Elsevier

Science of The Total Environment

Volume 407, Issue 18, 1 September 2009, Pages 4975-4985
Science of The Total Environment

Review
Urinary excretion rates of natural estrogens and androgens from humans, and their occurrence and fate in the environment: A review

https://doi.org/10.1016/j.scitotenv.2009.06.001Get rights and content

Abstract

Endocrine disrupting compounds (EDCs) are pollutants with estrogenic or androgenic activities at very low concentrations and are emerging as a major concern for water quality. For sewage of municipal wastewater treatment plants in cities, one of the most important sources of EDCs are natural estrogens and natural androgens (NEAs) excreted from humans. Therefore, estrogenic/androgenic potencies or relative binding affinity of the NEAs were first outlined from different sources, and data of urinary excretion rates of NEAs were summarized. To evaluate their estrogenic activities, their excretion rates of estrogen equivalent (EEQ) or testosterone (T) equivalent (TEQ) were also calculated. Based on our summary, the total excretion rates of EEQ by estrone (E1), 17β-estradiol (E2), and estriol (E3) only accounted for 66–82% of the total excretion rate of EEQ among four different groups, and the other corresponding natural estrogens contributed 18–34%, which meant that some of the other natural estrogens may also exist in wastewater with high estrogenic activities. Based on the contribution ratio of individual androgens to the total excretion rate of TEQ, five out of 12 natural androgens, T, dihydrotestosterone (DHT), androsterone (AD), 5β-androstanediol (β-ADL), and androstenediol (ANL) were evaluated as the priority natural androgens, which may exist in wastewater with high androgenic activities. Published data on occurrence and fate of the NEAs including natural estrogen conjugates in the environment were also summarized here.

Introduction

Endocrine disrupting compounds (EDCs) are chemicals with the potential to elicit negative effects on the endocrine systems of humans and wildlife. Research of EDCs in the past few decades has grown rapidly. With progress of research on EDCs, the definition has been widened to include a broad class of chemicals from natural estrogens, natural androgens, phytoestrogens, synthetic estrogens and androgens, to industrial chemicals (Liu et al., 2009). Among these, natural estrogens i.e., Estrone (E1), 17β-estradiol (E2) and Estriol (E3) are the core EDCs, which are the most commonly studied and monitored.

Health concerns over the effect of EDCs on the health of humans and wildlife accelerated the research of the estrogenic (androgenic) potencies of target chemicals evaluated by in vitro bioassay. Currently, there are several bioassays available such as Yeast based recombinant estrogen receptor reporter assay (YES, Routledge and Sumpter, 1996), MCF-7 cell proliferation (E-Screen, Soto et al., 1995), Estrogen receptor-mediated chemical activated luciferase gene expression assay (ER-CALUX, Legler et al., 1999), Estrogen receptor (ER) competitive ligand binding assay (ER-Binding, Bolger et al., 1998), Yeast based recombinant androgen receptor–reporter assay (YAS, Sohoni and Sumpter, 1998), Androgen receptor (AR) competitive ligand binding assay (AR-Binding, Fang et al., 2003), and so on. Among these bioassays, YES (YAS) is the most widely applied assay in environmental samples, but research has discovered that YES (YAS) would be influenced by anti-estrogens (anti-androgens) in complex environmental samples (Liu, Liu, 2004, Conroy et al., 2007, Urbatzka et al., 2007). This effect results in the findings of great different estrogenic activities between the wastewater samples and the total of their fractionations evaluated by YES/YAS (Nakada et al., 2004, Urbatzka et al., 2007, Salste et al., 2007). Although bioassays mentioned above were all applied by researchers in real wastewater samples, no bioassay was universally accepted as a standard method like the Chemical Oxygen Demand (COD). To prove the feasibility and validity of in vitro bioassays applied to wastewater samples, the relationship of sample estrogenic activity between chemical analysis and bioassay has become one of the topics of interest. In Nakada et al. (2004), the estrogenic activities of three wastewater effluent samples derived from chemical analysis were about 151.6–916.7% of those from YES assay; in Vermeirssen et al. (2005), the estrogenic activities of several river samples (sampled by Polar Organic Chemical Integrative Sampler, POCIS (pesticides)) calculated from chemical analysis were 51–353% of those from YES, in which only E1, E2 and 17α-ethynylestradiol (EE2) were monitored by LC-MS/MS. The same tendency was also observed by Salste et al. (2007), where the chemically derived estrogenic activities of two wastewater effluent samples were about 116.1–139.6% of those from another YES assay. Tan (2006) compared both influent and effluent results of five wastewater treatment plants (WWTPs) using GC-MS analysis and E-Screen, and chemical derived values ranged from about 0.1–1340% of those from E-Screen. Liu et al. (in press) monitored as much as 15 target EDCs of two WWTPs using GC-MS and LC-MS/MS, and the chemical-derived estrogenic activities were about 1.2–83.8% of those from the ER-Binding assay, and the corresponding chemical-derived androgenic activities were all less than 3% of those from the AR-Binding assay. These results above cannot adequately support the feasibility of bioassays applied for complex environmental samples. On the contrary, in a mini-review (Schlenk, 2008), the feasibility of in vitro assay (YES) for environmental samples was questioned, in which some of the water samples were detected with no estrogenic activities by YES assay, while they were proven to have in vivo response.

