Oestrogenic substances

C,flH2o02- White crystals, m.p. 168-171 °C. Prepared from deoxyanisoin by ethylation, conversion to the alcohol, dehydration and demethylation. It is an oestrogenic substance which is highly active when administered orally. It is used for treating menopausal symptoms, for the suppression of lactation and for treatment of cancer of the prostate. 

C. Desbrow, E. Routledge, D. Sheehan, M. Waldock and J. Sumpter, in The Identification and Assessment of Oestrogen Substances in Sewage Treatmen t Works Effinents, Environment Agency, Bristol, 1996. 

Another reason for scepticism with regard to the existence of threshold concentrations is that for some substances, and some effects, different chemicals act together so that the total effect depends on the sum of their concentrations. This has been found to be the case for a number of oestrogenic substances (Silva et al, 2002, and see Note 3 for Chapter 5). The apparent no-effect level of such chemicals crucially depends on which other chemicals are present. In other words, laboratory tests in which animals are exposed to individual substances may have little relevance to the real world situation in which we are exposed to hundreds of different chemicals. 

Desbrow C., Routledge E., Sheehan D., Waldock M., Sumpter J. (1996) The identification and assessment of oestrogen substances in sewage treatment works effluents (P2-i490/7). London MAFF Lab. Brunei University, Environment Agency. 

Environment Agency (1996) The Identification and Assessment of Oestrogenic Substances in Sewage Treatment Works Effluents. R D Technical Summary P38. London Environment Agency. 

One or two other oestrogenic substances are used pharmaceutically, and these are noted in Table 29. 

Natural oestrogens generally only retain a significant proportion of their activity if administered intravenously. Several synthetic analogues have been developed which can be administered orally. Most of these substances also display more potent activity than native oestrogen. The most important synthetic oestrogen analogues include ethinyloestradiol and diethylstilboestrol (often simply termed stilboestrol). These are orally active and are approximately 10 and 5 times (respectively) more potent than oestrone. 

Ferrando, R., M. M. Guilleux, and A. Guerrillot-Venet. Oestrogen content of plants as a function of conditions of culture. Nature 1961 192 1205. Ahmad, Y. S. A note of the plants of the medicinal value found in Pakistan. Govt of Pakistan Press, Karachi 1957. Walker, B. S., and J. C. Janney. Estrogenic substances. II. An analysis of plant sources. Endocrinology... 

Panter G.H., R.S. Thompson, N. Betesord, and J.P. Sumpter (1999). Transformation of a non-oestrogenic steroid metabolite to an oestrogenically active substance by minimal bacterial activity. Chemosphere 38 3579-3596. 

In the case of some oestrogenic chemicals (that mimic the effects of the female hormone oestrogen) it has been shown that what should be added to predict the combined effect of a mixture is not the effects of the individual chemicals but their concentrations (Silva et al, 2002). This means that a substance present at a concentration at which on its own it has no oestrogenic effect will contribute to the total oestrogenic effect of a mixture containing other oestrogenic chemicals. For such substances there is in practice no real threshold concentration below which they do not have an effect. Such no-effect levels are a crucial part of chemicals risk assessment, as I will explain in Chapter 7. 

Lacassagne A. Apparition d adenocarcinomes mammaires chez des souris males traites par une substance oestrogene synthetique. Comptes Rend Seances Soc Biol 1938 129 641-3. 

In contrast to the almost ubiquitous occurrence of the flavonoids in higher plants, the isoflavonoids have a very limited taxonomic distribution. They are in general confined to one group of plants - the sub-family Lotoideae of the Leguminosae [390, 391 ]. Occasionally they occur in a few other families [326], The overall biological properties also differ from those of the flavonoids flavonoids on the whole are innocuous substances [392], but isoflavonoids usually have oestrogenic, insecticidal, piscicidal and/or antifungal activities. 

As we have seen, there are many other chemicals capable of causing these effects, although they are generally very much less potent that the natural oestrogens and the synthetic oestrogens used in the contraceptive piU. Mixtures of these chemicals, which includes natural substances from plants, pesticides, and industrial chemicals, may be more potent than the individual components. This phenomenon is called synergy (see p. 35) and is currently an area of intense scientific interest, as is the subject of endocrine disruptors. 

Effects on the male reproductive system can also be produced by substances that interfere with male hormones, so-called anti-androgens. DDE is one such chemical, but attempts to correlate DDE levels in human breast fat tissue with the incidence of breast cancer have produced equivocal results. Dioxin shows significant anti-oestrogenic activity, but after the accident at Seveso a decreased incidence of breast cancer was observed in those who had been exposed. 

Substances that act like the natural hormones oestrogens. oncogenes Cancer genes. 

Other substances that are being evaluated in Alzheimer s disease include the antioxidant vitamin E, the monoamine oxidase type B inhibitor, selegeline (see p. 425) and the plant extract gingko biloba, which is though to have antioxidant and cholinergic activity. Oestrogens and nonsteroidal anti-inflammatory agents may also have protective effects. 

Plasma proteins. Oestrogens cause an increase in proteins, particularly the globulins that bind hydrocortisone, thyroxine and iron. As a result, the total plasma concentration of the boimd substances is increased, though the concentration of free and active substance remains normal. This can be misleading in diagnostic tests, e.g. of thyroid function. This effect on plasma proteins passes off about 6 weeks after cessation of the oestrogen. 

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