Oestrogens in the treatment of cancer.

The story of the isolation and characterization of the oestrogenic hormones begins in i923, when Allen and Doisy first used the vaginal smear method to test the activity of substances isolated from the ovary. The smear is spread on a microscopic slide and stained with a suitable dye and the type of cells observed shows at which stage of the sexual cycle an animal is. At the ' resting ' stage only epithelial debris and leucocytes are seen. As the reproductive period or oestrus approaches, the leucocytes disappear and the large epithelial cells increase in number. At the height of the reproductive period the nuclei or epithelial ,cells disappear and the smear shows keratinized plaques. In an ovariectomized animal these changes do not take place and only the ' resting' stage is seen. However, if an active oestrogenic substance is injected into the ovariectomized animal, the same characteristic changes can be reproduced as take place normally in the intact animal. Allen and Doisy found that by using a sufficient number of animals and graduating the dose, they could make this into a fairly accurate quantitative test. The next step forward was the discovery by Aschheim and Zondek (I927) that large quantities of oestrogenic substance are excreted in the urine of pregnant animals. This is much easier material to deal with than the ovarian extracts and large quantities of purifiable material became available. By I932 five oestrogenic compounds had been isolated in crystalline form. These are oestrone, oestriol, oestradiol, equiline and equilenine (Figs. I to 5). Two very striking facts now became apparent. The first was that there should be no less than five distinct substances to be found in natlre, all having oestrogenic activity in varying degrees. The second fact which came to light was that the proliferative changes occurring in the vagina in oestrus bear a certain resemblance to the proliferation caused by the application of carcinogenic hydrocarbons to the skin. It was obvious, therefore , that oestrogenic activity is not specific in the same way as other hormonal activities are specific and the possibility arose that it was not even confined to one chemical group of compounds. Two of the most potent carcinogenic hydrocarbons, namely, I:2:5:6-dibenzanthracene and I:2-benz-pyrene (Figs. 6 and 7), were tested and they proved to be weakly but quite definitely oestro-genic. At the same time a series of compounds, containing the phenanthrene nucleus, but without …