With the progress of chemical analysis on EDCs for environmental samples, more and more target estrogenic chemicals were monitored. As many as 30 EDCs were monitored by GC-HRMS in five Canadian wastewater samples (Fernandez et al., 2007), and the measurement of 13 androgenic chemicals was also constructed using ultra-performance liquid chromatography electrospray tandem mass spectrometry (UPLC-MS/MS) (Chang et al., 2008). These foundations enhanced the platform of EDCs on the estrogenic (androgenic) comparison of wastewater between chemical analysis and bioassay. It is difficult, time-consuming work to monitor target chemicals in complex wastewater samples. If the source of EDCs can be roughly estimated, it will be helpful for monitoring of EDCs in environmental water samples. To date, it is well known that NEAs are one of the strongest potent EDCs evaluated by in vitro assays, and their representative E2 and testosterone (Te) were often used as the standard chemicals in bioassays. For wastewater of municipal WWTPs, it is considerable that the estrogenic (androgenic) activity is mainly derived from urine or feces of humans. Although there are many reports about the concentrations of NEAs excreted in human urine or feces, few conclusions have been made.

The objectives of this review are: (1) highlight estrogenic potencies of NEAs measured by different in vitro assays, which have been proven as existing in urine or feces; (2) summarize urinary excretion rates of NEAs from humans; (3) summarize occurrence and fate of NEAs in the environment, including free estrogens, free androgens and estrogen conjugates.

Section snippets

Estrogenic/androgenic potencies of NEAs by in vitro assays

In recent research, as many as 16 estrogens, and more androgens, were measured in urine or feces of humans (de la Torre et al., 2001, Xu et al., 2005, Xu et al., 2006), and several bioassays were used to measure and evaluate their estrogenic/androgenic activities. To show the relationship between chemical analysis and bioassays, the estrogenic/androgenic potencies of NEAs are included in Tables 1 and 2, in which their physicochemical properties are also given. In Table 1, estrogenic/androgenic

Urinary excretion rates of natural estrogens

There is much data on excretion of natural estrogens from human urine or feces, and some conclusions on E1, E2 and E3 are now available ( Kiuru, 2005, Tan, 2006). Johnson and Williams (2004) gave a more detailed conclusion on excretions of E1, E2 and E3 from humans, and a model to estimate their influent and effluent concentrations was also established. However, other natural estrogens in urine or feces of humans, which may also exist in wastewater, were considered negligible. With progress of

Natural estrogen conjugates in the environment

It is known that NEAs initially excreted by humans are mainly in sulfate or glucuronide conjugates, and then they are changed to free NEAs, in which glucuronide estrogens were reported easily changed to their free estrogens, while sulfate estrogens were more recalcitrant to biotransformation (Ternes et al., 1999a, Panter et al., 1999, D’Ascenzo et al., 2003). In D'Ascenzo et al. (2003), conjugated estrogens were individually spiked to one septic tank wastewater with concentration of 25 µg/L,

Conclusions

Based on numerous data, urinary excretion rates of NEAs from humans were comprehensively summarized and results on their occurrence and fate in the environment were also outlined. In this review article, some conclusions below may merit attention.

