Interest in methoxylated oestrogens has been stimulated by the discovery of 2-methoxyoestrone and 2-methoxyoestriol in human urine (Kraychy & Gallagher, 1957; Fishman & Gallagher, 1958; Loke & Marrian, 1958). Furthermore, the 3-methyl ether of 17α-ethinyloestradiol is widely used as a potent oral oestrogen. The question arises whether the oestrogen methyl ethers can be demethylated in vivo to the parent phenols. To test this possibility, the 3-methyl ethers of oestrone, oestradiol and oestriol have been administered to human subjects, and the resulting outputs of oestrone, oestradiol and oestriol and of their methyl ethers in the urine have been measured.
The methyl ethers were purified by chromatography on alumina and recrystallization from ethanol. Their melting points (uncorrected) were: oestrone methyl ether 172° c; oestradiol methyl ether 97–98° c, 117–118° C; oestriol methyl ether 148–154° c. The pure compounds were dissolved in olive oil (2·5 mg./ml. for oestrone and oestradiol