The relationship of catechol estrogen metabolism to disease has seldom been investigated because of analytic difficulties. Estradiol (E2) and estrone (El) are oxidized simultaneously at either ring A or ring D, and the rate of catechol estrogen formation (rz) is reciprocally related to the rate of 16a-hydroxylation (r3). The rate of ovarian estrogen production (X,J can be summarized as to metabolic outcome: X,, = rlo + rz + r, + ru, where r,, is the loss of E l and E2 in urine, and ru is the fecal and urinary loss of unknown oxidative products. Assuming a constant ru between subjects: X,, -r,, = rz f r,. The value rl0 is only a very small fraction of X,, and does not affect the constancy of the XI, concentration between subjects during similar menstrual cycle phases. In the absence of xenobiotics, r2 and rn are reciprocally interrelated: rz x r3 = K (an oxidation constant whose limiting factor is the biologically available estrogen at the cell surface). To the extent that r,, approximates estrogens available for cellular metabolism, the rate of catechol estrogen metabolism may be determined from
From published data K = 12.4 f 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.