenobiotics, r 2 and r 3 are reciprocally interrelated: r 2 ± r 3 = K (an oxidation constant whose limiting factor is the biologically available estrogen at the cell surface). To the extent that r 10 approximates estrogens available for cellular metabolism, the rate of catechol estrogen metabolism may be determined fromr 2 =\documentclass{article}\pagestyle{empty}\begin{document}$$ {\rm r}_2 \frac{{[{\rm E}1\, + \,{\rm E}2]\, \times \,{\rm K}}}{{[{\rm E}3\, + \,16\alpha {\rm OHE}1]}} $$\end{document}From published data K = 12.4 ± 0.8 of the standard error of the mean. Pearson correlation coefficients between actual and estimated catechol estrogen excretion in groups of subjects ranged from 0.61 to 0.97 (median, 0.88). This method has been useful for clinical investigation of the relationship of catechol estrogen metabolism to disease until better methods to measure catechol estrogen directly are available.