Environmental Health Impacts of Equine Estrogens Derived from Hormone Replacement Therapy
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- 作者：Charles R. Tyler ; Amy L. Filby ; Lisa K. Bickley ; Rob I. Cumming ; Richard Gibson ; Pierre Labadie ; Yoshinao Katsu ; Katherine E. Liney ; Janice A. Shears ; Vanessa Silva-Castro ; Hiroshi Urushitani ; Anke La
- 刊名：Environmental Science & Technology
- 出版年：2009
- 出版时间：May 15, 2009
- 年：2009
- 卷：43
- 期：10
- 页码：3897-3904
- 全文大小：296K
- 年卷期：v.43,no.10(May 15, 2009)
- ISSN：1520-5851
文摘
Many factors have been considered in evaluations of the risk−benefit balance of hormone replacement therapy (HRT), used for treating menopausal symptoms in women, but not its potential risks for the environment. We investigated the possible environmental health implications of conjugated equine estrogens (CEEs), the most common components of HRT, including their discharge into the environment, their uptake, potency, and ability to induce biological effects in wildlife. Influents and effluents from four UK sewage treatment works (STWs), and bile of effluent-exposed fish, were screened for six equine estrogens. In vitro estrogen receptor (ER) activation assays were applied in humans and fish to compare their potencies, followed by in vivo exposures of fish to equine estrogens and evaluation of bioaccumulation, estrogenic responses, and ER gene expression. The equine estrogen equilenin (Eqn), and its metabolite 17β-dihydroequilenin (17β-Eqn), were detected by tandem GC-MSMS in all STW influent samples and 83% of STW effluent samples analyzed, respectively, at low concentrations (0.07−2.6 ng/L) and were taken-up into effluent-exposed fish. As occurs in humans, these estrogens bound to and activated the fish ERs, with potencies at ERα 2.4−3490% of that for 17β-estradiol. Exposure of fish for 21 days to Eqn and 17β-Eqn induced estrogenic responses including hepatic growth and vitellogenin production at concentrations as low as 0.6−4.2 ng/L. Associated with these effects were inductions of hepatic ERα and ERβ1 gene expression, suggesting ER-mediated mechanism(s) of action. These data provide evidence for the discharge of equine estrogens from HRT into the aquatic environment and highlight a strong likelihood that these compounds contribute to feminization in exposed wildlife.