Exposure to diethylstilbestrol (DES) induces persistent structural and functional alterations in the developing reproductive tract of males. It is possible that xenoestrogens other than DES alter sexual differentiation in males and account for the increasing incidence of developmental disorders of the reproductive tract in men and wild animals. Phytoestrogens (coumestans, isoflavonoids, flavonoids, and lignans) present in numerous edible plants are quantitatively the most important environmental estrogens when their hormonal potency is assessed in vitro. They exert their estrogenic activity by interacting with estrogen receptors (ERs) in vitro. They may also act as antiestrogens by competing for the binding sites of estrogen receptors or the active site of the estrogen biosynthesizing and metabolizing enzymes, such as aromatase and estrogen-specific 17β-hydroxysteroid oxidoreductase (type 1). In theory, phytoestrogens and structurally related compounds could harm the reproductive health of males also by acting as antiestrogens.
There are very little data on effects of phytoestrogens in males. Estrogenic effects in wildlife have been described but the evidence for the role of phytoestrogens is indirect and seen under conditions of excessive exposure. In doses comparable to the daily intake from soy- based feed, isoflavonoids such as genistein were estrogen agonists in the prostate of adult laboratory rodents. When given neonatally, no persistent effects were observed. In contrast, the central nervous system (CNS)-gonadal axis and the male sexual behavior of the rat appear to be sensitive to phytoestrogens during development. The changes were similar but not identical to those seen after neonatal treatment with DES, but higher doses of phytoestrogens were needed.There are no data on effects of phytoestrogens given as pure compounds to humans, and all evidence currently available is indirect and based on experiments with phytoestrogen- rich diets. The hormonal effects have so far been marginal. It is known that the intake of phytoestrogens is higher in countries where the incidence rates of clinical conditions linked to estrogen exposure, such as hypospadia or testicular and prostatic cancers, are low. This makes it unlikely that phytoestrogens, or structurally related compounds in amounts present in Asian diets, would have DES-like actions. This does not exclude possibilities that they influence concentrations of endogenous sex hormones and interact with the ER, and that through these mechanisms they alter male sex differentiation, and consequently increase the risks of male genital tract tumors or developmental disorders, particularly in doses exceeding the daily intake of phytoestrogens in Asian diets.
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