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Environmental science & technology2009; 43(10); 3897-3904; doi: 10.1021/es803135q

Environmental health impacts of equine estrogens derived from hormone replacement therapy.

Abstract: 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 U.K. 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 17beta-dihydroequilenin (17beta-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 ERalpha 2.4-3490% of thatfor 17beta-estradiol. Exposure of fish for 21 days to Eqn and 17beta-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 ERalpha and ERbeta1 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.
Publication Date: 2009-06-24 PubMed ID: 19544905DOI: 10.1021/es803135qGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research explores the potential environmental risks posed by equine estrogens (common components in hormone replacement therapy for menopausal women), specifically their effects on aquatic wildlife. The study discovered that these hormones could indeed enter the environment, bioaccumulate in aquatic organisms, and induce estrogen-related phenotypes and biological effects.

Methodology

  • The team investigated the presence of six equine estrogens in influents and effluents from four U.K. sewage treatment works (STWs), as well as in bile from fish exposed to these effluents. This was done via a screening method.
  • In vitro estrogen receptor (ER) activation assays were conducted on humans and fish to compare and contrast the effect of these hormones on different species.
  • Next, the researchers exposed fish to these equine estrogens in vivo to study their bioaccumulation, ER gene expression, and estrogenic responses, which include hepatic growth and vitellogenin production.

Results and Findings

  • They detected the presence of equine estrogen equilenin (Eqn), and its metabolite 17beta-dihydroequilenin (17beta-Eqn) in all the influent samples and 83% of STW effluent samples. These samples contained low concentrations of these hormones (ranging between 0.07-2.6 ng/L). Additionally, it was observed that these estrogens were absorbed by fish exposed to the STW effluents.
  • In vitro ER activation assays showed that these hormones could bind to and activate both human and fish ERs, with different levels of potency.
  • In vivo exposure to Eqn and 17beta-Eqn for 21 days resulted in estrogenic responses in fish at concentrations as low as 0.6-4.2 ng/L. These responses included hepatic growth and vitellogenin production. Additionally, genes expression of hepatic ERalpha and ERbeta1 was induced, indicating an ER-mediated mechanism of action.

Conclusion

  • The findings suggest that, due to the application of equine estrogens in hormone replacement therapy, these hormones are finding their way into the aquatic environment and are potentially causing feminization effects in exposed aquatic life.
  • This work underscores the need for considering environmental risks associated with pharmaceuticals like hormone replacement therapy, informing risk-benefit evaluations more above and beyond their effect on human health.

Cite This Article

APA
Tyler CR, Filby AL, Bickley LK, Cumming RI, Gibson R, Labadie P, Katsu Y, Liney KE, Shears JA, Silva-Castro V, Urushitani H, Lange A, Winter MJ, Iguchi T, Hill EM. (2009). Environmental health impacts of equine estrogens derived from hormone replacement therapy. Environ Sci Technol, 43(10), 3897-3904. https://doi.org/10.1021/es803135q

Publication

ISSN: 0013-936X
NlmUniqueID: 0213155
Country: United States
Language: English
Volume: 43
Issue: 10
Pages: 3897-3904

Researcher Affiliations

Tyler, Charles R
  • School of Biosciences, University of Exeter, Exeter, United Kingdom. c.r.tyler@exeter.ac.uk
Filby, Amy L
    Bickley, Lisa K
      Cumming, Rob I
        Gibson, Richard
          Labadie, Pierre
            Katsu, Yoshinao
              Liney, Katherine E
                Shears, Janice A
                  Silva-Castro, Vanessa
                    Urushitani, Hiroshi
                      Lange, Anke
                        Winter, Matthew J
                          Iguchi, Taisen
                            Hill, Elizabeth M

                              MeSH Terms

                              • Animals
                              • Environmental Exposure
                              • Environmental Health
                              • Estrogen Receptor alpha / metabolism
                              • Estrogen Replacement Therapy
                              • Estrogens / chemistry
                              • Estrogens / toxicity
                              • Fishes / metabolism
                              • Horses / metabolism
                              • Humans
                              • Sewage
                              • United Kingdom
                              • Waste Disposal, Fluid

                              Grant Funding

                              • Biotechnology and Biological Sciences Research Council

                              Citations

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