  • (1)

    Presently, research of natural estrogens in wastewater mainly focused on E1, E2 and E3, while other natural estrogens were considered negligible. However, based on the data of human urinary excretion rate, the contribution ratio of E1, E2, and E3 to

References (100)

  • FernandezM.P. et al.

    An assessment of estrogenic organic contaminants in Canadian wastewaters

    Sci Total Environ

    (2007)
  • FineD.D. et al.

    Quantitation of estrogens in ground water and swine lagoon samples using solid-phase extraction, pentafluorobenzyl/trimethylsiyl derivatizations and gas chromatography-negative ion chemical ionization tandem mass spectrometry

    J Chromatogr A

    (2003)
  • Fotsis

    The multicomponent analysis of estrogens in urine by ion exchange chromatography and GC-MS-II. Fraction and quantitation of the main groups of estrogen conjugates

    J Steroid Biochem

    (1987)
  • FotsisT. et al.

    The multicomponent analysis of estrogens in urine by ion exchange chromatography and GC-MS-I. Quantitation of estrogens after initial hydrolysis of conjugates

    J Steroid Biochem

    (1987)
  • HibberdA. et al.

    An improved method for the simultaneous analysis of phenolic and steroidal estrogens in water and sediment

    Talanta

    (2009)
  • HohenblumP. et al.

    Monitoring of selected estrogenic hormones and industrial chemicals in groundwaters and surface waters in Austria

    Sci Total Environ

    (2004)
  • IsobeT. et al.

    Determination of estrogens and their conjugates in water using solid-phase extraction followed by liquid chromatography–tandem mass spectrometry

    J. Chromatogr A

    (2003)
  • IsobeT. et al.

    Horizontal distribution of steroid estrogens in surface sediments in Tokyo bay

    Environ Pollut

    (2006)
  • JiangJ.Q. et al.

    Occurrence and treatment trials of endocrine disrupting chemicals (EDCs) in wastewaters

    Chemosphere

    (2005)
  • JohnsonA.C. et al.

    Estimating steroid oestrogen inputs into activated sludge treatment works and observations on their removal from the effluent

    Sci Total Environ

    (2000)
  • KolokA.S. et al.

    Occurrence and biological effect of exogenous steroids in the Elkhorn river, Nebraska, USA

    Sci Total Environ

    (2007)
  • LabadieP. et al.

    Analysis of estrogens in river sediments by liquid chromatography–electrospray ionisation mass spectrometry comparison of tandem mass spectrometry and time-of-flight mass spectrometry

    J Chromatogr A

    (2007)
  • LaganaA. et al.

    Analytical methodologies for determining the occurrence of endocrine disrupting chemicals in sewage treatment plants and natural waters

    Anal Chim Acta

    (2004)
  • LeuschF.D. et al.

    Bioassay-derived androgenic and estrogenic activity in municipal sewage in Australia and New Zealand

    Ecotoxicol Environ Safe

    (2006)
  • LiuZ.H. et al.

    Removal mechanisms for endocrine disrupting compounds (EDCs) in wastewater-physical means, biodegradation, and chemical advanced oxidation: a review

    Sci Total Environ

    (2009)
  • MatejicekD. et al.

    Combined isolation and purification procedures prior to the high-performance liquid chromatographic-ion-trap tandem mass spectrometric determination of estrogens and their conjugates in river sediments

    J Chromatogr A

    (2007)
  • Mauvais-jarvisP. et al.

