The evidence that catecholestrogens are formed in the brain and exert behavioral effects in animal models suggest that these steroids might have psychotropic activities. In the present investigation, the formation and metabolism of catecholestrogens were studied in depressed patients. Twenty-four-hr urine samples were collected from 6 male patients (59 +/- 8 years) with endogenous retarded depression (subtype primary, endogenous, and recurrent according to Research Diagnostic Criteria) and from 12 male control subjects (51 +/- 4 years). The patients were treated with the monoamine oxidase inhibitor tranylcypromine (10-40 mg/day for 3-4 weeks). The concentrations of primary estrogens, 4- and 2-hydroxyestrogens and 2-methoxyestrogens, were measured in the urine samples after multiple chromatographic separation steps by radioimmunoassay. In the depressed patients, the excretion rates of 4-hydroxyestrogens were significantly lower than in control subjects. The ratio 2-methoxyestrogens:2-hydroxyestrogens as an index for 2-O-methylation was 3.8 +/- 1.6 in patients and 1.8 +/- 0.7 in controls. The increased methylation and reduced 4-hydroxylation rates of patients were not affected by treatment with tranylcypromine though the psychopathological state was improved by 46%. Therefore, it seemed unlikely that the observed alterations were pathognomonically relevant in these depressed patients. The alterations in the formation and methylation of catecholestrogens show that the depressed patients exhibited remarkable metabolic disturbances. The functional role of these disturbances remains to be clarified.
