EXCRETION OF 2-MONOMETHYL AND 3-MONOMETHYL ETHERS OF 2-HYDROXYESTROGENS IN HEALTHY MALE-VOLUNTEERS

The formation of catecholestrogens by 2- and 4-hydroxylation of monoph enolic estrogens represents a major route of estrogen metabolism, In v itro and in vivo studies on catecholestrogens have shown that 2-hydrox ylated catecholestrogens are primarily inactivated by O-methylation, w hile O-methylation of l-hydroxylated estro en is of minor importance. In the present study the in vivo production of isomeric 2- and 3-monom ethyl ethers of 2-hydroxyestrogens was measured in 12 healthy omnivoro us male volunteers aged 51 +/- 4 years. The sum of estrone and 17 beta -estradiol, 2-hydroxyestrogens (sum of 2-hydroxyestrone and 2-hydroxye stradiol), 4-hydroxyestrogens (sum of 4-hydroxyestrone and 4-hydroxyes tradiol) and the sum of the isomeric monomethyl ethers of 2-hydroxyest rone and 2-hydroxyestradiol were measured in 24-h urinary samples. The determinations included hydrolysis of steroid conjugates, separation by chromatographic steps and final quantification by radioimmunoassay. The specificity of the antibodies enabled differentiation between the isomeric monomethyl ethers. The mean urinary excretion rates were 8.8 +/- 2.9 mu g/24h for estrone plus estradiol, 5.2 +/- 2.4 mu g/24 h fo r the 2-hydroxyestrogens and 1.3 +/- 0.5 mu g/24 h for the 4-hydroxyes trogens, The 2- and 3-monomethyl ethers of the 2-hydroxyestrogens were found in all individuals, with excretion rates of 5.8 +/- 2.6 mu g/24 h for 2-methoxyestrogens and 3.6 +/- 1.1 mu g/24 h for 2-hydroxyestro gen-3-methyl ethers. The findings indicated that 2-hydroxyestradiol is metabolized in vivo by 2-O-methylation and, to a lesser extent, by 3- O-methylation.