    Studies on testosterone metabolism. VI. Precursors of urinary androstanediols

    Steroids

    (1968)
  • PanterG.H. et al.

    Transformation of a non-oestrogenic steroid metabolite to an oestrogenically active substance by minimal bacterial activity

    Chemosphere

    (1999)
  • Rodriguez-MozazS. et al.

    Monitoring of estrogens, pesticides and bisphenol A in natural waters and drinking water treatment plants by solid-phase extraction–liquid chromatography mass spectrometry

    J Chromatogr A

    (2004)
  • SalsteL. et al.

    Determination of estrogens and estrogenic activity in wastewater effluent by chemical analysis and the bioluminescent yeas assay

    Sci Total Environ

    (2007)
  • SchlenkD.

    Are steroids really the cause for fish feminization? A mini-review of in vitro and in vivo guided TIEs

    Mar Pollut Bull

    (2008)
  • ServosM.R. et al.

    Distribution of estrogens, 17β-estradiol and estrone, in Canadian municipal wastewater treatment plants

    Sci Total Environ

    (2005)
  • ShenJ.H. et al.

    Toxicological profile of pollutants in surface water from an area in Taihu lake, Yangtze Delta

    Toxicology

    (2001)
  • ShoreL.S. et al.

    Washout of accumulated testosterone in a watershed

    Sci Total Environ

    (2004)
  • TernesT.A. et al.

    Behaviour and occurrence of estrogens in municipal sewage treatment plants-II. Aerobic batch experiments with activated sludge

    Sci Total Environ

    (1999)
  • TernesT.A. et al.

    Behavior and occurrence of estrogens in municipal sewage treatment plants-I. Investigations in Germany, Canada and Brazil

    Sci Total Environ

    (1999)
  • UrbatzkaR. et al.

    Androgenic and antiandrogenic activities in water and sediment samples from the river Lambro, Italy, detected by yeast androgen screen and chemical analyses

    Chemosphere

    (2007)
  • XiaoX.Y. et al.

    Analysis of estrogens in river water and effluents using solid-phase extraction and gas chromatography-negative chemical ionization mass spectrometry of the pentafluorobenzoyl derivatives

    J Chromatogr A

    (2001)
  • AdlercreutzH. et al.

    Oestrogen in human pregnancy faeces

    ACTA Endocrinologica

    (1976)
  • BarontiC. et al.

    Monitoring natural and synthetic estrogens at activated sludge sewage treatment plants and in a receiving river water

    Environ Sci Technol

    (2000)
  • BauerE.R.S. et al.

    Characterization of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor

    APMIS

    (2000)
  • BolgerR. et al.

    Rapid screening of environmental chemicals for estrogen receptor binding capacity

    Environ Health Environ

    (1998)
  • ChangH. et al.

    Occurrence of natural and synthetic glucocorticoids in sewage treatment plants and receiving river waters

    Environ Sci Technol

    (2007)
  • Conroy O., Estrogenic and anti-estrogenic activity present in wastewater effluent and reclaimed water. Doctor...
  • DrewesJ.E. et al.

    An assessment of endocrine disrupting activity changes during wastewater treatment through the use of bioassays and chemical measurements

    Water Environ Res

    (2005)
  • DurhanE.J. et al.

    Identification of metabolites of trenbolone acetate in androgenic runoff from a beef feedlot

    Environ Health Perspect

    (2006)
  • FangH. et al.

    Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor

    Chem Res Toxicol

    (2003)
  • GaoW.Q. et al.

    Chemistry and structural biology of androgen receptor

    Chem Rev

    (2005)
  • GentiliA. et al.

    Analysis of free estrogens and their conjugates in sewage and river waters by solid phase extraction then liquid chromatography–electrospray–tandem mass spectrometry

    Chromatographia

    (2002)
  • HommaK. et al.

    Urine steroid hormone analysis in cytochrome P450 oxidoreductase deficiency:implication for the backdoor pathway to dihydrotestosterone

    J Clin Endocrin Metab

    (2006)
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