Golden R J, Noller K L, Titus-Ernstoff L, Kaufman R H, Mittendorf R, Stillman R, Reese E A
Environmental Risk Sciences, Washington, D.C. 20007, USA.
Crit Rev Toxicol. 1998 Mar;28(2):109-227. doi: 10.1080/10408449891344191.
Recently, a great deal of attention and interest has been directed toward the hypothesis that exposure, particularly in utero exposure, to certain environmental chemicals might be capable of causing a spectrum of adverse effects as a result of endocrine modulation. In particular, the hypothesis has focused on the idea that certain organochlorine and other compounds acting as weak estrogens have the capability, either alone or in combination, to produce a variety of adverse effects, including breast, testicular and prostate cancer, adverse effects on male reproductive tract, endometriosis, fertility problems, alterations of sexual behavior, learning disability or delay, and adverse effects on immune and thyroid function. While hormones are potent modulators of biochemical and physiological function, the implication that exposure to environmental hormones (e.g., xenoestrogens) has this capability is uncertain. While it is reasonable to hypothesize that exposure to estrogen-like compounds, whatever their source, could adversely affect human health, biological plausibility alone is an insufficient basis for concluding that environmental endocrine modulators have adversely affected humans. Diethylstilbestrol (DES) is a potent, synthetic estrogen administered under a variety of dosing protocols to millions of women in the belief (now known to be mistaken) that it would prevent miscarriage. As a result of this use, substantial in utero exposure to large numbers of male and female offspring occurred. Numerous studies have been conducted on the health consequences of in utero DES exposure among the adult offspring of these women. There are also extensive animal data on the effects of DES and there is a high degree of concordance between effects observed in animals and humans. The extensive human data in DES-exposed cohorts provide a useful basis for assessing the biological plausibility that potential adverse effects might occur following in utero exposure to compounds identified as environmental estrogens. The effects observed in both animals and humans following in utero exposure to sufficient doses of DES are consistent with basic principles of dose response as well as the possibility of maternal dose levels below which potential non-cancer effects may not occur. Significant differences in estrogenic potency between DES and chemicals identified to date as environmental estrogens, as well as an even larger number of naturally occurring dietary phytoestrogens, must be taken into account when inferring potential effects from in utero exposure to any of these substances. The antiestrogenic properties of many of these same exogenous compounds might also diminish net estrogenic effects. Based on the extensive data on DES-exposed cohorts, it appears unlikely that in utero exposure to usual levels of environmental estrogenic substances, from whatever source, would be sufficient to produce many of the effects (i.e., endometriosis, adverse effects on the male reproductive tract, male and female fertility problems, alterations of sexual behavior, learning problems, immune system effects or thyroid effects) hypothesized as potentially resulting from exposure to chemicals identified to date as environmental estrogens.
最近，人们对这样一种假说给予了大量关注并产生了浓厚兴趣，即接触某些环境化学物质，尤其是子宫内接触，可能由于内分泌调节而导致一系列不良影响。特别地，该假说聚焦于这样一种观点，即某些作为弱雌激素起作用的有机氯及其他化合物，单独或联合起来有能力产生多种不良影响，包括乳腺癌、睾丸癌和前列腺癌、对男性生殖道的不良影响、子宫内膜异位症、生育问题、性行为改变、学习障碍或延迟，以及对免疫和甲状腺功能的不良影响。虽然激素是生化和生理功能的有力调节因子，但接触环境激素（如外源性雌激素）是否具有这种能力尚不确定。虽然假设接触类似雌激素的化合物，无论其来源如何，可能对人类健康产生不利影响是合理的，但仅凭生物学合理性不足以得出环境内分泌调节剂已对人类产生不利影响的结论。己烯雌酚（DES）是一种强效合成雌激素，曾按照多种给药方案给予数百万妇女，当时认为（现在已知是错误的）它能预防流产。由于这种使用方式，大量的雄性和雌性后代在子宫内受到了大量接触。针对这些妇女成年后代子宫内接触DES的健康后果进行了大量研究。关于DES影响的动物数据也很广泛，并且在动物和人类中观察到的影响之间有高度的一致性。DES暴露队列中的大量人类数据为评估子宫内接触被确定为环境雌激素的化合物后可能产生潜在不良影响的生物学合理性提供了有用的依据。子宫内接触足够剂量DES后在动物和人类中观察到的影响与剂量反应的基本原理以及母体剂量水平低于该水平可能不会发生潜在非癌症影响的可能性是一致的。在推断子宫内接触这些物质中的任何一种的潜在影响时，必须考虑DES与迄今被确定为环境雌激素的化学物质之间以及更多天然存在的膳食植物雌激素之间在雌激素效力上的显著差异。许多这些相同外源性化合物的抗雌激素特性也可能会减弱净雌激素效应。基于DES暴露队列的广泛数据，子宫内接触通常水平的环境雌激素物质，无论其来源如何，似乎不太可能足以产生许多被假设为由迄今被确定为环境雌激素的化学物质暴露可能导致的影响（即子宫内膜异位症、对男性生殖道的不良影响、男性和女性生育问题、性行为改变、学习问题、免疫系统影响或甲状腺影响）。
